[Influence of the subesophageal ganglion on the electrical activity of neurons of the metathoracic ganglion of the cockroach Periplaneta americana].
Studies have been made of non-specific effect of suboesophageal gnaglion on excitability of the segmental centers in the cockroach P. americana. It was shown that the electrical stimulation of the ganglion increases the frequency of the spontaneous activity and decreases the threshold of the evoked reactions in neurons of the metathoracic ganglion. The level of activation depends on the intensity of stimulation. Application of GABA (0.1 M) to the suboesophageal ganglion decreases the frequency of the background activity in the segmental neurons, this effect being presumably due to activation of the inhibitory structures. The descending influences from the suboesophageal ganglion may spread to centers of the metathoracic ganglion along monosynaptic pathways.


Biomarkers of end of shift exposure to disinfection byproducts in nurses.
Increased disinfectant use commonly takes place in hospitals and other health care settings. A cross-sectional study among active nurses in two Cypriot public hospitals (n=179) was conducted to examine the prevalence of exposure to disinfection byproducts (DBPs), such as trihalomethanes (THMs) using both self-reported information and biomarker measurements. The objectives of this study were to: i) quantify the magnitude and variability of occupational exposure to disinfectants/DBPs in nurses, ii) generate job exposure matrices (JEM) and job task exposure matrices (JTEM) for disinfectants, and iii) assess the major determinants of urinary THMs in nurses. End of shift urinary total THM values showed high variability among the nurses, but did not differ between hospitals. The disinfectant group of alcohols/phenols was used by >98% of nurses, followed by octenidine (82%), iodine and chlorine (39%, each), chlorhexidine (25%), formaldehyde (12%), hydrogen peroxide (11%), and peracetic acid/ammonia/quaternary ammonium compounds (QACs), all being <8% each. Chlorine use during the past 24hr was associated with significantly (p<0.05) lower brominated THMs (BrTHMs) after adjusting for age, gender and BMI, while a positive association was shown for TCM and the sum of all THMs (TTHMs), albeit not significant. Nurses were exposed to nearly double the levels of TTHMs and BrTHMs (median and IQR, 1027 [560, 2475] ng/g and 323 [212, 497] ng/g, respectively) when compared to those of the general population (552 [309,989] ng/g and 152 [87,261] ng/g, respectively). This was the first occupational health dataset reporting measurements of biomarkers of end of shift exposures to disinfectants/DBPs.


Malnutrition in hospitalized cancer patients: A single-center, cross-sectional study in Southern Vietnam.
Malnutrition in cancer patients reduces response to chemotherapy, increases the hospitalization costs, hospital infections, and deaths. The aim of this study was to determine the prevalence, level of malnutrition, and its related factors in cancer patients at a local hospital in Southern Vietnam. A descriptive cross-sectional study was performed on all 118 cancer patients who were undergoing inpatient treatment at Long An General Hospital, Vietnam from May to September 2020. Data were collected from patients by face-to-face interviewing using a subjective global assessment (SGA) and from medical records. Malnutrition is divided into three groups: SGA-A (normal), SGA-B (mild/moderate/suspected malnutrition), SGA-C (severe malnutrition). Multivariable logistic regression is used to identify factors related to malnutrition with statistical significance p < 0.05. Out of 118 participants, 72 (61.0%) were males and 84 (71.2%) aged ⩾60 years. The prevalence of malnutrition in cancer patients was 84.7% (100/118), in which 33% (39/118) were severe (SGA-C) and 51.7% (61/118) were mild-moderate (SGA-B). Pancreatic and lung cancers are the most malnourished. The results of multivariate logistic regression analysis showed that the factors related to malnutrition in cancer patients were gastrointestinal symptoms lasting 2 weeks (odds ratio: 6.10, 95% confidence interval: 1.12-33.35), patients with decreased motor function (odds ratio: 13.73, 95% confidence interval: 2.56-73.86), blood albumin <35 g/l (odds ratio: 6.42, 95% confidence interval: 1.54-26.82), and blood lymphocyte ⩽ 1700 cells/mm3 (odds ratio: 5.36, 95% confidence interval: 1.31-21.97). There was a high proportion of malnutrition in cancer patients. Therefore, it is necessary to strengthen nutrition counseling and intervention for these patients, especially those that have prolonged gastrointestinal symptoms, reduced motor function, and low blood albumin or low blood lymphocytes.


Use of Point-of-care Ultrasound for the Seizing Infant: An Adjunct for Detection of Abusive Head Trauma.
An eight-week-old infant presented to the emergency department in cardiac arrest. Return of spontaneous circulation was obtained and the patient subsequently began seizing. Point-of-care ultrasound of the anterior fontanelle revealed an extra-axial fluid collection consistent with subdural hematoma (SDH). Abusive head trauma is still frequently missed on initial presentation. In addition to validated screening clinical prediction rules, point-of-care cranial ultrasound can be used as a noninvasive adjunct for detection of SDH related to abusive head trauma in infants with an open fontanelle.


High efficiency degradation crude oil by a novel mutant irradiated from Dietzia strain by 12C6+ heavy ion using response surface methodology.
Crude oil is an extremely complex mixture of hydrocarbons; also contaminate environmental, leading to carcinogenic, teratogenic and mutagenic. Petroleum hydrocarbons degradation Dietzia strain DMYR9 was isolated from oilfield. Response surface methodology was applied for statistical designing of process parameters for dry weight of biomass production in the process of degradation. The optimization process parameters were successfully employed for degradation crude oil and confirmed through confirmatory experiments. On 28th day, analysis was done by GC-MS, These data show that the crude oil samples of n-Hexadecane, Octadecane, n-Nonadecanec, n-Pentacosane, n-Hexacosane, n-Heneicosane, n-Docosane, n-Tetracosane, n-Octacosane and Tetraethyl removal efficiency could reach up to 0%. RSM optimization and use of effective (12)C(6+)-ion irradiation methods can considerably enhance ability to degradation of microbial. Hence, bioresource Dietzia strain DMYR9, high ability to degradation, can be further used for subsequent repair hydrocarbons polluted of environment.


Formation of a covalent disulfide-linked antithrombin-albumin complex by an antithrombin variant, antithrombin "Northwick Park".
Antithrombin is a major proteinase inhibitor of the blood coagulation system. Its inherited deficiency or abnormality is often associated with thromboembolism. Antithrombin "Northwick Park," a functionally inactive variant antithrombin, has recently been shown by us (Lane, D.A., Flynn, A., Ireland, H., Erdjument, H., Samson, D., Howarth, D., and Thompson, E. (1987) Br. J. Haematol. 65,451-456) to be present in plasma, in part, as a high Mr (approximately 120,000) component which has a characteristic electrophoretic mobility in agarose gels in the absence of denaturing agents. In this communication, we present evidence that this Mr approximately 120,000 variant component is comprised of an antithrombin-albumin covalent disulfide-linked complex. This proposal is supported by results of: (a) fast atom bombardment mass spectrometry of the isolated reduced, S-carboxymethylated, trypsin-digested Mr approximately 120,000 complex; (b) sodium dodecyl sulfate-polyacrylamide gel electrophoresis of this complex and its reduced and S-carboxymethylated constituents; (c) immunoblotting of these polyacrylamide gels with antisera specific for antithrombin and albumin; (d) NH2-terminal sequence analysis of one of the isolated, S-carboxymethylated proteins that comprise the Mr approximately 120,000 complex; and (e) fast atom bombardment mass spectrometry of its tryptic peptides.


Escherichia coli RcsA, a positive activator of colanic acid capsular polysaccharide synthesis, functions To activate its own expression.
Capsule (cps) gene expression in Escherichia coli is controlled by a complex network of regulators. Transcription of the cps operon is controlled by at least two positive regulators, RcsA and RcsB. We show here that RcsA functions to activate its own expression, as seen by the 100-fold-increased expression of a rcsA::lacZ transcriptional fusion in strains with high levels of RcsA protein, either due to a mutation in lon or due to overexpression of RcsA from a multicopy plasmid. Expression of the rcsA::lacZ fusion is increased by but not dependent on the presence of RcsB. In addition, the effects of H-NS and RcsB on the expression of rcsA are independent of each other. A sequence motif, conserved between the E. coli cps promoter and the Erwinia amylovora ams promoter and previously shown to be the RcsA-RcsB binding site, was identified in the rcsA promoter region and shown to be required for high-level expression of rcsA.


Intracellular calcium and neurotoxic events.
Calcium is important in many intracellular regulatory processes. However, the maintenance of low levels of this cation within the cytosol is essential for maintenance of cell viability, in view of the large concentration gradient of ionic calcium across the plasma membrane. The expenditure of energy is needed to maintain intracellular calcium concentration [Ca2+]i at normal levels. In addition, the integrity of the limiting membrane is also vital for this function. Thus, any disruption of membrane characteristics or of mitochondrial anabolic processes may lead to deleterious levels of [Ca2+]i. The toxicity of a wide range of unrelated agents may, therefore, be in part due to elevation of cytosolic calcium. This general event may synergize with the more selective harmful properties of a compound, thus adversely affecting cell metabolism. The capacity now exists to measure levels of [Ca2+]i in isolated cells or organelles such as synaptosomes. The use of such in vitro models can be of value in the evaluation of the neurotoxic potential of compounds. This method, in conjunction with the use of pharmacological agents known to act at specific sites, and with the use of radioactive calcium in translocation studies, also has utility in the delineation of the biochemical mode of action of neurotoxic agents.


Multicenter study on finger systolic blood pressure test for diagnosis of vibration-induced white finger.
A multicenter study (six Rosai hospitals around Japan) was performed to investigate the diagnostic value of changes in finger systolic blood pressure (FSBP) after segmental local cooling for vibration-induced white finger (VWF). Subjects were 154 men without exposure to vibration and 135 men with occupational vibration exposure. They were classified into four groups: Group A, 154 unexposed control cases; Group B, 21 exposed cases without VWF; Group C, 31 cases with a history of VWF but without any signs of VWF within the last year; and Group D, 83 cases with active VWF within the last year. FSBP% measurements were taken at room temperatures of 23 +/- 1 and 21 +/- 1 degrees C, using a strain-gauge Digimatic 2000 plethysmograph (Medimatic). At a room temperature of 23 +/- 1 degrees C, there was a significant difference between Groups A and D, and B and D. At a room temperature of 21 +/- 1 degrees C, there was a significant difference between Groups A and C, A and D, and B and D. The values in Group D were the lowest at both room temperatures. Assuming a cut-off value of 75% at 23 +/- 1 degrees C, the sensitivity and specificity were 65.2 and 87.5%, respectively. Assuming the same cut-off value at 21 +/- 1 degrees C, the sensitivity and specificity were 73.9 and 82.5%, respectively. These values were not too high. Most of the subjects with WVF in this study were retired and had not used vibratory tools for many years. The situation of the subjects may affect the results of the FSBP test. Our data did not confirm a difference in diagnostic accuracy between room temperatures of 23 +/- 1 and 21 +/- 1 degrees C. Our study showed that the sensitivity and specificity of the FSBP test with a cut-off value of 75% at 23 +/- 1 degrees C, were 65.2 and 87.5%, respectively, and at 21 +/- 1 degrees C, they were 73.9 and 82.5%, respectively.


Clinical and legal correlates of inmates with bipolar disorder at time of criminal arrest.
In an effort to determine illness factors associated with criminality among bipolar patients, we identified bipolar arrestees housed in the psychiatric division of the Los Angeles County Jail who had a history of psychiatric treatment in the Los Angeles County community mental health system. Los Angeles County's computerized management information system was utilized to retrospectively identify all inmates evaluated over a 7-month period from July 1999 to Jan. 2000 with a DSM-IV diagnosis of bipolar I disorder, their symptoms at time of arrest, and the nature of community treatment preceding arrest. Criminal history was assessed using Sheriff's Department legal records. Demographic and clinical characteristics of these inmates were compared with characteristics present in a group of hospitalized bipolar patients without a history of arrest in Los Angeles County. Of the 66 inmates identified as having a clear diagnosis of bipolar disorder with previous community treatment in the Los Angeles County Mental Health system, the majority were manic (49/66, 74.2%) and psychotic (39/66, 59%) at time of arrest. Manic arrestees were recently released from community inpatient treatment and most were not involved in outpatient treatment postdischarge. The bipolar inmates had significantly higher rates of comorbid substance abuse than did the hospitalized bipolar patients without an arrest history (75.8% [50/66]) vs. 18.5% [10/54]). The results of this study suggest that manic symptoms place bipolar patients at significant risk for criminal offending and arrest. Intensive treatment intervention by the community mental health and criminal justice system may be needed, particularly in the immediate postmanic hospitalization period, in order to prevent incarceration of patients with bipolar disorder.


Inhibition and induction of metronidazole and antipyrine metabolism.
The effect of cimetidine, antipyrine and phenobarbitone on the pharmacokinetics of intravenous metronidazole and oral antipyrine has been examined in 7 healthy volunteers. The administration of cimetidine for 24 h before and throughout the sampling period failed to alter the total clearance of metronidazole or the rate of formation of the hydroxy metabolite, whereas the total and partial clearances of antipyrine were decreased 0.74 and 0.6-0.7-fold, respectively. Seven days of phenobarbitone or antipyrine administration increased the total clearance of metronidazole 1.51- and 1.86-fold, respectively, and the total antipyrine clearance was 1.22 or 1.46-fold increased, respectively. The rate of metronidazole hydroxylation was significantly enhanced by both enzyme inducers. The partial clearance of antipyrine to the normetabolite was significantly increased by both inducers, whereas the rate of 4-hydroxylation was significantly increased only by prior antipyrine administration. The results indicate that the hydroxylation of metronidazole is not inhibited by cimetidine, but that it is inducible by phenobarbitone or antipyrine. It is suggested that metronidazole and antipyrine are metabolized by different enzymatic pathways.


Substitution p.A350V in Na⁺/Mg²⁺ exchanger SLC41A1, potentially associated with Parkinson's disease, is a gain-of-function mutation.
Parkinson's disease (PD) is a complex multifactorial ailment predetermined by the interplay of various environmental and genetic factors. Systemic and intracellular magnesium (Mg) deficiency has long been suspected to contribute to the development and progress of PD and other neurodegenerative diseases. However, the molecular background is unknown. Interestingly, gene SLC41A1 located in the novel PD locus PARK16 has recently been identified as being a Na⁺/Mg²⁺ exchanger (NME, Mg²⁺ efflux system), a key component of cellular magnesium homeostasis. Here, we demonstrate that the substitution p.A350V potentially associated with PD is a gain-of-function mutation that enhances a core function of SLC41A1, namely Na⁺-dependent Mg²⁺ efflux by 69±10% under our experimental conditions (10-minute incubation in high-Na⁺ (145 mM) and completely Mg²⁺-free medium). The increased efflux capacity is accompanied by an insensitivity of mutant NME to cAMP stimulation suggesting disturbed hormonal regulation and leads to a reduced proliferation rate in p.A350V compared with wt cells. We hypothesize that enhanced Mg²⁺-efflux conducted by SLC41A1 variant p.A350V might result, in the long-term, in chronic intracellular Mg²⁺-deficiency, a condition that is found in various brain regions of PD patients and that exacerbates processes triggering neuronal damage.


Neurobehavioural and biochemical responses associated with exposure to binary waterborne mixtures of zinc and nickel in rats.
Environmental and occupational exposure to metal mixtures due to various geogenic and anthropogenic activities poses a health threat to exposed organisms. The outcome of systemic interactions of metals is a topical area of research because it may cause either synergistic or antagonistic effect. The present study investigated the impact of co-exposure to environmentally relevant concentrations of waterborne nickel (75 and 150 μg NiCl 2 L-1) and zinc (100 and 200 μg ZnCl2 L-1) mixtures on neurobehavioural performance of rats. Locomotor, motor and exploratory activities were evaluated using video-tracking software during trial in a novel arena and thereafter, biochemical and histological analyses were performed using the cerebrum, cerebellum and liver. Results indicated that zinc significantly (p < 0.05) abated the nickel-induced locomotor and motor deficits as well as improved the exploratory activity of exposed rats as verified by track plots and heat map analyses. Moreover, zinc mitigated nickel-mediated decrease in acetylcholinesterase activity, elevation in biomarkers of liver damage, levels of reactive oxygen and nitrogen species as well as lipid peroxidation in the exposed rats when compared with control. Additionally, nickel mediated decrease in antioxidant enzyme activities as well as the increase in tumour necrosis factor alpha, interleukin-1 beta and caspase-3 activity were markedly abrogated in the cerebrum, cerebellum and liver of rats co-exposed to nickel and zinc. Histological and histomorphometrical analyses evinced that zinc abated nickel-mediated neurohepatic degeneration as well as quantitative reduction in the widest diameter of the Purkinje cells and the densities of viable granule cell layer of dentate gyrus, pyramidal neurones of cornu ammonis 3 and cortical neurons in the exposed rats. Taken together, zinc abrogated nickel-induced neurohepatic damage via suppression of oxido-inflammatory stress and caspase-3 activation in rats.


Reducing dioxin formation by adding hydrogen in simulated fly ash.
In this study, simulated fly ash containing CuO/CuCl2 was heated at 350 °C in a flow of N2 and also in a nitrogen flow containing 10 vol% H2, to evaluate the influence of hydrogen adding on dioxin formation. The total polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) output derived from the CuO sample under N2 and 10 % H2 was 7.382 and 0.708 ng/g, respectively. As for CuCl2, it was 589 and 46.1 ng/g, respectively. The results show that the hydrogen adding has a good inhibition effect on PCDD/F formation; the inhibition rate was higher than 90 % for PCDD/Fs. HCl and NH3 were detected by Gasmet in the flue gas; the probable inhibition mechanism of hydrogen reaction was proposed, based on our measurements and others' researches.


The relationship between NTCP gene varieties and the progress of liver disease after HBV infection: an updated systematic review and meta-analysis.
The aim of this study was to analyze the relationship between sodium taurocholate cotransporting polypeptide (NTCP) gene varieties and hepatitis B virus (HBV) infection and the progress of HBV-related liver disease. PubMed, EMBASE, Web of Science and Cochrane library were used to search eligible studies. STATA software was performed to combine results. Pooled odds ratios (OR) was used to assess the potential genetic relationships. A total of 18 eligible case-control studies with 24960 cases and 28342 controls were included in this meta-analysis. The A allele of rs2296651 polymorphism was found to be significantly linked to a protection of HBV infection in the whole combined analysis (P = 0.000). Meanwhile, this allele was significantly associated with a decreased risk of hepatocellular carcinoma (HCC) (A vs. G: OR = 0.668, 95% CI: 0.571-0.782, P = 0.000), and was significantly associated with HBV nature clearance (A vs. G: OR = 0.744, 95% CI: 0.585-0.946, P = 0.016; AA+GA vs. GG: OR = 0.775, 95% CI: 0.613-0.980, P = 0.033; GA vs. GG: OR = 0.748, 95% CI: 0.588-0.952, P = 0.018). However, rs4646287 genetic varieties had no statistical differences in all models with HBV infection or HBV-related disease progress, liver cirrhosis, acute-on-chronic liver failure and HCC, as well as rs7154439, rs4646285, rs4646296. Rs2296651 polymorphism (A allele) may protect from HBV infection and the progress of HBV-related disease (HBV-related HCC). Future research about other single nucleotide polymorphisms (SNPs) (rs4646287, rs7154439, rs4646285, rs4646296) of NTCP may be needed to clarify the relationship of NTCP gene varieties with HBV infection and HBV-related disease.


Growth assessment in abnormal children.
Growth assessments are made in children to monitor their growth with time. In children with chronic disease, these data aid in determining the effect of disease on growth and planning and evaluating therapy. Stature is the most important aspect of physical growth, but weight, body composition, skeletal maturation, and sexual development are also important. Methods for making these assessments are given. Techniques for data reduction and statistical treatment of data comparing groups of children are discussed.


A rare cause of abdominal pain: Fibromuscular dysplasia.
A 50-year-old man had a sudden severe abdominal pain. An abdominal enhanced computed tomographic scan revealed irregular stenosis of the celiac artery, dissection of the hepatic artery and of the left common iliac artery, and mid stenosis of the right renal artery with extended renal parenchymal hypodensity. After careful evaluation, the patient was diagnosed with fibromuscular dysplasia. Systematic head and neck CT angiography revealed right vertebral arterial stenosis and saccular aneurysm of the left vertebral artery. We have chosen conservative medical treatment for the multifocal fibromuscular dysplasia.


[Cause of the change in the type of structural chromosomal mutations in the cell transition from the G1 to the S phase].
Cessation of exchange interactions among chromosomes and change of the chromosome type of aberrations for chromatid type were found on the model of the Crepis capillaris germinating seeds sychronized with 5-fluor-2-desoxyuridine at the end of G1-beginning of S-phase and then exposed to X-ray irradiation.


Single dose therapy of giardiasis with tinidazole and metronidazole.
In random order, a single dose of either tinidazole or metronidazole, calculated as 50mg/kg body weight, was given to 100 children with symptomatic giardiasis. Follow-up was done for 16 days and consisted of 4 clinical, parasitological and biochemical assessments at intervals of 4 days. The actual mean dose of the drugs received by the patients was 55.5 mg/kg of tinidazole and 52.0mg/kg of metronidazole. Success, i.e. parasitic clearance and symptomatic relief, was achieved in 80% of patients given tinidazole as opposed to 36% of patients given metronidazole (p less than 0.01). Moreover, control of diarrhoea and negative stool conversion for G. lamblia occurred earlier with tinidazole than with metronidazole (p less than 0.01). The incidence of gastrointestinal side-effects was 12% for tinidazole and 4% for metronidazole. Neither drug caused any abnormality of the blood count, blood urea, urine analysis or liver function tests.


The Adrenal Gland: Central Relay in Health and Disease.
Diseases of the adrenal gland are as important for the general practitioner as for the endocrine specialist. The high prevalence of some adrenal endocrinopathies, such as adrenal incidentalomas (1-2% of the population) and primary aldosteronism (6% of hypertensives), which affect millions of patients, makes adrenal diseases a relevant health issue. The high morbidity and mortality of some of the rarer adrenal diseases, i. e., Addison's disease and Cushing's syndrome (Table 1), make early detection and appropriate treatment such a challenge for the health care system.


Torrance type of lethal neonatal short-limbed platyspondylic dwarfism.
A rare case of lethal neonatal short-limbed platyspondylic dwarfism is described. Roentgenographic features of this case, distinctly different from those of the classical thanatophoric dysplasia, are indistinguishable from the other three types of short-limbed platyspondylic dwarfism. Histologic features of the cartilage in this case are not very different from those of the Torrance type, but the presence of focal disruption of column formation in this case suggests a wider spectrum for this entity.


Systems proteomics of healthy and diseased chromatin.
Differences in chromatin-associated proteins allow the same genome to participate in multiple cell types and to respond to an array of stimuli in any given cell. To understand the fundamental properties of chromatin and to reveal its cell- and/or stimulus-specific behaviors, quantitative proteomics is an essential technology. This chapter details the methods for fractionation and quantitative mass spectrometric analysis of chromatin from hearts or isolated adult myocytes, detailing some of the considerations for applications to understanding heart disease. The state-of-the-art methodology for data interpretation and integration through bioinformatics is reviewed.


Willingness of female sex workers in Kampala, Uganda to participate in future HIV vaccine trials: a case control study.
We anticipate large efficacy trials of novel HIV vaccines that have shown acceptable safety profiles. We determined willingness to participate (WTP) in future HIV vaccine efficacy trials among HIV negative female sex workers (FSWs) in Kampala Uganda. We conducted a case control study in the Good Health for Women Project cohort. Cases received HIV prevention services and, enrolled in a 12-month simulated vaccine efficacy trial (SiVET) that used Hepatitis B vaccine; they underwent vaccine trial procedures as would be in an actual trial. Controls received similar health services but did not enroll in SiVET. We matched cases and controls (ratio 2:1) for age and duration in the cohort. We described a hypothetical HIV vaccine trial to cases (after 9 months in SiVET) and controls including trial attributes: randomization, delaying pregnancy, frequent blood draws (80-100mls) and study visits for 3 years. We compared WTP and willingness for vaccine trial attributes by case/control using chi-squared or Fisher's exact tests and fitted conditional logistic regression models to determine independent predictors of WTP. We analyzed data for 311 volunteers (219 cases, 92 controls); median age 27 years (IQR: 23-32), 39.9% had ≥secondary education, 57.9% had sex work as their main job and 81.9% used illicit drugs. Compared to controls, more cases had lived in the community for > 1 year, (85.4% vs 64.1%; p < 0.001) and fewer cases reported illicit drug use in the past 3 months, (79.0% vs 89.1%; p = 0.03). Overall, 278 (89.4%) volunteers expressed WTP in an HIV vaccine trial, the most common reason being hope of protection against HIV. More cases than controls (58.2% vs 44.7%) did not need to consult anyone before trial participation (p = 0.03); cases were more willing to delay pregnancy (99.0% vs 94.0%; p = 0.03). Combining vaccine trial attributes, 249 (89.6%) of the 278 accepted all attributes. After controlling for case/ control status women with secondary education or higher expressed less WTP (aOR 0.17; 95% CI 0.04-0.80). FSWs in Kampala demonstrated high WTP. Prior experience with trial requirements like contraception may improve their uptake during actual trials. Family involvement is important for those without prior trial experience.


Emotional consequences of intensive care unit delirium and delusional memories after intensive care unit admission: a systematic review.
The aim of this study was to review literature exploring the emotional consequences of delirium and delusional memories in intensive care unit patients. A systematic review was performed using PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and PsychINFO. Fourteen articles were eligible for this review. Five of them assessed delirium during intensive care unit admission, and the remainder assessed delusional memories during or after admission. No association was found for delirium and adverse emotional outcome. Data regarding delusional memories and emotional outcome were heterogenic. Some studies presented worse scores on posttraumatic stress disorder screening tools in patients with delusional memories, whereas other studies found better scores in patients with delirium or delusional memories. Based on current literature, no relationship could be shown for delirium and emotional outcome. Regarding delusional memories and adverse emotional outcome, results were in contradiction.


Production of GABA in milk fermented by Bifidobacterium adolescentis strains selected on the bases of their technological and gastrointestinal performance.
There is an increasing interest in producing foods enriched in gamma-aminobutyric acid (GABA), due to their purported health promoting attributes. GABA is the main inhibitor neurotransmitter of the central nervous system, and several microbial species are capable to produce it through decarboxylation of glutamate. Among them, several lactic acid bacteria species have been previously investigated as an appealing alternative to produce GABA enriched foods via microbial fermentation. In this work we report for the first time an investigation into the possibility of utilizing high GABA-producing Bifidobacterium adolescentis strains as a mean to produce fermented probiotic milks naturally enriched in GABA. To this end, in silico and in vitro analyses were conducted in a collection of GABA-producing B. adolescentis strains, with the main goal to scrutinize their metabolic and safety traits, including antibiotic resistance patterns, as well as their technological robustness and performance to survive a simulated gastrointestinal passage. One of the strains, IPLA60004, exhibited better survival to lyophilization and cold storage (for up to 4 weeks at 4 °C), as well as survival to gastrointestinal passage, as compared to the other strains under investigation. Besides, the elaboration of milk drinks fermented with this strain, yielded products with the highest GABA concentration and viable bifidobacterial cell counts, achieving conversion rates of the precursor, monosodium glutamate (GMS), up to 70 %. To our knowledge, this is the first report on the elaboration of GABA enriched milks through fermentation with B. adolescentis.


Early onset horizontal gaze palsy and progressive scoliosis due to a noncanonical splicing-site variant and a missense variant in the ROBO3 gene.
Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified. We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene. We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700 bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional ROBO3 variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44 × 10-4 , by a review of our in-house database. This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy.


Dehydroepiandrosterone (DHEA) metabolism in the brain: identification by liquid chromatography/mass spectrometry of the delta-4-isomer of DHEA and related steroids formed from androstenedione by mouse BV2 microglia.
Studies to elucidate the role of dehydroepiandrosterone (DHEA) metabolism in neuroprotection have compared its relative 7-hydroxylation against estrogen formation by way of 4-androstenedione (AD) in various rodent brain cell lines. In all cases, the 7alpha- and 7beta-hydroxy epimers of DHEA were found to be the dominant products with one notable exception. BV2 mouse microglia were virtually unable to hydroxylate DHEA at C-7 and converted AD to a major unknown metabolite not observed with mouse BHc hippocampal cells. In this paper, we describe the identification of this compound based on its physical properties and analysis by TLC and HPLC. Its identity as 3beta-hydroxy-4-androstene-17-one, the Delta(4)-isomer of DHEA, was confirmed by mass spectrometry (LC/MS), as well as by reverse isotope dilution analysis involving co-crystallization with the synthetic steroid. Possible mechanisms for the formation of this isomer of DHEA by BV2 microglia are proposed, together with that of other C-19 steroids detected which include testosterone (T), 5alpha-dihydrotestosterone and 5alpha-androstanedione.


Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis: a new endemic variant in Spain.
The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain. Patients with the p.Glu109Lys ATTRv variant from 14 families were recruited at 7 centres. Demographics, complementary tests and clinical course were analysed. Haplotype analysis was performed in 7 unrelated individuals. Thirty-eight individuals (13 probands, mean age 40.4 ± 13.1 years) were studied. After median follow-up of 5.1 years (IQR 1.7-9.6), 7 patients died and 7 required heart transplantation (median age at transplantation 50.5 years). Onset of cardiac and neurological manifestations occurred at a mean age of 48.4 and 46.8 years, respectively. Median survival from birth was 61.6 years and no individual survived beyond 65 years. Patients treated with disease-modifying therapies exhibited better prognosis (p < 0.001). Haplotype analysis revealed a common origin from an ancestor who lived ∼500 years ago in southeast Spain. Glu89Lys ATTRv is a TTR variant with a founder effect in Spain. It is associated with near complete penetrance, early onset and mixed cardiac and neurologic phenotype. Patients have poor prognosis, particularly if not treated with disease-modifying therapies.


Misperceptions of nicotine replacement therapy within racially and ethnically diverse smokers.
Underuse of evidence-based treatment for smoking cessation, including use of nicotine replacement therapy (NRT), is widespread, particularly among minority smokers. This paper examines perceptions of NRT among and between racially and ethnically diverse groups of smokers. Nine focus groups were held among homogenous groups of African American, European American, and Hispanic smokers (N = 70). Specific themes included perceptions of: (a) the mechanism by which NRT works; (b) NRT development and regulation (ie, purpose and methods of clinical trials, Food and Drug Administration oversight, etc); (c) efficacy; (d) safety; and (e) overall cost effectiveness. Across all groups, there was a general lack of knowledge of NRT effects and its efficacy, with only moderate knowledge of the mechanism by which NRT works. Concerns about NRT safety were expressed in all groups, with particular apprehension about addictive potential and possible interactions with other medications. Among African American smokers in particular, there was strong suspicion of pharmaceutical industry and government oversight, which coincided with the consensus view that there are too many unknowns about NRT. Among Hispanic smokers, there was less suspicion of NRT but a strong cultural belief in personal responsibility for smoking cessation. Results highlight enduring misperceptions about NRT that likely undermine usage. More education about NRT is needed, not only about its efficacy and safety, but also with regard to its development and regulation. Health care professionals, many of whom are viewed as trustworthy sources of health information, have a particularly important role to promote wider use of proven cessation strategies.


Polylysine decelerates kinetics of negatively charged gramicidin channels as shown by sensitized photoinactivation.
Effect of a cationic polymer, poly(L-lysine), on the kinetic properties of ionic channels formed by neutral gramicidin A (gA) and its negatively charged analogue O-pyromellitylgramicidin (OPg) in a bilayer lipid membrane is studied using a method of sensitized photoinactivation. This newly developed method is based on the analysis of transmembrane current transients induced by a flash in the presence of a photosensitizer. It has been shown previously that the time course of the flash-induced current decrease in most cases follows a single exponential decay with an exponential factor (tau, the characteristic time of photoinactivation) that correlates well with the single-channel lifetime. Addition of polylysine does not affect tau for gA channels, but causes a substantial increase in tau for OPg channels. This effect is reversed by addition of polyacrylic acid. The deceleration of the photoinactivation kinetics is ascribed to electrostatic interaction of polylysine with OPg probably resulting in OPg clustering. The latter can stabilize the channel state by reducing the rotational and lateral mobility of OPg monomers and dimers, and thus increase the single channel lifetime.


Green synthesis of carbon quantum dots toward highly sensitive detection of formaldehyde vapors using QCM sensor.
In the present study, an eco-friendly method for the preparation of carbon quantum dots (CQDs) is demonstrated using hydrothermal treatment of laurel leaves. The optical and structural characteristics of the prepared CQDs are investigated using transmission electron microscopy (TEM), X-ray photoelectron (XPS), fluorescent and UV-visible spectroscopies, Fourier transform infrared (FTIR), and X-ray diffraction (XRD). The quartz crystal microbalance (QCM) sensor designed and modified with CQDs is capable of detecting formaldehyde vapors in the presence of other interfering chemical-vapor analytes. The changes in the frequency of the QCM sensor are linearly correlated with the injected formaldehyde concentrations. The sensing properties of formaldehyde, including sensitivity and reversibility, are investigated. Detection of formaldehyde in the presence of humidity is carefully discussed for home or workplace room environment use. The adsorption kinetics of various VOCs vapors are also calculated and discussed.


Production of a 26,000-dalton interleukin 1 inhibitor by human monocytes is regulated by granulocyte-macrophage colony-stimulating factor.
An interleukin 1 (IL 1) inhibitor is secreted into culture medium by a human promyelocytic cell line, H-161, upon stimulation with (PMA) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Since the morphological characteristics of this cell line were macrophage-like, human monocytes were tested for their ability to produce similar activity using the same induction conditions. Upon induction of adherent peripheral blood monocytes with rhGM-CSF and/or PMA, an IL 1 antagonistic activity was found in the cell supernatants, as determined by IL 1 receptor binding assay, using the murine EL-4.6.1C10 cell line as the cell target. Most of the inhibition of IL 1 binding induced by PMA or by PMA/rhGM-CSF was shown to be caused by IL 1, since it was neutralized by a mixture of anti-IL 1 alpha/beta antibodies and was active in the murine thymocyte proliferation assay (LAF). The activity induced by GM-CSF alone was not neutralized by anti-IL 1 alpha/beta antibodies and showed no LAF activity. The IL 1 inhibitor activity was induced by rhGM-CSF with a D50 around 40 pg/ml. The activity was produced for more than 3 wk in the presence of GM-CSF; removal of GM-CSF was followed by a rapid decrease of IL 1 antagonistic activity. The specific binding of biosynthetically labeled IL 1 inhibitor to target cells (EL-4.6.1C10) showed a protein of 26 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This molecule shares biological and physical characteristics with the urinary IL 1 inhibitor and the promyelocytic H-161-derived IL 1 inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)


Actinic granuloma of the conjunctiva in young women.
To report the occurrence of actinic granuloma of the conjunctiva in young women. Retrospective case series. Three eyes of 3 young women with a unilateral conjunctival mass of recent onset. Three young women (21, 23, and 23 years of age) sought treatment for painless red masses of the conjunctiva that were thought clinically to be pingueculitis, actinic keratosis, or ocular surface squamous neoplasia (OSSN), but were diagnosed histopathologically as actinic granuloma. Special stains were performed to exclude infectious and autoimmune causes of granulomatous inflammation, followed by dermatologic work-up and systemic investigations. Diagnosis of actinic granuloma of the conjunctiva was confirmed. Patients' characteristics (age, sex, early onset), clinical presentation, same geographical location, typical histopathologic features, and lack of systemic association. All 3 cases were in young women with a rapid-onset conjunctival growth with conjunctival feeder vessels and intrinsic vessels; however, there was no surface keratin, and rose bengal stain results were negative. Histopathologic analysis of all 3 cases revealed elastolysis and granulomatous inflammation characterized by multinucleated giant cells, some of which displayed elastophagocytosis that was highlighted by Verhoeff-van Giesen elastic stain. There was absence of cytologic atypia of surface epithelium. Mucin stains and special stains for an infectious cause demonstrated negative results. Serologic investigations and systemic work-up results were negative, which excluded any systemic associations with this condition. This led to the final diagnoses of actinic granuloma of the conjunctiva. Conjunctival actinic granuloma is an underrecognized entity. We present 3 cases of this condition to highlight its occurrence in young women and the role of histopathologic examination to avoid misinterpretation of this condition. Both clinician and pathologist should consider this entity as a differential diagnosis of benign conjunctival lesions and OSSN. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


An approach to a muscle force model with force-pulse amplitude relationship of human quadriceps muscles.
Recent advanced applications of the functional electrical stimulation (FES) mostly used closed-loop control strategies based on mathematical models to improve the performance of the FES systems. In most of them, the pulse amplitude was used as an input control. However, in controlling the muscle force, the most popular force model developed by Ding et al. does not take into account the pulse amplitude effect. The purpose of this study was to include the pulse amplitude in the existing Ding et al. model based on the recruitment curve function. Quadriceps femoris muscles of eight healthy subjects were tested. Forces responses to stimulation trains with different pulse amplitudes (30-100 mA) and frequencies (20-80 Hz) were recorded and analyzed. Then, specific model parameter values were identified by fitting the measured forces for one train (50 Hz, 100 mA). The obtained model parameters were then used to identify the recruitment curve parameter values by fitting the force responses for different pulse amplitudes at the same frequency train. Finally, the extended model was used to predict force responses for a range of stimulation pulse amplitudes and frequencies. The experimental results indicated that our adapted model accurately predicts the force-pulse amplitude relationship with an excellent agreement between measured and predicted forces (R2=0.998, RMSE = 6.6 N). This model could be used to predict the pulse amplitude effect and to design control strategies for controlling the muscle force in order to obtain precise movements during FES sessions using intensity modulation.


Vestibular evoked potentials (VsEPs) in patients with severe to profound bilateral hearing loss.
To confirm the exclusive vestibular dependence of the evoked potentials (P10 and N15) recorded in normal subjects, by recording the potentials evoked in response to bone-conducted sound stimulation in patients with bilateral hearing loss. Fourteen patients with severe to profound bilateral hearing loss were stimulated via a B71 bone-vibrator above the mastoid with bone-conducted tone bursts (500 Hz, 6 ms) at fixed levels above their individual vestibular evoked myogenic potential (VEMP) thresholds. Surface potentials were recorded from scalp electrodes at F7, F3, Fpz, F4, F8, T3, Cz, and T4 and referred to linked earlobes. Seven of 14 patients had suitable VEMPs to the maximal stimulus. P10 and N15 potentials were present in each of these 7 patients, but were absent in patients with absent VEMP responses. The potentials were only detected above VEMP threshold, and were similar in size, shape and latency to those recorded in normal controls at a matched intensity above VEMP threshold. Normal P10 and N15 potentials can be recorded from patients with profound bilateral hearing loss using bone-conducted acoustic stimulation of the vestibular apparatus. The P10 and N15 appear to be dependent purely upon vestibular activation.


1-(1-Arylethylidene)thiosemicarbazide derivatives: a new class of tyrosinase inhibitors.
A series of 1-(1-arylethylidene)thiosemicarbazide compounds and their analogues were synthesized and characterized by 1H NMR, MS. Their tyrosinase inhibitory activities were investigated by an assay based on the catalyzing ability of tyrosinase for the oxidation of L-DOPA, comparing with 4-methoxycinnamic acid and arbutin. The results showed that (1) all the synthesized compounds could perform a significant inhibitory activity for tyrosinase; (2) for these compounds, the main active moiety interacting with the center of tyrosinase would be thiosemicarbazo group; (3) the inhibitory activity was close related with thiosemicarbazide moieties and the groups attached on the aromatic ring.


Comparison of anti-reflux mechanism between Double-J-Stent and standart Double-J-Stent use for risk of BK nephropathy and urinary tract Infection in kidney transplantation.
There are studies that show that double J stenting (DJS) increase BK nephropathy (BKN) 4 fold. DJS may cause vesicoureteral reflux (VUR) with normal bladder contraction. The aim of this study is to comparison risk of BKN, urinary tract infections (UTI) and postoperative urologic complications with the use DJS with anti-reflux device (ARD-DJS) and standart double J stent (St-DJS). Matherial and methods: Ninety patients (male/female: 50/40) that had undergone kidney transplantations in Diyarbakır Training and Research Hospital and Dicle University, Faculty of Medicine Hospital between January 2012 and April 2015 were enrolled in the study. Demographic data, immunosuppression protocols, presence of rejection, graft loss, postoperative urologic complications, UTI, plasma BK levels of the patients were evaluated retrospectively. Median and IQR follow up time for ARD-DJS and St-DJS patients were 14 (12-18) months and 25 (16-30) months respectively. Five cases (5.5%) had BK viremia (P=0.025). All 5 cases with BK viremia were St-DJS users. As a result for postoperative UTI and postoperative urinary complication risk there were no statistically significant difference between ARD-DJS use and St-DJS use during ureteral anastomosis. BKN univariate analysis were significantly less than those st-DJS used. Risc factors were evaluated. But results were not statistically significant in the logistic regression analysis. We think that to demonstrate this benefit, we need randomized controlled studies with more patients and longer follow up.


Cholinergic and adrenergic control of enzyme secretion in isolated rat pancreas.
While cholinergic nervous control of pancreatic enzyme secretion is well documented, data concerning adrenergic regulation of the exocrine pancreas are contradictory. In the present study we attempted to elucidate the direct action of adrenergic stimulation on pancreatic enzyme secretion. Rat pancreatic segments were set up in an organ bath and superfused with modified Krebs-Henseleit solution. Electrical field stimulation (EFS) stimulated amylase release from the segments. This stimulation was subject to inhibition with atropine up to 80%. Atropine-resistant enzyme discharge in response to EFS could be blocked by propranolol. Cholinergic agonist urecholine-induced amylase release was completely blocked by atropine. Noradrenaline (NA) exhibited a biphasic effect on amylase release. It inhibited the urecholine-induced amylase release in lower concentrations (10(-8)-10(-7) M), while it stimulated basal enzyme secretion in higher concentrations (10(-5)-10(-4) M). The inhibitory effect was mimicked by phenylephrine and completely prevented by prazosin. Isoprenaline concentration dependently enhanced, while clonidine and guanfacine did not affect amylase discharge. In conclusion, in rat pancreatic acinar tissue it seems likely that acetylcholine is the main neurotransmitter. Adrenergic action can be dual, inhibitory via alpha 1-adrenoceptors or stimulatory via beta-adrenoceptors on amylase secretion.


Implementation of an integrated ambulatory care pharmacist collaborative care workflow model in specialty clinics in a large academic health system.
Ambulatory care and specialty pharmacy practices are rapidly growing in tandem with the accelerated development of advanced therapies for complex disease states. A coordinated and standardized interprofessional team-based approach is critical to providing high-quality care to specialty patients on complex, expensive, and high-risk therapies. Yale New Haven Health System dedicated resources to the creation of a medication management clinic under a unique care model that integrates ambulatory care pharmacists within specialty clinics who coordinate with centralized specialty pharmacists. The new care model workflow encompasses ambulatory care pharmacists, specialty pharmacists, ambulatory care pharmacy technicians, specialty pharmacy liaisons, clinicians, and clinic support staff. The strategies employed to design, implement, and optimize this workflow to meet the increasing demand for pharmacy support in specialty care is discussed. The workflow incorporated key activities from highly diverse existing specialty pharmacy, ambulatory care pharmacy, and specialty clinic practices. Standard processes were developed for patient identification, referral placement, visit scheduling, encounter documentation, medication fulfillment, and clinical follow-up. Resources were created or optimized to support successful implementation, including an electronic pharmacy referral, specialty collaborative practice agreements to facilitate pharmacist-led comprehensive medication management, and a standardized note template. Communication strategies were developed to facilitate feedback and process updates. Enhancements focused on eliminating documentation redundancies and delegating nonclinical tasks to a dedicated ambulatory care pharmacy technician. The workflow was implemented in 5 ambulatory rheumatology, digestive health, and infectious diseases clinics. Pharmacists utilized this workflow to complete 1,237 patient visits, serving 550 individual patients over 11 months. This initiative created a standard workflow to support an interdisciplinary standard of specialty patient care that is robust to accommodate planned expansion. This workflow implementation approach can serve as a road map for other healthcare systems with integrated specialty and ambulatory pharmacy departments undertaking similar models for specialty patient management.


The effect of epidermal growth factor on brush border surface area and function in the distal remnant following resection in the rabbit.
Epidermal growth factor (EGF) has been shown to increase intestinal absorptive surface area and transport function in normal animals. To examine the effect of EGF on absorptive surface area and brush border membrane function in a model of massive small bowel resection. New Zealand white rabbits were randomised into two groups: a resected group (60% proximal small bowel resection); and an unmanipulated control group. Distal remnant tissue was examined 10 and 21 days postsurgery. In separate experiments oral EGF (40 g/kg/day) was administered to resected animals from days 3 to 8 and animals were studied on day 10. Ten days postsurgery brush border surface area and total absorptive surface area were significantly increased in remnant tissue while brush border membrane vesicle (BBMV) glucose uptake was significantly decreased compared with controls. By 21 days brush border surface area returned to control levels though BBMV glucose uptake remained depressed. EGF treatment induced a further increase in brush border surface area in remnant intestine but did not alter BBMV glucose uptake. Surgical resection results in significant elevations in absorptive surface area coupled with a decrease in brush border membrane transport function distal to the site of anastomosis. EGF enhances glucose uptake in remnant intestine via recruitment of additional microvillus membrane into the brush border.


Relations between PTSD symptom clusters and pain in three trauma-exposed samples with pain.
Little is known about how the individual PTSD symptom clusters relate to intensity and interference of pain and whether these relationships differ across clinical groups. The present study examines relations between PTSD symptom clusters and pain in three trauma-exposed, unique clinical groups: 1) adults seeking treatment for chronic pain with current symptoms of PTSD, 2) trauma affected refugees seeking treatment for PTSD and chronic pain; and 3) individuals identified at admission to the emergency ward after whiplash injury. Network analysis was used to assess unique relations between pain intensity, pain interference, re-experiencing, avoidance, numbing, hyperarousal, depression, and anxiety separately in each sample. Links between PTSD clusters and pain were then compared within and between samples. No within-group differences were identified for the links between pain and any of PTSD clusters in the chronic pain and refugee groups. In the whiplash group, hyperarousal was more strongly related to pain than re-experiencing, avoidance, and numbing. Between group comparisons revealed a more pronounced relationship between hyperarousal and pain in the whiplash group, with no between-group differences between the chronic pain and refugee groups. The findings suggest that when depression and anxiety are accounted for, few unique associations are found between pain and the PTSD symptom clusters in trauma-exposed samples with pain, with the exception of a link between pain and hyperarousal in individuals with whiplash-related PTSD symptoms.


Malignant melanoma of penis.
We report a case of malignant melanoma of the penis. Appropriate staging of these rare cancers is discussed in light of current views of the biology of malignant melanoma arising at other skin sites, and the implications of Breslow thickness for management are considered. There is no good evidence in the literature that extirpation of the entire penis offers the only hope of cure for stage I penile melanoma.


Encapsulation of plasmid DNA in biodegradable poly(D, L-lactic-co-glycolic acid) microspheres as a novel approach for immunogene delivery.
A plasmid DNA encoding bacterial beta-galactosidase gene was encapsulated in poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres. Plasmid DNA extracted from PLGA microspheres retained both structural and functional integrity as evidenced by its restriction endonuclease digestion pattern and its ability to transfect COS-1 cells in vitro. PLGA microspheres protected plasmid DNA from digestion by deoxyribonuclease I (DNase I) in vitro. The encapsulation efficiency of plasmid DNA and its release rate depended on the molecular mass of PLGA. Lastly, J-774A macrophages phagocytosed PLGA microspheres loaded with plasmid DNA. Co-encapsulated monophosphoryl lipid A increased the rate of phagocytosis. These results suggest that biodegradable PLGA microspheres can deliver intact and functional plasmid DNA at controlled rates. Thus, PLGA microspheres may be used to jointly deliver genes and other biologically active molecules, e.g., immunomodulators, to antigen presenting cells.


Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism. Part 2. Metabolism of very low density lipoproteins in rabbits.
The metabolic fate of very low density lipoproteins (VLDL) in normal and hypercholesteremic (h.c.) rabbits has been investigated. VLDL were labelled with 125I in the protein moieties and injected into normal and h.c. animals. The turnover of h.c. VLDL is markedly delayed as compared to that of normal VLDL, and conversion into lipoprotein classes of higher density is considerably decreased. This is observed when h.c. VLDL are injected either into h.c., or into normal rabbits. Arterial uptake of radioactivity is much higher with h.c. VLDL than with the normal lipoproteins, and it is highest when h.c. VLDL are injected into normal recipients. These data, together with those reported in the previous study, support the hypothesis that h.c. VLDL have an inherent atherogenicity. Injection of h.c. VLDL into normal animals also offers an experimental model for testing drugs or diets against atherosclerosis, using untreated animals.


MHC class I immune evasion in MCMV infection.
Murine cytomegalovirus (MCMV) is a well-studied model of natural beta-herpesvirus infection. However, many questions remain regarding its control by and evasion of the immune response it generates. CD8 and CD4 T cells have both unique and redundant roles in control of the virus that differ based on the immunocompetence of the infected mice. MCMV encodes major histocompatibility complex (MHC) class I immune evasion genes that can have an impact in vitro, but their role in infection of immunocompetent mice has been difficult to identify. This review addresses the evidence for their in vivo function and suggests why they may be evolutionarily conserved.


Assessing agro-environmental sustainability of intensive agricultural systems.
Sustainable production in water-scarce regions entails not to overshoot the sustainable blue water availability (BWA), which in turn requires addressing environmental flow requirements (EFRs). We explored the long-term effects of agricultural development, before (1984-1997) and during (1998-2018) the operation of the modern irrigation and drainage network of Tajan (TIDN), northern Iran, on the sustainability of blue water consumptions. A combination of different methods were applied to estimate hydrological EFRs of rivers, ab-bandans (traditional water reservoirs), and groundwater resources. Three major pollutants in the region's water resources, including nitrogen, phosphorus, and salinity, were used to estimate water quality EFR. Monthly agriculture water footprints (WFs) were calculated using the AquaCrop model, and then were compared with the region's BWA, which was calculated by subtracting monthly EFRs from monthly natural runoff. When WF exceeded BWA, the production system includes unsustainable water consumption. The EFR satisfaction of surface water decreased after TIDN operation by about 19%. Unmanaged nitrogen application and post-TIDN overexploitation of groundwater resulted in substantial increase in groundwater EFR violation. The TIDN led to more water consuming cropping pattern resulting in increased agricultural water consumption by about 73%. Overall, agricultural development in TIDN was beyond the capacity of the area, which resulted in up to about 167 MCM y-1 unsustainable blue water consumption. Based on the results, the new framework presented for assessing agro-environmental sustainability could assist managers and policy makers to modify agricultural systems according to environment resilience.


Children's inference generation: The role of vocabulary and working memory.
Inferences are crucial to successful discourse comprehension. We assessed the contributions of vocabulary and working memory to inference making in children aged 5 and 6years (n=44), 7 and 8years (n=43), and 9 and 10years (n=43). Children listened to short narratives and answered questions to assess local and global coherence inferences after each one. Analysis of variance (ANOVA) confirmed developmental improvements on both types of inference. Although standardized measures of both vocabulary and working memory were correlated with inference making, multiple regression analyses determined that vocabulary was the key predictor. For local coherence inferences, only vocabulary predicted unique variance for the 6- and 8-year-olds; in contrast, none of the variables predicted performance for the 10-year-olds. For global coherence inferences, vocabulary was the only unique predictor for each age group. Mediation analysis confirmed that although working memory was associated with the ability to generate local and global coherence inferences in 6- to 10-year-olds, the effect was mediated by vocabulary. We conclude that vocabulary knowledge supports inference making in two ways: through knowledge of word meanings required to generate inferences and through its contribution to memory processes.


Traumatic left ventricular aneurysm: report of a case with normal coronary arteries.
A 26-year-old male had an anterior myocardial infarction following blunt chest trauma. He developed a left ventricular aneurysm despite coronary angiography being normal.


Lactation-related mammary gland pathologies-A neglected emergency in the bitch.
Mastitis is a common reproductive disorder in bitches, reaching a prevalence of 0.71%. Mastitis has a wide range of forms, from asymptomatic to severe gangrenous mastitis that can lead to septic shock and death of the bitch and nurslings. However, most of the time it is overlooked, undiagnosed or mistreated. The present systematic review was performed to revise and summarize the existing knowledge related to this disorder, including diagnosis, treatment and prevention.


Synthesis of a thermally stable hybrid acene-thiophene organic semiconductor via a soluble precursor.
An acene fused-thiophene hybrid p-semiconductor exhibiting high thermal stability has been synthesized via a soluble precursor bearing sterically interacting trimethylsilyl groups. [structure: see text]


A "Diabetes Acute Care Day" for medical students increases their knowledge and confidence of diabetes care: a pilot study.
Evidence suggests that junior doctors lack the confidence and skills to manage acute/inpatient diabetes. We investigated the impact of the introduction of a "Diabetes Acute Care Day" on undergraduate medical students' knowledge and confidence in acute/inpatient diabetes. Participants attended four short lectures on the basics of diabetes, diabetic emergencies, inpatient diabetes management and peri-operative/procedure care followed by case-based learning tutorials on diabetic ketoacidosis (DKA), hyperosmolar hyperglycaemic state (HHS) and hypoglycaemia using capillary blood glucose charts to interpret and practice subsequent insulin prescription and adjustment. Participants were asked to complete multiple-choice questions and confidence questionnaires using a visual analogue score pre and post participation. One hundred forty-four students completed the pre-course survey and 196 completed the post-course survey. Mean confidence using a visual analogue score increased in all areas with a mean at baseline of 46.9 mm rising to 71.2 mm post-participation (p < 0.001). The largest increases were in the management of HHS, patients on subcutaneous and intravenous insulin and perioperative/procedure care. The mean mark obtained in the pre-test multiple choice questions (MCQs) was 2.72 (27.2 %) and increased to 4.74 (47.4 %) on the post-score MCQs (p < 0.001). 56.9 % of participants answered all 10 pre-test MCQs with the mean number of questions answered = 4.71 rising to 82.0 % of students answered all ten questions and the mean number of questions answered = 9.56 in the post-test MCQs. An intensive "Diabetes Acute Care Day" consisting of themed live lectures and case-based learning tutorials is an effective way to increase medical students' knowledge and confidence in acute/inpatient diabetes. Further development and evaluation of this educational intervention is required to assess the impact of on patient care in the clinical setting post graduation.


Evaluation of dog bones in the indirect assessment of environmental contamination with trace elements.
The aim of this paper was to determine the level of five elements, two essential for life [zinc (Zn) and copper (Cu)] and three distinctly toxic [lead (Pb), cadmium (Cd), and mercury (Hg)], in four types of biological material in bones of the dog Canis lupus familiaris. The experiment was carried out on bones from the hip joints of dogs. The samples of cartilage, compact bone, spongy bone, and cartilage with adjacent compact bone came from 26 domestic dogs from northwestern Poland. Concentrations of Cu, Zn, Pb, and Cd were determined by ICP-AES (atomic absorption spectrophotometry) in inductively coupled argon plasma, using a Perkin-Elmer Optima 2000 DV. Determination of Hg concentration was performed by atomic absorption spectroscopy. In the examined bone material from the dog, the greatest concentrations (median) were observed for Zn and the lowest for Hg (98 mg Zn/kg and 0.0015 mg Hg/kg dw, respectively). In cartilage and spongy bone, metal concentrations could be arranged in the following descending order: Zn > Pb > Cu > Cd > Hg. In compact bone, the order was slightly different: Zn > Pb > Cd > Cu > Hg (from median 70 mg/kg dw to 0.002 mg/kg dw). The comparisons of metal concentrations between the examined bone materials showed distinct differences only in relation to Hg: between concentrations in spongy bone, compact bone, and in cartilage, being greater in cartilage than in compact bone, and lower again in spongy bone.


Pigeon pea waste as a novel, inexpensive, substrate for production of a thermostable alkaline protease from thermoalkalophilic Bacillus sp. JB-99.
Thermoalkaliphilic Bacillus sp. JB-99 was grown in a 250 ml Erlenmeyer flask containing 50 ml medium containing (g/l) Pigeon pea waste 10; NaNO3, 5.0; K2HPO4, 5.0; MgSO4 x 2H2O, 0.2 and Na2CO3, 10.0. Incubations were carried out at 50 degrees C on a rotary incubator shaker for 15 h. A high level of extra cellular thermostable protease activity was observed after 24 h incubation. The optimum temperature and pH for activity were 70 degrees C and 11, respectively, so this enzyme showed stable activity at high temperature and under alkaline conditions.


Is recurrent respiratory papillomatosis a manageable or curable disease?
Recurrent respiratory papillomatosis (RRP) is a relatively rare disease with potentially devastating consequences for the patient. The purpose of this study was to evaluate the patterns of recurrence of RRP after surgery and determine the effectiveness of combined concurrent adjuvant therapy. A total of 86 patients were diagnosed with and operated on for RRP. The clinical characteristics of 29 of the 86 patients who had undergone operations at other hospitals and who were followed up for >2 years were evaluated retrospectively. A combined concurrent adjuvant therapy was performed with microlaryngeal surgery, 585-nm pulsed dye laser (PDL) application, and an intralesional cidofovir injection. To evaluate the recurrence pattern, the larynx was divided into 10 subsites, and patients were investigated for the frequency of recurrence at the subsites after the operation. Twenty-nine subjects required a mean of 3.0 operations to achieve complete remission for 2 years. The most common subsites for recurrence were the anterior commissure, subglottis, and epiglottis according to increasing number of operations. The subsites of recurrence tended to be closely correlated with the laryngeal submucosal glandular density distribution. A complete en-bloc layer excision, including the submucosal glands, using cold instruments decreased the recurrence rate of RRP. Applying PDL minimized scarring and provided significant posttreatment voice-quality improvement. The results of the recurrent pattern analysis suggest that a combined concurrent adjunctive treatment might be promising as a cure for RRP and restoration of vocal function after treatment. 4. Laryngoscope, 126:1359-1364, 2016.


Current practices and improved recommendations for treating hereditary fructose intolerance.
A study of treatment practices of pediatric centers managing hereditary fructose intolerance and a review of recent literature on this subject were undertaken in an attempt to establish the degree of dietary liberalization allowable with age and the acceptability of foods containing trace amounts of fructose. The information was needed to plan optimal therapy and thus avoid the consequences of the disorder, namely intestinal dysfunction, metabolic imbalance, and hepatic and renal damage. Fifty responses to 113 letters to centers in Canada and the United States, as well as data from The Hospital for Sick Children, Toronto, Ontario, identified only 29 affected children and provided information on their care, including food lists and literature references. Major principles of treatment were similar, but the approach to allowing and quantifying dietary fructose differed. In response to the apparent need for standardization of treatment, the authors formulated improved recommendations for the control of dietary fructose (less than 1.5 gm/day). Only a few foods of vegetable origin are allowed, including a limited selection of vegetables and cereal products from grain endosperm. Repeated dietary counseling is advocated with regard to allowed foods, sweeteners, and medications to ensure long-term dietary compliance.


Perspective on liver regeneration by bone marrow-derived stem cells-a scientific realization or a paradox.
Bone marrow (BM)-derived stem cells are reported to have cellular plasticity, which provoked many investigators to use of these cells in the regeneration of nonhematopoietic tissues. However, adult stem cell plasticity contradicts our classic understanding on progressive restriction of the developmental potential of a cell type. Many alternate mechanisms have been proposed to explain this phenomenon; the working hypotheses for elucidating the cellular plasticity of BM-derived stem cells are on the basis of direct differentiation and/or fusion between donor and recipient cells. This review dissects the different outcomes of the investigations on liver regeneration, which were performed with the use of BM-derived stem cells in experimental animals, and reveals some critical factors to explain cellular plasticity. It has been hypothesized that the competent BM-derived stem/progenitor cells, under the influence of liver-regenerating cues, can directly differentiate into hepatic cells. This differentiation takes place as a result of genetic reprogramming, which may be possible in the chemically induced acute liver injury model or at the stage of fetal liver development. Cellular plasticity emerges as an important phenomenon in cell-based therapies for the treatment of many liver diseases in which tissue regeneration is necessary.


Changes in psychiatric symptoms related to EEG and cerebral blood flow following electroconvulsive therapy in depression.
Changes in psychiatric symptoms following electroconvulsive therapy (ECT) were related to alterations in global EEG and cerebral blood flow (CBF) in 21 in-patients suffering from depression. They were examined by clinical ratings, EEG, and CBF immediately before and 1 to 3 h after treatments during an ECT series and at follow-up. Four symptom clusters from a factor analysis of symptoms in depression, representing different dimensions of emotion, cognition, and psychomotor retardation, were used for clinical description. The changes in the separate symptom clusters showed different patterns and also different correlations with neurophysiological (EEG and CBF) changes during the course of serial ECT. Furthermore, acute clinical and neurophysiological effects following single ECT's were found to be different from non-acute changes, building up during the treatment course. Acute relief in symptoms of anxiety, depressed mood, and psychomotor retardation correlated with an acute slowing of the EEG. Regarding non-acute effects a reversed relationship was found, i.e. improvement in symptoms of depressed mood and psychomotor retardation was related to less EEG slowing. As opposed to the acute clinical changes, the non-acute changes, found following the first two or three treatments of a series, contained predictive information about the individual clinical outcome of the patients.


The relation of delusional content in psychotic depression to life-threatening behavior.
A retrospective analysis of all medically serious suicide attempts made by 45 patients hospitalized consecutively at the Payne Whitney Clinic with the DSM-III discharge diagnosis of Unipolar Major Depression, Recurrent, With Psychotic Features was undertaken. Patients with delusions of bodily disease, damage, and malfunction were significantly less likely to make medically serious suicide attempts than patients with delusions of sinfulness, guilt, deserved punishment, or persecution.


Hopping Pits Catch Fusing Granules.
In excitable cells, regulated exocytosis is coupled to endocytic membrane retrieval. Yuan et al. (2015) in this issue of Developmental Cell report a possible mechanism for such exo-endocytic coupling that is based on stimulation-induced hopping of clathrin-containing endocytic structures to nascent sites of insulin granule fusion.


A ring detector positron camera system: its merits: clinical experience.
A ring detector positron camera system for CT of the brain is described. The system uses 95 NaI (Tl) detectors, arranged with cylindrical geometry, for the simultaneous detection of coincidences from 1,900 detector combinations. With a new sampling technique an experimental system resolution of 7 mm FWHM has been obtained. The sensitivity was found to be 5,300 c/s with a 100-keV energy threshold and using a 19.2-cm-diameter cylindrical phantom with a homogeneous specific activity of 1 muCi/cm3. A clinical study of blood-brain barrier damage using 68Ga-EDTA is reported.


Vesicoureteric reflux in Kuwaiti children with first febrile urinary tract infection.
The prevalence of vesicoureteric reflux (VUR) in children with urinary tract infection (UTI) varies among different racial groups. The purpose of this study was to determine the frequency of VUR and associated renal changes in a group of Arab Kuwaiti children with their first documented febrile UTI and to compare our findings with those reported from other racial groups. One hundred and seventy-four children (38 males and 136 females) fulfilled the study criteria and were divided into three age groups (<1 year, 1-5 years, and >5 years). Patients in each group had both micturating cystourethrography (MCUG) and 99m-Tc-dimercaptosuccinic acid (DMSA) renal scan after diagnosis. VUR was detected in 39 children (22%). Two-thirds of cases had mild reflux (grade I and II). Females ( n=32) had more reflux than males ( n=7) (24% vs. 18%). Sixty-three patients (36%) had abnormal (DMSA) renal scans (acute pyelonephritis [AP] or renal scars). Of these, 79% were children below 5 years. Abnormal DMSA scans were found in 4 of 38 males (11%) versus 59 of 136 females (43%). Abnormal scans in children with VUR were seen in 1 of 7 males (14%) versus 19 of 32 females (59%). In total, the combination of abnormal scan with VUR occurred in 1 of 38 males (3%) and in 19 of 136 females (14%), whereas abnormal scan without demonstrable VUR was seen in 3 of 38 males (8%) versus 40 of 136 females (29%). Our data showed that the frequency of VUR in Arab Kuwaiti children with febrile UTI is midway between Caucasian and other racial groups. In this study, males had a lower-risk profile than females, the latter having a higher rate of reflux as well as a higher rate of abnormal DMSA scans, irrespective of demonstrable VUR.


Short term benefits of post-operative oral dietary supplements in surgical patients.
The present study was undertaken to investigate the short term clinical efficacy of oral dietary supplements administered post-operatively to patients undergoing predetermined moderate to severe gastrointestinal surgery. Trial end points for comparison included effects of oral dietary supplements on nutritional intake, nutritional status and incidence of serious complications. 54 patients who were scheduled to undergo predetermined moderate to major gastrointestinal surgical procedures entered the study. They were randomly assigned to receive a normal ward diet post-operatively or the same diet supplemented ad libitum by an oral nutritional sip feed. The study period was defined as commencing from the day patients were adjudged to be capable of ingesting 'free fluids' to the day of hospital discharge. 40 patients (20 in each group) completed the study. The mean daily energy intake (KCal/day) assessed from 7 day food diaries was significantly higher in the treatment group (1833 +/- SEM 99) than in the control group (1108 +/- 56, p < 0.0001). This increase occurred not only as a consequence of energy intake from the oral dietary supplements (470 +/- 30) but also because more energy was consumed from the ward diet by the treatment than the control patients (1353 +/- 92 vs 1108 +/- 56, p < 0.02). The mean daily protein intake g/day in the treatment group (66.0 +/- 3.4) was also greater than in the control group (52.9 +/- 29 p < 0.0001). This difference was due solely to the intake in protein from the oral dietary supplements (15.7 +/- 1.0), protein intake from the ward diet being similar in the treatment (50.1 +/- 3.2) and control (52.9 +/- 29) groups. Patients in the treatment group maintained their pre-operative weight where as control patients had lostsignificant amount of their pre-operative weight by study day 3 (4.5 +/- 12 kg and by discharge (4.7 +/- 1.2 kg, p < 0.02). Pre-operative muscle function as evidenced by grip strength dynamometry decreased to a greater extent in the control than treatment group patients by study day 3 (14.6 +/- 2.2 KPa vs 2.8 +/- 2.4 < 0.03) and by discharge (10.4 +/- 3.1 KPa vs 0.10 +/- 1.9 p < 0.03). The incidence of serious infections (pneumonia, wound infection) was significantly higher in the control group (10) than in the treatment group (3, p < 0.02). It is concluded that the prescription of oral dietary supplements on an ad libitum basis to post-operative patients undergoing moderate to major gastrointestinal surgery results in clinically significant short term benefits.


Can ChatGPT pass the thoracic surgery exam?
The capacity of ChatGPT in academic environments and medical exams is being discovered more and more every day. In this study, we tested the success of ChatGPT on Turkish-language thoracic surgery exam questions. ChatGPT was provided with a total of 105 questions divided into seven distinct groups, each of which contained 15 questions. Along with the success of the students, the success of ChatGPT-3.5 and ChatGPT-4 architectures in answering the questions correctly was analyzed. The overall mean score of students was 12.50 ± 1.20, corresponding to 83.33%. Moreover, ChatGPT-3.5 managed to surpass students' score of 12.5 with an average of 13.57 ± 0.49 questions correctly on average, while ChatGPT-4 answered 14 ± 0.76 questions correctly (83.3%, 90.48%, and 93.33%, respectively). When the results of this study and other similar studies in the literature are evaluated together, ChatGPT, which was developed for general purpose, can also produce successful results in a specific field of medicine. AI-powered applications are becoming more and more useful and valuable in providing academic knowledge.


Machine learning for metabolic engineering: A review.
Machine learning provides researchers a unique opportunity to make metabolic engineering more predictable. In this review, we offer an introduction to this discipline in terms that are relatable to metabolic engineers, as well as providing in-depth illustrative examples leveraging omics data and improving production. We also include practical advice for the practitioner in terms of data management, algorithm libraries, computational resources, and important non-technical issues. A variety of applications ranging from pathway construction and optimization, to genetic editing optimization, cell factory testing, and production scale-up are discussed. Moreover, the promising relationship between machine learning and mechanistic models is thoroughly reviewed. Finally, the future perspectives and most promising directions for this combination of disciplines are examined.


Mechanics and dynamics of reconstituted cytoskeletal systems.
The intracellular cytoskeleton is an active dynamic network of filaments and associated binding proteins that control key cellular properties, such as cell shape and mechanics. Due to the inherent complexity of the cell, reconstituted model systems have been successfully employed to gain an understanding of the fundamental physics governing cytoskeletal processes. Here, we review recent advances and key aspects of these reconstituted systems. We focus on the importance of assembly kinetics and dynamic arrest in determining network mechanics, and highlight novel emergent behavior occurring through interactions between cytoskeletal components in more complex networks incorporating multiple biopolymers and molecular motors.


The impact of portal vein tumor thrombus on long-term survival after liver resection for primary hepatic malignancy.
The aim of this study was to evaluate the effect of portal vein tumor thrombus (PVTT) on the prognosis of patients undergoing liver resection (LR) for primary liver malignancies (PLC). The recurrence-free survival (RFS) and overall survival (OS) for patients undergoing LR with and without PVTT for three primary liver malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepato-cholangio carcinoma (CHC) were compared using the Kaplan-Meier method and Cox regression analysis. In total, 3775 patients with PLC who underwent LR were included in this study. The incidence of PVTT in patients undergoing LR with HCC, IHC and CHC were 46%, 20%, and 17%, respectively. The median RFS and OS were significantly better for patients with HCC as compared to ICC or CHC (16 vs 11 vs 13 months; 21 vs 16 vs 18 months, respectively; P < 0.001). However, the presence of PVTT resulted in similarly poor RFS and OS in these 3 subgroups of patients (9 vs 8 vs 8 months, P = 0.062; 14 vs 13 vs 12 months, respectively, P = 0.052). Although the prognosis of patients with PLC varied by histological subtype, once PVTT occurred, survival outcomes after LR were similarly poor across all three subgroups.


Simultaneous detection and differentiation of Rice black streaked dwarf virus (RBSDV) and Southern rice black streaked dwarf virus (SRBSDV) by duplex real time RT-PCR.
The diseases caused by Rice black streaked dwarf virus (RBSDV) and Southern rice black streaked dwarf virus (SRBSDV) have been occurring epidemically in China and southeastern Asia in recent years. A sensitive, reliable and quantitative method is required to detect and distinguish for RBSDV and SRBSDV in rice and vector insects. We developed a sensitive and lineage-specific duplex real time RT-qPCR for detection of RBSDV and SRBSDV in a single or/and double infection in rice samples. The duplex RT-qPCR was optimized using standard samples transcribed by T7 Large Scale RNA Production System in vitro. We developed a reliable system for duplex RT-qPCR, in which its co-efficiency of RBSDV and SRBSDV, were 91.6% and 90.7%, respectively. The coefficient of determination was more than 0.990; the slope of linear equation was -3.542, and -3.567, respectively. Out of 30 samples collected in North and Central China, which were suspected to be infected with these two viruses, 10 samples were detected RBSDV positive by RT-PCR and 12 samples by RT-qPCR. No mixed infections were found. Simultaneously, out of total 60 samples collected from Southern China, which were also suspected to be infected with these two viruses, 41 samples were determined SRBSDV positive by RT-PCR and 47 samples by RT-qPCR. Also in this case no mixed infections were found. The rice genes eEF-1a and UBQ5 were selected as internal controls for quantification assay also performed as good expression stability. The duplex RT-qPCR assay provided as a sufficiently sensitive, specific, accurate, reproducible and rapid tool for the detection and differentiation of RBSDV and SRBSDV. The RT-qPCR assay can be used in routine diagnostic of these two viruses in order to study the disease epidemiology in rice crops.


NHPI and palladium cocatalyzed aerobic oxidative acylation of arenes through a radical process.
The NHPI and palladium cocatalyzed radical oxidative acylation of arenes with aldehydes and alcohols as acyl equivalents via selective C-H functionalization has been described. Molecular oxygen, the most environmentally friendly oxidant, was used as the terminal oxidant in this catalytic cycle.


A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations.
Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome (OMIM 160980). About 70% of cases are familiar; most have mutations of the PRKAR1A gene on chromosome 17q22-24. There is little phenotype-genotype correlation known to date. To study the genotype-phenotype correlation in a family with newly diagnosed CNC and three generations of subjects bearing the same PRKAR1A mutation. The proband was diagnosed with hepatocellular carcinoma, a tumour that appears to be associated with CNC. The study consisted of clinical and genetic analysis of a total of 10 individuals belonging to a large Italian family. The index case was referred for PRKAR1A gene mutation analysis because he met the diagnostic criteria for a clinical diagnosis of CNC. The PRKAR1A-inactivating mutation c.502 +1G > A in the intron 5 splice-donor site was detected after bidirectional sequencing of germline DNA. The mutation causes a frameshift in the transcribed sequence and a nonsense mRNA that was shown to be degraded; this leads to PRKAR1A haploinsufficiency in all tissues. All available relatives were screened first by DNA testing and, if the latter was positive, by clinical, biochemical and imaging means. A novel PRKAR1A mutation with an apparently low penetrance and variable expression is reported; the same mutation is also associated with a hepatocellular carcinoma. This is the first time a PRKAR1A mutation is reported in individuals who were diagnosed with CNC after retrospective family screening and following the identification of a proband; the finding has implications for genetic counselling on PRKAR1A and/or CNC.


Mast cells and c-Kit expression in liver allograft rejection.
The pathogenesis of rejection following liver transplantation is not fully understood. It has been postulated that mast cells may play a role in acute and chronic rejection of a number of other solid organ grafts. The aim of this study was to assess the possible role of mast cells and c-Kit+ cells in acute and chronic liver allograft rejection. Biopsy specimens from (i) 'time zero' grafts with a minimal degree of perfusion injury (controls), (ii) transplanted livers with different grades of acute rejection, and (iii) transplanted livers with end-stage chronic rejection, were stained immunohistochemically using monoclonal anti-mast cell tryptase and polyclonal anti-c-Kit antibodies. Tryptase- and c-Kit-positive cell densities were assessed by image analysis. Tryptase-positive mast cell densities (P<0.001) were strongly correlated with acute liver allograft rejection grades and chronic liver allograft rejection. Furthermore, a similarly strong relationship was found between c-Kit+ cell densities and increasing rejection grade (P<0.001). Tryptase- and c-Kit-positive mast cells form part of the inflammatory infiltrate in both acute and chronic liver allograft rejection, and may be important effector cells in these processes.


Comparative morphology of the pyloric armature of adult mosquitoes (Diptera: Culicidae).
The structure of the pyloric armature, hypothesized to aid in blood-meal digestion or parasite resistance, was compared quantitatively among the following 8 species in 5 genera of adult mosquitoes from the southeastern United States: Aedes albopictus, Aedes japonicus, Aedes triseriatus, Anopheles punctipennis, Culex pipiens s.l., Culex restuans, Orthopodomyia signifera, and Toxorhynchites rutilus. Females differed significantly among species in the structure of spines composing the armature, with Aedes spp. forming one general group, Culex spp. another, and An. punctipennis and Or. signifera a third. Relationships of species based on structural characters of the armature were consistent with recent culicid phylogenies. Although pyloric armature has been noted in mosquitoes and other insects, this is the first quantitative investigation of the mosquito pyloric armature.


Stress distribution and dimensional changes in chromatographic columns.
High pressures, in the kilobar range, are now used in liquid chromatography. Basic equations from mechanics are applied to investigate the stress state in several idealized chromatography tubes, and these stresses are evaluated with respect to the maximum allowable stresses predicted by several methods used in pressure vessel design. An analytical solution is developed for the dimensional changes of idealized tubes subjected to internal pressure, and the analytical solutions used to verify the results from a numerical approximation. Numerical approximations are then used to explore the effects of the end restraint provided by the end frits. Conclusions are derived regarding the requirements for a safe operation of these high pressure chromatography tubes.


Gallbladder and the risk of polyps and carcinoma in metachromatic leukodystrophy.
To assess frequency of gallbladder polyposis and carcinoma in metachromatic leukodystrophy (MLD). We evaluated 34 patients with MLD (average age 16.7 years, age range 2-39 years) screened for gallbladder abnormalities by ultrasound. In the case of cholecystectomy, findings at pathology were reviewed. Only 8 of 34 patients (23%) had a normal gallbladder at ultrasound. Gallbladder polyps were visible in 8 patients (23%). Cholecystectomy was performed in 11 patients (32%). In these, pathology revealed various abnormalities, including hyperplastic polyps, intestinal metaplasia, prominent Rokitansky-Aschoff sinuses, and sulfatide storage. Our results demonstrate that gallbladder involvement is the rule rather than the exception in MLD. The high prevalence of hyperplastic polyps, a known precancerous condition, and one death from gallbladder carcinoma at a young age suggest that MLD predisposes to neoplastic gallbladder abnormalities. As novel therapies for this patient group are emerging leading to increased life expectancy, we recommend screening for gallbladder abnormalities by ultrasound in order to prevent early death.


Functional analysis of keratin components in the mouse hair follicle inner root sheath.
Recently, a family of novel type I keratins of the inner root sheath of the hair follicle were discovered, increasing the number of keratins known to be expressed in the hair follicle. The mouse database shows three keratins that are possible orthologues of these inner root sheath keratins. The sequences of these keratins include rather unusual changes to a highly conserved motif at the end of the alpha-helical rod domain of the proteins, thought to be important in filament assembly. To investigate whether these keratins are expressed in the inner root sheath and to determine whether they assemble normally. To investigate this, polyclonal antibodies were raised for immunolocalization of the keratins and their cDNAs were cloned for transfection into cultured cells. At least two of these keratins were expressed in the inner root sheath but the timing of expression of the different keratins was variable. Transfection of the relevant cDNAs into cells in culture indicated that these keratins were capable of integrating into existing keratin networks without disruption, but that de novo filament assembly with the type II inner root sheath keratin, mK6irs, was poor. These results provide further evidence of the complexity of keratin expression in the three concentric layers of the inner root sheath.


What Zebrafish and Nanotechnology Can Offer for Cancer Treatments in the Age of Personalized Medicine.
Cancer causes millions of deaths each year and thus urgently requires the development of new therapeutic strategies. Nanotechnology-based anticancer therapies are a promising approach, with several formulations already approved and in clinical use. The evaluation of these therapies requires efficient in vivo models to study their behavior and interaction with cancer cells, and to optimize their properties to ensure maximum efficacy and safety. In this way, zebrafish is an important candidate due to its high homology with the human genoma, its large offspring, and the ease in developing specific cancer models. The role of zebrafish as a model for anticancer therapy studies has been highly evidenced, allowing researchers not only to perform drug screenings but also to evaluate novel therapies such as immunotherapies and nanotherapies. Beyond that, zebrafish can be used as an "avatar" model for performing patient-derived xenografts for personalized medicine. These characteristics place zebrafish in an attractive position as a role model for evaluating novel therapies for cancer treatment, such as nanomedicine.


DCFH2 interactions with hydroxyl radicals and other oxidants--influence of organic solvents.
The oxidation of 2',7'-dichlorofluorescin (DCFH(2)) is widely used as a measure to detect the generation of reactive oxygen species (ROS) and to analyze oxidative stress. Other factors beside commonly known radicals may influence the results of such measurements. Therefore, the effects of H(2)O(2), KMnO(4,) decomposition products of AAPH, ethanol and DMSO, antioxidants like ascorbic acid, different ferrous ion chelates, and heme-containing proteins like cytochrome c, myoglobin, hemoglobin, and horseradish-peroxidase were comparatively analyzed with respect to their impact on DCFH(2) oxidation. The study evaluates the effects of various oxidants with different oxidative potentials regarding their ability to induce DCF-fluorescence. Furthermore, we analyzed the inhibitory effect of organic solvents like ethanol or DMSO on the oxidation of DCFH(2) by hydroxyl radicals. The results of our study indicate that the potential of an oxidant does not always correlate with its efficiency to generate DCF-fluorescence.


Complete Genome Sequence of Genotype Ib Newcastle Disease Virus Isolated from a Mallard (Anas platyrhynchos) in Russia.
We report here the complete genome sequence of a Newcastle disease virus isolate, NDV/Yakutiya/mallard/852/2011, isolated from a mallard in Russia. On the basis of phylogenetic analysis, this strain was clustered into class II genotype Ib.


Shunt products of aminoansamycins from aas1 overexpressed mutant strain of Streptomyces sp. S35.
Constitutively expression of the pathway-specific activators is an effective method to activate silent gene clusters and improve natural product production. In this study, nine shunt products of aminoansamycins (1-9) were identified from a recombinant mutant strain S35-LAL by overexpressed the large-ATP-binding regulator of the LuxR family (LAL) gene aas1 in Streptomyces sp. S35. All the compounds showed no anti-microbial, anti-T3SS and cytotoxic activities.