A customized zirconia abutment design combined with a CAD/CAM laminate veneer: a clinical report.
An alternative prosthetic treatment approach for single implants in the maxillary esthetic zone with an improper implant axis, limited interocclusal distance, inadequate abutment retention, and screw holes located at the labial surface is presented in this clinical report. The gingiva and soft tissues were contoured with provisional composite restorations to mimic the emergence profile of lateral incisors. Prefabricated zirconia abutments were customized with laminate veneer preparations by appropriate ceramic build-up with reference from the reshaped gingiva to avoid labiolingual overcontour. The laminate veneers were fabricated by computer-aided design/ computer-assisted manufacture to cover the screw hole of the angulated abutment at the labial surface. Preliminary results revealed improvement in esthetics; however, long-term clinical follow-up should be performed.


Loss to follow-up in tuberculosis treatment and its relationship with patients' knowledge of the disease and other associated factors.
To identify factors associated with loss to follow-up in Tuberculosis (TB) treatment, including patients' level of knowledge regarding treatment of this disease. 42 loss to follow-up cases and 84 control cases that were finishing the sixth month of their first treatment for tuberculosis were selected for this study. Primary data were gathered through interviews, while secondary data were obtained from the notification form of the disease, between December 2011 and April 2012. Factors associated with loss to follow-up were analyzed by means of a conditional logistic regression multivariate model for matched case-control groups. No significant differences were observed between loss to follow-up cases and controls regarding socioeconomic factors, lifestyle, clinical condition, treatment-related behaviors and the access of patients to sources of information on TB. In the regression multivariate analysis, significant associations with retreatment after loss to follow-up that were detected include: scarce knowledge on tuberculosis, lack of adherence to consultation during the current treatment, noncompliance with follow-up consultation deadline, smoking and HIV negative. When compared to controls, cases undergoing TB retreatment after loss to follow-up have less knowledge on the disease, which is a sign for the professionals responsible for health education of the need to invest more time and efforts in activities that help the patient understand the disease and its treatment, as well as to have higher levels of adherence. In addition, noncompliance with the follow-up consultation deadline, failure to attend consultations during the current treatment and smoking are also factors that may be influenced by poor knowledge on the disease, which leads to the treatment loss to follow-up.


Effects of alkali ion dopants on the transport mechanisms and the thermal stabilities of imidazolium-based organic ionic plastic crystals.
Various dopant alkali ions have been introduced into organic ionic plastic crystals (OIPCs) in order to design solid electrolytes with the desired thermal stability and ionic conductivity. We performed extensive molecular dynamics simulations to investigate at the molecular level how dopant alkali ions affect the rotational and the translational diffusion of ions and the thermal stability of OIPCs. We introduced lithium (Li+), sodium (Na+), and potassium (K+) ions as dopants into 1-methyl-3-methylimidazolium hexafluorophosphate ([MMIM][PF6]) OIPCs at the molecular level. We found that as smaller alkali ions are doped, larger domains of the crystals are disrupted. This makes it harder for OIPCs doped with smaller alkali ions to maintain their crystal structure such that the melting temperature of OIPCs decreases and phase transitions between rotator phases change. The size of dopant alkali ions also affects the rotational diffusion of matrix ions of [MMIM]+ and PF6-: the rotational diffusion of matrix ions near Li+ ions becomes more heterogeneous and facilitated than those near other kinds of alkali ions. We also find that alkali ions of different kinds diffuse translationally in OIPCs via different transport mechanisms: while the Li+ ion undergoes continuous (anion-associated) diffusion through an amorphous region, the K+ ion hops between neighbor lattice sites. To investigate the effects of the relative size between matrix cations and dopant ions on translational diffusions, we also simulate OIPCs with longer alkyl chains such as 1-ethyl-3-methylimidazolium hexafluorophosphate ([EMIM][PF6]) and 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) crystals. We find that as the size of imidazolium cations increases, the hopping diffusion of the K+ ion becomes suppressed and the K+ ion is more likely to diffuse through amorphous domains.


Association of human leukocyte antigen variants and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A meta-analysis.
The association between human leukocyte antigen (HLA) variants and allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) was evaluated through a pooled analysis of published studies. A comprehensive search was performed in multiple databases, including PubMed, MEDLINE, ISI Web of Knowledge, EMBASE, Cochrane Register of Controlled Trials, and Science Direct. Studies investigating the association between HLA alleles with allopurinol-induced SJS or TEN were retrieved, and the data were independently extracted. The overall odds ratios (ORs) with corresponding 95% confidence intervals were calculated to determine the association between the presence of HLA variant in at least one allele and allopurinol-induced SJS or TEN. To test the robustness of the meta-analysis results, a sensitivity analysis was performed by removing each study one at a time and calculating the pooled ORs of the remaining studies. The fixed-effects and random-effects models were used to pool the collected data. A total of 4 studies with 81 allopurinol-induced SJS or TEN cases and matched controls (allopurinol-tolerant patients) or population controls (general population) were identified. SJS and TEN were found to be significantly associated with HLA-A*33:03 and HLA-C*03:02 alleles in both groups of studies with matched controls and population controls. All of the pooled ORs were not significantly affected by the remaining studies and different modeling methods, indicating robust results. A strong association was found between HLA-A*33:03 and HLA-C*03:02 alleles and allopurinol-induced SJS or TEN, especially in an Asian population.


Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension.
Human studies have shown that the blood pressure lowering effects of angiotensin converting enzyme inhibitors are accompanied by a reduction in plasma norepinephrine levels. Whether this is due to central or peripheral mechanisms is unknown, however. To evaluate the effects of chronic interference with the renin-angiotensin system on sympathetic nerve traffic and baroreflex control of vagal and adrenergic cardiovascular drive. In 18 untreated mild to moderate essential hypertensive patients aged 48.5+/-1.9 years (mean+/-SEM), we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), plasma renin activity (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography) and postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In nine patients, measurements were performed before and after 2 months of oral administration of lisinopril (10 mg/day), while in the remaining nine patients they were performed before and after a 2 month observation period, without the drug administration. Measurements were performed at rest and during baroreflex stimulation and deactivation elicited by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Lisinopril induced a marked increase in plasma renin activity (from 1.1+/-0.2 to 6.4+/-1.3 ng/ml per h, P< 0.01) and a reduction in mean arterial pressure (from 109.6+/-3.1 to 98.7+/-2.9 mmHg, P < 0.01) without affecting the heart rate. Plasma norepinephrine and muscle sympathetic nerve activity values were not significantly different before and after lisinopril treatment (plasma norepinephrine values changed from 290.4+/-39.2 to 308.1+/-67.1 pg/ml; muscle sympathetic nerve activity changed from 56.4+/-5.3 to 50.6+/-6.6 bursts/100 heart beats). Neither the sympathoinhibitory nor the sympathoexcitatory responses to phenylephrine and nitroprusside were affected by lisinopril, nor the concomitant bradycardia and tachycardia. The curves relating mean arterial pressure to heart rate and muscle sympathetic nerve activity values during baroreceptor manipulation were shifted to the left, indicating a resetting of the baroreflex to the lower blood pressure values achieved during treatment. CONCLUSIONS In essential hypertension, sympathetic nerve traffic is not affected by chronic angiotensin converting enzyme inhibitor treatment that effectively interferes with the renin-angiotensin system and lowers the elevated blood pressure. The baroreflex ability to modulate heart rate and central sympathetic outflow is also unaffected. These data argue against the existence of a central sympathoexcitatory effect of angiotensin II in this condition. They also indicate that antihypertensive treatment with an angiotensin converting enzyme inhibitor preserves autonomic reflex control, with favorable consequences for cardiovascular homeostasis.


Evaluation protocol of the implementation of a learning healthcare system in clinical practice: the Connected Health Cities programme in the north of England.
The 'learning healthcare system' (LHS) has been proposed to deliver better outcomes for patients and communities by analysing routinely captured health information and feeding back results to clinical staff. This approach is being piloted in the Connected Health Cities (CHC) programme in four regions in the north of England. This article describes the protocol of the evaluation of this programme. In designing this evaluation, we had to take a pragmatic approach to ensure the feasibility of completing the work within 1 year. Furthermore, we have designed the evaluation in such a way as to be able to capture differences in how each of the CHC regions uses a variety of methods to create their own LHS. A mixed methods approach has been adopted for this evaluation due the scale and complexities of the pilot study. A documentary review will identify how CHC pilot study deliverables were operationalised. To gain a broad understanding of CHC staff experiences, an online survey will be offered to all staff to complete. Semi-structured interviews with key programme staff will be used to gain a deeper understanding of key achievements, as well as how challenges have been overcome or managed. Our data analysis will triangulate the documentary review, survey and interview data. A thematic analysis using our logic model as a framework will also be used to assess progress against the CHC programme deliverables and to identify recommendations to support future programme decision-making. Ethical approval was granted by The University of Manchester Ethics Committee on 24 May 2018. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, the internet and various stakeholder/patient and public engagement activities.


Triple B←N Lewis Pair-Functionalized Triazatruxenes with Large Stokes Shifts.
A novel class of multiple B←N Lewis pair-functionalized polycyclic aromatic hydrocarbons with different BR2 groups (R = Cl or Et) directly attached at positions 1, 6, and 11 of triazatruxene was synthesized. The triazatruxene backbone of 4 displays a bowl shape, and its molecular skeleton shows a highly twisted propeller-like structure with C3 symmetry. The introduction of B←N Lewis pairs not only results in a large decrease in the HOMO-LUMO gap but also lowers the LUMO to -3.00 eV. Both compounds show excellent stability with large Stokes shifts of ≤8234 cm-1 and solvatochromic emission in solvents of different polarities.


Tunable biomimetic chalcogels with Fe4S4 cores and [Sn(n)S(2n+2)](4-)(n = 1, 2, 4) building blocks for solar fuel catalysis.
Biology sustains itself by converting solar energy in a series of reactions between light harvesting components, electron transfer pathways, and redox-active centers. As an artificial system mimicking such solar energy conversion, porous chalcogenide aerogels (chalcogels) encompass the above components into a common architecture. We present here the ability to tune the redox properties of chalcogel frameworks containing biological Fe(4)S(4) clusters. We have investigated the effects of [Sn(n)S(2n+2)](4-) linking blocks ([SnS(4)](4-), [Sn(2)S(6)](4-), [Sn(4)S(10)](4-)) on the electrochemical and electrocatalytic properties of the chalcogels, as well as on the photophysical properties of incorporated light-harvesting dyes, tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+)). The various thiostannate linking blocks do not alter significantly the chalcogel surface area (90-310 m(2)/g) or the local environment around the Fe(4)S(4) clusters as indicated by (57)Fe Mössbauer spectroscopy. However, the varying charge density of the linking blocks greatly affects the reduction potential of the Fe(4)S(4) cluster and the electronic interaction between the clusters. We find that when the Fe(4)S(4) clusters are bridged with the adamantane [Sn(4)S(10)](4-) linking blocks, the electrochemical reduction of CS(2) and the photochemical production of hydrogen are enhanced. The ability to tune the redox properties of biomimetic chalcogels presents a novel avenue to control the function of multifunctional chalcogels for a wide range of electrochemical or photochemical processes relevant to solar fuels.


Induced latency in pseudorabies vaccinated pigs.
A latent pseudorabies virus infection was established in pigs despite vaccination with a modified-live pseudorabies virus vaccine. Although the vaccinated pigs developed high concentrations of antibody, virus was recovered from the tonsils and lungs of pigs treated with dexamethasone three months after inoculation with virulent virus. These results may explain why vaccination programs have failed to eliminate the persistence and spread of virulent pseudorabies virus in infected herds.


Biochemical and Immunological Effects of Listeria monocytogenes Hemolysin.
The biochemical and immunological effects of Listeria monocytogenes hemolysin in CD-1 mice were studied. Intraperitoneal injection of 256 complete hemolytic units (CHU) caused a twofold increase in plasma beta-glucuronidase levels but was not lethal. In contrast, 256 or more CHU caused 100% lethality in 4 to 5 min when administered intravenously. Intravenous administration of 50 CHU caused a 10- to 11-fold increase in plasma beta-glucuronidase levels and was lethal for a variable percentage of the animals. Carbon clearance experiments showed the phagocytic index to be depressed by relatively small amounts of intravenously administered hemolysin and suggested that hemolysin may function as a leucocidal agressin during listeric infection. Increased plasma levels of ornithine carbamyltransferase after intravenous injection of hemolysin indicated hepatocellular damage. Liver carbohydrate and blood glucose determinations on fasted mice showed a reduced gluconeogenic capability in hemolysin-treated animals. Mice immunized with purified hemolysin or live vaccine were more resistant to several of the toxic parameters studied. The data indicate that hemolysin is produced during listeric infection and is antigenic, but not necessarily a protective immunogen.


Monitoring of antifouling booster biocides in water and sediment from the port of Osaka, Japan.
Concentrations of booster antifouling compounds in the port of Osaka, Japan were assessed. Concentrations of Sea-Nine 211 (4,5-dichloro-2-n-octyl-3-isothiazolone), thiabendazole (2-(4-thiazolyl)-benzimidazole), IPBC (3-iodo-2-propynyl butylcarbamate), Diuron (3,4-dichlorophenyl-N, N-dimethylurea), Irgarol 1051 (2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine), and M1 (2-methylthio-4-t-butylamino-6-amino-s-triazine) in port water samples were in the range of <0.003-0.004 microg L(-1), <0.0008-0.020 microg L(-1), <0.0007-1.54 microg L(-1), <0.0008-0.267 microg L(-1), and <0.0019-0.167 microg L(-1), respectively. IPBC was not detected in the water samples, but the concentration of Diuron was higher than any previously reported. The concentrations of Sea-Nine 211, thiabendazole, Diuron, Irgarol 1051, and M1 in sediment samples were in the range of <0.04-2.4 microg kg(-1) dry, <0.08-1.2 microg kg(-1) dry, <0.64-1350 microg kg(-1) dry, <0.08-8.2 microg kg(-1) dry, and <0.18-2.9 microg kg(-1) dry, respectively. IPBC was again not detected. The levels of Sea-Nine 211, Diuron, and Irgarol 1051 in water and sediment samples were high in a poorly flushed mooring area for small and medium-hull vessels. Levels of Diuron and Irgarol 1051 were highest in summer. The concentration of Sea-Nine 211 in water increased between August and October 2002. Except for M1, increases in the levels of booster biocides in sediment were observed during the study period. The sediment-water partition (Kd) was calculated by dividing the concentrations in sediment by the concentrations in water. The Kd values for Sea-Nine 211, thiabendazole, Diuron, Irgarol 1051, and M1 were 690, 180, 2700, 300, and 870. The Kd value for these alternative compounds was lower than for TBT.


Influence of surface stresses on indentation response.
Surface stresses lead to an effective change in the elastic constants of thin films and at surfaces. The development of modern scanning probe techniques like contact resonance atomic force microscopy empowers the experimenter to measure at scales where these effects become increasingly relevant. In this paper we employ a computational multiscale approach where we compare density functional theory (DFT) and molecular dynamics simulations as tools to calculate the thin-film/surface elastic behavior for silicon and strontiumtitanate. From the surface elastic constants gained by DFT calculations we develop a continuum finite-element multilayer model to study the impact of surface stresses on indentation experiments. In general the stress field of an indenter and thus the impact of surface stresses on the indentation modulus depends on its contact radius and on its particular shape. We propose an analytical model that describes the behavior of the indentation modulus as a function of the contact radius. We show that this model fits well to simulation results gained for a spherical and a flat punch indenter. Our results demonstrate a surface-stress-induced reduction of the indentation modulus of about 5% for strontiumtitanate and 6% for silicon for a contact radius of [Formula: see text], irrespective of the indenter shape.


[Treatment of intestinal failure by total parenteral nutrition at home in children and adults].
Intestinal failure is characterised by inability of the intestine to absorb sufficient nutrients to maintain the integrity and function of the body. This can be caused by malabsorption due to too short an intestine or an abnormality of the mucosa, or by a severe motility disorder. In addition to dietary measures, the prescription of total parental nutrition (TPN) at home is sometimes necessary. This treatment is a burden on the patient and the risk of complications must be reduced to a minimum. The risks of long-term parenteral nutrition can be limited and the quality of the provision of services can be increased if the co-ordination is in the hands of a centre for home parenteral nutrition. In the Netherlands there are two centres for home-TPN: the St Radboud University Medical Centre in Nijmegen and the University Medical Centre (AMC) in Amsterdam. In both children and adults, the most common indications are the short bowel syndrome and motility disorders. However, the syndromes that cause this are clearly different in the different age groups. Parenteral nutrition can be given for long periods of time. A large variety of complications can occur, related especially to the equipment or the nutrients. When the nutrition is given via a central venous catheter, then sepsis is a serious and possibly life-threatening complication. In case of administration via an arteriovenous shunt, thrombosis of the shunt is the most frequent problem. If the treatment by means of home-TPN fails, then transplantation of the small intestine should be considered.


Single Intravenous Dose of Novel Flurbiprofen-Loaded Proniosome Formulations Provides Prolonged Systemic Exposure and Anti-inflammatory Effect.
Vesicular and colloidal delivery systems can be designed to control drug release spatially and temporally to improve drug efficacy and side effect profiles. Niosomes (vesicles prepared from nonionic surfactants in aqueous media) are gaining interest as an alternative vesicular delivery system as they offer advantages such as biocompatibility, chemical stability, low cost, high purity, and versatility. However, the physical stability of niosomes, like other vesicular systems, is limited by vesicle fusion, aggregation, and leakage. Proniosomes (dehydrated powder or gel formulations that spontaneously form niosomes on hydration with aqueous media) can overcome these physical stability problems and are more convenient for sterilization, storage, transport, distribution, and dosing. Proniosomes have mostly been explored for their potential to enhance transdermal and oral absorption. In this study we assess, for the first time, the potential for hydrated proniosomes to sustain systemic exposure and therapeutic effect after intravenous delivery. Proniosomes carrying the anti-inflammatory drug, flurbiprofen, were prepared by spraying different nonionic surfactants (span 20, span 40, and span 60 in varying ratios with span 80) and cholesterol onto a sorbitol carrier. The proniosome powders were characterized for surface morphology and flow properties. Niosome formation was assessed at three different hydration temperatures (25, 37, and 45 °C), and the niosomes were assessed for vesicle size, entrapment efficiency, and sterility. OLP proniosomes prepared with a high ratio of span 80 to span 20 were found to spontaneously form vesicles of small size and high drug loading on hydration with aqueous media. The OLP derived niosomes successfully sustained in vitro drug release, in vivo pharmacokinetics, and the anti-inflammatory effect of flurbiprofen in an acute (rat paw edema) model of inflammation when compared to a control solution formulation. The study demonstrates that hydrated proniosomes can prolong systemic drug exposure over 3 days and provide a sustained therapeutic effect. The developed proniosomes represent a novel approach to treat acute pain and inflammation with the potential to be administered as a single intravenous dose by a clinician at the time of injury or surgery that provides adequate relief for several days and reduces fluctuations in therapy. Similar systems loaded with different drugs have potential for broader application in anesthesia, anti-infective, antiemetic, and cancer therapy.


Belowground Inoculation With Arbuscular Mycorrhizal Fungi Increases Local and Systemic Susceptibility of Rice Plants to Different Pest Organisms.
Plants face numerous challenges from both aboveground and belowground stressors, and defend themselves against harmful insects and microorganisms in many ways. Because plant responses to biotic stresses are not only local but also systemic, belowground interactions can influence aboveground interactions in both natural and agricultural ecosystems. Arbuscular mycorrhizal fungi (AMF) are soilborne organisms that form symbiotic associations with many plant roots and are thought to play a central role in plant nutrition, growth, and fitness. In the present study, we focused on the influence of AMF on rice defense against pests. We inoculated rice plants with AMF in several field and greenhouse experiments to test whether the interaction of AMF with rice roots changes the resistance of rice against two chewing insects, the rice water weevil (Lissorhoptrus oryzophilus Kuschel, RWW) and the fall armyworm (Spodoptera frugiperda, FAW), and against infection by sheath blight (Rhizoctonia solani, ShB). Both in field and greenhouse experiments, the performance of insects and the pathogen on rice was enhanced when plants were inoculated with AMF. In the field, inoculating rice plants with AMF resulted in higher numbers of RWW larvae on rice roots. In the greenhouse, more RWW first instars emerged from AMF-colonized rice plants than from non-colonized control plants. Weight gains of FAW larvae were higher on rice plants treated with AMF inoculum. Lesion lengths and susceptibility to ShB infection were higher in rice plants colonized by AMF. Although AMF inoculation enhanced the growth of rice plants, the nutritional analyses of root and shoot tissues indicated no major increases in the concentrations of nutrients in rice plants colonized by AMF. The large effects on rice susceptibility to pests in the absence of large effects on plant nutrition suggest that AMF colonization influences other mechanisms of susceptibility (e.g., defense signaling processes). This study represents the first study conducted in the U.S. in rice showing AMF-induced plant susceptibility to several antagonists that specialize on different plant tissues. Given the widespread occurrence of AMF, our findings will help to provide a different perspective into the causal basis of rice systemic resistance/susceptibility to insects and pathogens.


Pentagastrin potentiates nonadrenergic inhibitory neuromuscular transmission in orad stomach of the dog.
Mechanical and intracellular electrical activities were recorded separately from circular muscle of the orad corpus of the canine stomach. In normal Krebs solution, transmural electrical nerve stimulation produced excitatory and inhibitory responses. The excitatory response was blocked by atropine; the inhibitory response was unaffected by phentolamine or propranolol alone or in combination. Both responses were blocked by tetrodotoxin. In the presence of pentagastrin, the inhibitory response to electrical nerve stimulation was potentiated in a dose-dependent manner. The threshold concentration for this potentiating effect was 3 X 10(-11) M. Intracellular recordings showed that hyperpolarization of the resting membrane potential in response to inhibitory nerve stimulation was greater in the presence of pentagastrin than in its absence. These data suggest that, in addition to a direct stimulatory effect on the muscle, pentagastrin also potentiates the effect of ongoing activity of intramural inhibitory nerves. This latter effect is only apparent when the inhibitory neural network is active. Thus, the in vivo effect of pentagastrin on motor activity of the corpus will depend on the degree of ongoing activity of intramural inhibitory nerves.


Ultrasound-assisted lumbar puncture with a horizontal and perpendicular paramedian approach based on positioning in patients with abnormal spinal anatomy: a case report and technical description.
The use of ultrasound has been reported to be beneficial in challenging neuraxial procedures. The angled probe is responsible for the main limitations of previous ultrasound-assisted techniques. We developed a novel technique for challenging lumbar puncture, aiming to locate the needle entry point which allowed for a horizontal and perpendicular needle trajectory and thereby addressed the drawbacks of earlier ultrasound-assisted techniques. Patient 1 was an adult patient with severe scoliosis who underwent a series of intrathecal injections of nusinersen. The preprocedural ultrasound scan revealed a cephalad probe's angulation (relative to the edge of the bed) in the paramedian sagittal oblique view, and then the probe was rotated 90° into a transverse plane and we noted that a rocking maneuver was required to obtain normalized views. Then the shoulders were moved forward to eliminate the need for cephalad angulation of the probe. The degree of rocking was translated to a lateral offset from the midline of the spine through an imaginary lumbar puncture's triangle model, and a needle entry point was marked. The spinal needle was advanced through this marking-point without craniocaudal and lateromedial angulation, and first-pass success was achieved in all eight lumbar punctures. Patient 2 was an elderly patient with ankylosing spondylitis who underwent spinal anesthesia for transurethral resection of the prostate. The patient was positioned anteriorly obliquely to create a vertebral rotation that eliminated medial angulation in the paramedian approach. The procedure succeeded on the first pass. This ultrasound-assisted paramedian approach with a horizontal and perpendicular needle trajectory may be a promising technique that can help circumvent challenging anatomy. Larger case series and prospective studies are warranted to define its superiority to alternative approaches of lumbar puncture for patients with difficulties.


Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study.
In the National Heart, Lung and Blood Institute Type II Coronary Intervention Study, patients with Type II hyperlipoproteinemia and coronary artery disease (CAD) were placed on a low-fat, low-cholesterol diet and then were randomly allocated to receive either 6 g cholestyramine four times daily or placebo. This double-blind study evaluated the effects of cholestyramine on the progression of CAD as assessed by angiography. Diet alone reduced the low-density lipoprotein cholesterol 6% in both groups. After randomization, low-density lipoprotein cholesterol decreased another 5% in the placebo group and 26% in the cholestyramine-treated group. Coronary angiography was performed in 116 patients before and after 5 years of treatment. CAD progressed in 49% (28 of 57) of the placebo-treated patients vs 32% (19 of 59) of the cholestyramine-treated patients (p less than .05). When only definite progression was considered, 35% (20 of 57) of the placebo-treated patients vs 25% (15 of 59) of the cholestyramine-treated patients exhibited definite progression; the difference was not statistically significant. However, when this analysis was performed with adjustment for baseline inequalities of risk factors, effect of treatment was more pronounced. Of lesions causing 50% or greater stenosis at baseline, 33% of placebo-treated and 12% of cholestyramine-treated patients manifested lesion progression (p less than .05). Similar analyses with other end points (percent of baseline lesions that progressed, lesions that progressed to occlusion, lesions that regressed, size of lesion change, and all cardiovascular end points) all favored the cholestyramine-treated group, but were not statistically significant. Thus, although the sample size does not allow a definitive conclusion to be drawn, this study suggests that cholestyramine treatment retards the rate of progression of CAD in patients with Type II hyperlipoproteinemia.


Coronavirus multiplication: locations of genes for virion proteins on the avian infectious bronchitis virus genome.
Six overlapping viral RNAs are synthesized in cells infected with the avian coronavirus infectious bronchitis virus (IBV). These RNAs contain a 3'-coterminal nested sequence set and were assumed to be viral mRNAs. The seven major IBV virion proteins are all produced by processing of three polypeptides of ca. 23, 51, and 115 kilodaltons. These are the core polypeptides of the small membrane proteins, the nucleocapsid protein, and the 155-kilodalton precursor to the large membrane proteins GP90 and GP84, respectively. To determine which mRNAs specify these polypeptides, we isolated RNA from infected cells and translated it in a messenger-dependent rabbit reticulocyte lysate. Proteins of 23, 51, and 110 kilodaltons were produced. Two-dimensional tryptic peptide mapping demonstrated that these proteins were closely related to the major virion proteins. Fractionation of the RNA before cell-free translation permitted the correlation of messenger activities for synthesis of the proteins with the presence of specific mRNAs. We found that the smallest RNA, RNA A, directs the synthesis of P51, the nucleocapsid protein. RNA C, which contains the sequences of RNA A, directs the synthesis of the small membrane protein P23. RNA E directs the synthesis of the large virion glycoproteins. These results supported a model in which only the unique 5'-terminal domain of each IBV mRNA is active in translation and enabled us to localize genes for virion proteins on the IBV genome.


Kinetics of protein-modification reactions. Stoichiometry of modification-produced enzyme inactivation: modification of rhodanese by 2,4,6-trinitrobenzenesulphonic acid.
A mathematical treatment is presented for the dependence of enzyme activity loss on the numbers and reactivities of the groups essential for catalytic function, when enzyme protein modification is carried out by the use of concentrations of protein reactive groups well in excess of that of modifying agent. Experimentally obtained data on the modification of rhodanese (thiosulphate sulphurtransferase, EC 18.104.22.168) by 2,4,6-trinitrobenzenesulphonic acid are presented, and it is shown that, at pH9.00, the fractional concentration of rhodanese groups, or of rhodanese group reactivities, essential for enzyme catalytic function is 0.88; this value is found to decrease with decreasing pH of the reaction medium. The possibility that rhodanese inactivation by 2,4,6-trinitrobenzenesulphonic acid is brought about by modification of groups other than amino groups is ruled out by a comparison of the enzyme-inactivation and protein-modification stoichiometries, for putative reaction models for enzyme and modifying agent.


Mechanical energy flow in the recovery leg of elite race walkers.
The purpose of this study was to investigate the mechanical energy flow in the recovery leg and its relationship to performance descriptors of elite male race walkers in an official race. Male race walkers participating in official 20 km races were videotaped with a VTR camera (60 Hz) set perpendicular to the course. The 28 elite race walkers (race records 1:19'50"-1:33'58") were selected as subjects. A two dimensional 14-segment linked model was used to calculate biomechanical parameters from the walking motion in the early phase of the race. The walking speed was significantly related to the step length but not related to the step frequency. Large mechanical energy flows at the hip occurred from the trunk to the foot during the first half of the recovery phase and from the foot to the trunk during the second half by the joint force power. Joint force powers at the hip in the second half of the recovery phase were significantly related to the walking speed and the step length. It is suggested that large joint force power at the hip would be one of the important factors to obtain high walking speed.


Brain 5-hydroxytryptamine correlates of behavior: studies involving spontaneously hypertensive (SHR) and normotensive Wistar rats.
Brain area 5-hydroxytrhptamine (5-HT) turnover and behavioral correlates were compared in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. SHR appeared to have hyperfunctional 5-HT systems as evidenced by the finding that brain area 5-HT turnover times were 53% lower in SHR, with significant changes seen in the limbic forebrain. SHR, while less active upon initial testing of spontaneous motor activity than Wistar rats, did not habituate as readily to the testing procedures as evidenced by higher activity than Wistar rats in repeated testing stiuations. In the light of other data indicating that 5-ht systems are predominantly inhibitory to ongoing behavior, these data suggest that habituation, as determined in this study, is an active process that is retarded in the SHR because of hyperfunctional 5-HT systems. Spontaneous activity of SHR was inhibited less than that of Wistar rats by a conditioned stimulus which is consistent with the observations of others that 5-HT systems tend to suppress responsiveness to external stimuli. While spontaneous activity data suggested that SHR were more emothinal than Wistar rats, the SHR also exhibited a higher avoidance rate in an unsignaled shuttle avoidance procedure which is usually indicative of a lower emotional state.


Immunochemical, clical, and pathological features of alpha-chain disease.
Making the diagnosis of alpha-chain disease in the laboratory is difficult. Immunologic and structural characteristics of the abnormal protein were shown in results of cellular studies. There are clinicopathological features associated with the protein abnormality. The peculiar geographic origin of patients affected with alpha-chain disease and the possible reversibility of the hyperplastic process at its early stage lead to some considerations of cause.


Athletic trainers' attitudes and judgments of injured athletes' rehabilitation adherence.
Certified athletic trainers (ATCs) in District 2 (n=187) of the National Athletic Trainers' Association (NATA) were asked to complete a questionnaire that assessed the attitudes and judgments of ATCs concerning numerous factors presumed to influence sport injury rehabilitation. Gender and experience differences in ATCs' attitudes and judgments about rehabilitation adherence were examined. Successful and unsuccessful adherence strategies also were reported. The questionnaire consisted of 60 statements that were categorized into seven scales: athletic trainer's influence, environmental influences, athlete's personality, pain tolerance, selfmotivation, goals and incentives, and significant others. There were no significant differences for either gender or experience of ATCs on any of the seven scales. An analysis of questionnaire item responses revealed the following as factors ATCs deemed important to injury rehabilitation: a) good rapport and communication between the ATC and the injured athlete, b) explanation of the injury and rehabilitation regimen, c) convenience and accessibility of the rehabilitation facility, d) rehabilitation sessions planned around the athletes' busy schedules, e) athletes' beliefs that the program is worth pursuing, f) personal supervision and regular monitoring, g) need for injured athletes to see immediate results, and h) support from significant others. ATCs reported education, goal setting, encouragement, monitoring progress, and support systems as successful strategies. Threats and rehabilitation without monitoring were reported as unsuccessful strategies.


Experimental investigation on the effect of wavelength on aperture averaging in FSO communications.
Atmospheric turbulence is a major impairment in free-space optical (FSO) communication systems. Based on the fact that the size of receiver aperture is much larger than operation wavelength, aperture averaging extracts inherent receiver diversity gains and can be used as an effective fading mitigation technique. In this Letter, we consider the three most common wavelengths used in telecommunications, namely 1550, 1310, and 850 nm, and present a comparative performance evaluation of aperture averaging under the same emulated atmospheric conditions. Our emulator is in the form of an atmospheric chamber equipped with adjustable heaters, coolers, and fans to create the desired level of turbulence. Our results demonstrate that by changing the wavelength and/or aperture size, a strong turbulence condition with Gamma-Gamma statistics can turn into a weak turbulence condition with log-normal statistics. Such a phenomenon can be observed even for relatively small aperture sizes if the wavelength is sufficiently high.


Biphenylite as Anode Materials for Alkali Metal Ion Batteries with Self-Enhanced Storage Mechanism.
In this work, we theoretically investigate the feasibility of biphenylite, the van der Waals layered bulk structure from experimental biphenylene network monolayers, as an anode material for alkali metal ions. The results indicate that the theoretical properties of Li, Na, and K in biphenylite are generally beyond those in graphite. Li-biphenylite exhibits a high specific capacity of 744 mAh·g-1, with a corresponding voltage range of 0.90-0.36 V, low diffusion barrier (<0.30 eV), and small volume change (∼9.9%), far exceeding those of Li-graphite. Moreover, a novel self-enhanced storage mechanism is observed and unveiled, in which the heavy intercalation of Li atoms (i.e., electron doping) induces puckered distortion of the nonhoneycomb carbon frameworks to enhance the intercalation ability and capacity of Li ion via a chemical activation of carbon frameworks. Possessing excellent anode performance beyond graphite, biphenylite is a promising "all-around" anode material candidate for alkali metal ion batteries, especially for lithium ion batteries.


Expression of nerve growth factor-induced type 1 plasminogen activator inhibitor (PAI-1) mRNA is inhibited by genistein and wortmannin.
Nerve growth factor (NGF), which acts as a neurotrophic factor in a rat pheochromocytoma cell line (PC12), stimulated type 1 plasminogen activator inhibitor (PAI-1) mRNA expression from 1 to 5 h, after addition at 5 ng/ml. PAI-1 antigen in culture medium, which was measured using an enzyme linked immunosorbent assay (ELISA), was also increased dose dependently by the addition of NGF. Neither epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), phorbol myristate acetate (PMA) nor forskolin increased PAI-1 mRNA expression in PC12 cells. Genistein, an inhibitor of tyrosine protein kinase, completely inhibited NGF induced PAI-1 mRNA in the presence of 100 microM. Wortmannin, a potent and specific inhibitor of phosphatidylinositol 3-kinase (PI-3 kinase), decreased induction of PAI-1 mRNA level at doses of > or = 10(-7) M.


Tyrosine phosphorylation of HoxA10 decreases DNA binding and transcriptional repression during interferon gamma -induced differentiation of myeloid leukemia cell lines.
The DNA binding affinity of HoxA10 is increased by partnering with Pbx proteins. A consensus sequence for Pbx1-HoxA10 DNA binding has been derived, but genuine target genes have not been identified. We noted that the derived Pbx-HoxA10 DNA-binding consensus is similar to a repressor element in the CYBB promoter. The CYBB gene, which encodes the respiratory burst oxidase component gp91(phox), is expressed only in myeloid cells that have differentiated beyond the promyelocyte stage. In these studies, we demonstrate that interferon gamma (IFN-gamma)-induced differentiation of myeloid cell lines abolishes in vitro Pbx-HoxA10 binding to either the derived consensus or the similar CYBB sequence. We also demonstrate that HoxA10, overexpressed in myeloid cell lines, represses reporter gene expression from artificial promoter constructs with Pbx-HoxA10 binding sites. We determine that HoxA10 has endogenous repression domains that are not functionally altered by IFN-gamma treatment. However, IFN-gamma-induced differentiation of myeloid cell lines leads to HoxA10 tyrosine phosphorylation, which decreases in vitro DNA binding to Pbx-HoxA10 binding sites. Therefore, these investigations identify the CYBB gene as a potential target for HoxA10 and define repression of genes expressed in mature myeloid cells as a novel role for HoxA10 during myeloid differentiation.


Long-term histopathological developments in knee-joint components in a rat model of osteoarthritis induced by monosodium iodoacetate.
[Purpose] This study was performed to evaluate the long-term histopathological changes in knee-joint components including synovial membrane and joint capsule in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA). [Subjects and Methods] Fifty male rats were used. OA was induced through intra-articular injection of MIA, and ten rats were randomly allocated to each of five groups induced with OA for 1, 2, 4, 6, or 8 weeks. At the end of each period, the knee components were examined histopathologically. [Results] After 1 and 2 weeks, chondrocytes were weakly stained. After 4 weeks, fibrillation, fissuring, and eburnation were observed, whereas after 6 weeks, chondrocyte clustering and osteophyte formation were detected. In the synovial membrane, the proliferation of spindle-shaped cells and a multilayered structure of the surface cells were observed at 1 and 2 weeks, but the degree of these changes decreased over time. In the joint capsule, a narrowing of the space between collagen fiber bundles was observed at 4-8 weeks. [Conclusion] The long-term histopathological changes of the joint components observed in a rat model of OA induced by MIA were similar to those detected in OA, but differed at specific times and tissues.


Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions.
Chronic active multiple sclerosis lesions, characterized by a hyperintense rim of iron-enriched, activated microglia and macrophages, have been linked to greater tissue damage. Post-mortem studies have determined that chronic active lesions are primarily related to the later stages of multiple sclerosis; however, the occurrence of these lesions, and their relationship to earlier disease stages may be greatly underestimated. Detection of chronic active lesions across the patient spectrum of multiple sclerosis requires a validated imaging tool to accurately identify lesions with persistent inflammation. Quantitative susceptibility mapping provides efficient in vivo quantification of susceptibility changes related to iron deposition and the potential to identify lesions harbouring iron-laden inflammatory cells. The PET tracer 11C-PK11195 targets the translocator protein expressed by activated microglia and infiltrating macrophages. Accordingly, this study aimed to validate that lesions with a hyperintense rim on quantitative susceptibility mapping from both relapsing and progressive patients demonstrate a higher level of innate immune activation as measured on 11C-PK11195 PET. Thirty patients were enrolled in this study, 24 patients had relapsing remitting multiple sclerosis, six had progressive multiple sclerosis, and all patients had concomitant MRI with a gradient echo sequence and PET with 11C-PK11195. A total of 406 chronic lesions were detected, and 43 chronic lesions with a hyperintense rim on quantitative susceptibility mapping were identified as rim+ lesions. Susceptibility (relative to CSF) was higher in rim+ (2.42 ± 17.45 ppb) compared to rim- lesions (-14.6 ± 19.3 ppb, P < 0.0001). Among rim+ lesions, susceptibility within the rim (20.04 ± 14.28 ppb) was significantly higher compared to the core (-5.49 ± 14.44 ppb, P < 0.0001), consistent with the presence of iron. In a mixed-effects model, 11C-PK11195 uptake, representing activated microglia/macrophages, was higher in rim+ lesions compared to rim- lesions (P = 0.015). Validating our in vivo imaging results, multiple sclerosis brain slabs were imaged with quantitative susceptibility mapping and processed for immunohistochemistry. These results showed a positive translocator protein signal throughout the expansive hyperintense border of rim+ lesions, which co-localized with iron containing CD68+ microglia and macrophages. In conclusion, this study provides evidence that suggests that a hyperintense rim on quantitative susceptibility measure within a chronic lesion is a correlate for persistent inflammatory activity and that these lesions can be identified in the relapsing patients. Utilizing quantitative susceptibility measure to differentiate chronic multiple sclerosis lesion subtypes, especially chronic active lesions, would provide a method to assess the impact of these lesions on disease progression.


Identification and phylogeny of ascomycetous yeasts from analysis of nuclear large subunit (26S) ribosomal DNA partial sequences.
Approximately 500 species of ascomycetous yeasts, including members of Candida and other anamorphic genera, were analyzed for extent of divergence in the variable D1/D2 domain of large subunit (26S) ribosomal DNA. Divergence in this domain is generally sufficient to resolve individual species, resulting in the prediction that 55 currently recognized taxa are synonyms of earlier described species. Phylogenetic relationships among the ascomycetous yeasts were analyzed from D1/D2 sequence divergence. For comparison, the phylogeny of selected members of the Saccharomyces clade was determined from 18S rDNA sequences. Species relationships were highly concordant between the D1/D2 and 18S trees when branches were statistically well supported.


Welcoming relevant media reviews.
The journal editors hope that forthcoming issues of Families, Systems, and Health will provide valuable reviews of relevant media resources. Essential to this endeavor is our community- authors who identify key media items and submit reviews. As with all peer-reviewed publications, submission does not guarantee acceptance for publication. Media reviews for Families, Systems, and Health must reflect the scope of the journal (i.e., addressing one or more of the three domains: family functioning, systems thinking, or health). (PsycINFO Database Record (c) 2018 APA, all rights reserved).


The association of prenatal exposure to particulate matter with infant growth: A birth cohort study in Beijing, China.
Limited studies examined the associations of prenatal exposure to particulate matter (PM) and children's growth with inconsistent results, and no study focused on PM1. We matched a birth cohort (10,547 children) with daily PM1 and PM2.5 concentrations by maternal home addresses. Air pollution concentrations were predicted by satellite remote sensing data, meteorological factors, and land use information. The weight and length of children in the birth cohort were measured at approximately one year old. We calculated the Z-score of weight for length (WFL) and body mass index (BMI) and then defined overweight and obesity (OWOB) based on WHO Standards. Generalized linear regression and modified Poisson regression were used to identify the association of prenatal exposure to PM1 or PM2.5 with anthropometric measurements and risk of OWOB. We also determined the mediation effect of preterm birth on the associations. Results showed that a 10 μg/m3 increase in prenatal exposure to PM1 and PM2.5 was significantly associated with a 0.105 [95% confidence interval (CI): 0.067, 0.144] and 0.063 (95% CI: 0.029, 0.097) increase in WFL Z-score for one-year-old children. Similar associations were found for BMI Z-score. A 10 μg/m3 increase in prenatal PM1 and PM2.5 exposure was significantly associated with 1.012 (95%CI: 1.003, 1.021) and 1.010 (95%CI: 1.002, 1.018) times higher risk of OWOB. . Preterm birth mediated 7.5% [direct effect (DE) = 0.106, P < 0.001; indirect effect (IE) = 0.009, P < 0.001)] and 9.9% (DE = 0.064, P < 0.001; IE = 0.007, P < 0.001) of the association between prenatal PM1 and PM2.5 exposure and WFL Z-score of the children. The association of prenatal PM1 and PM2.5 exposure with BMI Z-score of children was also mediated by preterm birth by 6.6% (DE = 0.111, P < 0.001; IE = 0.008, P < 0.001) and 9.1% (DE = 0.064, P < 0.001; IE = 0.006, P < 0.001). These results remained robust in the sensitivity analyses. In conclusion, prenatal exposure to PM1 and PM2.5 increased WFL, BMI Z-scores and higher risk of OWOB for one-year-old children. The associations were partially mediated by preterm birth. These findings call for the urgent action on air pollution regulation to protect early-life health among children.


Involvement of protein kinases on the upregulation of endothelin receptors in rat basilar and mesenteric arteries.
Endothelin(B) (ET(B)) receptors are upregulated in experimental stroke or after 24 hrs of organ culture. This upregulation is manifested both as stronger contraction and as an increase in ET(B) receptor messenger RNA (mRNA) levels. The present study was designed to evaluate the importance of protein kinases (c-Jun N-terminal kinase [JNK], protein kinase C [PKC], and extracellular signal-regulated kinase [ERK1/2]) in ET(B) receptor upregulation after organ culture. Rat basilar and mesenteric arteries were incubated for 24 hrs in Dulbecco's modified Eagle's medium (DMEM) with or without the PKC inhibitor, RO-31-7549; the ERK1/2 inhibitor, SB386023; or the JNK inhibitor, SP600125, added 3, 6, or 12 hrs after initiation of incubation. Subsequently, vessel segments were mounted in myographs and the contractile responses to ET-1 and sarafotoxin 6c were studied. The ET(B) and ET(A) receptor mRNA levels were determined with a real-time polymerase chain reaction (PCR). The cellular localization and protein level of ET(B) receptors were evaluated by immunohistochemistry. The PKC and ERK1/2 inhibitors attenuated the contraction induced by S6c in the basilar arteries more than in the mesenteric arteries. The efficiency of the inhibitors was proportional to the incubation time. Real-time PCR showed a decrease in the ET(B) receptor mRNA levels in arteries treated with PKC or ERK inhibitors. The JNK inhibitor had a significant inhibitory effect on ET(B) receptor upregulation in the basilar arteries. Immunohistochemistry revealed that the ET(B) receptor upregulation occured in the smooth-muscle cells and that it had the same pattern as in the quantitative PCR. Our results show that the PKC, ERK1/2, and JNK are more important for the upregulation of contractile ET(B) receptors in cerebral arteries compared with mesenteric arteries. ERK1/2 seems to be more important for the ET(B) receptor upregulation, as compared with PKC and JNK. The evaluation of the time dependency suggests that the phenomenon can be reversed even after its initiation.


Contact studies of the canine femoropatellar joint.
During development of a closed impact-trauma model, using the canine femoropatellar articulation, animal weight or other readily measured physical characters were correlated with surface area, location, and shape of femoropatellar contact at various femorotibial angulations. The information allows making reasonable predictions regarding femoropatellar contact just before delivery of calibrated closed impact-trauma to the patella. Femoropatellar contact area location, shape, and size were determined in the left pelvic limbs of 10 dogs, ranging in weight from 20.0 to 40.9 kg (mean 27.2 kg). Determinations were made at 90, 110, and 130 degrees femorotibial angulations, using a new casting technique and at 70, 90, 110, 130, and 150 degrees, using a previously described dye technique. Location and shape of the contact areas were relatively constant for a given femorotibial angulation. Bipartite areas of contact were seen on 3 specimens. Using data from the dye technique, a definitive correlation was established between antemortem animal weight and contact area size. Patellar dimensions also correlated well with contact surface area. An inverse relationship between contact area per unit body weight and total body weight was observed. Contact area size did not vary significantly with increasing compressive force resulting from changes in femorotibial angulation. These determinations allow making reasonable predictions of both location and size of articular contact area immediately preceding delivery of closed impact to the joint.


Serum anti-p53 antibodies as a diagnostic tumor marker: observations in patients with malignant and premalignant oral cavity lesions.
To determine whether serum anti-p53 antibody (p53-Abs) positivity in patients with oral carcinoma corresponds with tumor localization, histological grade, stage, and recurrence. The study population was divided into three groups: controls; patients with a premalignant lesion; and patients with oral squamous cell carcinoma (SCC). The third group was composed of patients attending outpatient services for pathological diagnosis or for follow-up monitoring only. The cancer patients had undergone resective surgery in local anesthesia. Serum p53-Abs levels were measured using a commercial enzyme-linked immunosorbent assay (ELISA) and monitored over a 3-year follow-up period. Controls and patients with premalignant lesions did not test positive for p53-Abs at ELISA testing. Patients with a malignant lesion tested positive at initial diagnosis when a high histopathological grade lesion was present or localized to the posterior region of the oral cavity. Postoperative serum p53-Abs levels gradually declined until complete seronegativity. Patients with a recurrent tumor tested positive for p53-Abs. Seropositivity for p53-Abs may be associated with histopathological tumor grade, localization, and recurrence. The findings suggest that serum p53-Abs analysis is a useful diagnostic marker for oral SCC.


Cholesterol-producing transgenic Caenorhabditis elegans lives longer due to newly acquired enhanced stress resistance.
Because Caenorhabditis elegans lacks several components of the de novo sterol biosynthetic pathway, it requires sterol as an essential nutrient. Supplemented cholesterol undergoes extensive enzymatic modification in C. elegans to form other sterols of unknown function. 7-Dehydrocholesterol reductase (DHCR) catalyzes the reduction of the Delta7 double bond of sterols and is suspected to be defective in C. elegans, in which the major endogenous sterol is 7-dehydrocholesterol (7DHC). We microinjected a human DHCR expression vector into C. elegans, which was then incorporated into chromosome by gamma-radiation. This transgenic C. elegans was named cholegans, i.e., cholesterol-producing C. elegans, because it was able to convert 7DHC into cholesterol. We investigated the effects of changes in sterol composition on longevity and stress resistance by examining brood size, mean life span, UV resistance, and thermotolerance. Cholegans contained 80% more cholesterol than the wild-type control. The brood size of cholegans was reduced by 40% compared to the wild-type control, although the growth rate was not significantly changed. The mean life span of cholegans was increased up to 131% in sterol-deficient medium as compared to wild-type. The biochemical basis for life span extension of cholegans appears to partly result from its acquired resistance against both UV irradiation and thermal stress.


Molecular genetics of hepatocellular neoplasia.
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer deaths worldwide. Proper classification and early identification of HCC and precursor lesions is essential to the successful treatment and survival of HCC patients. Recent molecular genetic, pathologic, and clinical data have led to the stratification of hepatic adenomas into three subgroups: those with mutant TCF1/HNF1 alpha gene, those with mutant beta-catenin, and those without mutations in either of these loci. Hepatic adenomas with alpha-catenin mutations have a significantly greater risk for malignant transformation in comparison with the other two subgroups. Telangiectatic focal nodular hyperplasia has now been reclassified as telangiectatic adenoma due to the presence of non-random methylation patterns, consistent with the monoclonal origin which is similar to hepatic adenoma and HCC. HCC precursor lesions demonstrate unique molecular alterations of HSP70, CAP2, glypican 3, and glutamine synthetase that have proven useful in the histologic diagnosis of early HCC. Though specific genetic alterations depend on HCC etiology, the main proteins affected include cell membrane receptors (in particular tyrosine kinase receptors) as well as proteins involved in cell signaling (specifically Wnt/beta-catenin, Ras/Raf/MEK/ERK and PI3K/Akt/mTOR pathways), cell cycle regulation (i.e. p53, p16/INK4, cyclin/cdk complex), invasiveness (EMT, TGF-beta) and DNA metabolism. Advances in gene expression profiling have provided new insights into the molecular genetics of HCC. HCCs can now be stratified into two clinically relevant groups: Class A, the low survival subclass (overall survival time 30.3+/- 8.02 months), shows strong expression signatures of cell proliferation and antiapoptosis genes (such as PNCA and cell cycle regulators CDK4, CCNB1, CCNA2, and CKS2) as well as genes involving ubiquitination and sumoylation; Class B, the high survival subclass (overall survival time 83.7 +/-10.3 months), does not have the above expression signature. In fact, insights into HCC-specific alterations of signal transduction pathways and protein expression patterns have led to the development of new therapeutic agents with molecular targets such as EGFR, VEGF, or other multi-kinase inhibitors. In the future, these specific molecular alterations in HCC can potentially serve as diagnostic tools, prognostic markers, and/or therapeutic targets with the potential to alter clinical outcomes.


The relationship between body composition and blood pressure among primary school children in Eastern Cape province, South Africa.
In South Africa, especially in the Eastern Cape province, despite reported high prevalence of underweight and obesity, little is known regarding the relationship of body composition (BC) with blood pressure (BP) in primary school children. Understanding the relationship between BC and BP in these children is important because it is associated with adverse effects on health and social repercussion in both adolescence and adulthood. The aim of this study was to examine the relationship between BC and BP among South African primary school children. This study was conducted on a cohort of primary school learners in the Eastern Cape Province of South Africa. A school-based cross-sectional survey was conducted among 876 school children aged 9-14 years, using multistage sampling techniques. Body mass and stature were measured using a calibrated scale. Anthropometric measurements including weight, height, waist circumference, triceps, gluteal and subscapular were also collected. Body mass index, percentage body fat and waist-to-hip ratio were calculated. Of the 876 participants, 356 (40.6%) were boys and 520 (59.0%) were girls. The Spearman's rho correlation coefficients revealed positive significant correlations between systolic BP with age (r = 0.171; p 0.0001), stature (r = 0.205; p 0.0001), weight (r = 0.277; p 0.0001), body mass index (r = 0.243; p 0.0001), waist circumference (r = 0.259; p 0.0001), gluteal (r = 0.214; p 0.0001), triceps (r = 0.203; p 0.0001), subscapular (r = 0.167; p 0.0001), body fat percentage (r = 0.206; p 0.0001), fat mass (r = 0.257; p 0.0001) and fat-free mass (r = 0.238; p 0.0001). There was no statistically significant correlation between waist-to-hip ratio and systolic BP (r = 0.064; p = 0.059). In terms of diastolic BP, there existed no significant correlations with age (r = 0.026; p = 0.443) and waist-to-hip ratio (r = 0.002; p = 0.947). Collectively, the prevalence of hypertension was 76.4% in the normal group compared with those who were pre-hypertensive (18.4%) and hypertensive (5.3%). Girls showed a higher prevalence of pre-hypertension than boys (19.6% compared with 16.6%, respectively). There is a relationship between most of the BC variables and BP in children. The screening of BP as part of physical examinations of school children is necessary for early prevention and intervention programmes for hypertension.


Trends and Factors Associated With Receipt of Upfront Surgery for Stage II to III Rectal Adenocarcinoma in the United States, 2006 to 2016.
The German rectal study published in 2004 established neoadjuvant chemoradiation as a standard of care for locally advanced rectal cancer and current National Comprehensive Cancer Network guidelines endorse several preoperative regimens. Upfront surgery, however, is considered substandard care. In the era of evolving treatment paradigms for locally advanced rectal cancer, we sought to assess trends and predictors of receipt of upfront surgery for stage II to III rectal cancer. The National Cancer Database was used to identify patients diagnosed with clinical stage II to III rectal adenocarcinoma between 2006 and 2016. Multivariable logistic regression defined adjusted odds ratios and associated 95% confidence intervals of receipt of upfront definitive surgery. The timing of upfront surgery relative to day of diagnosis and rate of receipt of adjuvant therapy were also estimated. Among 51,562 patients, 6411 (12.4%) were treated with upfront surgery, which decreased from 16.7% in 2006 to 7.1% in 2016 (P<0.001). The majority of patients (5737 [89.5%]) had definitive surgery after initial diagnostic biopsy. Variables associated with receipt of upfront surgery included female sex, older age, higher comorbidity score, and treatment at a community cancer center (P<0.001). Among those receiving upfront surgery, 2904 (45.3%) received adjuvant radiation therapy, 3218 (50.2%) received adjuvant chemotherapy, and 2559 (39.9%) received no further treatment. The proportion of patients with clinical stage II to III rectal cancer treated with upfront surgery has steadily declined since 2006, however, certain subgroups appear to remain at greater risk. Further research is needed to better elucidate patient and systems-level factors contributing to these disparities in care.


Adolescent insightfulness toward a close friend: its roots in maternal insightfulness and child attachment in infancy.
Two antecedents of the insightfulness of adolescents into a close friend's experience were examined: The insightfulness of the mother and the attachment of the child, both measured when the adolescent was an infant. We hypothesized that both antecedents would be associated with adolescent insightfulness. Maternal insightfulness was assessed using the Insightfulness Assessment (IA) in which mothers are interviewed about their children's thoughts and feelings after viewing short video segments of their interactions with their children, and infant attachment was assessed using the Strange Situation Procedure. Adolescent insightfulness was assessed using an adaptation of the IA in which the adolescents were interviewed about their friend's thoughts and feelings after viewing short video segments of their interactions with them. As predicted, the results showed that adolescents were more likely to show insightfulness toward their friend when their mothers had been insightful toward them when they were infants and when they had secure attachment with their mothers. When both predictors were considered together, maternal insightfulness remained predictive of adolescent insightfulness but infant attachment was no longer significant.


Some characteristics of and structural requirements for the interaction of 24,25-dihydrofusidic acid with ribosome - elongation factor g Complexes.
Fusidic acid inhibits polypeptide chain elongation by binding to the ribosome - elongation factor-G - GDP complex and thereby preventing its dissociation. The experiments reported here quantitate the interaction of the antibiotic [3H]-24,25-dihydrofusidic acid, an active analog of fusidic acid, with the ribosome - elongation factor-G - GDP comples. All components of the complex are essential for [3H]-24,25-dihydrofusidic acid binding. The stoichiometry of the interaction is ca. 1:1, and the Ka apparent, as determined by equilibrium dialysis, is 2.6 times 10-6 M-minus 1. It is further shown that GTP and GDP are equally effective in forming complexes to which the antibiotic may bind, whereas GMP and beta,gamma-methyleneguanosine triphosphate will not form complexes to which the antibiotic may bind. In order to examine the structural basis of the mode of antibiotic action shown by fusidic acid, we have considered two activities of 21 structural analogs of this antibiotic: ability to bind to the aforementioned ternary complex and ability to stabilize this complex. The comparative binding capability of the analogs were extablished through competition experiments with [3H]-24,25-dihydrofusidic acid. The data obtained from these experiments can be summarized as follows. (1) The C17-20 double bond of fusidic acid appears to be critical for both binding and complex stabilization activities. (2) A carboxyl group in the vicinity of the C20 carbon is also essential for both activities. (3) Modifications of other functional groups in the molecule can lead to significantly decreased stabilization of the ternary ribosome complex and/or ability to compete with [3H]-24,25-dihydrofusidic acid for binding to the complex, but do not demonstrate absolute structural requirements for either activity.


Giant cystic pheochromocytoma located in the renal hilus.
A malignant tumor in the past medical history of a patient often makes the differential diagnosis of a second tumor more difficult, especially if one of the tumors does not show its characteristic features. The authors report a case of a 55-year-old male who presented with a malignant melanoma on his left shoulder. A retroperitoneal giant cystic mass, 200 mm in diameter, was found incidentally. Adrenal origin was ruled out by imaging techniques. The absence of typical clinical symptoms made a correct preoperative diagnosis unlikely, and severe cardiovascular complications set in during surgery. Considering the characteristics of the cutaneous malignant melanoma, the metastatic origin of the giant retroperitoneal tumor was not likely either. During surgery the left kidney, with a cystic tumor located in the hilus, was removed. The postoperative pathologic diagnosis was pheochromocytoma located in the hilus of the left kidney.


Model development and research vision for the future of multiple chemical sensitivity.
Multiple chemical sensitivity (MCS) is characterized by heightened self-reported sensitivity to extremely low concentrations of chemicals. It has numerous symptoms in common with the sick building syndrome, the Gulf War syndrome, and chronic fatigue. Despite much research, reproducible objective findings are lacking for MCS, as is a sound model to explain it. This paper proposes a 2-step model combining the needed epidemiologic terminology with that of psychophysiological activation and sensitization. It is suggested that different environmental stressors act as initiators. After initiation, the limbic system and other parts of the brain become sensitized and hyperreactive to environmental triggers. Odor acts as one important trigger. Future research should use more biological assessments in combination with environmental and psychosocial data and involve patient groups with similar symptoms, although diagnosed as suffering from different entities. The similarities and differences of patients with such entities need to be understood before the entities themselves can be understood, diagnosed, treated, and prevented.


A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping.
We have isolated a human cDNA clone encoding a novel acidic protein of MW 55,000 that we designated "myocilin" since it has homology to myosin and is localized preferentially in the ciliary rootlet and basal body of the connecting cilium of photoreceptor cells. The deduced amino acid sequence of human myocilin showed significant homologies with nonmuscle myosin of Dictyostelium discoideum in the N-terminal region and also with olfactomedin of bullfrog in the C-terminal region. Myocilin contained a leucine zipper-like motif similar to that seen in kinectin and other cytoskeletal proteins. These findings suggest that myocilin is a novel cytoskeletal protein involved in the morphogenesis of ciliated neuroepithelium such as photoreceptor cells. The myocilin gene (MYOC) was mapped to human chromosome 1q23-q24 by fluorescence in situ hybridization.


The effects of two cavity preparation methods on the longevity of glass ionomer cement restorations: an evaluation after 12 months.
The authors undertook a study to evaluate the effect of two cavity preparation methods on the initial survival of two more-viscous glass ionomer cements, or GICs, placed in the occlusal surfaces of permanent molar teeth. Three dentists placed 149 restorations in 68 adult patients in a hospital clinic. They used either atraumatic restorative treatment, or ART, or conventional cavity preparation methods to place two encapsulated esthetic conventional GICs: Fuji IX GP (GC International Corp., Tokyo) and Ketac-Molar Aplicap (3M ESPE, Seefeld, Germany). For comparison, they used high-copper-content GK Amalgam Alloy (Advanced Technology & Materials Co. Ltd., Beijing) in conventional preparations. They evaluated the restorations using both direct and indirect observation methods. Cavity preparations for which the authors used ART hand instruments took approximately twice as long to complete as did those for which they used conventional rotary instruments. After 12 months, no restorations had failed, but restorations comprising both GICs showed early losses of adjacent sealant material. Both GICs also showed relatively high restoration wear. At 12 months, the mean cumulative net occlusal wear for Fuji IX GP was 77 +/- 47 micrometers, and for Ketac-Molar 83 +/- 51 microm, without statistical significance (P > .05). Color matching improved significantly with time (P < .001), without significant differences in color between the two GICs by 12 months (P = .09). The amalgam alloy had minor surface tarnishing and marginal discrepancies increased with time (P < .00 1). All of the occlusal restorations were rated as satisfactory after 12 months. The method of cavity preparation did not affect the restoration performance of the GICs. However, their deterioration requires long-term monitoring. Clinical Implications. The more viscous GICs appear initially suitable for restricted use in clinical practice when placed using either of two cavity preparation methods in the occlusal surfaces of permanent molar teeth in adults.


ACE inhibition is renoprotective among obese patients with proteinuria.
Obesity may increase the risk for progression of CKD, but the effect of established renoprotective treatments in overweight and obese patients with CKD is unknown. In this post hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, we evaluated whether being overweight or obese influences the incidence rate of renal events and affects the response to ramipril. Of the 337 trial participants with known body mass index (BMI), 105 (31.1%) were overweight and 49 (14.5%) were obese. Among placebo-treated patients, the incidence rate of ESRD was substantially higher in obese patients than overweight patients (24 versus 11 events/100 person-years) or than those with normal BMI (10 events/100 person-years); we observed a similar pattern for the combined endpoint of ESRD or doubling of serum creatinine. Ramipril reduced the rate of renal events in all BMI strata, but the effect was higher among the obese (incidence rate reduction of 86% for ESRD and 79% for the combined endpoint) than the overweight (incidence rate reduction of 45 and 48%, respectively) or those with normal BMI (incidence rate reduction of 42 and 45%, respectively). We confirmed this interaction between BMI and the efficacy of ramipril in analyses that adjusted for potential confounders, and we observed a similar effect modification for 24-hour protein excretion. In summary, obesity predicts a higher incidence of renal events, but treatment with ramipril can essentially abolish this risk excess. Furthermore, the reduction in risk conferred by ramipril is larger among obese than nonobese patients.


Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG.
We studied galactose supplementation in SLC35A2-congenital disorder of glycosylation (SLC35A2-CDG), caused by monoallelic pathogenic variants in SLC35A2 (Xp11.23), encoding the endoplasmic reticulum (ER) and Golgi UDP-galactose transporter. Patients present with epileptic encephalopathy, developmental disability, growth deficiency, and dysmorphism. Ten patients with SLC35A2-CDG were supplemented with oral D-galactose for 18 weeks in escalating doses up to 1.5 g/kg/day. Outcome was assessed using the Nijmegen Pediatric CDG Rating Scale (NPCRS, ten patients) and by glycomics (eight patients). SLC35A2-CDG patients demonstrated improvements in overall Nijmegen Pediatric CDG Rating Scale (NPCRS) score (P = 0.008), the current clinical assessment (P = 0.007), and the system specific involvement (P = 0.042) domains. Improvements were primarily in growth and development with five patients resuming developmental progress, which included postural control, response to stimuli, and chewing and swallowing amelioration. Additionally, there were improvements in gastrointestinal symptoms and epilepsy. One patient in our study did not show any clinical improvement. Galactose supplementation improved patients' glycosylation with decreased ratios of incompletely formed to fully formed glycans (M-gal/disialo, P = 0.012 and monosialo/disialo, P = 0.017) and increased levels of a fully galactosylated N-glycan (P = 0.05). Oral D-galactose supplementation results in clinical and biochemical improvement in SLC35A2-CDG. Galactose supplementation may partially overcome the Golgi UDP-galactose deficiency and improves galactosylation. Oral galactose is well tolerated and shows promise as dietary therapy.


Exposure to mixtures of solvents among paint workers and biochemical alterations of liver function.
The objective of this study was to determine biochemical alterations of liver function among paint manufacturers and sprayers associated with exposure to organic solvents. Two paint manufacturing factories and 22 various kinds of spray painting factories (16 car painting, two aircraft painting, three video terminal painting; and one trailer painting) were included. Air concentrations of organic solvents were collected by personal samplers and analysed by gas chromatography. A total of 180 workers were given a comprehensive physical examination, a questionnaire, a liver function test, and a test for hepatitis B surface antigen. The questionnaire contained questions regarding detailed personal medical history, intake of alcohol, and use of medicine. Mixtures of solvents were used throughout the factories, and xylene and toluene were the major components found in almost all air samples with average contents of 46% and 29% on a weight basis of 67 air samples. No strong hepatotoxic solvents were detected. Workers were classified according to the different exposure patterns and different air concentrations of breathing zones as: high (eight hour time weighted average (8 h TWA) hygienic effects of solvents 0.25-9.83, median 1.66), short term high (8 h TWA hygienic effects of solvents 0-3.38, median 0.12), and low (8 h TWA hygienic effects of solvents all below 0.38). After applying a multivariate model to control the non-occupational factors (alcohol, medication, age, and hepatitis B viral infection), increase in gamma-glutamyl transferase (GGT) activity was found to be associated with severity of exposure to the mixture of solvents. Because the possible effects on GGT activity of non-occupational factors were controlled for, it is concluded that increased GGT activity among exposed workers may be due to a higher exposure to the mixture of solvents.


Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors.
Dozens of variants in the photoreceptor-specific transcription factor (TF) CRX are linked with human blinding diseases that vary in their severity and age of onset. It is unclear how different variants in this single TF alter its function in ways that lead to a range of phenotypes. We examined the effects of human disease-causing variants on CRX cis-regulatory function by deploying massively parallel reporter assays (MPRAs) in live mouse retinas carrying knock-ins of two variants, one in the DNA binding domain (p.R90W) and the other in the transcriptional effector domain (p.E168d2). The degree of reporter gene dysregulation caused by the variants corresponds with their phenotypic severity. The two variants affect similar sets of enhancers, while p.E168d2 has stronger effects on silencers. Cis-regulatory elements (CREs) near cone photoreceptor genes are enriched for silencers that are de-repressed in the presence of p.E168d2. Chromatin environments of CRX-bound loci were partially predictive of episomal MPRA activity, and silencers were notably enriched among distal elements whose accessibility increases later in retinal development. We identified a set of potentially pleiotropic regulatory elements that convert from silencers to enhancers in retinas that lack a functional CRX effector domain. Our findings show that phenotypically distinct variants in different domains of CRX have partially overlapping effects on its cis-regulatory function, leading to misregulation of similar sets of enhancers, while having a qualitatively different impact on silencers.


Calcium regulation of flagellation in Naegleria gruberi.
The amoeba-to-flagellate transformation of Naegleria gruberi was studied, exploring the role of calcium in control of this pattern of morphogenesis. A direct and an indirect role for calcium are postulated based on experimental results. Direct inhibition in the presence of calcium is caused by ionophore A23187, substances with ionophore-like activity (amphotericin) and the hormone calcitonin, which facilitate calcium uptake into the cytosol. The indirect role is difficult to assess, but is believed to be related to calcium regulatory protein and its control of cyclic nucleotide levels in the cell, based on inhibition by trifluoperazine. Calcium flux was studied by addition of 45Ca2+ to cell cultures, and tracing its movement during the transformation period. Ultrastructural localization of calcium was attempted in amoeboid and flagellate stages, as well as in reverting flagellates. Deposits that might represent calcium were observed under the plasma membrane and, in calcium-induced reversion, in electron-dense spheres seen in the cytoplasm and at sub-membrane locations, suggesting expulsion of excess calcium.


Laser facial plastic surgery for men.
The demand for laser facial plastic surgery for men has been increasing. Because men tend not to wear make-up and do not wish to take the time off from work associated with surgical procedures, they prefer laser type procedures that usually have minimal associated recovery. These procedures can be used to treat multiple conditions including: photoaging, acne, acne scars, superficial cutaneous problems, and rhinophyma.


Editorial: Sequential therapy for eradication of Helicobacter pylori: a new guiding light or a false dawn?
Helicobacter pylori-related diseases are a major global problem, and currently recommended regimens are achieving disappointing eradication rates. Trials of sequential therapy have suggested that it is superior to standard proton pump inhibitor (PPI)-based triple therapy. Gatta et al. report a rigorous systematic review that identified 13 trials evaluating 3,271 patients. Their data suggest that the sequential therapy achieves a 12% better absolute eradication rate than the standard PPI triple therapy. There is no evidence of publication bias or other small study effects. The quality of all but one of the studies, however, is poor; therefore, this limits the confidence that can be placed in these data. Most of the studies were conducted in Italy, and there is evidence that the efficacy of sequential therapy in Asia is more disappointing, emphasizing the need to study this regimen in North America and other settings. Sequential therapy is not ready for prime time, but it is a promising approach that merits further study.


Ascitic growth of a spontaneous transplantable T cell lymphoma induces thymic involution. 2. Induction of apoptosis in thymocytes.
It has been observed that the progressive ascitic growth of a transplantable T cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), induces inhibition of various immune responses and is associated with an involution of the thymus accompanied by a massive depletion of the cortical region and alteration in the distribution of thymocytes, with a decrease in CD4+CD8+, CD4+CD8- and CD4-CD8+ thymocytes. Morphological evaluation of thymocytes from DL-bearing mice revealed that with the progression of DL, a majority of thymocytes exhibited morphological features characteristic of apoptotic cell death, which included contracted cell bodies, condensed, uniformly circumscribed and densely stained chromatin, and membrane-bound apoptotic bodies containing one or more nuclear fragments. Quantitative and qualitative analysis of the DNA extracted from the thymocytes of DL-bearing mice revealed DNA fragmentation that increased concomitantly with the progression of DL and showed an oligonucleosomal DNA ladder pattern upon agarose gel electrophoresis, a hallmark of apoptotic cell death. Attempts to identify apoptotic factor(s) showed that the serum of DL-bearing mice contained certain soluble factor(s) that augmented the induction of apoptotis in thymocytes in a time- and dose-dependent manner. Although DL cells or their products, such as DL-cell-conditioned medium or DL-cell-free ascitic fluid, could also induce apoptosis of thymocytes in vitro, the magnitude of the same was consistently lower than that induced by the serum of DL-bearing mice. Further, elucidation of the mechanism of apoptosis induction in thymocytes with respect to the involvement of apoptosis-related genes revealed that the death pathway followed an interleukin-1 beta-converting-enzyme-dependent, Fas-mediated apoptotic cascade, with a concomitant increase in the protein products of the bax, bad, p53, fas and fasL genes and cleavage of the 23-kD N-terminal fragment of Bcl-2 that exhibited Bax-like death effector properties.


A Review of Topical Cyclosporine A Formulations-A Disease-Modifying Agent for Keratoconjunctivitis Sicca.
Keratoconjunctivitis sicca (KCS) is a multifactorial disease characterized by tear hyperosmolarity, inflammation, and ocular surface damage. Cyclosporine A (CsA) is used as an effective disease-modifying agent to improve the signs and symptoms of KCS by reducing inflammation, which interferes with tear production. This review provides an overview of efficacy, safety, and limitations of currently marketed topical CsA formulations-including CsA ophthalmic emulsion, cationic nanoemulsion, and aqueous nanomicelles-and highlights newer technologies for controlled ocular delivery of CsA and their clinical implications. Long available emulsion formulations of CsA are oil-based and have several limitations, including slow onset of efficacy and low intraocular penetration and bioavailability. Aqueous CsA nanomicelle carriers produce rapid improvement in objective signs of KCS such as corneal and conjunctival staining as early as 4 weeks and have acceptable safety profiles. CsA formulations using semifluorinated alkanes or polyaphrons are currently in clinical development, having recently completed Phase 2 studies. Other carriers for CsA currently in the preclinical phase include microemulsions, polymeric aqueous and lyophilized micelles, and hydrogels; these novel formulations have yet to undergo clinical trials. Formulations that improve tissue availability of CsA may be beneficial in clinical practice by providing faster onset of relief and improving patient adherence.


Plasma lipid transport in the preruminant calf, Bos spp: primary structure of bovine apolipoprotein A-I.
The preruminant calf (Bos spp.) is a model of considerable interest with regard to hepatic and intestinal lipoprotein metabolism (Bauchart et al., J. Lipid Res. (1989) 30, 1499-1514 and Laplaud et al., J. Lipid Res. (1990) 31, 1781-1792). As a preliminary step towards future experiments dealing with HDL metabolism in the calf, we have purified apoA-I from this animal and determined its complete amino acid sequence. Thus, approx. 10% of calf apoA-I was shown to contain a propeptide, with the sequence Arg-His-Phe-Trp-Gln-Gln. Enzymatic cleavage of apoA-I resulted in 10 proteolytic peptides. The complete apoA-I sequence was obtained after alignment of peptides on the basis of their homologies with those from rabbit apoA-I. Thus calf apoA-I consists of 241 amino acid residues, and exhibits high sequence homology with all mammalian apoA-I's studied to date. The bovine protein contained 10 hydrophobic amphipathic helical regions, occurring between residues 43-64, 65-86, 87-97, 98-119, 120-141, 142-163, 164-184, 185-206, 207-217 and 218-241. A computer-constructed phylogenetic tree showed that bovine apoA-I was more closely related to its dog counterpart, including the presence of a single methionine, than to the corresponding macaque and human proteins. Comparative predictions of the respective antigenic structures of human and bovine apoA-I's using the Hopp-Woods algorithm indicated similar positions for all 13 detectable antigenic sites, among which 7 were of identical, or closely related, amino acid composition. This finding was confirmed by demonstration of partial immunological identity between the two proteins upon immunodiffusion analysis, a result obtained using a monospecific rabbit antiserum against bovine apoA-I. Finally, comparison of sequence homology between bovine apoA-I and the lecithin:cholesterol acyl transferase (LCAT) activating region of human apoC-I suggests that several LCAT activating domains may be present in calf apoA-I.


Detection of Anti-mitochondrial Antibodies Accompanied by Drug-induced Hepatic Injury due to Atorvastatin.
A 44-year-old Japanese woman was admitted to our hospital with fatigue and an altered liver function. She had been receiving atorvastatin treatment for 10 months. Although no jaundice was seen, the patient's serum alkaline phosphatase and γ-glutamyl transpeptidase levels were markedly elevated. Based on the results of a drug-induced lymphocyte-stimulation test, her liver disease was diagnosed as atorvastatin-induced hepatic injury. Subsequently, anti-mitochondrial antibodies (AMAs) were detected in her serum; however, a liver biopsy specimen did not show the characteristic features of primary biliary cholangitis. We herein report the detection of AMAs accompanied by drug-induced hepatic injury caused by atorvastatin.


[Telemedicine in Ophthalmology: A Useful Tool in Store-and-Forward Counselling?].
Side by side with the progress in computers and imaging, telemedicine has already been used successfully in a large number of specialties of medicine. But high-quality images are not always suitable for transfer via modem because of their file size. The present experimental study was conducted to determine the effects of image compression by the JPEG algorithm on image quality and on the reliability of diagnosis after compression. Digital photographs of the retina were taken and the JPEG compressed images assessed by an experienced ophthalmologist. The present study showed a high reliability of diagnosis and a good agreement between the observations taken at the patient and at the computer. For this reason, JPEG image compression algorithm is suitable for reducing image size for producing high-quality images manageable for transmitting via modem in a store-and-forward teleophthalmological system.


The effect of pinealectomy on immune parameters in different age groups in rats: results of the weekly alteration of the zinc level and the effect of melatonin administration on wound healing.
It is generally accepted that the pineal gland is a neuroendocrine organ. Several recent experiments have shown that the pineal gland has functional and anatomic connections with many organs and systems, particularly with the immune system, and, therefore, the gland is now recognised as an important immunoneuroendocrine organ both in man and animals. The present study investigates the effect of pinealectomy on some immune parameters including zinc pool alterations and wound healing process in different age group in rats and also investigates the effect of melatonin administration on wound healing in different age groups. Experiments were performed on two different age groups of rats (neonatal and young). We have experimentally shown the induction of immune depression by pinealectomy and the restorative competence of melatonin administration in the present study. The results also showed that the plasma zinc level was significantly reduced in the third week after the pinealectomy particularly in pinealectomised neonatal rats and the wound healing process affected only in pinealectomised neonatal rats but restored to normal by melatonin administration. In view of these data, as described previously, the pineal gland has a main regulatory function in immune physiology, but our study indicates that only neonatal immune functions are significantly affected by pinealectomy.


The spectrum of beta-globin gene mutations in children with beta-thalassaemia major from Kota Kinabalu, Sabah, Malaysia.
Beta-thalassaemia major is one of the commonest genetic disorders in South East Asia. The strategy for the community control of beta-thalassaemia major requires the characterisation of the spectrum of beta-globin gene mutations in any multi-ethnic population. There is only a single report of mutation analyses of the beta-globin gene in an isolated Kadazandusun community in Kota Belud, Sabah, Malaysia, which showed the presence of a common 45 kb deletion. To confirm the observation that this large deletion is the commonest beta-globin gene mutation among the Kadazandusun and other indigenous populations in Sabah, Malaysia, we performed polymerase chain reaction (PCR) analysis of the beta-globin gene in ten children with beta-thalassaemia major attending the Thalassaemia Centre, Queen Elizabeth Hospital, the major paediatric referral centre in Kota Kinabalu, Sabah. The 45 kb deletion was confirmed to be the commonest mutation found in the Kadazandusun, Bajau and Murut populations, whereby it was detected in 19 out of the 20 (95 percent) alleles analysed. The other mutation was due to an IVS-1 position 1 G > T mutation. This finding confirmed the deletion in the homozygous state was associated with a severe phenotype. The reason for the predominance of this mutation in Kota Kinabalu is most likely to be due to founder effects and possibly intermarriages between the various ethnic groups. Prenatal diagnosis using PCR for this common mutation is feasible in this community. Medical workers and scientists at molecular diagnostic centres serving large South East Asian populations should incorporate a diagnostic strategy for this deletion in the appropriate population. Future studies on these indigenous ethnic groups in other areas and other groups in Sabah are required.


Comparison of 2 Anesthetic Methods for Transforaminal Endoscopic Lumbar Discectomy: A Prospective Randomized Controlled Study.
Randomized controlled trial. To compare the effect and safety of 2 anesthetic methods using in the operation of Transforaminal Endoscopic Lumbar Discectomy. From the January of 2020 to the December of 2021, 230 consecutive patients that underwent TELD were applied with two methods of anesthesia. All the patients were divided into two groups. The Monitored Anesthesia Care (MAC) group used the local anesthesia (LA) with MAC that based on the combination of dexmedetomidine and butorphanol tartrate. The LA group used the local anesthesia only. Then the Visual Analogic Scale (VAS) through the operating period was compared between the two groups at the time points of before operation (T0), inserting of the puncture needle (T1), establishing of the working cannula (T2), excision of the fibrous rings (T3) and immediately postoperatively (T4). Also, the satisfaction degree of the patients for the course of the operations and the occurrence of the complications were compared between the two groups. There were no differences of the VAS around the operating area at the time point of T0. Then the MAC group expressed lower scores at all other points of T1, T2, T3 and T4. Then the satisfaction degree of the MAC group was superior than the LA group. No difference was observed for the occurrence of the complications. MAC based on the combination of dexmedetomidine and butorphanol tartrate is an ideal method of anesthesia for TELD with enough effect and safety.


Benzene and its effects on cell signaling pathways related to hematopoiesis and leukemia.
Benzene is an environmental toxicant found in many consumer products. It is an established human carcinogen and is known to cause acute myeloid leukemia in adults. Epidemiological evidence has since shown that benzene can cross the placenta and affect the fetal liver. Animal studies have shown that in utero exposure to benzene can increase tumor incidence in offspring. Although there have been risk factors established for acute myeloid leukemia, they still do not account for many of the cases. Clearly then, current efforts to elucidate the mechanism by which benzene exerts its carcinogenic properties have been superficial. Owing to the critical role of cell signaling pathways in the development of an organism and its various organ systems, it seems plausible to suspect that these pathways may have a role in leukemogenesis. This review article assesses current evidence of the effects of benzene on critical hematopoietic signaling pathways. Pathways discussed included Hedgehog, Notch/Delta, Wingless/Integrated, nuclear factor-kappaB and others. Following a review of the literature, it seems that current evidence about the effects of benzene on these critical signaling pathways remains limited. Given the important role of these pathways in hematopoiesis, more attention should be given to them.


[Effect of L-arginine on the oxygen balance of the liver and its bile secretion function].
In acute experiments on anesthetized rats we showed that L-arginine causes an increase in oxygen-dependent synthetic processes in the liver, particularly associated with mitochondrial polyenzyme systems biosynthesis of bile acids with simultaneous activation in hepatocytes tissue respiration. The level of oxygen tension in the gland is not changed. Implementation of these effects partly involves nitric oxide. In addition, the L-arginine inhibits cholepoiesis without involving to the reaction NO. Dose-dependent influence L-arginine on the bile cholates content may indicate a different effect of this amino acids on metabolic transformation of bile acids such as hydroxylation and conjugation.