Adherence with recommended well-child visits has grown, but large gaps persist among various socioeconomic groups.
A goal of federal policy is to improve preventive health care for children. However, little is known about how adherence to recommendations by the American Academy of Pediatrics for well-child visits has changed over time. Using the 1996-2008 Medical Expenditure Panel Surveys, we examined trends in adherence and whether differences across population subgroups narrowed or widened over time. We found that the ratio of actual to recommended well-child visits rose from 46.3 percent during the 1996-98 time period to 58.9 percent during the 2007-08 time period. Although this increase in adherence is important, improvement occurred unevenly. We observed large differences in adherence at the start of the study period across income, race or ethnicity, parent education, region, insurance coverage, and having a usual source of care. None of these differences had narrowed significantly by the end of the study period. Indeed, differences widened across parent education, between those with and without insurance coverage, by usual source of care, and between the Northeast and the Midwest and West regions. Our results highlight the importance of provisions in the Affordable Care Act to expand coverage, strengthen incentives for preventive services, and improve the measurement of preventive services.


Remediation of soil contaminated with persistent organic pollutants in Sumgait, Azerbaijan.
The Sumgait remediation project was implemented in 2015 as a partnership between Blacksmith Institute and the site owner Azerikimya Joint Stock Company (Azerikimya) in Sumgait City, Azerbaijan Republic, about 30 km northwest of Baku. The project was financed by the European Commission and supported by the Ministry of Ecology and Natural Resources (MENR) and Sumgait Municipality. The site is a place on the Caspian Sea coast that was formerly an industrial area highly contaminated with various pollutants and particularly benzo(a)pyrene, benzene, and polychlorinated biphenyls (PCBs). As part of initial environmental assessment, the project team took soil samples at 19 locations at the surface and at the depth of 0.5 m. The maximum topsoil benzo(a)pyrene concentration was 76.21 mg/kg, benzene, 121.5 mg/kg, and PCBs, 121.02 mg/kg. The remediation project involved the removal of 804 m3 of contaminated soil and disposal of the contaminated soil at the MENR Hazardous Waste Polyqon (landfill). A comparison of pre- and post-excavation sampling shows that average contaminant levels in soils in the upper 0.5 m were reduced by an average of 97%. These actions were followed by bioremediation activities. More than 13,000 m3 of clean soil and organic fertilizer were placed and leveled over an area of two hectares. Approximately 1200 locally grown native tree species were planted, and a drip irrigation system was installed. The area is now a park close to the beach.


A model of metabolic syndrome and related diseases with intestinal endotoxemia in rats fed a high fat and high sucrose diet.
We sought develop and characterize a diet-induced model of metabolic syndrome and its related diseases. The experimental animals (Spague-Dawley rats) were randomly divided into two groups, and each group was fed a different feed for 48 weeks as follows: 1) standard control diet (SC), and 2) a high sucrose and high fat diet (HSHF). The blood, small intestine, liver, pancreas, and adipose tissues were sampled for analysis and characterization. Typical metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD), and type II diabetes (T2DM) were common in the HSHF group after a 48 week feeding period. The rats fed HSHF exhibited signs of obesity, dyslipidemia, hyperglycaemia, glucose intolerance, and insulin resistance (IR). At the same time, these animals had significantly increased levels of circulating LPS, TNFα, and IL-6 and increased ALP in their intestinal tissue homogenates. These animals also showed a significant reduction in the expression of occluding protein. The HSHF rats showed fatty degeneration, inflammation, fibrosis, cirrhosis, and lipid accumulation when their liver pathologies were examined. The HSHF rats also displayed increased islet diameters from 12 to 24 weeks, while reduced islet diameters occurred from 36 to 48 weeks with inflammatory cell infiltration and islet fat deposition. The morphometry of adipocytes in HSHF rats showed hypertrophy and inflammatory cell infiltration. HSHF CD68 analysis showed macrophage infiltration and significant increases in fat and pancreas size. HSHF Tunel analysis showed significant increases in liver and pancreas cell apoptosis. This work demonstrated the following: 1) a characteristic rat model of metabolic syndrome (MS) can be induced by a high sucrose and high fat diet, 2) this model can be used to research metabolic syndrome and its related diseases, such as NAFLD and T2DM, and 3) intestinal endotoxemia (IETM) may play an important role in the pathogenesis of MS and related diseases, such as NAFLD and T2DM.


Attenuation of Inflammatory Mediators (TNF-α and Nitric Oxide) and Up-Regulation of IL-10 by Wild and Domesticated Basidiocarps of Amauroderma rugosum (Blume & T. Nees) Torrend in LPS-Stimulated RAW264.7 Cells.
Amauroderma rugosum, commonly known as "Jiǎzī" in China, is a wild mushroom traditionally used by the Chinese to reduce inflammation, to treat diuretic and upset stomach, and to prevent cancer. It is also used by the indigenous communities in Malaysia to prevent epileptic episodes and incessant crying by babies. The aim of this study was to compare the wild and domesticated basidiocarps of A. rugosum for antioxidant and in vitro anti-inflammatory effects in LPS-stimulated RAW264.7 cells. The wild basidiocarps of A. rugosum were collected from the Belum Forest, Perak, Malaysia and the domesticated basidiocarps of A. rugosum were cultivated in the mushroom house located in the University of Malaya, Kuala Lumpur, Malaysia. Both the wild and domesticated basidiocarps were subjected to ethanolic extraction and the extracts were tested for antioxidant and anti-inflammatory activities. In this study, the crude ethanolic extract of wild (WB) and domesticated (DB) basidiocarps of A. rugosum had comparable total phenolic content and DPPH scavenging activity. However, WB (EC50 = 222.90 μg/mL) displayed a better ABTS cation radical scavenging activity than DB (EC50 = 469.60 μg/mL). Both WB and DB were able to scavenge nitric oxide (NO) radical and suppress the NO production in LPS-stimulated RAW264.7 cells and this effect was mediated through the down-regulation of inducible nitric oxide synthase (iNOS) gene. In addition, both WB and DB caused down-regulation of the inflammatory gene TNF-α and the up-regulation of the anti-inflammatory gene IL-10. There was no inhibitory effect of WB and DB on nuclear translocation of NF-κB p65. In conclusion, the wild and domesticated basidiocarps of A. rugosum possessed antioxidant and in vitro anti-inflammatory properties. WB and DB inhibited downstream inflammatory mediators (TNF-α and NO) and induced anti-inflammatory cytokine IL-10 production. No inhibitory effects shown on upstream nuclear translocation of NF-κB p65. WB and DB exhibited antioxidant activity and attenuation of proinflammatory mediators and therefore, A. rugosum may serve as a potential therapeutic agent in the management of inflammation.


[Changes in urine vitamin C, creatinine and uropepsin levels as a result of workload at standard work stations in the shipyard].
In 30 randomly selected workers at standard shipyard work-stations, energetic expenditure was estimated by comparing the results with those of biochemical tests used for evaluating the workload degree, such as: creatinine and vitamin C content in urine, uropepsin activity, degree of saturating the organism with vitamin C. The same examinations were carried out in 20 auxiliary and administrative employees composing a control group. The results demonstrate decreased vitamin C level in urine and saliva towards the end of the working day in the productive" group (the one under examination) as compared to the control one." The total creatinine level and uropepsin activity were also enhanced in the urine of the productive workmen. The differences between the mean values between the examined and control groups were statistically significantly different. A correlation was found between the energetic expenditure and changes in the mentioned biochemical parameters in urine.


Targeting the α4-α5 interface of RAS results in multiple levels of inhibition.
Generation of RAS-targeted therapeutics has long been considered a "holy grail" in cancer research. However, a lack of binding pockets on the surface of RAS and its picomolar affinity for guanine nucleotides have made isolation of inhibitors particularly challenging. We recently described a monobody, termed NS1, that blocks RAS signaling and oncogenic transformation. NS1 binds to the α4-β6-α5 interface of H-RAS and K-RAS thus preventing RAS dimerization and nanoclustering, which in turn prevents RAS-stimulated dimerization and activation of RAF. Interestingly, NS1 reduces interaction of oncogenic K-RAS, but not H-RAS, with RAF and reduces K-RAS plasma membrane localization. Here, we show that these isoform specific effects of NS1 on RAS:RAF are due to the distinct hypervariable regions of RAS isoforms. NS1 inhibited wild type RAS function by reducing RAS GTP levels. These findings reveal that NS1 disrupts RAS signaling through a mechanism that is more complex than simply inhibiting RAS dimerization and nanoclustering.


[Prenylation: from bacteria to eukaryotes].
For their protection from host cell immune defense, intracellular eukaryotic parasites developed a variety of mechanisms, including secretion systems III and IV which inject bacterial effectors directly into eukaryotic cells. These effectors may be posttranslational modified by host cell machinery and may function inside the host cell. Recently, to the list of possible posttranslational modifications of bacterial proteins the prenylation was added. In this work we describe current state of the knowledge about the prenylation of eukaryotic and prokaryotic proteins and its inhibitors. The bioinformatics analyses suggest possibility of prenylation for a number of Francisella genus proteins.


Note: Evaluation of magnetometry data acquired from elongated samples.
We document and validate an analytic expression for the flux integral characterizing the response (or sensitivity) of a magnetometer equipped with second-order axial gradiometer coils to long, thin, uniformly magnetized samples. We then demonstrate an application inspired by this analysis, in which magnetometric sensitivity to weak magnetic signatures is readily and appreciably enhanced by increasing the sample volume (and hence the quantity of analyte) well beyond conventional limits.


An assessment of the generation times of neuronal precursors in the sensory retina and subventricular zone of the newborn rat.
Generation times and the times for their respective phases were determined for neuronal precursors in the sensory retina and subventricular zone of the brain of newborn CD rats. These regions can be induced to form retinoblastoma and medulloepitheliomas, respectively, following injection of adenovirus-12. Through use of autoradiographic techniques, it was shown that the cell cycle duration in the subventricular zone was almost twice as long as in the sensory retinal layer. The G1 phase durations were found to account for the majority of the time difference.


Combinatorial discovery of tumor targeting peptides using phage display.
Peptides possess appropriate pharmacokinetic properties to serve as cancer imaging or therapeutic targeting agents. Currently, only a small number of rationally-derived, labeled peptide analogues that target only a limited subset of antigens are available. Thus, finding new cancer targeting peptides is a central goal in the field of molecular targeting. Novel tumor-avid peptides can be efficiently identified via affinity selections using complex random peptide libraries containing millions of peptides that are displayed on bacteriophage. In vitro and in situ affinity selections may be used to identify peptides with high affinity for the target antigen in vitro. Unfortunately, it has been found that peptides selected in vitro or in situ may not effectively target tumors in vivo due to poor peptide stability and other problems. To improve in vivo targeting, methodological combinatorial chemistry innovations allow selections to be conducted in the environment of the whole animal. Thus, new targeting peptides with optimal in vivo properties can be selected in vivo in tumor-bearing animals. In vivo selections have been proven successful in identifying peptides that target the vasculature of specific organs. In addition, in vivo selections have identified peptides that bind specifically to the surface of or are internalized into tumor cells. In the future, direct selection of peptides for cancer imaging may be expedited using genetically engineered bacteriophage libraries that encode peptides with intrinsic radiometal-chelation or fluorescent sequences.


The bradykinin B1 receptor antagonist B9858 inhibits a nociceptive spinal reflex in rabbits.
There are two bradykinin receptor subtypes, designated B1 and B2. Whilst both have been implicated in nociception, it is believed that there is a low level of constitutive expression of B1 receptors and that their expression is induced by inflammation or tissue damage. The present study investigated the role of B1 receptors in spinal nociceptive processing using an in vivo electrophysiological assay in decerebrate, spinalized rabbits, a species that shares close B1 receptor homology with the human receptor. Inflammation was induced in the paw by an injection of complete Freund's adjuvant at least 1 h before recording single motor unit activity of the semitendinous/biceps femoris muscle in response to a noxious pinch of the foot. Control animals received an intraplantar injection of saline. The peptide B1 receptor antagonist B9858 was administered i.v. and caused dose-dependent and complete inhibition of the nociceptive spinal reflex (ID50 = 1 mg x kg(-1)). In control animals without paw inflammation, B9858 had no effect. These findings are consistent with other evidence that peptide B1 receptor antagonists inhibit spinal nociceptive reflexes only after induction of B1 receptors by inflammation and support the potential therapeutic utility of B1 receptor antagonists as analgesic and anti-inflammatory drugs.


Attenuated total reflectance spectroscopy of plant leaves: a tool for ecological and botanical studies.
Attenuated total reflectance (ATR) spectra of plant leaves display complex absorption features related to organic constituents of leaf surfaces. The spectra can be recorded rapidly, both in the field and in the laboratory, without special sample preparation. This paper explores sources of ATR spectral variation in leaves, including compositional, positional and temporal variations. Interspecific variations are also examined, including the use of ATR spectra as a tool for species identification. Positional spectral variations generally reflected the abundance of cutin and the epicuticular wax thickness and composition. For example, leaves exposed to full sunlight commonly showed more prominent cutin- and wax-related absorption features compared with shaded leaves. Adaxial vs. abaxial leaf surfaces displayed spectral variations reflecting differences in trichome abundance and wax composition. Mature vs. young leaves showed changes in absorption band position and intensity related to cutin, polysaccharide, and possibly amorphous silica development on and near the leaf surfaces. Provided that similar samples are compared (e.g. adaxial surfaces of mature, sun-exposed leaves) same-species individuals display practically identical ATR spectra. Using spectral matching procedures to analyze an ATR database containing 117 individuals, including 32 different tree species, 83% of the individuals were correctly identified.


FLAIRfusion Processing with Contrast Inversion : Improving Detection and Reading Time of New Cerebral MS Lesions.
To evaluate the performance of an innovative image processing approach for detection of T2-weighted hyperintense multiple sclerosis (MS) lesions. In this study 20 consecutive patients with inflammatory demyelinating lesions were retrospectively evaluated of whom 10 patients featured progressive disease and 10 a stable lesion load. 3 mm transversal FLAIRfusion imaging was processed and archived. Image processing was performed through landmark-based 3D co-registration of the previous and current isotropic FLAIR examination followed by inversion of image contrast. Thereby, the hyperintense signals of the unchanged MS plaques extinguish each other, while newly developed lesions appear bright on FLAIRfusion. Diagnostic performance was evaluated by 4 experienced readers. Consensus reading supplied the reference standard. Sensitivity, specificity, NPV (negative predictive value), PPV (positive predictive value), interreader agreement and reading time were the outcome measures analyzed. Combined sensitivity was 100% at a specificity of 88.2%, with PPV ranging from 83.3% to 90.1% and NPV at 100%. Reading time was nearly 5‑fold faster than conventional side by side comparison (35.6 s vs. 163.7 s, p < 0.001). Cohen's kappa was excellent (>0.75; p < 0.001) and Cronbach's alpha was 0.994. FLAIRfusion provides reliable detection of newly developed MS lesions along with strong interreader agreement across all levels of expertise in 35 s of reading time.


Blood supply to the amphibian mesonephros.
The purpose of the present study was to describe geometry of branching, topography and sources of blood vessels supplying the mesonephros of three different species of amphibia and to infere from the results their common and species-specific features. The detailed information on arrangement of portal and arterial blood supply to mesonephros is necessary for better understanding of the conditions under which these kidneys function. For this reason the blood vessels of the mesonephros of adult Hynobius Keyserlingi, Triturus vulgaris and Rana temporaria were injected with stained gelatin. The urodelian kidneys were shown to be supplied by numerous segmental arteries. Three types of arterial supply to glomeruli were distinguished: those mediated by short, medium and long branches, which create different physical conditions for the glomerular filtration in pertinent nephrons--as the blood pressure necessarily decreases with the increasing distance from the aorta. The tributaries to the renal portal vein were identified in all three species as the veins draining hind limbs, tail, pelvis and body wall. It is being suggested that the purpose of this large drainage area is to secure a sufficient volume of blood to the peritubular network.


Enzyme Substrate Specificity Conferred by Distinct Conformational Pathways.
Substrate recognition is one of the hallmarks of enzyme catalysis. Enzyme conformational changes have been linked to selectivity between substrates with little direct evidence. Aldolase, a glycolytic enzyme, must distinguish between two physiologically important substrates, fructose 1-phosphate and fructose 1,6-bisphosphate, and provides an excellent model system for the study of this question. Previous work has shown that isozyme specific residues (ISRs) distant from the active site are responsible for kinetic distinction between these substrates. Notably, most of the ISRs reside in a cluster of five surface α-helices, and the carboxyl-terminal region (CTR), and cooperative interactions among these helices have been demonstrated. To test the hypothesis that conformational changes are at the root of these changes, single surface-cysteine variants were created with the cysteine located on helices of the cluster and CTR. This allowed for site-specific labeling with an environmentally sensitive fluorophore, and subsequent monitoring of conformational changes by fluorescence emission spectrophotometry. These labeled variants revealed different spectra in the presence of saturating amounts of each substrate, which suggested the occurrence of different conformations. Emission spectra collected at various substrate concentrations showed a concentration dependence of the fluorescence spectra, consistent with binding events. Lastly, stopped-flow fluorescence spectrophotometry showed that the rate of these fluorescence changes was on the same time-scale as catalysis, thus suggesting a link between the different fluorescence changes and events during catalysis. On the basis of these results, we propose that different conformational changes may be a common mechanism for dictating substrate specificity in other enzymes with multiple substrates.


The renin-angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad.
Pregnancy demands major changes of the cardiovascular system, and this involves, among others, activation of the RAAS (renin-angiotensin-aldosterone system), allowing an aldosterone-dependent increase in volume. Remarkably, a relative resistance to the pressor response of AngII (angiotensin II) develops simultaneously to prevent the increase in blood pressure that would normally accompany RAAS activation. The increase in volume, the degree of RAAS activation and the diminished pressor response to AngII are less pronounced in pre-eclampsia. However, animal models displaying excessive RAAS activation also result in a pre-eclampsia-like syndrome, and the aldosterone/renin ratio is elevated in pre-eclampsia compared with a normal pregnancy. New insights into the pathogenesis of pre-eclampsia have revealed a major role for VEGF (vascular endothelial growth factor), VEGF-inactivating sFlt-1 (soluble fms-like tyrosine kinase-1) and AT1 (angiotensin II type 1) receptor autoantibodies. The last mentioned activate AT(1) receptors, thereby potentially suppressing circulating renin and aldosterone. VEGF, both directly and indirectly (by increasing capillary density), affects adrenal aldosterone synthesis. The present review summarizes all of the recent findings regarding RAAS regulation in pre-eclampsia compared with normal pregnancy, concluding that factors such as sFlt-1 and AT(1) receptor autoantibodies disturb the delicate balance that normally results in a volume increase and a diminished vasoconstrictor response to AngII in pregnant women. It is possible that there are non-parallel changes in the circulating and renal RAAS in pre-eclampsia, which are potentially reflected by the urinary levels of renin.


Attitudes toward smoking policies in eight states--United States, 1993.
Legislation regulating smoking has at least two functions: to protect nonsmokers from the adverse health effects of environmental tobacco smoke and to prevent young persons from smoking (1). To characterize public attitudes toward such legislation, the National Cancer Institute (NCI) and the American Cancer Society used the Behavioral Risk Factor Surveillance System (BRFSS) to survey persons in eight states during July-August 1993 as part of the American Stop Smoking Intervention Study for Cancer Prevention (2). This report summarizes the survey findings.


Budd-Chiari syndrome in China: A 30-year retrospective study on survival from a single center.
To investigate 30-year treatment outcomes associated with Budd-Chiari syndrome (BCS) at a tertiary hospital in China. A total of 256 patients diagnosed with primary BCS at our tertiary hospital between November 1983 and September 2013 were followed and retrospectively studied. Cumulative survival rates and cumulative mortality rates of major causes were calculated by Kaplan-Meier analysis, and the independent predictors of survival were identified using a Cox regression model. Thirty-four patients were untreated; however, 222 patients were treated by medicine, surgery, or interventional radiology. Forty-four patients were lost to follow-up; however, 212 patients were followed, 67 of whom died. The symptom remission rates of treated and untreated patients were 81.1% (107/132) and 46.2% (6/13), respectively (P = 0.009). The cumulative 1-, 5-, 10-, 20-, and 30-year survival rates of the treated patients were 93.5%, 81.6%, 75.2%, 64.7%, and 58.2%, respectively; however, the 1-, 5-, 10-, 20-, and 30-year survival rates of the untreated patients were 70.8%, 70.8%, 53.1%, 0%, and unavailable, respectively (P = 0.007). Independent predictors of survival for treated patients were gastroesophageal variceal bleeding (HR = 3.043, 95%CI: 1.363-6.791, P = 0.007) and restenosis (HR = 4.610, 95%CI: 1.916-11.091, P = 0.001). The cumulative 1-, 5-, 10-, 20-, and 30-year mortality rates for hepatocellular carcinoma were 0%, 2.6%, 3.5%, 8%, and 17.4%, respectively. Long-term survival is satisfactory for treated Chinese patients with BCS. Hepatocellular carcinoma is a chronic complication and should be monitored with long-term follow-up.


Restenosis after stenting in symptomatic vertebral arterial orifice disease and considerations for better outcome.
We have performed stenting in 11 patients with symptomatic vertebral arterial orifice stenosis refractory to medical treatment or impairment in anterior circulation. Three of the 11 patients experienced asymptomatic severe in-stent restenosis or occlusion. Bare metal stents were used in those three patients, two of whom received revascularization therapy. Development of sufficient cervical collateral channels reconstituting the distal vertebral artery was the common feature in patients with asymptomatic in-stent restenosis. In selecting appropriate stents, consideration of mechanical strength and drug-eluting properties of a stent according to characteristics of the target vessel is important to reduce the risk of in-stent restenosis. Any decision to perform revascularization should be based on the presence of abundant cervical collaterals as well as clinical symptoms of vertebrobasilar ischemia.


[Plant-derived terpenes in treating patients with urolithiasis].
Numerous metabolic abnormalities intrinsic to urolithiasis require drug therapy. At the same time, despite the constant expansion of synthetic drugs, plant-derived medications play a large role in the treatment and prevention of the disease. To evaluate the effect of a plant-derived preparation Rowatinex in patients with urolithiasis after extracorporeal shock wave lithotripsy (ESWL) and analyze the changes in blood and urine parameters in patients receiving the preparation. Depending on the type of post-ESWL treatment, patients were divided into two groups. After ESWL, patients of group A (n=107) and group B (n=50) were administered Rowatinex and antispasmodic drugs, respectively. Clearance of stone fragments after ESWL within 1-5 days was achieved in 76 (71.1%) patients of group A and in 20 (40.4%) of group B. Analysis of the effect of the therapy on blood count, biochemistry tests and 24h excretion (magnesium, uric acid, calcium, etc.) did not reveal significant differences between group A group B and reference values. Increased diuresis caused by antispasmodic effects of Rowatinex resulted in the complete clearance of stone fragments. Urinalysis in patients of the two groups showed decreased leukocyturia. Furthermore, stabilization of urine pH within the 6.2-6.8 was noted in group A, which is important and necessary in metaphylaxis of recurrent stone formation. Administration of Rowatinex increases the percentage of stone fragment clearance after ESWL and reduces pain intensity. Rowatinex reduces leukocyturia, increases 24h diuresis and stabilizes the pH of urine. Increasing and stabilizing urine pH in patients with calcium oxalate and urate stones reduces the risk of recurrence after ESWL. No complications associated with Rowatinex were reported, allowing long-term administration of the preparation in the complex lithokinetic therapy and for metaphylaxis of recurrent stone formation.


Novel spherical assembly of gold nanoparticles mediated by a tetradentate thioether.
The ability to construct three- and two-dimensional architectures via nanoscale engineering is important for emerging applications of nanotechnology in sensors, catalysis, controlled drug delivery, microelectronics, and medical diagnostics. In this paper, we report novel 3D assembly using multidentate molecular building blocks. It is demonstrated that the interparticle linking of gold nanoparticles (3.7 nm core size) by a tetradentate thioether, tetra[(methylthio)methyl]silane, leads to the formation of a spherical assembly. The spherical size (30-80 nm diameter) is dependent on reaction time and relative ratio of the building blocks. The novelty of this approach is the viability of multidentate thioethers to link nanoparticles and produce spherical assemblies that can be readily assembled and disassembled. The spherical assembly can also be partially "melted" depending on the nature of interfacial interactions between the assembly and the substrate. These unusual morphological properties in shape and surface interaction and the intriguing assembling-disassembling capabilities may form the basis of designing and fabricating novel functional nanostructures.


Farnesoid X Receptor an Emerging Target to Combat Obesity.
Obesity and its associated diseases, including type 2 diabetes, have reached epidemic levels worldwide. However, available treatment options are limited and ineffective in managing the disease. There is therefore an urgent need for the development of new pharmacological solutions. The bile acid (BA) Farnesoid X receptor (FXR) has recently emerged as an attractive candidate. Initially described for their role in lipid and vitamin absorption from diet, BAs are hormones with powerful effects on whole body lipid and glucose metabolism. In this review, we focus on FXR and how 2 decades of work on this receptor, both in rodents and humans, have led to the development of drug agonists with potential use in humans for treatment of conditions ranging from obesity-associated diseases to BA dysregulation.


Adjustments in epidermal UV-transmittance of leaves in sun-shade transitions.
Epidermal UV transmittance (TUV ) and UV-absorbing compounds were measured in sun and shade leaves of Populus tremuloides and Vicia faba exposed to contrasting light environments under field conditions to evaluate UV acclimation potentials and regulatory roles of photosynthetically active radiation (PAR) and UV in UV-shielding. Within a natural canopy of P. tremuloides, TUV ranged from 4 to 98% and showed a strong nonlinear relationship with mid-day horizontal fluxes of PAR [photon flux density (PFD) = 6-1830 µmol m⁻² s⁻¹]; similar patterns were found for V. faba leaves that developed under a comparable PFD range. A series of field transfer experiments using neutral-density shade cloth and UV blocking/transmitting films indicated that PAR influenced TUV during leaf development to a greater degree than UV, and shade leaves of both species increased their UV-shielding when exposed to full sun; however, this required the presence of UV, with both UV-A and UV-B required for full acclimation. TUV of sun leaves of both species was largely unresponsive to shade either with or without UV. In most, but not all cases, changes in TUV were associated with alterations in the concentration of whole-leaf UV-absorbing compounds. These results suggest that, (1) moderate-to-high levels of PAR alone during leaf development can induce substantial UV-protection in field-grown plants, (2) mature shade leaves have the potential to adjust their UV-shielding which may reduce the detrimental effects of UV that could occur following sudden exposures to high light and (3) under field conditions, PAR and UV play different roles in regulating UV-shielding during and after leaf development.


The impact of a nurse-led chronic musculoskeletal pain clinic on healthcare utilization.
To determine whether a nurse-led chronic musculoskeletal pain clinic for fibromyalgia patients can reduce utilization of healthcare services. People with fibromyalgia often consult multiple specialities due to the vast nature of their symptoms but receive little or no help in managing their symptoms. A retrospective evaluation of a nurse consultant-led chronic pain management clinic. The frequency of hospital attendances in the five years before and three years after pain clinic attendance was evaluated. General practitioner (GP) attendances in the 12-month period before and after pain clinic attendance were compared with attendances for two groups of patients from an established GP cohort: (i) patients referred to rheumatology new patient clinics and (ii) all patients with fibromyalgia referred to any hospital new patient clinic. In the three years following attendance at the pain clinic, the mean number of hospital appointments fell significantly from 2.8 to 1.4 per annum (p < 0.001). The mean reduction seen in hospital clinic attendances in the first year (0.8/annum) improved in the second (1.2/annum) and third (2.1/annum) years. Seventy-eight per cent of pain clinic patients reduced their visits to their GP in the 12 months following treatment in the pain service, compared with 53% of patients referred to rheumatology clinics and 46% of patients with fibromyalgia. A nurse-led chronic pain clinic for fibromyalgia patients can have a positive impact on primary and secondary healthcare utilization. Having a designated nurse-led pain clinic can enable patients to access the appropriate service at an earlier stage in their condition and receive the support needed to manage the impact of their pain.


Transverse thoracic muscle plane block as a routine strategy for cardiac enhanced recovery after surgery in sternotomy: A retrospective analysis.
The aim of this study is to retrospectively analyze and evaluate the effect of transverse thoracic muscle plane (TTP) block as a routine analgesic strategy for cardiac enhanced recovery after surgery in sternotomy.Patients received TTP block after general anesthesia and tracheal intubation were included in this study. The baseline clinical data of the patients, intraoperative use of sufentanil, internal mammary artery separating time, the postoperative duration of invasive ventilation, visual analogue scale, the compression times of patient-controlled intravenous analgesia in the first 3 days after surgery, and postoperative nausea and vomiting were recorded.A total of 104 cases was included and divided to G group (without TTP block) and TTP group (with TTP). Sufentanil use (sufentanil dose/min, sufentanil dose/kg body weight, sufentanil dose/[min kg]) in TTP group was significantly lower than that of G group. In G group, intraoperative use of sufentanil was correlated to the duration of anesthesia (P = .035). The postoperative visual analogue scale pain scores and the compression times of patient-controlled intravenous analgesia in the TTP group were significantly decreased compared with G group (P < .01). The postoperative duration of invasive ventilation of patients with normal and mildly impaired pulmonary function was significantly correlated to the use of sufentanil (P = .027, .009).TTP block has certain analgesic effect and can reduce sufentanil use in medium-length cardiac surgery and postoperative use of opioids. It is indicated that TTP block can be used as a routine enhanced recovery after surgery strategy for sternotomy in cardiac surgery.


Role of internalization of M2 muscarinic receptor via clathrin-coated vesicles in desensitization of the muscarinic K+ current in heart.
In the heart, ACh activates the ACh-activated K(+) current (I(K,ACh)) via the M(2) muscarinic receptor. The relationship between desensitization of I(K,ACh) and internalization of the M(2) receptor has been studied in rat atrial cells. On application of the stable muscarinic agonist carbachol for 2 h, I(K,ACh) declined by approximately 62% with time constants of 1.5 and 26.9 min, whereas approximately 83% of the M(2) receptor was internalized from the cell membrane with time constants of 2.9 and 51.6 min. Transfection of the cells with beta-adrenergic receptor kinase 1 (G protein-receptor kinase 2) and beta-arrestin 2 significantly increased I(K,ACh) desensitization and M(2) receptor internalization during a 3-min application of agonist. Internalized M(2) receptor in cells exposed to carbachol for 2 h was colocalized with clathrin and not caveolin. It is concluded that a G protein-receptor kinase 2- and beta-arrestin 2-dependent internalization of the M(2) receptor into clathrin-coated vesicles could play a major role in I(K,ACh) desensitization.


A Mitomycin C-Sparing Novel Technique for Subscleral Trabeculectomy in Primary Congenital Glaucoma.
To evaluate the safety and efficacy of a novel modified subscleral trabeculectomy technique in management of primary congenital glaucoma. This study included 25 infants diagnosed of having bilateral primary congenital glaucoma. For each patient, one eye was assigned to undergo subscleral trabeculectomy with trimming of the edges of the scleral bed (group I), while the contralateral eye underwent subscleral trabeculectomy with application of mitomycin C (0.4 mg/ml for 3 min) (group II). All the patients were followed up for a period of 14 ± 3 months (range 13-22 months). 25 eyes were included in each group. Patients' mean age was 2.5 ± 0.5 months (range 1.8-6.5 months). The mean preoperative intraocular pressure was 31 ± 4.9 mmHg and 32.1 ± 4.0 mmHg in group I and II, respectively. The mean postoperative intraocular pressure was 9.0 ± 1.0, 11.0 ± 3.2, 12.5 ± 0.9, 13.0 ± 2.9, and 15.5 ± 1.5 mm Hg in group I and was 10.3 ± 1.2, 12.0 ± 2.5, 13.5 ± 1.7, 15.0 ± 1.5, and 17.1 ± 2.8 mm Hg in group II at the first week and 1, 3, 6, and 12 months, respectively. There was no statistically significant difference between the mean intraocular pressure values recorded at both groups preoperatively and at each follow-up visit. Failure necessitating further surgical interventions was recorded in 4 eyes (16%) in group I as compared to 3 eyes (12%) in group II (P > 0.05). Postoperative complications included mild hyphema, which occurred in one eye (4%) in group I and 2 eyes (8%) in group II, and shallow anterior chamber in 3 eyes (12%) in group I and in 2 eyes (8%) in group II. One eye (4%) in group I developed drawn-up pupil. Choroidal effusion developed in one eye (4%) at each group. Trimming the edges of the scleral bed adjacent to the sclera flap is a safe and effective surgical step which can be added to the subscleral trabeculectomy procedure to effectively control the intraocular pressure in patients with primary congenital glaucoma, sparing them the hazards associated with mitomycin C application.


Small bowel volvulus versus adhesive small bowel obstruction: a diagnostic dilemma in a 19-year-old woman.
Small bowel volvulus (SBV) is often challenging to diagnose. Research suggests that the clinical presentation of this disease is often very similar to other more common causes of small bowel obstruction (SBO) such as intraabdominal adhesions and no single preoperative diagnostic study is sensitive or specific enough to identify this rare cause of mechanical SBO. This report describes a case of a 19-year-old woman who presented with irretractable vomiting and abdominal pain secondary to SBV. This case is unusual as her history of recurrent adhesive SBO presented a diagnostic dilemma that required a higher degree of clinical suspicion to tease these differential diagnoses apart. She underwent laparoscopy which facilitated successful detorsion and resection of the floppy tongue of jejunum. This report aims to increase the awareness among surgeons.


Sturge-weber syndrome: a case report with persistent headache.
Sturge-Weber syndrome (SWS) is a rare congenital disorder characterized by a facial vascular nevus associated with an ipsilateral leptomeningeal angioma. Headache is a rare component of SWS and when it occurs it usually occurs as a migraine-like headache. We aimed to present a SWS patient with episodic tension type headache and to draw attention in different types of headaches that can be seen in SWS. A 21 year old female patient with the diagnosis of SWS was suffering from severe headaches. At her physical examination a facial nevus -occurred due to choroid angioma- was observed. On her neurological examination a mild asymmetry of upper extremities was visible. She had a 2 year history of frequent non-pulsating headaches. There was no nausea or aura like symptoms accompanying the headache. Headaches were lasting for hours. The pain was bilateral and pressing in quality. SWS are a very rare and challenging disease for both the patients and their families. Usually migraine type headache is seen in SWS but it should not be forgotten that more generalized headaches like tension type may also be seen.


Fabrication and Cell Responsive Behavior of Macroporous PLLA/Gelatin Composite Scaffold with Hierarchical Micro-Nano Pore Structure.
Scaffolds providing a 3D environment which can effectively promote the adhesion, proliferation and differentiation of cells are crucial to tissue regeneration. In this study, the poly-l-lactic acid (PLLA) scaffold with hierarchical pore structural was fabricated via two-step thermally induced phase separation (TIPS). To mimic both physical architecture and chemical composite of natural bone extracellular matrix (ECM), gelatin fibers were introduced into the pores of PLLA scaffolds and formed 3D network structure via TIPS. Human adipose tissue-derived stem cells (ADSCs) were harvested and seeded into PLLA/gel hybrid scaffolds and cultured in vitro for biocompatibility assay. The surface morphology, porosity and compressive modulus of scaffolds were characterized by scanning electron microscopy (SEM), density analysis and compression test respectively. The results showed that hybrid scaffolds had high porosity (91.62%), a good compressive modulus (2.79 ± 0.20 MPa), nanometer fibers (diameter around 186.39~354.30 nm) and different grades of pore size from 7.41 ± 2.64 nm to 387.94 ± 102.48 nm. The scaffolds with mild hydrolysis by NaOH were modified by 1-ethyl-3-(3-dimethyl ami-nopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS). Gelatin was performed onto PLLA scaffold via TIPS aiming at enhancement cell-material interaction. In comparison with PLLA scaffold, the PLLA/gel scaffold had better biological performance and the mechanical properties because the gelatin fibers homogeneously distributed in each pore of PLLA scaffold and formed 3D network structure.


Blood boron levels and anthropometric measurements in prepubertal children.
This study was conducted to assess the blood boron levels (BBL) in prepubertal children in the West and Central Anatolia regions of Turkey and its relationship with chosen anthropometric measurements. A multistage sampling design that combined multicluster (West Anatolia vs. Central Anatolia regions and rural vs. urban residents) and simple random sampling methods were used for the sample selection. BBL was measured using inductively coupled plasma mass spectrometry. Weight, height, mid-arm circumference, and triceps skinfold thickness were measured. Z-scores for weight-for-age, height-for-age, and body mass index (BMI)-for-age were calculated. Furthermore, arm-muscle area, arm-fat area, and fat percentage were measured. This study enrolled 2126 children, of whom 50.7% were male. The mean age was 8.9 years. The mean concentration of BBL was 15.6 μg/L (interquartile range: 11.7-19.6 μg/L). Children in urban areas had significantly higher BBL than those in rural areas (17.2 ± 5.5 vs. 11.9 ± 4.6 μg/L; p < .001). Children in the West Anatolia region had significantly lower BBL than those in the Central Anatolia region (14.5 ± 5.9 μg/L vs. 17.8 ± 5.0 μg/L; p < .001). BBL was not affected by maternal education, occupation, sex, and anemia. BBL was found to be significantly lower in children with low BMI, low triceps skinfold thickness, low arm fat area, and low-fat percentage. Change in BBL was associated with the region and residence in Turkey. BBL differed between well-nourished and malnourished children. Further studies are needed to evaluate the relationship between anthropometry and BBL.


Vero cell invasiveness of Proteus mirabilis.
Vero cell invasiveness was studied for a group of Proteus mirabilis strains isolated from the urinary tract and feces and for a limited group of urinary isolates of Escherichia coli. Experimental conditions affecting this invasiveness were studied. All of the P. mirabilis strains tested were capable of cell invasion, whereas none of the E. coli strains was. Correlation between the hemolytic activity of the P. mirabilis strains and their invasive ability suggested that the bacterial hemolysin may be involved in the invasion process. Other experimental evidence supporting this hypothesis is discussed. The differences in the invasive capacities of P. mirabilis and of E. coli may be important for the apparent differences in the pathogenesis of urinary tract infection by both species.


Oxidative stress in the rats brain capillaries in sepsis--the influence of 7-nitroindazole.
As a part of blood-brain barrier, brain capillaries participate in pathophysiological events during systemic inflammation. We investigated the effects of 7-nitroindazole (7-NI), selective neuronal nitric oxide synthase (NOS) inhibitor, to oxidative status (OS) of brain capillaries. Adult Wistar rats were randomized at groups: control group (CG) (sham operated), sepsis group (GS) (cecal ligation and perforation with inoculation of Escherichia coli (ATCC 25922), 7-NI group (G7-NI), (30 mg/kg b/w i.p.) and 7-NI + sepsis group (G7-NIS), (7-NI was applied 30 minutes before operation). Lipid peroxidation index (LPI), nitrite concentration, superoxide dismutase (SOD) activity and superoxide anion (O2*-) content were determined 3, 6, 24 and 48 hour in each group. Cerebral capillaries were separated from non-vascular brain tissue using sucrose gradient. Compared to controls, LPI, nitrite and O2*- increased at SG. In the G7-NIS, LPI reached control values at the 24th and 48th hour, while nitrite were decreased at the 3rd and 24th hour, compared to controls. In the same group, O2*- decreased at the 3rd, 6th and 24th hour, although SOD showed variable activity. The systematic nNOS inhibition with 7-NI forces OS on early terms of sepsis, but lately it contributes to the normalization of OS in cerebral capillaries.


Citric acid monohydrate as a release-modifying agent in melt extruded matrix tablets.
Incomplete drug release and particle size-dependent dissolution performance can compromise the quality of controlled release matrix systems. The objective of the current study was to investigate the ability of citric acid monohydrate (CA MH) to enhance the release of diltiazem hydrochloride from melt extruded Eudragit RS PO tablets and to eliminate drug particle size effects. Preformulation studies demonstrated the thermal stability of all components, drug insolubility in the polymer but miscibility with the CA MH. Tablets with either constant polymer levels or constant drug-to-polymer ratios and containing different drug particle size fractions and increasing amounts of CA MH were manufactured by melt extrusion and characterized by dissolution testing, powder X-ray diffraction and scanning electron microscopy. The addition of CA MH to the formulation promoted the thermal processibility and matrix integrity by plasticization of the polymer. The drug release from systems with constant drug-to-polymer ratio was significantly increased when CA MH was added as a result of enhanced pore formation. Particle size effects were eliminated when large amounts of CA MH were used due to the loss of drug crystallinity. Matrix tablets with CA MH furthermore showed a faster and more complete drug release compared to systems with drug only or alternative pore formers (sucrose, NaCl, or PEG 3350). The enhanced drug release was attributed to the amorphous character of the soluble components, improved drug dispersion in the plasticized polymer along with increased polymer permeability. In summary, CA MH promoted the miscibility between the drug and Eudragit RS PO during hot-melt extrusion, resulting in the extrusion of an amorphous system with improved dissolution characteristics.


Off-Time Work-Related Smartphone Use and Bedtime Procrastination of Public Employees: A Cross-Cultural Study.
While previous studies have examined the negative effects of work-related smartphone use after hours, little is known about whether and how it influences employees' unhealthy sleep behavior (i.e., bedtime procrastination). Drawing on the ego depletion theory, this study explored the effects of work-related smartphone use after hours on bedtime procrastination. To further uncover potential cross-cultural differences, a sample of 210 public employees from the United States and 205 public employees from China were used. Results via path analysis revealed that off-time work-related smartphone use positively influenced bedtime procrastination via the mediating role of self-control depletion. These findings were consistent between the United States and Chinese sample; however, off-time work-related smartphone use after hours increased the likelihood of self-control depletion more strongly in the United States than in China. The implications of our findings for both theory and practice were discussed.


[Iodine deficiency and other potential goitrogens in the persistence of endemic goiter in Mexico].
To measure the frequency of goiter and the presence of potential goitrogens in a sample of school-age children and pregnant women. Cross-sectional study in a purposive sample in three regions, one with known high prevalence of goiter (Huejutla), one with unknown prevalence (Ixmiquilpan) and one with no expected deficiency (Pachuca). Children were sampled from schools and pregnant women from rural reference hospitals. Goiter was evaluated by manual exam and ultrasound. Goiter prevalence in 673 children between 6 and 14 years old was 8% in Pachuca, 9% in Ixmiquilpan, and 14% in Huejutla. In 300 pregnant women, goiter prevalence was 19% in Pachuca, 20% in Ixmiquilpan, and 52% in Huejutla. In 936 interviews on salt consumption, 98% of families consumed table salt, but only 50% of the samples were adequately iodized. Twenty-four percent of families obtained water from wells contaminated with arsenicum and mercury in Pachuca and Ixmiquilpan, and with colibacilli in Ixmiquilpan. Even at the end of the millenium, endemic goiter is still a public health problem in this sample of school-age children and pregnant women. Despite consumption of iodized salt, ingestions of goitrogens may be contributing to the persistence of this problem.


Gut microbiota profile and the influence of nutritional status on bacterial distribution in diabetic and healthy Tunisian subjects.
Gut microbiota plays a key role in the regulation of metabolism and immunity. We investigated the profile of gut microbiota and the impact of dietary intake on gut bacterial distribution in diabetic and healthy Tunisian subjects, aiming to identify a dysbiotic condition, hence opening the way to restore eubiosis and facilitate return to health. In the present research, we enrolled 10 type 1 diabetic (T1D), 10 type 2 diabetic (T2D) patients and 13 healthy (H) subjects. Illumina Miseq technology was used to sequence V3-V4 hypervariable regions of bacterial 16SrRNA gene. Data were analyzed referring to QIIME 2 pipeline. RStudio software was used to explore the role of nutrition in gut bacterial distribution. At the phylum level, we identified an imbalanced gut microbiota composition in diabetic patients marked by a decrease in the proportion of Firmicutes and an increase in the abundance of Bacteroidetes compared with H subjects. We observed higher amounts of Fusobacteria and a decline in the levels of TM7 phyla in T1D patients compared with H subjects. However, we revealed a decrease in the proportions of Verrucomicrobia in T2D patients compared with H subjects. At the genus level, T2D subjects were more affected by gut microbiota alteration, showing a reduction in the relative abundance of Faecalibacterium, Akkermansia, Clostridium, Blautia and Oscillibacter, whereas T1D group shows a decrease in the proportion of Blautia. The gut bacteria distribution was mainly affected by fats and carbohydrates consumption. Gut microbiota composition was altered in Tunisian diabetic patients and affected by dietary habits.


Highly efficient expression of transgenic proteins by naked DNA-transfected dendritic cells through terminal differentiation.
Dendritic cells (DCs) play a key role in the induction and control of immunity. Genetic engineering of DCs is a promising approach for the development of a broad range of immunomodulatory strategies, for purposes ranging from genetic immunization to tolerance induction. The development of DC-based immunotherapies is limited by the inability to efficiently transfect DCs using naked DNA. Here we demonstrate that after plasmid DNA delivery, the transgene expression level controlled by the human immediate-early cytomegalovirus promoter (hIE-CMVp) is higher in mature DCs than in immature DCs and is further increased after terminal differentiation of DCs by agonist anti-CD40 monoclonal antibody (mAb) or after DC interaction with CD4(+) T cells. CD40 signaling of DCs resulted in nuclear translocation of the transcription factors nuclear factor-kappaB (NF-kappaB), activator of protein-1 (AP-1), and cyclic adenosine monophosphate (cAMP)-responsive element, necessary for the activation of hIE-CMVp. Transgene expression by DCs diminished after the inhibition of these transcription factors or the blockade of adhesion molecules involved in the DC-T-cell synapse. Importantly, CD40 signaling of DCs results in the highly efficient expression and presentation of transgenic antigens and the induction of "in vivo" cytotoxic T-cell (CTL) responses specific for transgenic antigen peptides, demonstrating the functional potential of genetically engineered DCs.


Rechallenge with platinum plus fluoropyrimidine +/- epirubicin in patients with oesophagogastric cancer.
There is no standard second-line therapy for patients with oesophagogastric cancer who progress following first-line chemotherapy for advanced disease or relapse following radical multi-modality therapy. The aim of this retrospective study was to evaluate survival following rechallenge with platinum plus fluoropyrimidine (PF) +/- epirubicin. Patients treated with PF +/- epirubicin for oesophagogastric cancer at our institution were identified from the electronic prescribing database. Patients rechallenged with PF +/- epirubicin >3 months after completing initial chemotherapy were eligible. Primary endpoint was survival, calculated from day 1 of rechallenge treatment to date of death or last follow-up. Secondary endpoints were progression-free survival and response rate to PF-based re-challenge. Between 2000 and 2008, 950 patients treated with PF +/- epirubicin for oesophagogastric cancer were identified. 298 patients progressed or relapsed >3 months after completing chemotherapy, of whom 106 patients were rechallenged with PF-based chemotherapy. Median progression-free survival and overall survival were 5.1 and 10 months, respectively, from date of rechallenge for patients treated with initial radical intent and 3.9 and 6.6 months, respectively, in patients treated with palliative intent from diagnosis. In a survival analysis, no significant prognostic factors were identified. Selected patients with oesophagogastric cancer who relapse or progress >3 months after initial treatment with PF +/- epirubicin may benefit from re-introduction of PF-based chemotherapy.


Gas6/Axl Axis Contributes to Chemoresistance and Metastasis in Breast Cancer through Akt/GSK-3β/β-catenin Signaling.
Chemoresistance in breast cancer has been of great interest in past studies. However, the development of rational therapeutic strategies targeting chemoresistant cells is still a challenge in clinical oncology. By integrating data from global differences of gene expression and phospho-receptor tyrosine kinases between sensitive parental cells (MCF-7) and doxorubicin-resistant cells (MCF-7/ADR), we identified Axl as a potential target for chemoresistance and metastasis in multidrug resistant breast cancer cells. We analyzed Axl expression in 57 breast cancer cell lines and detected a dramatic increase in its expression level in mesenchymal breast cancer cell lines. Axl silencing suppressed invasive and metastatic potentials of chemoresistant breast cancer cells as well as increased elimination of cancer cells when combined with doxorubicin. Furthermore, in preclinical assays, an Axl inhibitor R428 showed increased cell death upon doxorubicin treatment. Additionally, using phospho-kinase array based proteomic analysis, we identified that Akt/GSK-3β/β-catenin cascade was responsible for Axl-induced cell invasion. Nuclear translocation of β-catenin then induced transcriptional upregulation of ZEB1, which in turn regulated DNA damage repair and doxorubicin-resistance in breast cancer cells. Most importantly, Axl was correlated with its downstream targets in tumor samples and was associated with poor prognosis in breast cancer patients. These results demonstrate that Gas6/Axl axis confers aggressiveness in breast cancer and may represent a therapeutic target for chemoresistance and metastasis.


Imaging of benign hypervascular hepatocellular nodules in alcoholic liver cirrhosis: differentiation from hypervascular hepatocellular carcinoma.
To retrospectively describe imaging analyses of benign hypervascular hyperplastic liver nodules (HHN) that resulted from alcoholic liver cirrhosis and to examine the possibility of imaging differentiation between these nodules and hypervascular hepatocellular carcinoma (HCC). Ten histopathologically confirmed HHN arise in alcoholic liver cirrhosis, and 9 HCC were examined. Magnetic resonance imaging (MRI) (10 HHN and 9 HCC), superparamagnetic iron oxide-enhanced T2-weighted MRI (6 HHN and 4 HCC), and dual-phase computed tomography hepatic arteriography (5 HHN and 6 HCC) were performed, respectively. On T1-weighted magnetic resonance images, 7 HHNs showed hyperintensity and 3 showed iso- to hypointensity, and all HCCs showed hypointensity compared with surrounding liver. On T2-weighted magnetic resonance images, 2 HHNs showed hyperintensity and 8 showed iso- to hypointensity. In contrast, 1 HCC showed hypointensity and 8 showed hyperintensity. On superparamagnetic iron oxide-enhanced T2 MRI, all HHNs showed iso- to hypointensity, and all HCCs showed hyperintensity. All HHN and HCCs subjected to dual-phase computed tomography hepatic arteriography showed enhancement on early-phase images and coronalike enhancement on late-phase images. Imaging findings of highly-well differentiated HCCs possibly overlap with HHN. So, for correct diagnosis of HHN, at first, we should suspect HHN based on clinical findings and MRI findings, and then perform core needle biopsy to verify the radiological diagnosis.


Stiffness of Aligned Fibers Regulates the Phenotypic Expression of Vascular Smooth Muscle Cells.
Electrospun uniaxially aligned ultrafine fibers show great promise in constructing vascular grafts mimicking the anisotropic architecture of native blood vessels. However, understanding how the stiffness of aligned fibers would impose influences on the functionality of vascular cells has yet to be explored. The present study aimed to explore the stiffness effects of electrospun aligned fibrous substrates (AFSs) on phenotypic modulation in vascular smooth muscle cells (SMCs). A stable jet coaxial electrospinning (SJCES) method was employed to generate highly aligned ultrafine fibers of poly(l-lactide- co-caprolactone)/poly(l-lactic acid) (PLCL/PLLA) in shell-core configuration with a remarkably varying stiffness region from 0.09 to 13.18 N/mm. We found that increasing AFS stiffness had no significant influence on the cellular shape and orientation along the fiber direction with the cultured human umbilical artery SMCs (huaSMCs) but inhibited the cell adhesion rate, promoted cell proliferation and migration, and especially enhanced the F-actin fiber assembly in the huaSMCs. Notably, higher fiber stiffness resulted in significant downregulation of contractile markers like alpha-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain, calponin, and desmin, whereas upregulated the gene expression of pathosis-associated osteopontin ( OPN) in the huaSMCs. These results allude to the phenotype of huaSMCs on stiffer AFSs being miserably modulated into a proliferative and pathological state. Consequently, it adversely affected the proliferation and migration behavior of human umbilical vein endothelial cells as well. Moreover, stiffer AFSs also revealed to incur significant upregulation of inflammatory gene expression, such as interleukin-6 ( IL-6), monocyte chemoattractant protein-1 ( MCP-1), and intercellular adhesion molecule-1 ( ICAM-1), in the huaSMCs. This study stresses that although electrospun aligned fibers are capable of modulating native-like oriented cell morphology and even desired phenotype realization or transition, they might not always direct cells into correct functionality. The integrated fiber stiffness underlying is thereby a critical parameter to consider in engineering structurally anisotropic tissue-engineered vascular grafts to ultimately achieve long-term patency.


Association of Fas Ligand gene polymorphism with Stevens-Johnson syndrome.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute severe blistering diseases of the skin and also two of the most devastating ocular surface diseases leading to corneal damage and loss of vision. The extreme rarity of cutaneous and ocular surface reactions to drug therapies led us to suspect individual susceptibility. SJS/TEN patients in the acute stage were reported to manifest increased serum levels of Fas Ligand (FasL). Thus, we performed SNP association analysis of the FasL gene. In 76 Japanese SJS/TEN patients with ocular surface complications and 160 Japanese healthy controls, we examined four SNPs of FasL reported in the Japanese Single Nucleotide Polymorphisms (JSNP) database by sequencing. The SNP rs.3830150 A/G showed a significant strong inverse association with SJS/TEN. Analysis of the genotype pattern of SNPs rs.3830150 and rs.2639614 (rs.3830150 A/A-rs.2639614 G/G) also manifested a strong inverse association with SJS/TEN. FasL gene polymorphisms might be associated with SJS/TEN.


[Normalization of fetal heart rate and fetal blood pressure following reduction of uterine blood circulation].
To analyze the variability of fetal heart rate (FHR) after a temporary definite hypoxia, uterine blood flow (QUT) was totally reduced in 8 pregnant sheep. In 13 experiments the reduction lasted 60 sec and in 13 further experiments 180 sec. The normalization of FHR after reduction of QUT was compared with the change of fetal blood pressure (BP) and fetal oxygen saturation (SO2). During reduction of QUT the fall of FHR and the decrease of SO2 was significant (r = -0,43, 2 alpha less than 0,05). With the start of normalization there was a temporary correlation between the increase of FHR and the restauration of SO2 after 12-18 sec (r = 0,79, 2 alpha less than 0,001). Thus the initial rise of FHR might be caused by the chemoreceptors. Above all after longer reduction of QUT there were three typical reactions during the recovery period: increase of FHR and BP, short fall of FHR and BP and increase of FHR and continous fall of BP. The start of normalization of FHR after reduction of QUT depends on the restauration of SO2. Because of the variable FHR response it is not possible to describe the duration of the preceding hypoxia.


Aggressive periodontitis: the silent tooth killer.
Aggressive periodontitis comprises a group of rapidly progressive forms of periodontitis characterized by early onset of clinical manifestations at a young age and a distinctive tendency for cases to aggregate in families. Though once believed to be a rare condition, recent evidence suggest that aggressive periodontitis is more common than assumed. The etiology of aggressive periodontitis is probably due to the expression of highly virulent causative agents in combination with high levels of susceptibility of the individual patient. In addition, there are several factors, such as cigarette smoking and ethnicity, that are associated with higher prevalence or severity of aggressive periodontitis. Since the disease usually appears at a young age, the importance of early detection is paramount in order to avoid tooth loss in early childhood or adolescence.


Compensation effects and relation between the activation energy of spin transition and the hysteresis loop width for an iron(ii) complex.
The enthalpy-entropy compensation was observed for the cooperative → spin transition (the phase is a mononuclear complex [FeL2](BF4)2, L is 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2-(pyridin-2-yl)-6-methylpyrimidine). The physical origin of this effect is the fact that the → spin transition is the first order phase transition accompanied by noticeable variations in the Tonset↑, ΔH and ΔS values. Higher ΔH and ΔS values are correlated with higher Tonset↑ values. The higher the enthalpy and entropy of the spin transition, the wider the hysteresis loop. The kinetic compensation effect, i.e. a linear relationship between ln A and Ea, was observed for the → spin transition. Moreover, an isokinetic relationship was detected in this system: the Arrhenius lines (ln k vs. 1/T) obtained from magnetochemical data for different samples of the phase undergoing the → transition show a common point of intersection (Tiso = 490 ± 2 K, ln kiso = -6.0 ± 0.2). The validity of this conclusion was confirmed by the Exner-Linert statistical method. This means that the isokinetic relationship and the kinetic compensation effect (ln A vs. Ea) in this system are true ones. The existence of a true kinetic compensation effect is supported independently by the fact that the hysteresis loop width for the cooperative spin transition ↔ increases with increasing activation barrier height. Estimating the energy of excitations for the phase with Tiso ∼ 490 K yields wavenumbers of ca. 340 cm(-1) corresponding to the frequencies of the stretching vibrations of the Fe(LS)-N bonds, i.e. the bonds directly involved in the mechanism of the spin transition. This is the first observation of the kinetic compensation effect (ln A vs. Ea) and the isokinetic relationship for a cooperative spin crossover system showing thermal hysteresis. Our results provide the first experimental evidence that the higher the activation barrier for the spin transition, the wider the hysteresis loop for a series of related spin crossover systems.


Unprecedented highest electro-optic coefficient of 226 pm/V for electro-optic polymer/TiO₂ multilayer slot waveguide modulators.
We investigated the electrical properties and optical quality of two layers a titanium dioxide (TiO₂) selective layer and a sol-gel silica cladding layer for use as coating layers for nonlinear optic (NLO) polymers in electro-optic (EO) polymer/TiO₂ multilayer slot waveguide modulators. We used a simple ellipsometric reflective technique developed by Teng and Man to measure the electro-optic (EO) coefficients of poled thin films of an EO polymer in an EO multilayer device. The Pockels coefficient was enhanced up to 226 and 198 pm/V at wavelengths of 1.31 and 1.55 μm, respectively, when optimally poled with TiO₂ and a sol-gel silica cladding.


Alteration in membrane protein, antioxidant status and hexokinase activity in erythrocytes of CCl4- induced cirrhotic rats.
Several studies have shown that hepatocyte membrane composition changes in patients with cholestasis and cirrhosis. These alterations that are because of intracellular oxidative stress are supposed to be reflected in erythrocyte membrane. The aim of this study was to investigate the modification of erythrocyte membrane along with hexokinase and antioxidant enzymes during development of cirrhosis. Cirrhosis was induced by intraperitoneal injection of CCl4 in male Wistar rats. The test groups were: baseline, cholestatic, early cirrhotic and advanced cirrhotic along with an equal number of sham-control animals. The erythrocyte membrane modifications (protein sulfhydryl, protein carbonyl, and lipid peroxidation), as well as NO metabolites, were assessed. Activities of GPX, CAT, SOD and HK were also measured. Protein sulfhydryl content of the erythrocyte membrane (after 2, 6 and 10 weeks of injection) had significant progressive decrease. In contrast, protein carbonyls were remarkably increased 2 weeks after injection but significantly decreased after 6 weeks and returned to normal levels after 10 weeks. No significant difference in erythrocyte HK activity or MDA content was observed. Test groups showed significantly lower erythrocyte GPx activity after six weeks and CAT and SOD activities along with NO metabolites content after two weeks (P<0.05). This study indicates that the progression of cirrhosis is accompanied by alterations in antioxidant enzyme and decreased NO metabolites. Protein carbonyl alteration occurs in the early stages of cirrhosis while protein sulfhydryl alterations have a progressive decrease in advanced cirrhosis.


Oxygen consumption and luminescence of Porichthys photophores stimulated by potassium cyanide.
Isolated photophores of Porichthys notatus, maintained in saline at 20 degrees C, do not luminesce and show an oxygen consumption rate of 0.07 +/- 0.01 nmol min-1 photophore-1. In the presence of 10(-6) M-KCN, the photophores do not luminesce but the resting respiration decreases by about 50%. In the presence of 10(-5) M-KCN, some photophores do not luminesce and their respiration rate decreases by about 75%. Others show a response and resting oxygen consumption slowly increases. At high concentration (10(-4) and 10(-3)M), KCN induces a large light emission and increase in oxygen consumption. The stimulatory effect of KCN on the photophore oxygen consumption is tentatively explained by an activation of the luciferin-luciferase system by calcium ions.


Balancing Hole and Electron Conduction in Ambipolar Split-Gate Thin-Film Transistors.
Complementary organic electronics is a key enabling technology for the development of new applications including smart ubiquitous sensors, wearable electronics, and healthcare devices. High-performance, high-functionality and reliable complementary circuits require n- and p-type thin-film transistors with balanced characteristics. Recent advancements in ambipolar organic transistors in terms of semiconductor and device engineering demonstrate the great potential of this route but, unfortunately, the actual development of ambipolar organic complementary electronics is currently hampered by the uneven electron (n-type) and hole (p-type) conduction in ambipolar organic transistors. Here we show ambipolar organic thin-film transistors with balanced n-type and p-type operation. By manipulating air exposure and vacuum annealing conditions, we show that well-balanced electron and hole transport properties can be easily obtained. The method is used to control hole and electron conductions in split-gate transistors based on a solution-processed donor-acceptor semiconducting polymer. Complementary logic inverters with balanced charging and discharging characteristics are demonstrated. These findings may open up new opportunities for the rational design of complementary electronics based on ambipolar organic transistors.


Bacterial microbiomes from vertically transmitted fungal inocula of the leaf-cutting ant Atta texana.
Microbiome surveys provide clues for the functional roles of symbiotic microbial communities and their hosts. In this study, we elucidated bacterial microbiomes associated with the vertically transmitted fungal inocula (pellets) used by foundress queens of the leaf-cutting ant Atta texana as starter-cultures for new gardens. As reference microbiomes, we also surveyed bacterial microbiomes of foundress queens, gardens and brood of incipient nests. Pseudomonas, Acinetobacter, Propionibacterium and Corynebacterium were consistently present in high abundance in microbiomes. Some pellet and ant samples contained abundant bacteria from an Entomoplasmatales-clade, and a separate PCR-based survey of Entomoplasmatales bacteria in eight attine ant-genera from Brazil placed these bacteria in a monophyletic clade within the bacterial genus Mesoplasma. The attine ant-Mesoplasma association parallels a similar association between a closely related, monophyletic Entomoplasmatales-clade and army ants. Of thirteen A. texana nests surveyed, three nests with exceptionally high Mesoplasma abundance died, whereas the other nests survived. It is unclear whether Mesoplasma was the primary cause of mortality, or Mesoplasma became abundant in moribund nests for non-pathogenic reasons. However, the consistent and geographically widespread presence of Mesoplasma suggests an important functional role in the association with attine ants.


[Effect of probucol on lipid metabolism and the clinical course of ischemic heart disease and arteriosclerosis obliterans of the vessels of the lower extremities].
Thirty-eight men with chronic coronary heart disease (CHD) aged 38 to 65 years (ten patients with attendant obliterating atherosclerosis of lower extremity vessels) were treated with the hypolipidemic drug probucol in a dose of 1000 mg/day for three months. Probucol exerted a beneficial effect on the clinical course of CHD and obliterating atherosclerosis of the lower limb vessels. The drug has a marked hypocholesterolemic effect in CHD patients with high cholesterol levels in the blood serum which warrants the advisability of its use in type IIa and IIb hyperlipoproteinemia. The probucol therapy is associated with a decrease in the cholesterol/erythrocyte membrane phospholipids molar ratio which improves the rheological properties of the blood in CHD patients. The drug produces no side effects.


MicroRNAs in the tumour microenvironment: big role for small players.
MicroRNAs (miRNAs) represent a class of small non-coding RNAs with an important regulatory role in various physiological processes as well as in several pathologies including cancers. It is noteworthy that recent evidence suggests that the regulatory role of miRNAs during carcinogenesis is not limited to the cancer cells but they are also implicated in the activation of tumour stroma and its transition into a cancer-associated state. Results from experimental studies involving cells cultured in vitro and mice bearing experimental tumours, corroborated by profiling of clinical cancers for miRNA expression, underline this role and identify miRNAs as a potent regulator of the crosstalk between cancer and stroma cells. Considering the fundamental role of the tumour microenvironment in determining both the clinical characteristics of the disease and the efficacy of anticancer therapy, miRNAs emerge as an attractive target bearing important prognostic and therapeutic significance during carcinogenesis. In this article, we will review the available results that underline the role of miRNAs in tumour stroma biology and emphasise their potential value as tools for the management of the disease.


[The sympatho-adrenal system. Implications for the pathogenesis, diagnosis and therapy of cardiac arrhythmias].
Changes in biosynthesis, storage, release and inactivation of the catecholamines noradrenaline and adrenaline, as well as in the dynamic regulation and localization (internalization/externalization) of post- and presynaptic alpha- and beta-receptors and their subpopulations have implications for the pathogenesis of cardiac arrhythmias. Circulating levels of plasma catecholamines provide a reliable biochemical index for sympatho-adrenal activity and reactivity as well as for diagnosis and prognosis of these arrhythmias. Therapeutic interventions should consequently prefer blockade of myocardial alpha- and/or beta-adrenoceptors, especially after postischaemic arrhythmias with externalization of beta-adrenoceptors.


The potential association between COVID-19 disease and Guillain-Barré syndrome.
The aim is to investigate the rate of GBS in the pre- and postpandemic period and potential differences in probable COVID-19-associated Guillain-Barré syndrome (GBS) cases and nonassociated cases. The medical records of individuals older than 18 years who were hospitalized with acute and rapidly developing progressive extremity weakness between March 2019 and March 2021 were analyzed retrospectively, and the rate of GBS 1 year before the first reported COVID-19 case (March 2020) in Turkey and 1 year later was compared. Neurological symptoms, medical histories, and GBS disability scores, as well as the findings of electrophysiological, blood, and cerebrospinal fluid (CSF) investigations at the time of presentation, were reviewed. The GBS cases were divided into those with confirmed COVID-19 within 6 weeks before the clinical presentation of GBS and those without COVID-19. The rate of COVID-19 was significantly higher in the patients with GBS as an etiological factor. When the probable COVID-19-associated GBS cases and nonassociated cases were compared, there was a significant between-group difference with respect to sedimentation, C-reactive protein, D-dimer, ferritin, albumin, lymphocyte number, mean platelet volume, neutrophil-lymphocyte ratio, fibrinogen, and lactate dehydrogenase values. In addition, there was a significant between-group difference in admission and discharge disability scores. The GBS rate did not increase after the COVID-19 pandemic, but probable COVID-19-associated GBS significantly affected inflammatory markers and admission-discharge GBS disability scores.


Co-Doped Zn1-xCdxS nanocrystals from metal-organic framework precursors: porous microstructure and efficient photocatalytic hydrogen evolution.
Nanoporous Co-doped Zn1-xCdxS were facilely fabricated via adopting ZIFs as templates, and Cd(NO3)2 and thiourea as precursors. The highly porous microstructure and uniform Co-doping of the photocatalyst afford a high H2-production rate (45.2 and 422.2 times larger than those of Zn0.5Cd0.5S and CdS), providing an effective way for the development of high performance nanoporous photocatalysts.


Preserving salivary gland physiology against genotoxic damage - the Tousled way.
Tousled and its homologs are evolutionarily conserved serine/threonine kinases present in plants and animals. Human Tousled-like kinases, TLK1 and TLK2, are implicated in chromatin assembly during DNA replication, chromosome segregation during mitosis, as well as in DNA damage response and repair. They share a high degree of sequence similarity, but have few non-redundant functions. Our laboratory has studied TLK1 and found that it increases the resistance of cells to ionizing radiation (IR) damage through expedited double-strand break (DSB) repair. DSBs are life-threatening lesions which when repaired restore DNA integrity and promote cell survival. A major focus in our laboratory is to dissect TLK1's role in DSB response and repair and study its usefulness in averting salivary gland hypofunction, a condition that invariably afflicts patients undergoing regional radiotherapy. The identification of anti-silencing factor 1 (ASF1), histone H3, and Rad9 as substrates of TLK1 links the protein to chromatin organization and DNA damage response and repair. However, recent findings of new interacting partners that include NEK1 suggest that TLK1 may play a broader role in DSB repair. This review provides a brief overview of the DNA damage response and DSB repair, and it highlights our current understanding of TLK1 in the process.


Gaze-induced laughter.
Pathological laughter was stimulated by pursuit eye movements with a large extramedullary brainstem tumour. Laughter was also evoked by intense direct light. The mechanism by which visual stimuli could induce pathological laughter is discussed.


IMA to conduct training courses in family planning.
For the last six and a half decades, the Indian Medical Association (IMA) has been actively engaged in Public Health issues, ranging from immunization, ORT, maternal and child health care, and has been cooperating with the Government of India in various National Health Programs. Recently, IMA organized a new and exciting program on India's most significantly health issue--family planning. The training is to be competency based and participatory, with the main emphasis on knowledge, attitude and skills required to provide comprehensive child spacing. IMA has developed this multilevel program to train personnel in all methods of family planning, like: participation in basic oral contraceptive training; supplementary training in other methods; clinical practice for providing information on how to select and manage non-clinical family planning services; simulated practice in IUCD; and clinical practice in IUCD training. Training can also be arranged for vasectomy practicum and minilaparotomy. The main purpose of the training program is to realize the Government's goal of 60% contraceptive prevalence usage by the year 2000. In India, less than 2% of the 132.5 million reproductives, couples use oral contraceptives, because of widespread misconceptions regarding the pill among the general populace and the medical community. This program has been designed to counter these misgivings and thus encourage the "use of modern family planning methods" to take on the menace of the population explosion.


Presence of a Septal Occluder Is No Longer an Obstacle for Pulmonary Vein Isolation by Cryoablation.
Cryoablation for pulmonary vein isolation in atrial fibrillation has been considered a relative contraindication in the presence of a septal occluder device. We describe the successful conduct of this technique with a multimodality imaging approach.


Immunomagnetic separation of normal rat testicular cells from Roser's T-cell leukaemia cells is ineffective.
Elimination of contaminating malignant cells is crucial to avoiding cancer relapse in association with transplantation of autologous spermatogonial stem cells. In the clinical setting, there is presently no effective procedure for separating testicular cells from cancer cells. Here, CD4, a selective surface marker for Roser's rat leukaemic T-cells, was utilized to eliminate cancer cells from testicular cell samples from leukaemic piebald variegated (PVG) rats by magnetic-activated cell sorting (MACS). All animals receiving MACS-selected testicular cells died within 14-15 days. Only one-third of the contaminating leukaemic cells could be removed from testicular samples. An increase in antibody concentration enhanced the proportion of leukaemic cells removed from 27 to 49%. Variations in the cell size and expression of surface antigens on testicular leukaemic cells were the major obstacles to purification based on this marker. It is concluded that MACS does not prevent transmission of leukaemia to syngenic PVG rats when cells from leukaemic testes are used for testicular cell transplantation.


Prenatal exposure to perfluoroalkyl substances, immune-related outcomes, and lung function in children from a Spanish birth cohort study.
Prenatal exposure to perfluoroalkyl substances (PFASs) has been associated with impaired immune and respiratory health during childhood but the evidence is inconsistent and limited for lung function. We studied the association between prenatal PFASs exposure and immune and respiratory health, including lung function, up to age 7 years in the Spanish INMA birth cohort study. We assessed four PFASs in maternal plasma samples collected during the 1st trimester of pregnancy (years: 2003-2008): perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA). Mothers reported the occurrence (yes/no) of lower respiratory tract infections, wheezing, asthma, and eczema in the previous 12 months at 1.5 and 4 years of the child (n = 1188) and at 7 years (n = 1071). At ages 4 (n = 503) and 7 (n = 992) years lung function was assessed using spirometry tests. The most abundant PFASs were PFOS and PFOA (geometric means: 5.80 and 2.31 ng/mL, respectively). The relative risk of asthma during childhood per each doubling in PFNA concentration was 0.74 (95 CI%: 0.57, 0.96). The relative risk of eczema during childhood per every doubling in PFOS concentration was 0.86 (95 CI%: 0.75, 0.98). Higher PFOA concentrations were associated with lower forced vital capacity and lower forced expiratory volume in 1 s z-scores at 4 years [β (95 CI %): -0.17 (-0.34, -0.01) and -0.13 (-0.29, 0.03), respectively], but not at 7 years. This longitudinal study suggests that different PFASs may affect the developing immune and respiratory systems differently. Prenatal exposure to PFNA and PFOS may be associated with reduced risk of respiratory and immune outcomes, particularly asthma and eczema whereas exposure to PFOA may be associated with reduced lung function in young children. These mixed results need to be replicated in follow-up studies at later ages.


Flattened facial colliculus on magnetic resonance imaging in Machado-Joseph disease.
Atrophy of the pontine tegmentum and facial colliculus is a characteristic pathological feature of Machado-Joseph disease. We assessed whether this finding can be detected by conventional brain magnetic resonance imaging. A total of 17 patients with genetically confirmed Machado-Joseph disease, 15 disease controls (spinocerebellar ataxia type 6 and dentatorubral-pallidoluysian atrophy), and 17 normal subjects were examined using a 1.5-Tesla magnetic resonance imaging scanner. The widths of the facial colliculus, pontine tegmentum, and pontine base and the area of the fourth ventricle were measured on axial T2-weighted imaging. Pathological examination was performed in 9 Machado-Joseph disease patients. In addition, visual inspection of the facial colliculus was evaluated by receiver operating characteristic analysis. The width of the facial colliculus was significantly smaller in Machado-Joseph disease patients (0.37 ± 0.16 mm; mean ± standard deviation) than in normal subjects (0.73 ± 0.30 mm; P < .01), whereas the width of the pontine tegmentum was smaller in both Machado-Joseph disease (4.85 ± 0.58 mm) and dentatorubral-pallidoluysian atrophy (4.72 ± 0.59) patients than in normal subjects (6.35 ± 0.74 mm; P < .01). Visual evaluation of the facial colliculus showed sufficient area under the receiver operating characteristic curves to differentiate Machado-Joseph disease from dentatorubral-pallidoluysian atrophy (0.78) and spinocerebellar ataxia type 6 (0.87). Pathological evaluation showed significant atrophy of the facial colliculus in all Machado-Joseph disease patients. Atrophy of the facial colliculus is a feasible magnetic resonance imaging finding for diagnosing Machado-Joseph disease, and it is easily found as a flattening of the fourth ventricular floor.


Decreased platelet peripheral-type benzodiazepine receptors in persistently violent schizophrenia patients.
Peripheral-type benzodiazepine receptors (PBR) have been shown to be sensitive to stressful conditions. This study aimed to explore a possible association of platelets PBR binding with aggressive behavior and homicidal history in schizophrenia patients. The authors compared [(3)H] PK 11195 binding to platelet membrane among 11 currently aggressive schizophrenia patients, 15 schizophrenia patients with homicidal history, 14 nonaggressive schizophrenia patients, and 15 healthy volunteers. Subjects were assessed for aggressive behavior, psychopathology, anxiety, anger, and emotional distress using standardized instruments. We found that currently aggressive patients had significantly lower (-30%) platelet PBR density (B(max)), and scored significantly higher on hostility, anxiety, state anger, and emotional distress compared to homicidal and nonaggressive schizophrenia patients and healthy controls. Predominance of positive or negative symptoms, homicidal or suicidal attempt history, emotional distress levels, and conventional or atypical antipsychotic therapy is not associated with the expression of platelet PBR binding sites. Significant negative correlations emerged between PBR density and scores for aggressive behavior, hostility and anxiety. Thus, decreased platelet PBR density in aggressive schizophrenia patients is associated with higher scores for overt aggression, hostility and anxiety, but independent of illness subtype, homicidal and suicidal attempt history, distress level and type of antipsychotic treatment.


Orthopaedic care of children with spina bifida: you've come a long way, baby!
The prognosis of children born with spina bifida has dramatically changed in the past several decades. Children with spina bifida with appropriate medical care can now expect to live into adulthood. Orthopaedic care of children with spina bifida has evolved to increase function, promote long-term mobility, and improve overall health. This article looks at current orthopaedic treatment against the backdrop of historical care. Treatment of the foot, knee, hip, and spine are reviewed, as well as neurologic implications. Issues of ambulation, orthotics, assistive devices, and insensate skin are addressed.


Tramadol. Focus on musculoskeletal and neuropathic pain.
In the light of the most recent acquisitions published in the international literature, this review analyzes the pharmacologic features and modes of use of tramadol, one of the most widely used, on a worldwide scale, analgesic agents in acute and chronic pain of moderate to severe intensity. The action of the 2 enantiomers of tramadol--which exert different pharmacologic effects--and of metabolite M1, is differentiated. The global activity of tramadol results from the sum of their specific actions. Data of kinetics show a very high oral bioavailability and the sustained-release (SR) formulations assure a 24-h coverage through the constant blood levels. Data reported in the relevant literature show that tramadol is effective in the treatment of arthrosic and neuropathic pain, with a value of Number Needed to Treat (NNT) of 3.4, and in the mixed nociceptive-neuropathic pain, especially in persistent or chronic pain. Moreover, tramadol maintains a good tolerability profile in the elderly subjects and a good analgesic efficacy in the long-term treatments with reduced pharmacological interactions and a low incidence of constipation. These global features assured its inclusion into the most recent guidelines on the management of chronic pain. Furthermore, data from literature showed that tramadol is devoid of immunosuppressive activity, has a poor tendency to tolerance and a minimum risk of addiction and abuse.


Matrix solid-phase dispersion as a multiresidue extraction technique for beta-agonists in bovine liver tissue.
A procedure for the extraction of salbutamol including conjugated forms of the drug, from liver samples, is described. It combines matrix solid-phase dispersion with radioimmunoassay for the measurement of salbutamol residues at the sub-ppb level. Inter- and intra-assay validation, carried out on fortified liver samples, show good recoveries over the range 1-5 ppb of salbutamol. An enzyme hydrolysis procedure was optimized for the deconjugation of incurred residue. The developed procedure is shown to be suitable for the extraction and determination of other beta-agonists such as clenbuterol, mabuterol, terbutaline, and cimaterol at residue levels of less than 1 ng g-1.


THE EFFECT OF BODY AWARENESS THERAPY AND AEROBIC EXERCISES ON PAIN AND QUALITY OF LIFE IN THE PATIENTS WITH TENSION TYPE HEADACHE.
This study is to investigate the effect of Body Awareness Therapy (BAT) and Aerobic Exercises on pain and quality of life in patients with Tension-Type Headache (TTH). Sixty individuals with TTH diagnosis who referred Neurologist were incorporated into study. The individuals were randomly grouped into 3 as BAT (n=20), aerobic exercise (n=20) and control group (n=20). Pain severity of the individuals was evaluated by Visual Analog Scale (VAS) and pain diary, disability with ache; by Pain Disability Index (PDI) and Headache Impact Tests (HIT) and quality of life was evaluated by SF-36. Subsequent to first assessments, 3 sessions of 60 minutes per week throughout 6 weeks totally. When the groups were compared at the end of the study, a significant decrease was observed in VAS, PDI and HIT values in the individuals in the BAT and aerobic exercise groups. With the individuals in group BAT and aerobic exercise all parameters of quality of life were observed to be increased significantly. BAT and aerobic exercise programs to be applied on TTH patients were concluded to be important in decreasing the pain, in increasing the quality of life and in reducing pain-related daily constraints of the individuals.


Seripauperins of Saccharomyces cerevisiae: a new multigene family encoding serine-poor relatives of serine-rich proteins.
A gene, PAU1, has been cloned from Saccharomyces cerevisiae and sequenced. It is located in a telomeric region, probably on chromosome IV, and contains an open reading frame encoding a protein of 120 amino acids (aa) (approx. 13 kDa). The deduced sequence is nearly identical to two other genes found in GenBank (named PAU2 and PAU3 by us), which are located close to the ends of chromosomes V and III, respectively. Blotting of separated chromosomes with a PAU1 probe at high stringency revealed that at least six chromosomes in addition to III, IV and V possessed related sequences, suggesting a large gene family. Probing of an ordered array of phage lambda clones containing yeast genomic DNA inserts ('Olson filters') revealed ten additional hybridizing sequences, located close to the ends of the left and/or right arms of chromosomes I, II, VII, VIII, X, XII, XIV and XV. Transcription of these sequences could not be demonstrated, however, under a wide variety of growth and culture conditions. The deduced PAU1, PAU2 and PAU3 aa sequences are all highly homologous with the SRP1 aa sequences, which contains eight serine-rich tandem repeats of 12 aa each, at its C terminus. This homology is limited, however, to the N-terminal half of SRP1, and does not include the repeats. In fact, PAU1 is quite serine-poor (5.8%), leading to the suggested name of seripauperins for this family of genes.


Vascular development: cellular and molecular regulation.
The vascular system forms through a combination of vasculogenesis and angiogenesis. In vasculogenesis, vessels form de novo via the assembly of endothelial precursors called angioblasts, whereas in angiogenesis new vessels arise by migration and proliferation of endothelial cells from preexisting vessels. Although the two processes are distinct in some respects, recent evidence suggests that they share a number of regulatory mechanisms. The identification of a number of defined growth factors, observations of genetically manipulated mice, and the recognition of the importance of cell-cell interactions have greatly expanded our understanding of the regulation of vascularization. The paracrine actions of a variety of polypeptide growth factors, including platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-beta, and the angiopoietins, appear to be orchestrated in a complex sequence of steps that lead to the development of the adult vascular system. Thus, communication between the forming vasculature and the tissue parenchyma, as well as interactions among cells of the vascular wall, all appear to influence vascular development and growth.


Examining reliability and validity of job analysis survey data.
Historically, job analysis has played a fundamental role for developing and validating licensure and certification examinations. Still, research on what constitutes reliable and valid job analysis data is lacking. This paper illustrates several ways to examine the reliability and validity of job analysis survey results. Generalizability theory and the many-facets Rasch model are applied to investigate consistency and generalizability in task importance measures, to suggest reliable sample size, and to justify the number and use of rating scales. By using random samples from job analysis data for two professions with divergent job activities, this study finds that a representative sample as small as 400 respondents produces reliable estimates of task importance to the same degree of generalizability as obtained from a larger sample of job analysis respondents. Analyses of rating scales suggest that the effectiveness of using different numbers and types of rating scales depends on the nature of a profession.


Intraoperative microvascular Doppler sonography in aneurysm surgery.
The goal was to evaluate the efficacy and reliability of intraoperative microvascular doppler sonography for the assessment of cerebral hemodynamics in aneurysm surgery. For 35 patients who underwent surgery for the treatment of 42 intracranial aneurysms, microvascular doppler sonography with a 20-MHz probe (1-mm diameter) was used before and after clip application, to confirm the obliteration of aneurysms. Assessment of the patency of the parent vessels and all branching arteries was performed. The findings from doppler sonography were confirmed with either intraoperative angiography or immediate postoperative angiography. The 1-mm microprobe was able to insonate all vessels of the circle of Willis and their major branches; furthermore, perforating arteries were reliably insonated. For 11 patients (31%), doppler sonography exposed parent artery or branching artery stenosis or occlusion and guided the immediate adjustment of aneurysm clip placement. The findings from intraoperative microvascular doppler sonography correlated with findings from angiography in all cases. There were no complications of microvascular doppler probe use. Intraoperative microvascular doppler sonography is a safe, instantaneous, effective, reliable, and cost-effective method for documenting the patency of parent vessels, arterial branches, and major perforators and the complete occlusion of cerebral aneurysms. This technique can be reliably used, in many instances, instead of intraoperative angiography for the surgical treatment of aneurysms.