Citizens' opinions and experiences related to costs and reimbursements for medications in times of retrenchment: cross-sectional population surveys in 2015 and 2017.
Finland has universal coverage for prescription medications under the National Health Insurance. Eligibility schemes target higher reimbursements to individuals with chronic illness. Nevertheless, co-payments always apply, and austerity reforms implemented in 2016 and 2017 led to further increases in co-payments. We examined the extent to which people with chronic illness experienced financial difficulties in purchasing medications, how perceptions of fairness regarding the national reimbursements differs by exposure to policies and medicine use, and in what way do these experiences and opinions vary between surveys collected before and after the reforms. We used two waves of Medicines Barometer (2015 and 2017, pooled n = 10,801), a national, biennial, cross-sectional population survey. Logistic regression analyses were performed with experiences of financial difficulties and perceptions of fairness as dependent variables. We compared people with and without prescription medication use, eligibilities, and/or diabetes (exposure groups), controlling for age, gender, survey type and geographic area (NUTS2). To examine the modifying effect of study year, we fitted models with an interaction term between group and year. Respondents with diabetes or eligibility based on chronic illness had a notably higher risk than other respondents with at least some prescription medication use to have experienced financial difficulties in affording medications. The share of respondents experiencing difficulties increased the most among people with diabetes. Three-quarters of respondents were either critical or unsure of whether the reimbursements for medications were fair and just. People with recent prescription medication use tended to be more sceptical than people without. Overall, scepticism tended to be more prevalent in 2017 than in 2015. Despite the protective policies in place, individuals with chronic illness were disproportionately burdened by costs of medications already before the reforms. Among individuals with diabetes, financial difficulties were even more prevalent in 2017 than in 2015, which is likely attributed to the particularly high co-payment increases targeted to type 2 diabetes medicines. Perceived fairness of the processes and outcomes of policies and regulations is a key dimension of trust in public policy. Thus, increasing scepticism implies that retrenchment may also have implications in terms of public legitimacy.


Dynamics of highly excited barium atoms deposited on large argon clusters. I. General trends.
Ba(Ar)(approximately 750) clusters were generated by associating the supersonic expansion and the pick-up techniques. A femtosecond pump (266.3 nm)-probe (792 or 399.2 nm) experiment was performed to document the dynamics of electronically excited barium within the very multidimensional environment of the argon cluster. Barium was excited in the vicinity of the 6s9p (1)P state and probed by ionization. The velocity imaging technique was used to monitor the energy distribution of photoelectrons and photoions as a function of the delay time between the pump and the probe pulses. A complex dynamics was revealed, which can be interpreted as a sequence/superposition of elementary processes, one of which is the ejection of barium out of the cluster. The latter has an efficiency, which starts increasing 5 ps after the pump pulse, the largest ejection probability being at 10 ps. The ejection process lasts at a very long time, up to 60 ps. A competing process is the partial solvation of barium in low lying electronic states. Both processes are preceded by a complex electronic relaxation, which is not fully unraveled here, the present paper being the first one in a series.


Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis.
Recent studies indicate that metabolic oxidative stress, autophagy, and inflammation are hallmarks of nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanisms that link these important events in NASH remain unclear. In this study, we investigated the mechanistic role of purinergic receptor X7 (P2X7) in modulating autophagy and resultant inflammation in NASH in response to metabolic oxidative stress. The study uses two rodent models of NASH. In one of them, a CYP2E1 substrate bromodichloromethane is used to induce metabolic oxidative stress and NASH. Methyl choline-deficient diet feeding is used for the other NASH model. CYP2E1 and P2X7 receptor gene-deleted mice are used to establish their roles in regulating metabolic oxidative stress and autophagy. Autophagy gene expression, protein levels, confocal microscopy based-immunolocalization of lysosome-associated membrane protein (LAMP)2A and histopathological analysis were performed. CYP2E1-dependent metabolic oxidative stress induced increases in P2X7 receptor expression and chaperone-mediated autophagy markers LAMP2A and heat shock cognate 70 but caused depletion of light chain 3 isoform B (LC3B) protein levels. P2X7 receptor gene deletion significantly decreased LAMP2A and inflammatory indicators while significantly increasing LC3B protein levels compared with wild-type mice treated with bromodichloromethane. P2X7 receptor-deleted mice were also protected from NASH pathology as evidenced by decreased inflammation and fibrosis. Our studies establish that P2X7 receptor is a key regulator of autophagy induced by metabolic oxidative stress in NASH, thereby modulating hepatic inflammation. Furthermore, our findings presented here form a basis for P2X7 receptor as a potential therapeutic target in the treatment for NASH.


p63 is an essential proapoptotic protein during neural development.
The p53 family member p63 is required for nonneural development, but has no known role in the nervous system. Here, we define an essential proapoptotic role for p63 during naturally occurring neuronal death. Sympathetic neurons express full-length TAp63 during the developmental death period, and TAp63 levels increase following NGF withdrawal. Overexpression of TAp63 causes neuronal apoptosis in the presence of NGF, while cultured p63-/- neurons are resistant to apoptosis following NGF withdrawal. TAp63 is also essential in vivo, since embryonic p63-/- mice display a deficit in naturally occurring sympathetic neuron death. While both TAp63 and p53 induce similar apoptotic signaling proteins and require BAX expression and function for their effects, TAp63 induces neuronal death in the absence of p53, but p53 requires coincident p63 expression for its proapoptotic actions. Thus, p63 is essential for developmental neuronal death, likely functioning both on its own, and as an obligate proapoptotic partner for p53.


Is auditory brainstem response a prognostic factor in patients with sudden sensorineural hearing loss?
Background: Serum thyroid hormone levels are closely related to the normal functioning of the cochlea. However, the relationship between initial auditory brainstem response (ABR) results and levels of thyroid hormone remained unclear until we adopted ABR as a prognostic factor in Idiopathic sudden sensorineural hearing loss (ISSNHL) patients. Objective: This investigation aimed to elucidate the association between ABR and outcomes in patients with ISSNHL. Material and methods: Thirty-three patients presenting with unilateral ISSNHL underwent blood sampling and ABR tests on the day of admission. The mean latencies of the ABR results were compared among the groups which were classified by ISSNHL outcome, based on Siegel's criteria. The association between the ABR results and the thyroid hormone serum levels (TSH, T3, and free T4) were assessed. Results: The overall successful recovery rate was 60.6% (n = 20). The mean latencies of all the ABR parameters were not significantly different between the different treatment outcome groups (Mann-Whitney U test). Wave V latency, III-V interval and I-V interval were negatively associated with T3 serum levels. Conclusion: The results indicate that clinical caution should be exercised when conducting ABR tests without assessing thyroid hormone levels.


The Binding Properties of Glycosylated and Non-Glycosylated Tim-3 Molecules on CD4CD25 T Cells.
T cell immunoglobulin and mucin domain containing 3 protein (Tim-3) expressed on terminally differentiated Th1 cells plays a suppressive role in Th1-mediated immune responses. Recently, it has been shown that N-glycosylation affects the binding activity of the Tim-3-Ig fusion protein to its ligand, galectin-9, but the binding properties of non-glycosylated Tim-3 on CD4(+)CD25(+) T cells has not been fully examined. In this study, we produced recombinant Tim-3-Ig fusion proteins in different cellular sources and its N-glycosylation mutant forms to evaluate their binding activities to CD4(+)CD25(+) T cells. We isolated and cloned Tim-3 cDNA from BALB/C mouse splenocytes. Then, we constructed a mammalian expression vector and a prokaryotic expression vector for the Tim-3-Ig fusion protein. Using a site directed mutagenesis method, plasmid vectors for Tim-3-Ig N-glycosylation mutant expression were produced. The recombinant protein was purified by protein A sepharose column chromatography. The binding activity of Tim-3-Ig fusion protein to CD4(+)CD25(+) T cells was analyzed using flow cytometry. We found that the nonglycosylated Tim-3-Ig fusion proteins expressed in bacteria bound to CD4(+)CD25(+) T cells similarly to the glycosylated Tim-3-Ig protein produced in CHO cells. Further, three N-glycosylation mutant forms (N53Q, N100Q, N53/100Q) of Tim-3-Ig showed similar binding activities to those of wild type glycosylated Tim-3-Ig. Our results suggest that N-glycosylation of Tim-3 may not affect its binding activity to ligands expressed on CD4(+)CD25(+) T cells.


Laboratory assessment of a gravity-fed ultrafiltration water treatment device designed for household use in low-income settings.
Interventions to improve water quality, particularly when deployed at the household level, are an effective means of preventing endemic diarrheal disease, a leading cause of mortality and morbidity in the developing world. We assessed the microbiologic performance of a novel water treatment device designed for household use in low-income settings. The device employs a backwashable hollow fiber ultrafiltration cartridge and is designed to mechanically remove enteric pathogenic bacteria, viruses, and protozoan cysts from drinking water without water pressure or electric power. In laboratory testing through 20,000 L (approximately 110% of design life) at moderate turbidity (15 nephelometric turbidity unit [NTU]), the device achieved log(10) reduction values of 6.9 for Escherichia coli, 4.7 for MS2 coliphage (proxy for enteric pathogenic viruses), and 3.6 for Cryptosporidium oocysts, thus exceeding levels established for microbiological water purifiers. With periodic cleaning and backwashing, the device produced treated water at an average rate of 143 mL/min (8.6 L/hour) (range 293 to 80 mL/min) over the course of the evaluation. If these results are validated in field trials, the deployment of the unit on a wide scale among vulnerable populations may make an important contribution to public health efforts to control intractable waterborne diseases.


Immunopsychiatry: an update on autoimmune encephalitis for neuropsychiatrists.
Autoimmune encephalitis (AIE) is a group of immune-mediated inflammatory processes of the brain with marked psychiatric features. Although relatively rare, they might offer difficult differential diagnosis with psychiatric conditions, especially catatonia and psychotic syndromes. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most common AIE, presenting with psychiatric syndromes in 90% of cases. The associated psychopathology is complex, pleomorphic, and best characterized when there is involvement of a psychiatrist in the assessment. This text will review the main aspects of AIE to psychiatrists and/or neuropsychiatrists. Immune system dysfunction has been implicated in the pathophysiology of psychiatric symptoms and disorders. The use of diagnostic criteria for possible AIE, especially when specific antibodies of AIE are not available, allows early diagnosis and prompt treatment which are associated with better clinical outcomes. The study of the psychiatric aspects of AIE can broaden our knowledge of the underlying mechanisms of various psychiatric manifestations.


[Klotho - a new regulator of mineral homeostasis].
Research on the regulation of mineral homeostasis have been continuing for the decades, with an effect of establishing the impression that the governing mechanisms are already fairly well known and understood. Revealing of the molecular mechanism of action of the Klotho protein, forced us to revise this knowledge. It is known already that Kloto is a unique regulatory efector playing key role in reversing the imbalanced extracellular Ca(++) concentrations, by affecting the intensity of the transepithelial transport and modulation of the parathormone excretion. In cooperation with the phosphaturic hormone - Fgf23 it regulates calcium concentration by suppression of 1,25(OH)(2)D synthesis, and reabsorption of phosphate in a distal convoluted part of nephron. Acting through these mechanisms Klotho takes part in the regulation of the mineral homeostasis of cerebrospinal fluid, blood and body fluids acting on the choroid plexus, parathyroid glands and distal convoluted nephrons. In that way Klotho becomes one of the main players in a complex and multilevel system of maintaining the mineral homeostasis of the organism.


Nanoparticles Toxicity in Fish Models.
The increasing production and use of nanoparticles (NP) have raised concerns regarding the potential toxicity to human and environmental health. In this review, we address the up to date information on nanotoxicity using fish as models. Firstly, we carried out a systematic literature search (articles published up to February 2019 in the Scopus database) in order to quantitatively assess the scientific research on nanoparticles, nanotoxicity and fish. Next, we carried out a narrative synthesis on the main factors and mechanisms involved in NP toxicity in fish. According to the bibliometric analysis, there is a low contribution of scientific research on nanotoxicity compared with the general nanoparticles scientific production. The literature search also showed that silver and titanium NP are the most studied nanomaterials and Danio rerio is the fish species most used. In comparison with freshwater fish, the effects of nanomaterials on marine fish have been little studied. After a non-systematic literature analysis, we identified several factors involved in nanotoxicity, as well as the effects and main toxicity mechanisms of NP on fish. Finally, we highlighted the knowledge gaps and the need for future research.


Safety of hypertonic hyperoncotic solutions--a survey from Austria.
Hypertonic hyperoncotic solutions (HHS), composed of 7.2 to 7.5% sodium chloride and 6 to 10% dextran or hydroxyethyl starch, are able to restore the disturbed macro- and microcirculation in hypovolemic states within a short period of time. Even small amounts of HHS induce a relevant fluid shift from the extravasal into the intravasal space, and the use of HHS has thus been recommended in acute hypovolemia and hypovolemic shock (principle of "small-volume resuscitation"). Recently, attention has also focused on the treatment of elevated intracranial pressure using HHS. Austria is the only European country where market authorization of HHS was already obtained several years ago and where HHS have been widely used in clinical routine for a comparatively long time. This offers the unique possibility of evaluating, for the first time, the safety profile of HHS solutions. In this study, we analyzed the reported adverse drug reactions of HHS in a large number of applications. Marketing and pharmacovigilance data as well as other relevant information obtained in Austria during the years 1991 to 2000, were used for analysis of safety aspects of HHS applications in routine clinical practice. From 1991 to 2000, four adverse drug reactions related to HHS were reported, none of which was fatal. Out of these, 3 have to be regarded as anaphylactoid/anaphylactic reactions to hydroxyethyl starch. In one case an extreme overdose was infused resulting in a hyperosmolar syndrome. In the same time period approximately 56,000 HHS units were used in Austria in about 18,500 to 37,000 patients. With these numbers, the frequency of adverse drug reactions related to the prescribed application of HHS can be calculated: approximately 5 adverse drug reactions per 100,000 HHS units used; approximately 8-16 adverse drug reactions per 100,000 HHS-treated patients. Austrian experience with the use of a large number of HHS in clinical routine during nearly a decade indicates that the prescribed application of a combination of hydroxyethyl starch and hypertonic sodium chloride has a low potential for complications.


Chiral and nonchiral [OsX2(diphosphane)(diamine)] (X: Cl, OCH2CF3) complexes for fast hydrogenation of carbonyl compounds.
The osmium complexes trans-[OsCl(2)(dppf)(diamine)] (dppf: 1,1'-bis(diphenylphosphino)ferrocene; diamine: ethylenediamine in 3, propylenediamine in 4) were prepared by the reaction of [OsCl(2)(PPh(3))(3)] (1) with the ferrocenyl diphosphane, dppf and the corresponding diamine in dichloromethane. The reaction of derivative 3 with NaOCH(2)CF(3) in toluene afforded the alkoxide cis-[Os(OCH(2)CF(3))(2)(dppf)(ethylenediamine)] (5). The novel precursor [Os(2)Cl(4)(P(m-tolyl)(3))(5)] (2) allows the synthesis of the chiral complexes trans-[OsCl(2)(diphosphane)(1,2-diamine)] (6-9; diphosphane: (R)-[6,6'-dimethoxy(1,1'-biphenyl)-2,2'-diyl]bis[1,1-bis(3,5-dimethylphenyl)phosphane] (xylMeObiphep) or (R)-(1,1'-binaphthalene)-2,2'-diylbis[1,1-bis(3,5-dimethylphenyl)phosphane] (xylbinap); diamine=(R,R)-1,2-diphenylethylenediamine (dpen) or (R,R)-1,2-diaminocyclohexane (dach)), obtained by the treatment of 2 with the diphosphane and the 1,2-diamine in toluene at reflux temperature. Compounds 3-5 in ethanol and in the presence of NaOEt catalyze the reduction of methyl aryl, dialkyl, and diaryl ketones and aldehydes with H(2) at low pressure (5 atm), with substrate/catalyst (S/C) ratios of 10,000-200,000 and achieving turnover frequencies (TOFs) of up to 3.0 x 10(5) h(-1) at 70 degrees C. By employment of the chiral compounds 6-9, different ketones, including alkyl aryl, bulky tert-butyl, and cyclic ketones, have successfully been hydrogenated with enantioselectivities up to 99% and with S/C ratios of 5000-100,000 and TOFs of up to 4.1 x 10(4) h(-1) at 60 degrees C.


Facile covalent immobilization of cadmium sulfide quantum dots on graphene oxide nanosheets: preparation, characterization, and optical properties.
A facile approach for the preparation of a novel hybrid material containing graphene and an inorganic semiconducting material, cadmium sulfide quantum dots (CdS QDs), is demonstrated for the first time. First, amino-functionalized CdS QDs were prepared by modifications of the kinetic trapping method. Then, pristine graphite was oxidized and exfoliated to obtain graphene oxide nanosheets (GONS), which were then acylated with thionyl chloride to introduce acyl chloride groups on their surface. Subsequently, immobilization of the CdS QDs on the GONS surface was achieved through an amidation reaction between the amino groups located on the CdS QDs surface and the acyl chloride groups bound to the GONS surface. Fourier transform infrared spectroscopy (FT-IR), (1)H nuclear magnetic resonance ((1)H-NMR), x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS), and energy dispersive x-ray (EDX) spectroscopy were employed to investigate the changes in the surface functionalities, while high resolution transmission electron microscopy (HR-TEM) and field emission scanning electronic microscopy (FE-SEM) were used to study the morphologies and distribution of the CdS QDs on the GONS surface. Thermogravimetric analysis (TGA) was employed to characterize the weight loss of the samples on heating. Photoluminescence (PL) measurements were used to study the optical properties of the prepared CdS QDs and the CdS-graphene hybrid material.


Idiopathic pulmonary hypertension associated with nodular pulmonary infiltrates and portal venous thrombosis.
A case of idiopathic pulmonary hypertension is associated with portal venous thrombosis. The patient's chest roentgenogram revealed numerous nodular densities which at necropsy were found to have been caused by an exuberant fibroblastic reaction around small pulmonary arterioles. This is an example of the unusual association of idiopathic pulmonary hypertension and portal venous thrombosis, and to our knowledge, the first report of roentgenographically visible pulmonary nodules secondary to the pathologic alterations of idiopathic pulmonary hypertension.


Computed tomographic angiography for the diagnosis of blunt cervical vascular injury: is it ready for primetime?
Although the reported sensitivity of computed tomographic angiography (CTA) for the diagnosis of blunt cervical vascular injury (BCVI) has been inadequate, we hypothesized that advances in computed tomographic technology have improved the diagnostic sensitivity of CTA at least to that of invasive catheter angiography (CA). Data from all patients at risk for BCVI presenting to a Level I trauma center were collected prospectively. Each patient was evaluated with CTA and these findings were confirmed with standard catheter arteriograms (CA). Over 11 months, 162 patients were at risk for BCVI. In all, 146 patients received both CTA and CA. Forty-six BCVIs were identified among 43 patients. In 45 of 46 cases (98%), the results of CTA and CA were concordant. There was a single false-negative CTA in a patient with a grade I vertebral artery injury (VAI). The remaining 103 patients had normal CTAs confirmed by a normal CA. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CTA for the diagnosis of BCVI were 97.7%, 100%, 100%, 99.3%, and 99.3%, respectively. CTA, using a 16-channel detector, can be used to accurately screen at-risk patients for BCVI.


Molecular mechanisms of thalassemia in southeast Asia.
Hemoglobinopathies are the most common genetic disorders in Southeast Asia. alpha-Thalassemia is most often due to a alpha-globin gene deletion. Hb Constant Spring (CS) occurs from the mutation at the termination codon of the alpha-globin gene resulting in an elongated polypeptide; alpha(CS)-globin mRNA is also unstable and only small amounts of Hb CS are produced. Thus Hb CS has an alpha-thalassemia 2-like effect. beta-Thalassemia results from a variety of molecular mechanisms, most of which are single base substitutions or deletions or insertions of one to four nucleotides. Hemoglobin E occurs from a Glu --> Lys substitution at position 26 of the beta-globin chain. The abnormal gene also results in reduced amounts of beta E-mRNA and hence of beta E-globin chains. Therefore, Hb E has a mild beta + thalassemia phenotype. Homozygous beta-thalassemia and beta-thalassemia/Hb E are the major beta-thalassemic syndromes in Southeast Asia. In spite of seemingly identical genotypes, severity of beta-thalassemia/Hb E patients can vary greatly. Some may have a severe clinical disorder approaching that seen in homozygous beta-thalassemia. A number of genetic factors have been shown to determine the differences in severity of anemia in beta-thalassemia/Hb E, including co-inheritance of alpha-thalassemia determinants and co-inheritance of other determinants which elevate Hb F expression. A correlation between the extent of beta E-globin mRNA cryptic splicing and the severity of anemia in beta(zero)-thalassemia/Hb E patients has been observed. Complete characterization of mutations causing hemoglobinopathies will help to bolster the establishment of prenatal diagnosis of these genetic disorders in the region.


Outcome of ulnohumeral arthroplasty in osteoarthritis of the elbow.
Ulnohumeral arthroplasty is commonly used to treat mild or moderate osteoarthritis (OA) of the elbow. Previous studies have reported good to excellent results, but have not focused on the continuing degenerative process which can alter the outcome. The authors retrospectively evaluated 10 patients with elbow OA who were treated with the Outerbridge-Kashiwagi procedure from 2004 to 2006. The mean increase in the overall Andrews and Carson scores was 91 points (range: 70 to 100) at 3 months followup. The overall gain in range of motion, patient satisfaction rate and VAS and Andrews and Carson scores was found to be significantly diminished at the last follow-up, as compared with early postoperative values. Although ulnohumeral arthroplasty is an accepted procedure for elbow osteoarthritis, the deterioration of the overall gain in pronation/supination and progression of the disease can affect the final scores and patient satisfaction.


[A good care of students in their residency (PJ students)--a win-win-situation].
The provision of good mentors and education to medical students in their residency (PJ students) bears three essential advantages: 1) If the students feel themselves in good hands, they will co-operate effectively, thereby reducing the burden of the medical staff. 2) Contented students are potential advertisers for other interns, clinical trainees, medical students in residency and Ph.D. students. 3) Given the lack of doctors, providing students with good mentors and training is a valuable long-term strategy for the recruitment of doctors; in the event of later employment, former students in residency represent employees who are motivated, well trained, and familiar with hospital routine--a classical win-win situation.


Identification of the Regulators of Epidermis Development under Drought- and Salt-Stressed Conditions by Single-Cell RNA-Seq.
As sessile organisms, plants constantly face challenges from the external environment. In order to meet these challenges and survive, plants have evolved a set of sophisticated adaptation strategies, including changes in leaf morphology and epidermal cell development. These developmental patterns are regulated by both light and hormonal signaling pathways. However, our mechanistic understanding of the role of these signaling pathways in regulating plant response to environmental stress is still very limited. By applying single-cell RNA-Seq, we determined the expression pattern of PHYTOCHROME INTERACTING FACTOR (PIF) 1, PIF3, PIF4, and PIF5 genes in leaf epidermal pavement cells (PCs) and guard cells (GCs). PCs and GCs are very sensitive to environmental stress, and our previous research suggests that these PIFs may be involved in regulating the development of PCs, GCs, and leaf morphology under environmental stress. Growth analysis showed that pif1/3/4/5 quadruple mutant maintained tolerance to drought and salt stress, and the length to width ratio of leaves and petiole length under normal growth conditions were similar to those of wild-type (WT) plants under drought and salt treatment. Analysis of the developmental patterns of PCs and GCs, and whole leaf morphology, further confirmed that these PIFs may be involved in mediating the development of epidermal cells under drought and salt stress, likely by regulating the expression of MUTE and TOO MANY MOUTHS (TMM) genes. These results provide new insights into the molecular mechanism of plant adaptation to adverse growth environments.


Reversible impairment of neonatal hepatobiliary function by maternal cholestasis.
The effect of total blockage of maternal biliary excretion during the last third of the pregnancy on the maturation of hepatobiliary function was investigated in neonatal rats. Extrahepatic obstruction of the common bile duct on day 14 of pregnancy induced a marked enhancement in serum bilirubin--mainly conjugated bilirubin--and bile acid concentrations as compared with sham-operated pregnant rats. Excretion of bile acids by the kidney was significantly increased, whereas fecal elimination of these compounds was almost abolished. Most of the cholestatic mothers (CMs) (77%) were able to carry pregnancy to term and lactation until weaning (21 days after birth). The body and liver weights of their offspring were lower than for offspring of control healthy mothers in all postnatal periods considered. Serum bile acid concentrations were higher in the fetuses and neonates of CMs. This difference was evident up to 1 week after weaning and disappeared in young adult animals (8 weeks old). When the bile secretion rate was investigated in these animals at 4 or 8 weeks of age, no significant difference was found as far as nonstimulated bile flow and bile acid output was concerned. However, the biliary response to stepwise sodium taurocholate (TC) intravenous infusion showed that 4-week-old neonates of CMs had impaired bile acid secretion. Moreover, the maximal secretion rate (SRmax) for TC was significantly reduced (-30%), whereas the choleretic ability of taurocholate was not modified. This alteration was not selective for bile acids. The SRmax for bromosulfophthalein (BSP) was also significantly lowered (-40%). These dysfunctions were overcome during subsequent development. No impaired biliary response to either TC or BSP infusion was observed at 8 weeks of age. Morphological abnormalities in the canaliculi were found in animals with impaired biliary function. In summary, these results indicate that maternal cholestasis may profoundly but transiently impair the normal liver maturation. The importance of the implications derived from these findings both in the nutrition and management of human neonates demands further evaluation of the hepatobiliary function of babies born after alterations of fetal-maternal bile acid homeostasis, such as in maternal obstetric cholestasis.


Dual-Resonance (16/32 MHz) Piezoelectric Transducer With a Single Electrical Connection for Forward-Viewing Robotic Guidewire.
Peripheral artery disease (PAD) affects more than 200 million people globally. Minimally invasive endovascular procedures can provide relief and salvage limbs while reducing injury rates and recovery times. Unfortunately, when a calcified chronic total occlusion is encountered, ~25% of endovascular procedures fail due to the inability to advance a guidewire using the view provided by fluoroscopy. To enable a sub-millimeter, robotically steerable guidewire to cross these occlusions, a novel single-element, dual-band transducer is developed that provides simultaneous multifrequency, forward-viewing imaging with high penetration depth and high spatial resolution while requiring only a single electrical connection. The design, fabrication, and acoustic characterization of this device are described, and proof-of-concept imaging is demonstrated in an ex vivo porcine artery after integration with a robotically steered guidewire. Measured center frequencies of the developed transducer were 16 and 32 MHz, with -6 dB fractional bandwidths of 73% and 23%, respectively. When imaging a 0.2-mm wire target at a depth of 5 mm, measured -6 dB target widths were 0.498 ± 0.02 and 0.268 ± 0.01 mm for images formed at 16 and 32 MHz, respectively. Measured SNR values were 33.3 and 21.3 dB, respectively. The 3-D images of the ex vivo artery demonstrate high penetration for visualizing vessel morphology at 16 MHz and ability to resolve small features close to the transducer at 32 MHz. Using images acquired simultaneously at both frequencies as part of an integrated forward-viewing, guidewire-based imaging system, an interventionalist could visualize the best path for advancing the guidewire to improve outcomes for patients with PAD.


Effects of climate change on the design of subsurface drainage systems in coastal aquifers in arid/semi-arid regions: Case study of the Nile delta.
The influence of climate change on the availability and quality of both surface- and ground-water resources is well recognized nowadays. In particular, the mitigation of saline water intrusion mechanisms in coastal aquifers is a recurrent environmental issue. In the case of the Nile delta, the presence of sea level rise and the perspective of other human-induced stressors, such as the next operation of the Grand Ethiopian Renaissance Dam, are threats to be taken into account for guaranteeing resilient agricultural practices within the future possible scenarios. Subsurface drainage offers a practical solution to the problem of upward artesian water movement and the simultaneous downward flow of excess irrigation water, to mitigate the salinization in the root zone. Subsurface draining systems can contribute to mitigate the vulnerability to climate change and to the increased anthropic pressure insofar they are able to receive the incremented flow rate due to the foreseen scenarios of sea level rise, recharge and subsidence. This paper introduces a rational design of subsurface drainage systems in coastal aquifers, taking into account the increment of flow in the draining pipes due to future possible conditions of sea level rise, artificial recharge and subsidence within time horizons that are compatible with the expected lifespan of a buried drainage system. The approach proposed in this paper is characterized by the assessment of the incremental flow through the drains as a function of various possible scenarios at different time horizons. Our calculations show that the impact on the discharge into the existing subsurface drainage system under the new foreseen conditions is anything but negligible. Thus, future climate-related scenarios deeply impact the design of such hydraulic structures, and must be taken into account in the frame of the next water management strategies for safeguarding agricultural activities in the Nile delta and in similar coastal contexts.


Interactive Student-Centered Neuroscience Workshops for Sixth Graders Enhance Science Knowledge and Education Attitudes.
UCNeuro, a University of California, Riverside student-run organization, developed, implemented, and tested a school-based supplemental science intervention. The purpose of this intervention was to improve students' neuroscience knowledge and education attitudes and meet, in part, California's new elementary science education standards. The intervention consisted of interactive, hands-on neuroscience workshops on the structure of a neuron, neuron-to-neuron communication, brain structure and function, autonomic nervous system function, and drug effects on the brain. Under the supervision of a faculty neuroscientist, undergraduate students implemented the intervention with 77 sixth-grade students in one school in Riverside County, California. Pre- and post-test results showed increases in students' neuroscience knowledge, confidence in achieving their goals, likeliness to go to college, and desire to attend school. Excitement about learning science material and school learning opportunities did not change after the workshops. We hope that the UCNeuro workshops can be employed and adapted to the existing curriculum to improve knowledge in the life sciences while California's new elementary science standards are being operationalized.


Introduction to Focus Issue: nonlinear and stochastic physics in biology.
Frank Moss was a leading figure in the study of nonlinear and stochastic processes in biological systems. His work, particularly in the area of stochastic resonance, has been highly influential to the interdisciplinary scientific community. This Focus Issue pays tribute to Moss with articles that describe the most recent advances in the field he helped to create. In this Introduction, we review Moss's seminal scientific contributions and introduce the articles that make up this Focus Issue.


Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells.
The regulated interactions of leukocytes with vascular endothelial cells are crucial in controlling leukocyte traffic between blood and tissues. Vascular adhesion protein-1 (VAP-1) is a novel, human endothelial cell molecule that mediates tissue-selective lymphocyte binding. Two species (90 and 170 kD) of VAP-1 exist in lymphoid tissues. Glycosidase digestions revealed that the mature 170-kD form of VAP-1 expressed on the lumenal surfaces of vessels is a heavily sialylated glycoprotein. The sialic acids are indispensable for the function of VAP-1, since the desialylated form of VAP-1 no longer mediates lymphocyte binding. We also show that L-selectin is not required for binding of activated lymphocytes to VAP-1 under conditions of shear stress. The 90-kD form of VAP-1 was only seen in an organ culture model, and may represent a monomeric or proteolytic form of the larger species. These data indicate that L-selectin negative lymphocytes can bind to tonsillar venules via the VAP- 1-mediated pathway. Moreover, our findings extend the role of carbohydrate-mediated binding in lymphocyte-endothelial cell interactions beyond the known selectins. In conclusion, VAP-1 naturally exists as a 170-kD sialoglycoprotein that uses sialic acid residues to interact with its counter-receptors on lymphocytes under nonstatic conditions.


Office recognition and management of adolescent substance abuse.
Substance misuse and substance use disorders are important pediatric public health concerns. The prevalence is high, beginning in adolescence through adulthood, and there is marked morbidity. This is especially true in the adolescent population, in whom the three leading causes of death are all associated with substance abuse. The primary care physician is ideally situated to recognize, prevent, and triage significant substance abuse problems. This review will provide recent, relevant information for primary care physicians (PCP) to enable them to have the current knowledge, tools, and attitudes needed to address these issues. Epidemiologic studies continue to document the widespread use of licit and illicit substances by youth. Understanding of substance use disorders is moving forward with an increasing clarity of the multiple factors important in the development of these disorders. This has already led to the establishment of effective prevention programs, which may be applicable to the primary care setting. Research into psychosocial treatment is proceeding rapidly, and psychopharmacologic approaches are also being investigated. Evidence-supported approaches to treatment now exist. Substance abuse in youth is a serious public health problem, with significant morbidity and mortality. The primary care physician can make major inroads into effective prevention and treatment by recognizing and addressing these issues in the outpatient office setting.


The role of the transcription factor Foxp3 in the development of regulatory T cells.
Early studies of mice subjected to neonatal thymectomy and analyses of adoptive T-cell transfer into lymphopenic hosts led to the identification of a specialized subset of regulatory CD4+ T cells capable of suppressing various manifestations of autoimmunity. Recently, a combination of genetic, molecular, and traditional cellular approaches provided novel powerful means to investigate the biology of these cells. Here, we review earlier and current work from our laboratory, establishing a dedicated function for the transcription factor Foxp3 in the process of regulatory T-cell lineage commitment and a role for TCR- and cytokine-mediated signals in regulation of Foxp3 expression.


Aberrant methylation of secreted apoptosis-related protein 2 (SARP2) in pure pancreatic juice in diagnosis of pancreatic neoplasms.
Secreted apoptosis-related protein (SARP) families are considered to counteract the oncogenic Wnt signaling pathway, and inactivation of this gene may aid cancer development and progression. Recently, the aberrant methylation of SARP2 was detected frequently in pancreatic carcinoma (PCa) tissue, but not in normal pancreatic tissue. We evaluated the hypermethylation of SARP2 in pure pancreatic juices (PPJ) aspirated endoscopically from patients with PCa, intraductal papillary mucinous neoplasm of the pancreas (IPMN), chronic pancreatitis (CP), and a control group who were consequently free of pancreatic diseases according to the differential diagnosis of PCa. We investigated the aberrant methylation of SARP2 in 9 human PCa cell lines and in the PPJ samples from 33 patients with PCa, 20 with IPMN, 19 with CP, and 10 control patients. DNAs extracted from not only sediment, but also the supernatant of the PPJ and PCa cell lines were treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction (PCR) (MSP). Moreover, real-time MSP was also performed for the melting curve analysis and the quantitative analysis of SARP2 in the PPJ. The incidence of the aberrant methylation of SARP2 using MSP was 8/9 (89%) in PCa cell lines, 26/33 (79%) in the PPJ with PCa, and 17/20 (85%) with IPMN. However, it was only 1/19 (5%) in the PPJ with CP, and 0/10 (0%) in the PPJ of the control patients, respectively. The incidences of aberrant methylation of SARP2 in the PPJ with PCa and IPMN were significantly higher than that in the PPJ with CP (P < 0.001, P < 0.001). Melting curve analysis by real-time MSP revealed that the incidences of aberrant methylation of SARP2 in PPJ was 28/33 (85%) with PCa, 9/11 (82%) with the malignant group of IPMN, 5/9 (56%) with the benign group of IPMN and 5/19 (26%) with CP. In this analysis, there were significant differences between PCa and CP (P < 0.001), and between the malignant group of IPMN and CP (P < 0.005). In the quantitative analysis by real-time MSP with a suitable cut-off value, the incidences of aberrant methylation of SARP2 in the PPJ with PCa, the malignant group of IPMN, the benign group of IPMN, and CP were 19/33 (58%), 6/11 (55%), 3/9 (33%), and 2/19 (11%), respectively. The incidence of the aberrant methylation of SARP2 in the PPJ was significantly different between PCa and CP and between the malignant group of IPMN and CP (P < 0.005 and P < 0.05, respectively). Hypermethylation of SARP2 in the PPJ may be a highly sensitive and useful marker for the detection of pancreatic neoplasms, including PCa and the malignant group of IPMN.


[Relationship between impulse noise and continuous noise inducing hearing loss by dosimeter measurement in working populations].
To compare the dose-response relationship differences between impulse noise exposure workers and continuous noise exposure workers in prevalence of noise inducing hearing loss using dosimeter measurement. Thirty-two mechanical workers in a workshop were selected as impulse noise group and 163 textile workers in a textile factory as continuous noise group. SH-126 dosimeter was used to measure A weighted equal sound level of eight hours (L(Aeq.8 h)) during full working duration with equal energy rule for the selected workers. The cumulative noise exposure (CNE) was calculated by L(Aeq.8 h) and noise working years with equal energy rule for each worker. Hearing thresholds were measured by audiometer by routine method and adjusted by age and gender with GBZ49 - 2002. Hearing loss was diagnosed by GBZ49 - 2002 for each worker. CNE of impulse noise group [(103.2 +/- 4.2) dB (A) .year] was found lower than the continuous noise group [(110.6 +/- 6.0) dB (A) .year] by significance, P < 0.05. The hearing loss prevalence of impulse noise group (68.8%) was similar as continuous noise group (65%) without significance, P > 0.05. Strata analysis showed the hearing loss prevalence in 100 - 104 dB (A) .year and 105 - 109 dB (A) .year of impulse noise group was double than that of continuous noise group (76.9%, 90.9% vs 30.4%, 50.0%), P < 0.05. The chi-square test showed a relationship between CNE and hearing loss prevalence that was in high significance (P < 0.01) in both impulse noise group and continuous noise group. Logistic regression model showed the dose-response relationship curve of impulse noise group was left shift and sharp slope. The damage of impulse noise on hearing loss was much more than that of continuous noise according to equal energy rule of dosimeter data.


In vivo magnetic resonance imaging of mice liver tumors using a new gadolinium-based contrast agent.
We compared the enhancement effect between a newly synthesized tissue-specific contrast agent, [Gd-DOTA-FPβG], and a commercially available agent, [Gd(DOTA)](-), in a murine model of liver tumor using a clinical magnetic resonance imaging scanner. The colon cancer cell lines with and without β-glucuronidase (βG) expression were implanted into the liver of mice. Self-synthesized gadolinium-based magnetic resonance contrast agent, [Gd(DOTA-FPβG)], was administered to measure enhancement on magnetic resonance images using a commercially available agent, [Gd(DOTA)](-), as control in a clinical 3.0 tesla (T) magnetic resonance scanner. In vivo fluorescence imaging and histopathology of the liver were also performed to compare and correlate with the magnetic resonance studies. The in vivo fluorescence imaging failed to depict a sufficiently intense signal for liver or liver tumor of mice without exposure of the liver following an incision on the abdominal wall. The tissue-specific magnetic resonance agent, [Gd(DOTA-FPβG)], caused significantly stronger enhancement in tumors expressing βG (CT26/mβG-eB7) than in tumors not expressing βG (CT26) (p < 0.05). In the magnetic resonance imaging studies using control agent [Gd(DOTA)](-), the tumors with and without βG expression depicted no significant difference in enhancement on the T1-weighted images. The [Gd(DOTA-FPβG)] also provided significantly more contrast uptake in the CT26/mβG-eB7 tumor than in the normal liver parenchyma, whereas the [Gd(DOTA)](-) did not. This study confirms that better contrast enhancement can be readily detected in vivo by the use of a tissue-specific magnetic resonance contrast agent to target tumor cells with specific biomarkers in a clinical magnetic resonance imaging scanner.


The Effects of Storm Runoff on Water Quality and the Coping Strategy of a Deep Canyon-Shaped Source Water Reservoir in China.
Storm runoff events in the flooding season affect the water quality of reservoirs and increase risks to the water supply, but coping strategies have seldom been reported. The phenomenon of turbid current intrusion resulting in water turbidity and anoxic conditions reappearing after storm runoff, resulting in the deterioration of water quality, was observed in the flooding season in the deep canyon-shaped Heihe Reservoir. The objective of this work was to elucidate the effects of storm runoff on the Heihe Reservoir water quality and find a coping strategy. In this study, an intensive sampling campaign measuring water temperature, dissolved oxygen, turbidity, nutrients, and metals were conducted in the reservoir over a period of two years, and the water-lifting aerators were improved to achieve single aeration and a full layer of mixing and oxygenation functions using different volumes of gas. The operation of the improved water-lifting aerators mixed the reservoir three months ahead of the natural mixing time, and good water quality was maintained during the induced mixing period, thereby extending the good water quality period. The results can provide an effective coping strategy to improve the water quality of a source water reservoir and ensure the safety of drinking water.


A response to Rudolf Klein: a battle may have been won but perhaps not the war.
The British National Health Service (NHS) is undergoing possibly the most far-reaching set of changes in its sixty-five-year history. While some commentators (like Rudolf Klein) insist that little of substance is likely to change, others consider that the politics of reform may prove quite different on this occasion. The coalition government is committed to restructuring the welfare state and public services and to rolling back the state. The NHS as a popular monopoly public service runs counter to its neoliberal ideology. While (for now) remaining committed to a publicly funded system of health care that is largely free at point of use, the government wishes to encourage much greater diversity in the provision of care, including a much larger role for the for-profit private sector. Despite significant opposition to its proposals, few concessions have been forthcoming, and the legislation that passed onto the statute book in March 2012 remained essentially unchanged. Notwithstanding the lack of convincing evidence, the government is wedded to encouraging greater competition and choice. Thosewho believe the changes will amount to far less than its architects hope for are being too complacent and overlooking the strength of the government's ideological convictions. These threaten to dismantle the NHS and replace it with a more costly, fragmented, and less effective system of care that is driven by profit in place of the public interest.


Multi-image acquisition-based distance sensor using agile laser spot beam.
We present a novel laser-based distance measurement technique that uses multiple-image-based spatial processing to enable distance measurements. Compared with the first-generation distance sensor using spatial processing, the modified sensor is no longer hindered by the classic Rayleigh axial resolution limit for the propagating laser beam at its minimum beam waist location. The proposed high-resolution distance sensor design uses an electronically controlled variable focus lens (ECVFL) in combination with an optical imaging device, such as a charged-coupled device (CCD), to produce and capture different laser spot size images on a target with these beam spot sizes different from the minimal spot size possible at this target distance. By exploiting the unique relationship of the target located spot sizes with the varying ECVFL focal length for each target distance, the proposed distance sensor can compute the target distance with a distance measurement resolution better than the axial resolution via the Rayleigh resolution criterion. Using a 30 mW 633 nm He-Ne laser coupled with an electromagnetically actuated liquid ECVFL, along with a 20 cm focal length bias lens, and using five spot images captured per target position by a CCD-based Nikon camera, a proof-of-concept proposed distance sensor is successfully implemented in the laboratory over target ranges from 10 to 100 cm with a demonstrated sub-cm axial resolution, which is better than the axial Rayleigh resolution limit at these target distances. Applications for the proposed potentially cost-effective distance sensor are diverse and include industrial inspection and measurement and 3D object shape mapping and imaging.


Role of ethylene in the senescence of detached rice leaves.
The role of ethylene in the senescence of detached rice leaves in relation to their changes in 1-aminocyclopropane-1-carboxylic acid (ACC) content and ethylene production was studied. In freshly excised rice leaf segments, ACC level and ethylene production rates were very low. Following incubation, the rates of ethylene production increased and reached a maximum in 12 h, and subsequently declined. The rise of ethylene production was associated with a 20- to 30-fold increase in ACC level.Ethylene seems to be involved in the regulation of the senescence of detached rice leaves. This conclusion was based on the observations that (a) maximum ethylene production preceded chlorophyll degradation, (b) ACC application promoted chlorophyll degradation, (c) inhibitors of ethylene production and ethylene action retarded chlorophyll degradation, and (d) various treatments such as light, cycloheximide, alpha,alpha-dipyridyl, Ni(2+), and cold temperature, which retarded chlorophyll degradation, also inhibited ethylene production.Abscisic acid promoted senescence but significantly decreased ethylene production, whereas benzyladenine retarded senescence but promoted ethylene production. This is interpreted to indicate that abscisic acid treatment increased the tissue sensitivity to ethylene, whereas benzyladenine treatment decreased it.


Tissue concentrations of ofloxacin in the middle ear.
Twenty patients with chronic otitis media underwent tympanoplasty and were given an oral dose (two 200-mg tablets) of a new antibiotic, ofloxacin, three to seven hours before surgery. The study aimed to demonstrate satisfactory concentrations of ofloxacin in the middle ear as the basis for that agent's well-known clinical efficacy. The main pathogens responsible for bacterial infections in the ear, nose, and throat, especially those in the ear, are Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and alpha-streptococci. The chemotherapeutic agent used must reach adequate concentrations in the bone, mucous membrane, and serum. Mucous membrane, bone, and serum samples were obtained from the middle ear and examined for ofloxacin levels. The medication was also administered for a minimum of five days postoperatively. The average serum level of ofloxacin was 2.1 micrograms/ml, and the concentrations in both the mucous membrane and bone (2.2 micrograms/gm) were above the serum levels. The extent to which the concentrations at the possible site of infection exceeded the minimal inhibitory concentrations (MICs) for the pathogens was investigated at our clinic in 190 isolates. The study showed that, with the leading pathogens such as staphylococci, tissue concentrations were about four times higher than the MICs and that even Pseudomonas organisms were effectively inhibited. All patients had a satisfactory clinical response to therapy. The authors thus recommend a dosage of 400 mg of ofloxacin three to five hours prior to surgery for middle ear infection.


Does patient-specific instrumentation increase the risk of notching in the anterior femoral cortex in total knee arthroplasty? A comparative prospective trial.
Patient-specific instrumentation (PSI) was usually applied in total knee arthroplasty (TKA) to acquire a favourable alignment. We hypothesized that using PSI had a potential risk of notching in the anterior femoral cortex, because the femoral component may be placed in an overextension position due to the distal femoral sagittal anteversion. The aim of this study was to figure out the relationship between the notch and the distal femoral sagittal anteversion in PSI-assisted TKA. One hundred thirty-one patients who were to undergo total knee arthroplasty (TKA) were randomly divided into conventional instrumentation (CI) group and PSI group. The computed tomography (CT) data of lower extremities was collected and imported to the Mimics software to reconstruct the three-dimensional (3D) bone image of the femur. The angle between distal femoral anatomic axis (DFAA) and femoral mechanical axis (FMA) on sagittal plane was defined as distal femoral sagittal anteverted angle (DFSAA) and measured. The number of notch intra-operative and post-operative was recorded. Then, we calculated the incidence of the notch and analyzed its relationship with DFSAA. The average DFSAA of 262 femurs is 2.5° ± 1.5° (range, 0.0°-5.7°). When DFSAA ≥ 3°, the incidence of notch was 7.10% in CI group and 33.30% in PSI group, respectively, which shows significant statistical difference in the two groups (P = 0.016 < 0.05). When DFSAA < 3°, the incidence of notch was 6.50% in CI group and 5.30% in PSI group, respectively, which shows no significant statistical difference in the two groups (P = 0.667 > 0.05). DFSAA could be taken as an indicator to predict the notch when performing TKA assisted with PSI. Especially when the DFSAA ≥ 3°, the risk of notch could be markedly increased.


Genomic organization and expression pattern of mouse neuroglycan C in the cerebellar development.
Neuroglycan C (NGC) is a membrane-spanning chondroitin sulfate proteoglycan with an epidermal growth factor module that is expressed predominantly in the brain. Cloning studies with mouse NGC cDNA revealed the expression of three distinct isoforms (NGC-I, -II, and -III) in the brain and revealed that the major isoform showed 94. 3% homology with the rat counterpart. The NGC gene comprised six exons, was approximately 17 kilobases in size, and was assigned to mouse chromosome band 9F1 by fluorescence in situ hybridization. Western blot analysis demonstrated that, although NGC in the immature cerebellum existed in a proteoglycan form, most NGC in the mature cerebellum did not bear chondroitin sulfate chain(s), indicating that NGC is a typical part-time proteoglycan. Immunohistochemical studies showed that only the Purkinje cells were immunopositive in the cerebellum. In the immature Purkinje cells, NGC, probably the proteoglycan form, was immunolocalized to the soma and thick dendrites on which the climbing fibers formed synapses, not to the thin branches on which the parallel fibers formed synapses. This finding suggests the involvement of NGC in the differential adhesion and synaptogenesis of the climbing and parallel fibers with the Purkinje cell dendrites.


Valuing tacit nursing knowledge during the COVID-19 pandemic.
Public health nurses in Ontario, Canada, support the healthy growth and development of children across the province through a variety of programs including home visits for pregnant individuals and families with young children. During the COVID-19 global pandemic the needs of families increased while access to health and social services decreased. During this time, home visiting teams closely involved in supporting families also experienced staff redeployment to support pandemic efforts (e.g., case and contact management, vaccinations) and changes to the nature of home visiting work, including shifts to remote or virtual service delivery. To support nursing practice in this new and evolving context, a framework for capturing and sharing the tacit or how-to knowledge of public health nurses was developed. A valuing of this type of knowledge for informing future public health nursing practice - well beyond the pandemic response - was recognized as a pandemic silver lining when reflecting on two years of supporting home visiting teams in our province.


Biochemical responses of pea root tissue to cytokinin: enhanced rates of RNA synthesis.
Rates of RNA synthesis were studied in cultured pea (Pisum sativum) root segments and cortical explants which require the hormone cytokinin for DNA replication and cell proliferation. Rate calculations were based on the specific radioactivity of the extracted RNA and the specific radioactivity of the extracted ATP pool after a pulse with (3)H-adenosine. The kinetics of RNA synthesis was studied after 24 hours of culture with or without kinetin. We found that kinetin stimulated a 2- to 4-fold enhancement in the rate of RNA synthesis after 24 hours of culture as compared to controls. A similar order of magnitude of stimulation of RNA synthesis was found when RNA was isolated by cesium chloride centrifugation. Pulses during the first 24 hours indicate that kinetin stimulates the rate of RNA synthesis as early as 9 hours after treatment has begun. During the first 24 hours of culture, kinetin did not affect the specific radioactivity of the ATP pool. The ATP pool equilibrated slowly with the exogenous label ((3)H-adenosine) in the presence or absence of kinetin. After 3 days in culture, we found kinetin to cause an expansion of the extractable ATP pool and a corresponding reduction in the ATP pool specific radioactivity. We interpret these results to indicate a stimulation in the rate of RNA synthesis due to kinetin treatment prior to any other known response.


Relationships of lipid and glucose metabolism with waist-hip ratio and physical fitness in obese men.
The waist-hip ratio (WHR) is an indirect index of abdominal type obesity which has been shown to be strongly correlated with the risk of coronary heart disease. Empirically, men who have a higher WHR seem to have a lower level of physical fitness. In the present study, the relationships of lipid and glucose metabolism with WHR and physical fitness were examined in 207 Japanese obese men. Physical fitness was evaluated by the oxygen uptake at the onset of blood lactate accumulation (OBLA-VO2; ml/kg/min) which corresponds to 4 mmol/l of blood lactate during graded exercise test and is one of the best indicators of the muscle oxidative capacity. The WHR and percentage of body fat (% body fat) were significantly correlated with OBLA-VO2. The WHR and % body fat were significantly related to each other. After adjusting for % body fat, a significant negative correlation was observed between the WHR and OBLA-VO2 (r = -0.24; P < 0.05). A multiple linear regression was calculated for parameters relating to lipids, and glucose and insulin areas separately, when the WHR, OBLA-VO2, % body fat and age were entered as independent variables. OBLA-VO2 significantly showed a negative relationship with triglyceride (TG), HDL-C/total cholesterol, and the insulin area, while the WHR was only independently related to TG. From these results, we conclude that the physical fitness level evaluated by OBLA-VO2, which represents the capacity of the aerobic metabolism in muscle, may thus be a determinant of lipid and glucose metabolism in obese men.


Evaluation of the American Society of Anesthesiologists Physical Status Classification System in Risk Assessment for Lower Extremity Reconstruction with Free Tissue Transfer.
The applicability of free flap reconstruction for lower extremity (LE) defects in high-risk patients continues to require ongoing review. The aim of this study was to analyze the risk factors, management, and outcome of LE free flap reconstruction in high-risk (American Society of Anesthesiologists [ASA] class 3 or 4) patients. A retrospective chart review was performed for all patients who underwent LE reconstruction in our Institution (Level I Trauma Center) from 2013 to 2019. Medical records and the authors' prospectively maintained database were analyzed with respect to ASA class, comorbidities, and postoperative complications. All patients were treated using the same pre-, intra-, and postoperative multidisciplinary approach. A total of 199 patients were analyzed. Sixty-six flaps were transferred in 60 patients with an ASA class 3 or higher. High-risk patients did not present a higher rate of flap loss or LE amputation. The overall flap success rate was 92%. There were five flap losses in high-risk patients. Three of these five patients underwent a successful second free flap reconstruction. The overall success rate of LE reconstruction in high-risk patients was 90%. Four patients with successful free flap ended up in LE amputation due to bone infection and two patients underwent an amputation after the first free flap failure. Free flap reconstruction for LE defects in high-risk patients is a safe and reliable procedure for selected patients when an experienced multidisciplinary team is involved. Bone infection was the only variable associated with LE amputation.


Role of the Helicobacter hepaticus flagellar sigma factor FliA in gene regulation and murine colonization.
The enterohepatic Helicobacter species Helicobacter hepaticus colonizes the murine intestinal and hepatobiliary tract and is associated with chronic intestinal inflammation, gall stone formation, hepatitis, and hepatocellular carcinoma. Thus far, the role of H. hepaticus motility and flagella in intestinal colonization is unknown. In other, closely related bacteria, late flagellar genes are mainly regulated by the sigma factor FliA (sigma(28)). We investigated the function of the H. hepaticus FliA in gene regulation, flagellar biosynthesis, motility, and murine colonization. Competitive microarray analysis of the wild type versus an isogenic fliA mutant revealed that 11 genes were significantly more highly expressed in wild-type bacteria and 2 genes were significantly more highly expressed in the fliA mutant. Most of these were flagellar genes, but four novel FliA-regulated genes of unknown function were identified. H. hepaticus possesses two identical copies of the gene encoding the FliA-dependent major flagellin subunit FlaA (open reading frames HH1364 and HH1653). We characterized the phenotypes of mutants in which fliA or one or both copies of the flaA gene were knocked out. flaA_1 flaA_2 double mutants and fliA mutants did not synthesize detectable amounts of FlaA and possessed severely truncated flagella. Also, both mutants were nonmotile and unable to colonize mice. Mutants with either flaA gene knocked out produced flagella morphologically similar to those of wild-type bacteria and expressed FlaA and FlaB. flaA_1 mutants which had flagella but displayed reduced motility did not colonize mice, indicating that motility is required for intestinal colonization by H. hepaticus and that the presence of flagella alone is not sufficient.


Re-evaluation of DNA Index as a Prognostic Factor in Children with Precursor B Cell Acute Lymphoblastic Leukemia.
We aimed to investigate the prognostic value of DNA index (DI) in children with precursor B cell acute lymphoblastic lymphoma (pre-B ALL). From January 2003 to December 2014, 72 children diagnosed with pre-B ALL were analyzed. We analyzed the prognostic value of DI and its relations with other prognostic factors. The DI cut-point of 1.16 did not discriminate significantly the groups between high and low survivals (DI≥1.16 versus <1.16; 5-year OS, 90.5% vs. 82.8%, p=0.665). We explored the survivals according to the level of DI (<1.00, 1.00, 1.01-1.30, 1.31-1.60, 1.61-1.90, and >1.90), and the survival of children with a DI between 1.00-1.90 were significantly higher than that of children with DI of <1.00 or >1.90 (5-year OS, 90.6% vs. 50.0%, p<0.001). The DI of 1.16 was not a significant cut-point discriminating the risk group in children with pre-B ALL. However, the DI divided by specific ranges of values remained an independent prognostic factor. Further studies are warranted to re-evaluate the prognostic value and cut-point of DI in children treated with recent treatment protocols.


From Sponges to Nanotubes: A Change of Nanocrystal Morphology for Acute-Angle Bent-Core Molecules.
The crystalline (B4 ) phase made of acute-angle bent-core molecules (1,7-naphthalene derivatives), which exhibits an unusual, highly porous sponge-like morphology, is presented. However, if grown in the presence of low-weight mesogenic molecules, the same crystal forms nanotubes with a very high aspect ratio. The nanotubes become unstable upon increasing the amount of dopant molecules, and the sponge-like morphology reappears. The phase is optically active, and the optical activity is an order of magnitude smaller than in the B4 phase made of conventional bent-core molecules. The optical activity is related to the spatial inhomogeneity of the layered structure and is reduced due to the low apex angle and low tilt of the molecules. The arrangement of molecules within the layers was deduced from the bathochromic absorption shift in the B4 phase.


Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial.
Late treatment failures after artemisinin-based combination therapies (ACTs) for falciparum malaria have increased in the Greater Mekong subregion in southeast Asia. Addition of amodiaquine to artemether-lumefantrine could provide an efficacious treatment for multidrug-resistant infections. We conducted an open-label, randomised trial at five hospitals or health centres in three locations (western Cambodia, eastern Cambodia, and Vietnam). Eligible participants were male and female patients aged 2-65 years with uncomplicated Plasmodium falciparum malaria. Patients were randomly allocated (1:1 in blocks of eight to 12) to either artemether-lumefantrine alone (dosed according to WHO guidelines) or artemether-lumefantrine plus amodiaquine (10 mg base per kg/day), both given orally as six doses over 3 days. All received a single dose of primaquine (0·25 mg/kg) 24 h after the start of study treatment to limit transmission of the parasite. Parasites were genotyped, identifying artemisinin resistance. The primary outcome was Kaplan-Meier 42-day PCR-corrected efficacy against recrudescence of the original parasite, assessed by intent-to-treat. Safety was a secondary outcome. This completed trial is registered at ClinicalTrials.gov (NCT03355664). Between March 18, 2018, and Jan 30, 2020, 310 patients received randomly allocated treatment; 154 received artemether-lumefantrine alone and 156 received artemether-lumefantrine plus amodiaquine. Parasites from 305 of these patients were genotyped. 42-day PCR-corrected treatment efficacy was noted in 151 (97%, 95% CI 92-99) of 156 patients with artemether-lumefantrine plus amodiaquine versus 146 (95%, 89-97) of 154 patients with artemether-lumefantrine alone; hazard ratio (HR) for recrudescence 0·6 (95% CI 0·2-1·9, p=0·38). Of the 13 recrudescences, 12 were in 174 (57%) of 305 infections with pfkelch13 mutations indicating artemisinin resistance, for which 42-day efficacy was noted in 89 (96%) of 93 infections with artemether-lumefantrine plus amodiaquine versus 73 (90%) of 81 infections with artemether-lumefantrine alone; HR for recrudescence 0·44 (95% CI 0·14-1·40, p=0·17). Artemether-lumefantrine plus amodiaquine was generally well tolerated, but the number of mild (grade 1-2) adverse events, mainly gastrointestinal, was greater in this group compared with artemether-lumefantrine alone (vomiting, 12 [8%] with artemether-lumefantrine plus amodiaquine vs three [2%] with artemether-lumefantrine alone, p=0·03; and nausea, 11 [7%] with artemether-lumefantrine plus amodiaquine vs three [2%] with artemether-lumefantrine alone, p=0·05). Early vomiting within 1 h of treatment, requiring retreatment, occurred in no patients of 154 with artemether-lumefantrine alone versus five (3%) of 156 with artemether-lumefantrine plus amodiaquine, p=0·06. Bradycardia (≤54 beats/min) of any grade was noted in 59 (38%) of 154 patients with artemether-lumefantrine alone and 95 (61%) of 156 with artemether-lumefantrine plus amodiaquine, p=0·0001. Artemether-lumefantrine plus amodiaquine provides an alternative to artemether-lumefantrine alone as first-line treatment for multidrug-resistant P falciparum malaria in the Greater Mekong subregion, and could prolong the therapeutic lifetime of artemether-lumefantrine in malaria-endemic populations. Bill & Melinda Gates Foundation, Wellcome Trust.


[Epidemiology of gastroduodenal complications associated with nonsteroidal anti-inflammatory drug use].
Nonsteroidal anti-inflammatory agents (NSAIDs) are among the most widely prescribed drugs worldwide. In France, about 25% of individuals aged 40 years or older are treated with NSAIDs at least one week in the year. Although the therapeutic benefits of these drugs are substantial, their use is limited by their gastroduodenal toxicity. Dyspepsia occurs in about 30% of patients receiving NSAIDs, an approximately two-fold enhancement of risk compared with control subjects. Asymptomatic endoscopic lesions are observed in 20 to 80% of patients, depending on population characteristics, individual NSAIDs and definitions of endoscopic lesions. The risk of symptomatic ulcer, complicated ulcer (haemorrhage, perforation, stenosis) and death related to ulcer complication is multiplied by 4 in patients treated with NSAIDs. Established risk factors for NSAID-induced gastroduodenal complications are age, ulcer history, heavy alcohol consumption, individual NSAIDs, dose, association with corticoid or aspirin or anticoagulants (ulcer haemorrhage) while the role of treatment duration and Helicobacter pylori infection are controversial.


Undiscovered Biodiversity of the European Moss Flora: Neodicranella hamulosa (Aongstroemiaceae), a New Genus and Species from SW Portugal.
A new genus is described to accommodate Neodicranella hamulosa, a novel species resolved in the family Aongstroemiaceae, from the Monchiquense district in SW Portugal. Characterized by its small size, erect spreading to subsecund non-sheathing leaves, plane bistratose leaf margins, and rhizoidal gemmae with slightly protruberant cells, it differs from all other European Dicranellaceae in the uniquely patterned distal peristome segments with backward-pointing papillae resembling hooked barbs. The species appears to be endemic to the sub-Mediterranean bioclimatic zone, in wooded biomes where humidity remains relatively high throughout the year. Morphological and molecular data strongly support the singularity of this new taxon. The species is illustrated by photomicrographs and SEM, and its ecology and conservation are discussed.


Transcriptional Regulation by the Short-Chain Fatty Acyl Coenzyme A Regulator (ScfR) PccR Controls Propionyl Coenzyme A Assimilation by Rhodobacter sphaeroides.
Propionyl coenzyme A (propionyl-CoA) assimilation by Rhodobacter sphaeroides proceeds via the methylmalonyl-CoA pathway. The activity of the key enzyme of the pathway, propionyl-CoA carboxylase (PCC), was upregulated 20-fold during growth with propionate compared to growth with succinate. Because propionyl-CoA is an intermediate in acetyl-CoA assimilation via the ethylmalonyl-CoA pathway, acetate growth also requires the methylmalonyl-CoA pathway. PCC activities were upregulated 8-fold in extracts of acetate-grown cells compared to extracts of succinate-grown cells. The upregulation of PCC activities during growth with propionate or acetate corresponded to increased expression of the pccB gene, which encodes a subunit of PCC. PccR (RSP_2186) was identified to be a transcriptional regulator required for the upregulation of pccB transcript levels and, consequently, PCC activity: growth substrate-dependent regulation was lost when pccR was inactivated by an in-frame deletion. In the pccR mutant, lacZ expression from a 215-bp plasmid-borne pccB upstream fragment including 27 bp of the pccB coding region was also deregulated. A loss of regulation as a result of mutations in the conserved motifs TTTGCAAA-X4-TTTGCAAA in the presence of PccR allowed the prediction of a possible operator site. PccR, together with homologs from other organisms, formed a distinct clade within the family of short-chain fatty acyl coenzyme A regulators (ScfRs) defined here. Some members from other clades within the ScfR family have previously been shown to be involved in regulating acetyl-CoA assimilation by the glyoxylate bypass (RamB) or propionyl-CoA assimilation by the methylcitrate cycle (MccR). Short-chain acyl-CoAs are intermediates in essential biosynthetic and degradative pathways. The regulation of their accumulation is crucial for appropriate cellular function. This work identifies a regulator (PccR) that prevents the accumulation of propionyl-CoA by controlling expression of the gene encoding propionyl-CoA carboxylase, which is responsible for propionyl-CoA consumption by Rhodobacter sphaeroides. Many other Proteobacteria and Actinomycetales contain one or several PccR homologs that group into distinct clades on the basis of the pathway of acyl-CoA metabolism that they control. Furthermore, an upstream analysis of genes encoding PccR homologs allows the prediction of conserved binding motifs for these regulators. Overall, this study evaluates a single regulator of propionyl-CoA assimilation while expanding the knowledge of the regulation of short-chain acyl-CoAs in many bacterial species.


The incidence and patterns of lung cancers in Sri Lanka from 2001 to 2010: Analysis of national cancer registry data.
Epidemiological studies carried out on lung cancer have shown varying incidence patterns in Asia. We aimed to examine the trends in lung cancer incidence and patterns in Sri Lanka. All newly diagnosed lung cancer patients in Sri Lanka during 2001-2010 included in the National Cancer Registry were analysed. Trends in incidence were analysed using the Joinpoint regression software. A total of 8482 lung cancer patients (males = 6831, 80.5%, mean age: 60.2 years) were analysed. The WHO age-standardised incidence rate (ASR) has increased from 3.77 per 100,000 in 2001 (95% confidence interval [95% CI]: 3.47-4.07) to 5.74 per 100,000 in 2010 (95% CI: 5.38-6.09; a 1.52-fold increase (p < 0.05 for trend), with an estimated annual percentage change (EAPC) of 5.4 (95% CI: 3.9-7.0). The proportional increase in incidence was higher for females [ASR: 1.2 to 2.3, EAPC = 6.8(95% CI: 4.0-9.7)] than males [ASR: 6.6 to 9.55, EAPC = 5.2(95% CI: 3.8-6.6)] and with similar patterns. In Sri Lanka, the incidence of lung cancer has shown as increasing trend with a greater proportional rise in females. Although the observed trends could be partly due to better reporting, the greater increase in females who are generally non-smokers is intriguing. Further studies are required to identify reasons for observed incidence trends in lung cancer in Sri Lanka.


Low-dose nitrendipine in mild hypertension: a double-blind, placebo-controlled, comparative study.
The objective of this study was to determine whether 10 mg of nitrendipine once daily is adequate for treatment of mild hypertension. The study was a randomized, double-blind, multicenter, and placebo-controlled group comparison over 8 weeks (a 2-week placebo-controlled washout phase followed by a 6-week treatment phase) with measurement of blood pressure, routine laboratory tests, compliance monitoring, and recording of side effects every 2 weeks. The study subjects were 141 outpatients with mild arterial hypertension and were given one 10-mg tablet of nitrendipine or placebo once daily. The end point used was reduction in diastolic blood pressure (DBP) by at least 10 mm Hg or to less than or equal to 90 mm Hg; the responder rate at the end of the treatment phase was determined. After 6 weeks of treatment, the mean reduction in DBP was 11.8 mm Hg under nitrendipine compared with 5 mm Hg under placebo. The responder rates were 73% (53 of 73 patients) in the nitrendipine group and 26% (18 of 68 patients) in the placebo group. This difference is statistically significant. Side effects were reported by a total of 14 patients (6 in the nitrendipine group, 8 in the placebo group). There was one dropout in each group. No changes in laboratory parameters were observed. In conclusion, nitrendipine is suitable for monotherapy of mild arterial hypertension in the dosage of 10 mg once daily used in this study.


Cyclic AMP phosphodiesterase 4D (PDE4D) Tethers EPAC1 in a vascular endothelial cadherin (VE-Cad)-based signaling complex and controls cAMP-mediated vascular permeability.
Vascular endothelial cell (VEC) permeability is largely dependent on the integrity of vascular endothelial cadherin (VE-cadherin or VE-Cad)-based intercellular adhesions. Activators of protein kinase A (PKA) or of exchange protein activated by cAMP (EPAC) reduce VEC permeability largely by stabilizing VE-Cad-based intercellular adhesions. Currently, little is known concerning the nature and composition of the signaling complexes that allow PKA or EPAC to regulate VE-Cad-based structures and through these actions control permeability. Using pharmacological, biochemical, and cell biological approaches we identified and determined the composition and functionality of a signaling complex that coordinates cAMP-mediated control of VE-Cad-based adhesions and VEC permeability. Thus, we report that PKA, EPAC1, and cyclic nucleotide phosphodiesterase 4D (PDE4D) enzymes integrate into VE-Cad-based signaling complexes in human arterial endothelial cells. Importantly, we show that protein-protein interactions between EPAC1 and PDE4D serve to foster their integration into VE-Cad-based complexes and allow robust local regulation of EPAC1-based stabilization of VE-Cad-based adhesions. Of potential translational importance, we mapped the EPAC1 peptide motif involved in binding PDE4D and show that a cell-permeable variant of this peptide antagonizes EPAC1-PDE4D binding and directly alters VEC permeability. Collectively, our data indicate that PDE4D regulates both the activity and subcellular localization of EPAC1 and identify a novel mechanism for regulated EPAC1 signaling in these cells.


Effect of Congo red on wild-type and mutated prion proteins in cultured cells.
Transmissible spongiform encephalopathies form a group of fatal neurodegenerative disorders that have the unique property of being infectious, sporadic, or genetic in origin. Although some doubts remain on the nature of the responsible agent of these diseases, it is clear that a protein called PrP(Sc) (which stands for the scrapie isoform of the prion protein) has a central role in their pathology. PrP(Sc) represents a conformational variant of a normal protein of the host: the cellular isoform of the prion protein, or PrP(C). Compounds such as glycosaminoglycans and Congo red (CR) have been shown to interfere with both in vitro and in vivo PrP(Sc) formation. It was hypothesized that CR acts by overstabilizing the conformation of PrP(Sc) molecules or by modifying trafficking of PrP(C). Using transfected cells expressing 3F4-tagged mouse PrPs, we show here that CR does not interfere with conversion of PrP molecules carrying pathogenic mutations. On the contrary, after incubation with the drug, some of their properties, such as insolubility and protease resistance, are enhanced and are even acquired by the wild-type molecule. This last observation suggests an alternative mechanism of action of CR and leads us to reconsider the relationship between the biochemical properties of PrP and conformational alteration of the protein.


FES/FER kinase signaling in hematopoietic cells and leukemias.
FES and FES-related (FER) comprise a unique subfamily of protein-tyrosine kinases (PTKs) that signal downstream of several classes of receptors involved in regulating hematopoietic cell development, survival, migration, and inflammatory mediator release. Activated alleles of FES are potent inducers of myeloid differentiation, however FES-deficient mice have only subtle differences in hematopoiesis. This may reflect overlapping function of other kinases such as FER. Studies of FES- and FER-deficient mice have revealed more prominent roles in regulating the activation of mature innate immune cells, including macrophages and mast cells. Recently, new insights into regulation of FES/FER kinases has emerged with the characterization of their N-terminal phospholipid-binding and membrane targeting FER/CIP4 homology-Bin/Amphyphysin/Rvs (F-BAR) and F-BAR extension (FX) domains. The F-BAR/FX domains regulate subcellular localization and FES/FER kinase activation. FES kinase activity is also enhanced upon ligand binding to its SH2 domain, which may lead to further phosphorylation of the same ligand, or other ligand-associated proteins. In mast cells, SH2 ligands of FES/FER include KIT receptor PTK, and the high affinity IgE receptor (FceRI) that trigger rapid activation of FES/FER and signaling to regulators of the actin cytoskeleton and membrane trafficking. Recently, FES/FER have also been implicated in growth and survival signaling in leukemias driven by oncogenic KIT and FLT3 receptors. With further definition of their roles in immune cells and their progenitors, FES/FER may emerge as relevant therapeutic targets in inflammatory diseases and leukemias.


Contact thermal burns of the cornea.
The records of 59 patients (66 eyes) with contact thermal burns of the cornea (unilateral in 52 cases and bilateral in 7) were reviewed to determine the causes, clinical presentation, management and complications of such injuries. Most of the injuries (90%) occurred at home. The commonest cause was splashing of boiling fluids (42% of cases), followed by contact with red-hot firecracker particles (18%) and lit match heads (17%). In 59 eyes (89%) the burn was limited to the corneal epithelium, in 5 (8%) the superficial stroma was also involved, and in 2 (3%) there was associated corneal perforation caused by mechanical impact of foreign bodies. Débridement of the coagulated epithelium with patching was the most successful treatment, healing 48 (73%) of the eyes. Postburn complications were rare, the most common being development of inferior symblepharon, in three eyes (4%).


Structure and Magnetic Properties of Co40Fe40V20 Thin Films.
This study investigated the structure and magnetic properties of Co40Fe40V20 thin films with a thicknesses (tf) of 10 nm to 100 nm on a glass substrate. The X-ray diffraction (XRD) patterns of the CoFeV films demonstrated a significant crystalline body-centered cubic (BCC) CoFe (110) structure when the thickness was between 60 and 100 nm, and an amorphous status were shown when the thickness was from 10 to 50 nm. The strongest crystalline XRD peak was at 60 nm because it had a continuous mode of film growth and induced a large grain distribution. The low-frequency alternating current magnetic susceptibility (ϰac) property decreased when the frequency increased. The lowest ϰac value was detected at 60 nm owing to the large grain distribution inducing high coercivity (Hc) and then enhancing the spin coupling strength. The external field (Hext) was difficult to rotate spin state, then deduces the spin sensitivity and ϰac value is decreased. The highest ϰac meant the spin sensitivity was maximized at the optimal resonance frequency. The 50-mm thickness had the highest ϰac 0.045 value at an fres of 100 Hz. The fres value was less than 1000 Hz at all CoFeV thicknesses, suggesting that CoFeV films would be suitable for low-frequency magnetic component applications. Moreover, the saturation magnetization (Ms) revealed a thickness effect when the thicknesses had a larger Ms. The Hc values were between 3 Oe and 10 Oe at all CoFeV films, except for 60 nm. The Hc of the 60 nm film was about 80 Oe due to the larger grain distribution, and it induced strong remanent magnetization (Mr) and a larger squareness ratio (Mr/Ms) of 92%. The results of the magnetic measurement showed that the 60 nm Co40Fe40V20 film had greater Hc and a good squareness ratio.


Costs of conventional radical radiotherapy versus continuous hyperfractionated accelerated radiotherapy (CHART) in the treatment of patients with head and neck cancer or carcinoma of the bronchus. Medical Research Council CHART Steering Committee.
The objective of this study was to compare the costs of treatment with continuous hyperfractionated accelerated radiotherapy (CHART) and those of conventional radiotherapy for patients with (1) head and neck cancer and (2) carcinoma of the bronchus. The study was conducted concurrently with two multicentre randomized controlled trials. Data were collected on the use of hospital and community service resources and patients' travel for treatment. Data on resource use up to 3 months after entry to the study were available for 526 head and neck patients (314 receiving CHART and 212 conventional therapy) and 284 bronchus patients (175 CHART and 109 conventional therapy). For patients with head and neck cancer, CHART cost Pounds 1092 (P < 0.001; 95% CI 763-1421) more than conventional therapy. For patients with carcinoma of the bronchus, CHART was also more costly, with a cost differential of Pounds 698 (P < 0.001; 95% CI 392-1003). The magnitude of the cost differentials could be reduced if the working hours of radiotherapy departments were rearranged and all hospitals had access to hostel facilities. The results of this cost analysis will help to facilitate a decision about whether the benefits of CHART, as determined by the clinical trials, are worth the additional costs of hospital-based resource use. The collection of detailed patient-specific resource-use data from a number of centres allows the determination of ways for reducing the cost differential between therapies and making CHART a more cost effective treatment alternative.


Smoldering (asymptomatic) multiple myeloma: revisiting the clinical dilemma and looking into the future.
Recent studies show that multiple myeloma (MM) is consistently preceded by an asymptomatic precursor state. Smoldering MM (SMM) is a MM precursor defined by an M-protein concentration >or= 3 g/dL and/or >or= 10% bone marrow plasma cells, in the absence of end-organ damage. Compared with individuals diagnosed with monoclonal gammopathy of undetermined significance (MGUS), patients with SMM have a much higher annual risk of developing MM. However, based on clinical observations, the natural history of SMM varies greatly, from stable MGUS-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into 3 risk groups. Importantly, because of considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Furthermore, until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early MM treatment strategies. Consequently, current clinical guidelines emphasize the application of close clinical monitoring followed by treatment when the patient develops symptomatic MM. This review focuses on novel biomarkers, molecular profiles, and microenvironmental interactions of interest in myelomagenesis. We also discuss how the integration of novel biologic markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future.


[Blocking effects of dimethoate on acetylcholine receptor channels].
The patch-clamp technique was used to study the inhibitory effect of dimethoate, an organophosphrous pesticide, on the membrane of embryoinc Xenopus musle cells in culture. Using whole-cell clamp and cell-attached clamp, we found that the direct inhibitory effects of dimethoate was evidenced on both miniature end-plate currents (MEPC) and single channel currents. Dimethoate increased the amplitude and frequency of MEPC at a lower concentration (21.6 mumol/L) while both decreased at a higher concentration (237 mumol/L). The dimethoate at a concentration of 146 mumol/L shortened the opening time and decreased the opening probability of the single channel. The results show that dimethoate is an AChR channel blocker.


[Present situation of leprosy in highly endemic area of tropical Asia--a seroepidemiological study of Mycobacterium leprae infection in general inhabitants].
One of the most important unsolved problems in epidemiology of leprosy is the heterogeneous geographic distribution of the disease. There are highly endemic area called "Pocket" in the endemic countries. Little is known why leprosy is so endemic in the area. We conducted, therefore, an epidemiological study on M. leprae infection and distribution of leprosy bacilli in the environment by using serological and molecular biological techniques. It was found that considerable number of general inhabitants in the pocket are infected with leprosy bacilli and more than 20% of the villagers are carrying M. leprae on the surface of the nasal cavity; suggesting that leprosy bacilli in the residential environment play an important role in high prevalence of leprosy in the endemic area. New preventive measures such as chemoprophylaxis, in addition to MDT, will be needed for global elimination of the disease.


'Neutralizing the patient': therapists' accounts of sexual boundary violations.
Sexual contact between psychological therapists and their clients is regarded as highly damaging, both to the clients and to the professions, and regulatory bodies impose increasingly severe sanctions upon those practitioners who are disciplined. The present study captured therapists' accounts of sexual boundary violations through interpretative phenomenological analysis of interviews with three disciplined practitioners about their relationships with clients and former clients. The results highlighted two key themes relating to (i) therapists' efforts to neutralize the power imbalances between themselves and the clients by minimizing the clients' mental health problems, stressing the conventionality of the relationships and not testing the appropriateness of the relationship with their supervisors, and (ii) a shifting identity of the therapist between hero, victim, perpetrator, which permeated their accounts as the relationship moved from success to failure. In order for a sexual boundary violation to occur, the therapist needed to generate a sense of equivalent status between themselves and the client. As the relationships failed, the therapists' accounts of the clients shifted and the inequality of the relationship re-emerged. The results are discussed in terms of implicit theories and the implications for both training and supervision in the prevention of sexual boundary violations.


Current progress of aptamer-based molecular imaging.
Aptamers, single-stranded oligonucleotides, are an important class of molecular targeting ligand. Since their discovery, aptamers have been rapidly translated into clinical practice. They have been approved as therapeutics and molecular diagnostics. Aptamers also possess several properties that make them uniquely suited to molecular imaging. This review aims to provide an overview of aptamers' advantages as targeting ligands and their application in molecular imaging.


[A case of carbon monoxide intoxication presenting subacute dementia as the initial symptom].
We reported a 67-year-old woman who had developed abnormal behavior and dementia from January 21, 2001 and deteriorated to akinetic mutism on February 15. T2-weighted magnetic resonance imaging showed high intensity in bilateral globus pallidus and a rapid spreading of diffuse high intensity in bilateral deep white matter. Later on, we got an important information that she had used a little coal stove three times about three weeks before presenting the initial symptom. She was diagnosed as carbon monoxide intoxication and treated with hyperbaric oxygen from March 1. A remarkable improvement on dementia and motor disability was observed. We conclude that this case is the first reported example of a case of intermittent carbon monoxide intoxication presenting subacute dementia as an initial symptom.


International care models for chronic kidney disease: methods and economics--United States.
In the United States, there is a major chronic kidney disease (CKD) problem with over 8 million adults having stage 3 or 4 CKD. There is good medical evidence that many of these patients can benefit from focused interventions. And while there are strong theoretical reasons to believe these interventions are cost-effective, there are little published data to back up this assertion. However, despite the lack of financial data proving cost-effectiveness and against the background of a disorganized health care system in the US, some models of CKD care are being employed. At the present time, the most comprehensive models of care in the US are emerging in vertically integrated health care programs. Other models of care are developing in the setting of managed care health plans that employ CKD disease management programs, either developed internally or in partnership with renal disease management companies.


Gastrointestinal Histoplasmosis as an Obstructing Ileocecal Mass.
Histoplasmosis is a self-limiting and asymptomatic disease in immunocompetent individuals. Patients in an immunocompromised state are susceptible to disseminated disease. We present a case of a 60-year-old male with a history of psoriatic and rheumatoid arthritis treated with a tumor necrosis factor inhibitor (adalimumab), who presented with abdominal pain and was found to have gastrointestinal histoplasmosis as an obstructing ileocecal mass. Although gastrointestinal involvement is common in disseminating disease, symptomatic involvement is rare. This case presentation has implications in rheumatological patients on biologic medications.


Influence of UiO-66(Zr) Preparation Strategies in Its Catalytic Efficiency for Desulfurization Process.
Porous metal-organic framework (MOF) materials UiO-66(Zr) obtained by solvothermal and microwave advanced synthesis (MWAS) procedures were characterized, and their catalytic efficiency was investigated for oxidative desulfurization (ODS) processes using a multicomponent model diesel containing benzothiophene and dibenzothiophene derivatives. The preparation parameters as the cooling time after oven use in the solvothermal procedure, and also the reaction time in the MWAS method seemed to play an important role in the catalytic performance of the UiO-66(Zr) material, as well as in its recycle capacity. The material prepared by the solvothermal procedure with a fast cooling time showed the best catalytic performance (desulfurization efficiency of 99.5% after 3 h). However, the application of the UiO-66(Zr) material prepared by the MWAS method (desulfurization efficiency of 96% after 3 h) conciliated a higher number of advantages, such as shorter reaction time preparation (15 min) and high catalytic activity for a higher number of reaction cycles. The UiO-66(Zr) prepared by the MWAS method was used for the first time in an oxidative desulfurization process, and according to the catalytic results obtained (high recycle capacity and stability) and shorter reaction time preparation, seems to be a promising material for industrial application.


In vivo performance of the Nitinol shape-memory stapes prosthesis during hearing restoration surgery in otosclerosis: a first report.
The limitations of manual prosthesis crimping in hearing restoration surgery for otosclerosis are thought to have a key role in the occurrence of incomplete postoperative elimination of conductive hearing loss and postoperative recurrences of conductive hearing loss. To eliminate manual crimping, the self-crimping, shape-memory alloy Nitinol stapes piston was introduced in nine otosclerosis patients. The results were compared with those in a database of surgeries performed with conventional titanium pistons. The effects of the self-crimping Nitinol prosthesis on the postoperative elimination of conductive hearing loss and its postoperative variations were investigated. The variations of postoperative residual conductive hearing loss were significantly smaller and the extent of conductive hearing-loss elimination greater in the Nitinol group. The mean postoperative residual conductive hearing loss was smaller in the Nitinol group. The postoperative stability of conductive hearing loss elimination was similar in both patient groups. Preliminary results suggest that the self-crimping shape-memory alloy Nitinol stapes piston overcomes the drawbacks of manual crimping in hearing restoration surgery for otosclerosis.