B-type natriuretic peptide can predict the medium-term risk in patients with acute heart failure and preserved systolic function.
Half of patients with heart failure (HF) have preserved left ventricular ejection fraction (LVEF). Neurohormonal activation characterizes the disease and measurement of plasma B-type natriuretic peptide (BNP) indicates the severity of left ventricular dysfunction. The purpose of this study was to test the hypothesis that measurement of BNP levels in ambulatory patients with HF and preserved LVEF can predict the occurrence of cardiovascular events in the next 6 months. We enrolled 233 consecutive patients admitted to the Outpatient Heart Failure Clinic (OHFC), on stabilization after an episode of acute HF, with a LVEF > 50%. Standard echocardiography was performed and left ventricular systolic/diastolic function was assessed. Plasma BNP levels were measured on admission to OHFC. Patients were followed for 6 months; the main endpoint combined cardiovascular death or readmission for HF. Among the 233 patients discharged, 48 endpoints occurred (death: n = 15; readmission: n = 33). Receiver operated curve analysis shows that BNP levels are strong predictors of subsequent events (area under the curve = 0.84; CI = 0.78-0.88). Multivariate Cox regression showed that the cutoff values identified by receiver operated curve analysis (200-500 pg/mL) of the neurohormone are the most accurate predictors of events: HR = 2.2 (P < .04) and HR = 5.8 (P < .001), respectively, for 201-499 pg/mL and > or = 500 pg/mL ranges. BNP level is a strong predictor for cardiovascular mortality and early readmission in patients with diastolic HF. The results suggest that BNP levels might be used successfully to guide the intensity of follow-up after a decompensation, because increased BNP levels were associated with a progressively bad prognosis.


Numerical analysis of the method of internal dialysis of giant axons.
This paper presents a numerical analysis of the method of internal dialysis used for studies of membrane transport in giant axons. Account is taken of the complete geometry, end effects, and finite dialyzate flow rates. Both influx and efflux experimental conditions are considered. Results place quantitative limits on system performance that are sufficiently general for use in experimental design. The completeness of solute equilibration and the uniformity of solute concentration at the axon membrane are assessed, as well as the sensitivity to dialysis solution flow rate. The effects of undialyzed axon ends on the equilibration rate and on the uniformity of concentration are determined, and the contribution of undialyzed ends to influx measurements is evaluated. Equilibration times are correlated with physical properties of axoplasm and dialysis tubing, and with dialysis solution flow rate. Numerical results confirm the general qualitative assessments of the method that are based on years of successful application.


Origin and immunophenotype of aberrant IEL in RCDII patients.
Aberrant intra-epithelial lymphocytes (IELs) are the hallmark of refractory coeliac disease type II RCDII and considered a premalignant cell population from which aggressive enteropathy-associated T cell lymphoma (EATL) can evolve. The aim of this study was to gain further insight in the origin and characteristics of aberrant IELs by analysing T-cell receptor (TCR) rearrangements, and by immunophenotypic analysis of aberrant IELs. Duodenal biopsies from 18 RCDII patients and three RCDII cell lines were analysed for the presence of TCR delta, gamma, and beta rearrangements. In addition, IELs isolated from biopsies derived from RCDII patients were phenotypically analysed. Aberrant IELs showed an upregulated expression of granzyme B and decreased expression of PCNA. TCR rearrangements in the aberrant IEL population in biopsies of RCDII patients were heterogenic, which is most likely due to a variation in maturity. Similarly, RCDII cell lines displayed a heterogenic TCR rearrangement pattern. Aberrant IELs originate from deranged immature T lymphocytes and display clear differentiation to a cytotoxic phenotype. Aberrant IELs displayed different stages of maturity between RCDII patients, of which only the patients harbouring the most mature aberrant IEL population developed an EATL.


Prevention by a carbacyclin analogue (ZK 36 374) of digoxin-induced ventricular extrasystoles in guinea-pig myocardium.
Intravenous infusion of ZK 36 374 to the anesthetized guinea-pig or addition of the compound to the perfusion medium of the isolated perfused guinea-pig heart prevented digoxin-induced ventricular premature beats without altering the prolongation of the P-R interval by the glycoside. The prevention by ZK 36 374 of the ventricular extrasystoles induced by digoxin was obtained at lower concentrations while higher doses of the compound produced a dysrhythmic effect which terminated within a few min after the cessation of drug application.


Impact of closure of a sexually transmitted disease clinic on public health surveillance of sexually transmitted diseases--Washington, D.C., 1995.
In April 1995, a public sexually transmitted disease (STD) clinic in the northwest (NW) ward of the District of Columbia closed, leaving one public STD clinic in the southeast (SE) ward to provide public STD services for the entire city. This report summarizes an investigation by CDC following a request from the District of Columbia Department of Health's STD program to evaluate the impact of the NW STD clinic closure on STD case reports. The findings of this investigation indicate that the clinic closure resulted in a marked decrease in reported syphilis in the NW ward, and suggest that NW ward residents with syphilis and their partners may not have received proper diagnostic testing, therapy, and counseling.


Long-term global trends in crop yield and production reveal no current pollination shortage but increasing pollinator dependency.
There is evidence that pollinators are declining as a result of local and global environmental degradation [1-4]. Because a sizable proportion of the human diet depends directly or indirectly on animal pollination [5], the issue of how decreases in pollinator stocks could affect global crop production is of paramount importance [6-8]. Using the extensive FAO data set [9], we compared 45 year series (1961-2006) in yield, and total production and cultivated area of pollinator-dependent and nondependent crops [5]. We investigated temporal trends separately for the developed and developing world because differences in agricultural intensification, and socioeconomic and environmental conditions might affect yield and pollinators [10-13]. Since 1961, crop yield (Mt/ha) has increased consistently at average annual growth rates of approximately 1.5%. Temporal trends were similar between pollinator-dependent and nondependent crops in both the developed and developing world, thus not supporting the view that pollinator shortages are affecting crop yield at the global scale. We further report, however, that agriculture has become more pollinator dependent because of a disproportionate increase in the area cultivated with pollinator-dependent crops. If the trend toward favoring cultivation of pollinator-dependent crops continues, the need for the service provided by declining pollinators will greatly increase in the near future.


pH-controlled quaternary ammonium herbicides capture/release by carboxymethyl-β-cyclodextrin functionalized magnetic adsorbents: Mechanisms and application.
In our work, the pH-controlled magnetic solid phase extraction for the determination of paraquat and diquat was introduced firstly. Furthermore, to clarify the mechanism of carboxymethyl-β-cyclodextrin functionalized magnetic adsorbents, we studied the pH-responsive supramolecular interaction between carboxymethyl-β-cyclodextrin (CM-β-CD) and paraquat/diquat by ultraviolet-visible (UV-vis) spectroscopy and nuclear magnetic resonance (NMR) experiment, and the energy-minimized structures were also obtained. Then, the functional group CM-β-CD was modified on the surface of magnetic materials to synthesize the adsorbent. The Fourier transform infrared spectrum (FT-IR) results proved the successful modification of CM-β-CD. Thus, this absorbent was applied for the determination of paraquat and diquat in water. Under the optimal condition, limits of detection (LODs) of paraquat and diquat were 0.8 μg L(-1) and 0.9 μg L(-1), relative standard deviations (RSD) and recoveries varied 0.7-4.6% and 86.5-106.6%, respectively. Good recoveries (70.2-100.0%) and low RSD (1.7-9.6%) were achieved in analyzing spiked water samples. Furthermore, with the capillary electrophoresis (CE) as the analyser, the whole analytical process did not need the attendance of organic solvents.


Structural investigation of HIV-1 genomic RNA dimerization process reveals a role for the Major Splice-site Donor stem loop.
The 5'UnTranslated Region (5'UTR) of HIV-1 genomic RNA, which precedes the Gag coding sequence, fulfills several roles during the lentivirus life cycle. This 335 nucleotides leader contains many stable structures that are crucial for the regulation of genetic expression at the level of transcription, splicing, and translation. In the late steps of the virus cycle, i.e. virions formation, the genomic RNA serves as propagated genome and its encapsidation in new particles relies on its ability to form non-covalent dimers. Dimerization is proposed to be initiated by the intermolecular pairing of a self-complementary sequence located in the apical loop of the DIS hairpin (Dimer Initiation Sequence). The regulation of this phenomenon and the extraordinary stability of the dimers imply that structural elements other than this kissing complex remain to be identified. Here, we show that swapping the Gag open reading frame (ORF) by reporter genes interferes with dimers formation efficiency. Importantly, the nature of the ORF alters specific structures of the 5'UTR. By using a systematic "SHAPE" approach, we pointed out that sequences within the Major Splice Site are involved in the dimerization process. Furthermore, by the use of an antisense oligonucleotide specific for the MSD associated to a SHAPE analysis of the 5'UTR structure, we demonstrated that interfering with the MSD results both in an impaired dimerization and in modifications of the 5'UTR structure. All together these data support a recently proposed model in which intramolecular base pairings are important determinants for the dimerization process. We further conclude that much care should be taken when comparing translation activity of reporter constructs with the viral situation.


Increase of serum high density lipoprotein with progression and regression of aortic lipid deposition in rats.
The progression and regression of aortic lipid deposition was studied in male ExHC rats. Rats in the progression group were fed an atherogenic diet containing 2% cholesterol, 0.4% sodium cholate and 10% olive oil for periods up to 32 weeks. Rats in the regression group were first fed the atherogenic diet for 16 weeks, and then maintained on a basal low cholesterol diet. Half the rats were killed at 4 weeks and the other half at 16 weeks after cessation of the atherogenic diet. Rat aortas of the progression group contained progressively more lipid pari passu with the duration of cholesterol feeding, but connective-tissue proliferation was absent. Deposited lipid in the aorta of cholesterol-fed rats disappeared very slowly after the rats were returned to the basal diet. serum HDL decreased in the hypercholesterolemic ExHC rats fed the atherogenic diet for 4 weeks. By contrast, serum HDL and apo A-I increased in both hypercholesterolemic ExHC rats fed the atherogenic diet for 32 weeks and slightly hypercholesterolemic ExHC rats fed the basal diet for 16 weeks in the regression period.


Insights into controlling role of substitution mutation, E315G on thermostability of a lipase cloned from metagenome of hot spring soil.
Rational mutagenesis was performed (at the vicinity of the active site residues D317 and H358 of a mature polypeptide) to investigate the role of amino acids in the thermostability/activity of a lipase enzyme. The single variant enzyme created with E315G (lip M2) mutation near one of the active site residue (D317) found to be an important residue in controlling the thermal stability, the variant with E315G mutation demonstrated biochemical properties similar to that of native lipase. However, we found that this mutation strongly affected the activity and stability of the lip M1 mutant, reported in our previous study (Sharma et al. in Gene 491:264-271, 2012b). The dual mutant with E315G/N355K mutation in the Wt showed small increase in the protein thermostability compared to the native lipase, however, the thermostability of the mutant lip M1 was reduced several fold. Presumably, E315G (lip M2) mutation reverted the thermostability evolved by N355K (lip M1). The native and variant enzymes also displayed large variation in enzyme kinetics and their preference for pNP-esters (substrates). We further generated 3D models and studied the loop modelling of the WT and variants. Interestingly, loop region Leu314-Asn321 showed structural flexibility on introducing E315G mutation in the native lipase. On the other hand, lysine in mutant N355K exhibited side chain conformational changes in the loop Thr353-His358 which resulted in its H-bonding with Glu284. In addition, replacing glutamic acid by glycine at 315 position in lip M3 distorted the electrostatic interactions between Glu315 and Lys355 in the flexible loop region Leu314-Asn321.


Perinatal exposure to aluminum alters neuronal nitric oxide synthase expression in the frontal cortex of rat offspring.
Disturbance of the neuronal nitric oxide signaling pathway by chronic exposure to aluminum (Al) in drinking water may be a causal factor of neurological disorders in offspring. In order to investigate the relationship between Al administration and expression of neuronal nitric oxide synthase (nNOS), the numbers and distribution patterns of nNOS-immunoreactive neurons were examined in the frontal cortex of offspring after exposure to 0, 5, and 10 mM of Al in drinking water during prenatal and neonatal periods. At the bregma 0.20 level, the number of nNOS-positive neurons was significantly increased (10%) and decreased (17%) following exposure to 5 and 10 mM of Al in drinking water, respectively. The change was more severe in the upper layer than in deep layer of the cortex. In contrast, at the bregma -2.80 level, the number and distribution pattern was not significantly changed following exposure to Al. These data suggest that Al toxicity may be mediated through disturbances to the nitric oxide signaling pathway and exhibits a biphasic effect, especially in the frontal area of the cortex. In addition, the results suggest that impaired expression of nNOS plays an important role in the development of neurological syndrome caused by an exposure to Al during the early developmental stage.


An investigation of the effect of operational conditions on a sequential extraction procedure for arsenic in soil in Thailand.
Sequential Extraction Procedure (SEP) can be used to evaluate the toxicity characteristics of heavy metals in soil, including arsenic (As), by separating the metals into several different fractions using selective extraction solvents in sequence. To accomplish this separation task, various factors that are known to affect the extraction process should be carefully considered. This research aimed to investigate the effect of the operational conditions on the SEP for As in soil using experimental designs. In the first step, a Plackett-Burman design was used twice to screen the important extraction variables from a total of 19 studied variables. As a result, SSR, extraction time of the first fraction (F1), and concentrations of sodium acetate (NaOAc) in F2 and ammonium oxalate (NH4Ox) in F6 were identified as significant to the amount of the extracted As. The selected variables were further investigated using a central composite design with response surface methodology. The optimized SEP characterized by 1:75 g:mL of SSR, an extraction time of 7 h 20 min of F1, 0.16 M of NaOAc and 0.11 M of NH4OAc were applied to extract a sample from contaminated agricultural soil obtained from the north of Thailand. The fractionation result was compared with the result obtained from a previously reported SEP method. It was found that similar extraction results could be achieved (91-97% As recovery). However, the optimized method revealed certain advantages in that it required dramatically less operation time (from 68 h to 32 h) and lower concentrations of the extraction solvents.


Spouse caregivers and behavioral and psychological symptoms of dementia.
Only a few studies have specifically considered the role of caregiver characteristics in the presence of behavioral and psychological symptoms of dementia (BPSD). The aim of this study was to determine whether there were differences in the presence of individual BPSD between community-dwelling dementia care recipients with spouse caregivers and those with non-spouse caregivers. Care recipients (n = 109) and their primary caregivers were recruited from memory clinic outpatients at the public psychiatric hospital in Sapporo City, Japan. Data were collected by questionnaire. Relationship with the care recipient was categorized as either 'spouse' or 'non-spouse.' The frequency of BPSD occurrence observed by the caregiver was assessed using the Troublesome Behavior Scale (TBS). Logistic regression analyses were performed to examine whether there were differences with regard to each of the 14 TBS items between spouse and non-spouse caregivers. The number of spouse caregivers was 47 (43.1%). TBS items presented by >50% care recipients were 'repetition and/or clinging' and 'ill-natured denial and/or distortion.' After adjustment for the characteristics of caregivers and care recipients, non-spouse caregivers were found to be significantly associated with the presence of 'hiding and/or losing things,' 'rummaging,' 'crying and/or screaming,' and 'interfering with a happy home circle,' compared with spouse caregivers. Our results suggest that non-spouse caregivers need more support with regard to certain symptoms of individual BPSD compared with spouse caregivers. Identifying caregiver characteristics that are independently associated with each individual BPSD may help customize interventions for caregivers with specific characteristics.


Enlargement of the blind spot caused by papilledema.
Blind spot enlargement in papilledema has been attributed to either mechanical disruption of the integrity of the peripapillary percipient elements by the swollen optic disk or to the Stiles-Crawford effect. We investigated the possibility that blind spot enlargement in papilledema is caused, at least in part, by a refractive scotoma due to peripapillary hyperopia. We reduced the enlarged blind spot in a patient with focal peripapillary hyperopia, without papilledema, to near normal size by using progressively stronger plus lenses. Similarly, with the addition of plus sphere, we reduced the size of the blind spot in five of six patients with papilledema, but in none of our normal subjects.


Influence of prostaglandin inhibition on dihydralazine induced acute effects in patients with essential hypertension.
In order to determine whether vasodilator prostaglandins (PG) contribute to the acute vascular and endocrine responses to intravenously administered dihydralazine, we examined its effects on systolic and diastolic blood pressure (BP), heart rate (HR), plasma renin activity (PRA) and the plasma catecholamines (CA) noradrenaline (NA), adrenaline (A) and dopamine (DA) as well as on sodium, potassium and creatinine clearance (CNa, CK and CCr respectively), urinary flow rate, urinary catecholamines (NA, A, DA) and iPGE2 and i6-keto-PGF1 alpha excretion rate in six patients (three females, three males) with essential hypertension before and after PG synthesis inhibition by the nonsteroidal, anti-inflammatory agent diclofenac. Diclofenac, which reduced urinary iPGE2 and i6-keto-PGF1 alpha excretion by 62% (P = 0.026) and 45% (P = 0.037), respectively, antagonized dihydralazine induced diastolic BP reduction (P = 0.0009), HR increase (P = 0.01), noradrenaline and adrenaline increase in plasma (P = 0.02 and P = 0.05, respectively), increase in urine flow rate (P = 0.03), sodium clearance (P = 0.01) and tended to reduce PRA. We conclude that dihydralazine-mediated changes can be reduced by cyclo-oxygenase inhibition, most likely on the basis of a reduction of its effect on peripheral resistance, thereby leading to less reflex activation of the sympathetic nervous and renin-angiotensin systems.


Endoscopic submucosal dissection specimens in early colorectal cancer: lateral margins, macroscopic techniques, and possible pitfalls.
Endoscopic submucosal dissection (ESD) allows en-bloc resection of superficial gastrointestinal tumors, providing specimens on which lateral margin analysis can be performed reliably. Positive lateral margins have been linked to higher rates of recurrence/residual tumor. There are no guidelines for macroscopic processing of lateral margins. Currently, most institutions use parallel lateral sections, which are difficult to interpret. We use perpendicular lateral sections, hypothesizing that it decreases potential artifactually positive lateral margins. We analyzed positive lateral margin rates in colorectal ESD specimens according to sectioning method. We also looked at morphological factors associated with margin positivity as a function of technique used. We studied 166 ESD specimens, on which parallel sectioning practiced from 2006 to 2011 (n = 75). Perpendicular sectioning was used from 2010 to 2015 (n = 91). We recorded the number of positive margins, along with grade of dysplasia/carcinoma. Other information such as histopathological type, specimen size, lesion location, and patient follow-up was also recorded for evaluation. Forty of seventy-five (63%) margins were positive for parallel sections. In contrast, perpendicularly cut margins were significantly less frequently positive: 22/91 (24%) (p = 0.0001). Positive margins were found significantly more frequently in tubulo-villous lesions compared to tubular lesions in both the parallel and perpendicular groups (p = 0.03 and p = 0.02, respectively). Specimen size was not significantly associated with positive margins. Using perpendicular sectioning of colorectal ESD specimens, the proportion of cases with a positive lateral margin was significantly lower than when parallel sectioning was used. We suggest perpendicular sectioning to improve accuracy in histopathological analysis. This method is particularly important to use in future studies, as it may prevent authors from making conjectures based on overestimation of positive lateral margins.


Defining culturally safe primary care for people who use substances: a participatory concept mapping study.
People who use substances experience high levels of substance-related stigma, both within and outside of health care settings, which can prevent people from help-seeking and contribute further to health inequities. Recognizing and respecting how political, social, economic, and historical conditions influence health and health care, cultural safety, with origins in addressing Indigenous racism, is a potential strategy for mitigating stigma and marginalization in health care. Using a participatory research approach, we applied the concept of cultural safety to develop a model of safe primary care from the perspective of people who use substances. People who use or used substances were involved in all phases of the research and led data collection. Study participants (n = 75) were 42.5 years old on average; half identified as female and one quarter as Indigenous. All were currently using or had previous experience with substances (alcohol and/or other drugs) and were recruited through two local peer-run support agencies. Concept mapping with hierarchical cluster analysis was used to develop the model of safe primary care, with data collected over three rounds of focus groups. Participants identified 73 unique statements to complete the focus prompt: "I would feel safe going to the doctor if …" The final model consisted of 8 clusters that cover a wide range of topics, from being treated with respect and not being red-flagged for substance use, to preserving confidentiality, advocacy for good care and systems change, and appropriate accommodations for anxiety and the effects of poverty and criminalization. Developing a definition of safe care (from the patient perspective) is the necessary first step in creating space for positive interactions and, in turn, improve care processes. This model provides numerous concrete suggestions for providers, as well as serving as starting point for the development of interventions designed to foster system change.


Proton magnetic resonance spectra of adrenodoxin: features of the aromatic region.
This paper presents the first 1H-NMR spectra of the aromatic region of adrenodoxin, a mammalian mitochondrial 2Fe-2S non-heme iron ferredoxin. One-dimensional proton NMR spectra of both reduced and oxidized adrenodoxin were recorded as a function of pH. Resonances due to two of the three histidines of adrenodoxin gave sharp signals in the one-dimensional proton NMR spectra. The pKa values of the resolved histidine resonances in the oxidized protein were 6.64 +/- 0.03 and 6.12 +/- 0.06. These values were unchanged when adrenodoxin was reduced by the addition of sodium dithionite. In addition, the oxidized protein showed a broadened histidine C-2H resonance with a pKa value of approx. 7. This resonance was not apparent in the spectra of the reduced protein. The resonances due to the single tyrosine in adrenodoxin were identified using convolution difference spectroscopy. In addition, a two-dimensional Fourier-transform double quantum filtered (proton, proton) chemical shift correlated (DQF-COSY) spectrum of oxidized adrenodoxin was obtained. The cross peaks of the resonances due to the tyrosine, the four phenylalanines, and two of the three histidines of adrenodoxin were resolved in the DQF-COSY spectrum. Reduction of the protein caused several changes in the aromatic region of the NMR spectra. The resonances assigned to the C2 proton of the histidine with a pKa of 6.6 shifted upfield approx. 0.15 ppm. In addition, when the protein was reduced one of the resonances assigned to a phenylalanine residue with a chemical shift of 7.50 ppm appeared to move downfield to 7.82 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)


QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents.
Malaria is a disease caused by protozoan parasites of the genus Plasmodium that affects millions of people worldwide. In recent years there have been parasite resistances to several drugs, including the first-line antimalarial treatment. With the aim of proposing new drugs candidates for the treatment of disease, Quantitative Structure⁻Activity Relationship (QSAR) methodology was applied to 83 N-myristoyltransferase inhibitors, synthesized by Leatherbarrow et al. The QSAR models were developed using 63 compounds, the training set, and externally validated using 20 compounds, the test set. Ten different alignments for the two test sets were tested and the models were generated by the technique that combines genetic algorithms and partial least squares. The best model shows r² = 0.757, q²adjusted = 0.634, R²pred = 0.746, R²m = 0.716, ∆R²m = 0.133, R²p = 0.609, and R²r = 0.110. This work suggested a good correlation with the experimental results and allows the design of new potent N-myristoyltransferase inhibitors.


Molecular Characterization of a Fungus Producing Membrane Active Metabolite and Analysis of the Produced Secondary Metabolite
The majority of studies on soil Aspergillus concern the isolation and characterization of the antimicrobial compounds produced by this organism. Our previous studies indicated an isolated Aspergillus strain soil to be of interest, and this subject is further investigated here. Soil samples of various locations in Iran were collected. Extract from Aspergillus sp. culture was obtained using ethyl acetate fractionation. Antimicrobial activity testing was performed using broth microdilution assay against Escherichia coli, Candida albicans, and Staphylococcus aureus microorganisms. One metabolite PA3-d10 was isolated from these active extracts and identified using thin layer chromatography, preparative thin-layer chromatography, HPLC, 1HNMR (proton nuclear magnetic resonance), 2D NMR, and LC-MS (liquid chromatography-mass spectrometry). According to morphological and biochemical properties as well as ITS rDNA sequencing, we identified an isolate of Aspergillus flavus. The ethyl acetate fraction of the fermentation medium containing membrane active metabolites showed antimicrobial effects against different bacterial and yeast indicator strains. One metabolite from these active extracts was finally identified. Membrane active fraction produced by Aspergillus strain in this research demonstrated antimicrobial activities against bacteria and yeast strains. Therefore, this metabolite can be considered as a potential antimicrobial membrane active agent.


Linkage relationships among eleven biochemical loci in Peromyscus.
Interspecific F1 hybrids of Peromyscus maniculatus (deermice) and P. polionotus (oldfield mice) were backcrossed to P. maniculatus. Backcross progeny were electrophoretically typed for 11 variant protein markers: albumin, transferrin, leucine aminopeptidase, amylase, 6-phosphogluconate dehydrogenase, nucleoside phosphorylase, dipeptidase, tripeptidase, glutamate oxaloacetate transaminase, alcohol dehydrogenase, and sorbitol dehydrogenase. Genetic variation for each protein was attributed to a single autosomal locus. The alcohol dehydrogenase (Adh), salivary amylase (Amy), and albumin (Alb) loci appeared to be linked in the sequence of Adh-11.5 cM-Amy-33.3 cM-Alb. The tripeptidase locus, Pep-2, also may be loosely linked to Alb in this group. Variants at all other loci assorted independently. These and other known linkage relationships in Peromyscus correspond closely to those of the house mouse, Mus musculus. The available evidence in Peromyscus further supports the concept of linkage conservation by natural selection.


Regression analysis of factorially designed trials--a logical approach to protein crystallization.
The specific composition of the mother liquor that induces the formation of protein crystal is usually quoted as the 'best condition' for crystallization. However, very little is described about how these conditions were determined. These missing and non-reported details would certainly lead to a better understanding of why a specific purified protein does not crystallize, and why crystallization seems to be a totally unpredictable enterprise. In this paper, it is shown that a simple regression model applied to a set of factorially designed experiments (comprising successful and failed experiments) is a useful tool for the analysis of crystallization outcomes. The applications of this approach to the proteins lysozyme and calmodulin yielded results that did not substantially differ from published accounts. When this procedure is applied to myelin basic protein (MBP) and to a MBP and calmodulin complex no crystals formed, which would suggest that neither is easy to crystallize. In summary, factorial design and regression analysis can be an important methodological approach for crystallizing proteins.


Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity?
In obesity the cellular capacity to switch from using lipid to carbohydrate and vice versa as the energy substrate, known as 'metabolic flexibility', is impaired. Mitofusin 2 (MFN2), a mitochondrial membrane protein, seems to contribute to the maintenance and operation of the mitochondrial network, and its expression is reduced in obesity. The aim of this study was to verify whether MFN2 might be implicated in the metabolic inflexibility of obesity. Insulin sensitivity was measured in six morbidly obese women before and 2 years after malabsorptive bariatric surgery (BMI 53.3+/-10.5 vs 30.3+/-4.0 kg/m2). Skeletal muscle MFN2, SLC2A4 (formerly known as GLUT4), COX3 (encoding cytochrome c oxidase subunit III) and CS (encoding citrate synthase) mRNA levels were measured by real-time PCR. Following bilio-pancreatic surgery, significant increases in MFN2 mRNA (from 0.4+/-0.2 to 1.7+/-1.1 arbitrary units [AU], p=0.019) and SLC2A4 mRNA (0.38+/-0.12 to 0.76+/-0.24 AU, p=0.04) were observed, while increases in COX3 mRNA (from 14.2+/-6.4 to 20.2+/-12.5 AU) and CS mRNA (from 0.4+/-0.1 to 0.7+/-0.3 AU) failed to reach statistical significance. Insulin-mediated whole-body glucose uptake significantly (p<0.0001) increased from 21.2+/-4.1 to 52.8+/-5.9 micromol kg fat-free mass(-1) min(-1) and glucose oxidation rose from 11.1+/-2.1 to 37.7+/-4.7 micromol kg fat-free mass(-1) min(-1) (p<0.0001). Levels of MFN2 mRNA were strongly correlated with the absolute values for the glucose oxidation rate, both during fasting (glucose oxidation =3.55 MFN2 mRNA + 3.93; R2=0.92, p<0.0001) and during the clamp (glucose oxidation=18.8 MFN2 mRNA+34.7; R2=0.80, p<0.0001). The percentage changes in MFN2 mRNA were positively correlated with the percentage change in glucose oxidation during the clamp (glucose oxidation percent (%) change=0.3 MFN2 mRNA percent (%) change+153.2; R2=0.61, p<0.001). We propose that the significant increase in MFN2 mRNA levels may explain the increase in glucose oxidation observed in morbid obesity following bariatric surgery.


Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study.
Hodgkin's lymphoma (HL) has no standard of care for patients who are relapsed or refractory to autologous stem-cell transplantation (ASCT). This phase II study examined safety and activity of panobinostat in this population. Panobinostat 40 mg was administered orally three times per week. The primary end point was objective response rate (ORR) based on investigator assessment of radiologic imaging. Secondary end points included ORR by independent central review, time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival, and safety. Exploratory biomarker analyses were performed. The 129 treated patients (median age, 32 years; range, 18 to 75 years) were heavily pretreated with a median of four (range, two to seven) prior systemic regimens, and 41% did not respond to the regimen immediately preceding panobinostat. Tumor reductions occurred in 96 patients (74%). Objective response was achieved by 35 patients (27%), including 30 (23%) partial responses and five (4%) complete responses. The median TTR was 2.3 months, median DOR was 6.9 months, and median PFS was 6.1 months. The estimated 1-year overall survival rate was 78%. Common nonhematologic adverse events (AEs)-diarrhea, nausea, vomiting, and fatigue-were generally grade 1 and 2. Most common grade 3 and 4 hematologic AEs-thrombocytopenia, anemia, and neutropenia-were manageable. Early reductions in thymus and activation-regulated chemokine were observed in patients achieving complete or partial response. In the largest, prospective, multicenter, international trial conducted in heavily pretreated patients with HL who relapsed or were refractory to ASCT, panobinostat monotherapy demonstrated antitumor activity, resulting in durable responses.


A field comparison of neck and shoulder postures in symptomatic and asymptomatic office workers.
Poor neck and shoulder postures have been suggested to be a cause of neck and shoulder pain in computer workers. The present study aimed to evaluate and compare the head, neck and shoulder postures of office workers with and without symptoms in these regions, in their actual work environments. The two all female subject groups reported significantly different discomfort scores across five trials repeated in a single working day. The results of repeated video capture and two-dimensional motion analysis showed that there were trends for increased head tilt and neck flexion postures in the symptomatic subjects (n = 8), compared to the asymptomatic subjects (n = 8). Symptomatic subjects also tended to have more protracted acromions compared with asymptomatic subjects and showed greater movement excursions in the head segment and the acromion. All subjects demonstrated an approximately 10% increase in forward head posture from their relaxed sitting postures when working with the computer display, but there were no significant changes in posture as a result of time-at-work.


The effect of metal ions on the Spf1p P5A-ATPase. High sensitivity to irreversible inhibition by zinc.
The Spf1p protein from Saccharomyces cerevisiae belongs to the family of P5A-ATPases that have recently been shown to protect the endoplasmic reticulum by dislocating misinserted membrane proteins. The loss of function of P5A-ATPases leads to endoplasmic reticulum stress with a pleiotropic phenotype including protein, sterol and metal ion dyshomeostasis. Like other P-ATPases, Spf1p requires Mg2+. We found that free Mg2+ stimulated the Spf1p ATPase activity along a double hyperbolic curve with two components of K1/2 = 14 and 800 μM Ca2+, Mn2+ and Co2+ lowered about 50% of the Spf1p ATPase with relatively low affinity (Ki ∼75 μM) and the activity was fully recovered after metal ion chelation with EGTA. In contrast, low concentrations of Zn2+ and Cd2+decreased the activity to less than 20% and lead to slow irreversible inactivation of the enzyme. After the treatment with Zn2+, Spf1p exhibited a reduced apparent affinity for ATP and formed lower levels of the catalytic phosphoenzyme. The inactivation by Zn2+ occurred preferentially at a pH > 6 and could be prevented by adding either ATP or ADP to the inactivation media. These results suggest that Zn2+ inactivated Spf1p by binding to amino acid residues from the nucleotide binding-phosphorylation domains that are protonated at lower pH. Alternatively the binding of nucleotides may indirectly compete with a conformational change leading to the Zn2+-inactive form of the enzyme. Exposure of yeast cells to high concentrations of Zn2+ led to changes similar to the phenotype characteristic of the Spf1Δ cells. Altogether, our data, point out a possible mechanism by which the inhibition of P5A-ATPases could potentiate metal ion-induced ER stress and proteotoxicity.


Evolution and current challenges in the teaching of functional MRI and functional brain imaging.
The report of any new and successful method for studying the world triggers the need to train people in the use of that method. In the case of functional magnetic resonance imaging and its use for examining human brain function in vivo, expertise is required in a greater collection of domains than usual. Development of fMRI training programs started shortly after the announcement of BOLD-based fMRI in humans. These programs had a variety of durations and primary content areas. All programs had to deal with the challenge of bringing interested researchers from a wide variety of areas-many of whom had little or no understanding of MR physics, and/or experimental psychology, and/or the nuances of data analysis and modeling-to a sufficiently detailed level of knowledge that both the funding agencies, and the existing proprietors of the technology (often radiologists or MR physicists at hospitals) would take the research proposals of new investigators seriously. Now that fMRI-based research is well established, there are new educational challenges. Some have to do with the growing list of technologies used to study human brain function in vivo. But perhaps more daunting is the challenge of training consumers of the reports and claims based on fMRI and other brain imaging modalities. As fMRI becomes influential in contexts beyond the research environment-from the clinic to the courtroom to the legislature-training consumers of fMRI-based claims will take on increasing importance, and represents its own unique challenges for education.


Ublituximab: A new FDA-approved anti-CD20 mAb for relapsing forms of multiple sclerosis.
Ublituximab, an intravenous glycoengineered chimeric anti-CD20 IgG1 monoclonal antibody (mAb), is a new FDA-approved treatment for relapsing forms of Multiple Sclerosis (MS). Reassembling the other three anti-CD20 mAbs already in use for MS (rituximab, ocrelizumab and ofatumumab), ublituximab leads to depletion of B cells but spars long-lived plasma cells. Here, we discuss the main findings obtained during the phase 3 clinical trials (ULTIMATE I and II) for ublituximab versus teriflunomide. The current emergence and approval of new anti-CD20 mAbs with different dose regimens, routes of application, glycoengineering and mechanisms of action may contribute to different clinical outcomes.


The acute phase response and its relation to amyloid A degrading activity in serum of patients with rheumatoid arthritis undergoing arthroplasty.
The sequential changes in the concentration of specific serum proteins and their relation to amyloid A degrading activity were studied in ten patients with rheumatoid arthritis undergoing arthroplasty of the knee or hip. Serum amyloid A protein increased from a preoperative level of 78 +/- 20 gm/l (mean +/- SEM) to a peak level of 623 +/- 93 mg/l on the third postoperative day (P less than 0.001). The serum amyloid A protein response was greater than that of any other protein including C-reactive protein, to which it was closely related (r = 0.84, P less than 0.001). The concentrations of alpha 1-antitrypsin and alpha 1-antichymotrypsin were highest on the fourth postoperative day (mean changes + 35%, P less than 0.01, and +44%, P less than 0.05, respectively). Serum albumin, pre-albumin and alpha 2-macroglobulin behaved like negative acute phase reactants; the concentrations of albumin and alpha 2-macroglobulin were significantly decreased from the second to sixth and seventh postoperative days, respectively, and the concentration of pre-albumin was significantly decreased on the third and fourth postoperative days. A significant fall in the amyloid A degrading activity of serum occurred during the acute phase reaction. The degradative activity was lowest on the third and fourth postoperative days (P less than 0.001). The results show that the acute phase state in patients with rheumatoid arthritis induces a rise in the concentration of serum amyloid A protein, the putative serum precursor of tissue amyloid A fibrils, and a concomitant reduction in the ability of serum to degrade these fibrils. These factors together may be important in the development of inflammation-associated amyloidosis.


Functionalized calcium carbonate as a novel pharmaceutical excipient for the preparation of orally dispersible tablets.
To overcome the limitation of insufficient hardness during the production of rapidly disintegrating orally dispersible tablets (ODTs). Furthermore, we investigated the properties and usefulness of functionalized calcium carbonate (FCC) as a new pharmaceutical excipient for the production of ODTs. A highly sensitive tensiometer-based method was developed to measure kinetics of weight loss during tablet disintegration. With this method we were able to determine the residence time of tablets placed on a basket immersed into a test medium. The shapes of tensiometer plots allowed us to categorize substances into four different types of disintegration. At the same volume and hardness, the tablet formulations with FCC showed a significantly higher porosity (over 60%) than all other formulations. Residence time depended mainly on the tablet composition rather than on porosity. When combined with disintegrants, FCC formulations exhibited favorable disintegration properties, comparable to those of the marketed drug risperidone oro (disintegration time ca. 10 s). Oral dosage forms--based on the new pharmaceutical excipient FCC--can be designed to have a short disintegration time combined with good mechanical strength. Due to these properties, FCC can be used for the preparation of ODTs.


Cytomegalovirus enteritis with ischemia in an immunocompetent patient: A rare case report.
Cytomegalovirus (CMV) is predominantly an opportunistic infection in the immunocompromised patients. Though, there are few cases of CMV colitis being reported in the immunocompetent individuals, CMV enteritis is exceedingly rare and enteritis leading into small bowel ischemia has never been reported yet. A-78-year-old male patient presented with distal small obstruction for 4 days duration. Clinical examination revealed a distended abdomen and localised peritonism in right iliac fossa. An initial computed tomography (CT) scan revealed distended small bowel loops up to the thickened inflammed terminal illeum with no free fluid or gas and a normal appendix. No immunosuppressive risk factors such as human immunodeficiency virus, transplant procedures, or steroid therapy were present. Hematologic investigations showed leucocytosis with neutrophilia. Diagnostic laparoscopy confirmed a thickened terminal ileum causing small bowel obstruction. Laparoscopy converted to laparotomy and right hemicolectomy was performed. Histology showed isolated small bowel ischemia with ulcerative changes and cytomegalovirus inclusions. The patient was started on ganciclovir therapy and subsequently had an uneventful recovery and discharged after 16 days. Cytomegalovirus enteritis was initially not suspected in our patient. In this case CMV caused ischemia of the small bowel without evidence of colonic involvement. Even in elderly patients, the small bowel remains resilient to the ischemic changes because of the copious blood supply. We report possibly the first case of isolated small bowel ischaemia caused by cytomegalovirus in immunocompetent individuals, needed surgical resection.


After Detection: The Improved Accuracy of Lung Cancer Assessment Using Radiologic Computer-aided Diagnosis.
The aim of this study was to evaluate the improved accuracy of radiologic assessment of lung cancer afforded by computer-aided diagnosis (CADx). Inclusion/exclusion criteria were formulated, and a systematic inquiry of research databases was conducted. Following title and abstract review, an in-depth review of 149 surviving articles was performed with accepted articles undergoing a Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-based quality review and data abstraction. A total of 14 articles, representing 1868 scans, passed the review. Increases in the receiver operating characteristic (ROC) area under the curve of .8 or higher were seen in all nine studies that reported it, except for one that employed subspecialized radiologists. This systematic review demonstrated improved accuracy of lung cancer assessment using CADx over manual review, in eight high-quality observer-performance studies. The improved accuracy afforded by radiologic lung-CADx suggests the need to explore its use in screening and regular clinical workflow.


Long-term efficacy and safety of canakinumab in the treatment of systemic juvenile idiopathic arthritis in Japanese patients: Results from an open-label Phase III study.
The objective of the study was to report the efficacy and safety of canakinumab treatment in Japanese patients with systemic juvenile idiopathic arthritis (sJIA) over a 48-week study period. Patients were administered canakinumab 4 mg/kg (maximum dose 300 mg) every 4 weeks, with no dose adjustments. The key outcome measures included adapted American College of Rheumatology paediatric (aACR pedi) 30/50/70/90/100 response, proportion of patients with inactive disease, and corticosteroid (CS) tapering. In total, 16/19 (84.2%) patients received canakinumab for ≥96 weeks reaching end-of-study (EOS) visit without premature discontinuation. Regardless of the level of joint involvement at baseline, high aACR pedi responses were observed throughout the study; at the EOS, aACR pedi 90/100 response rates were 84.2%/63.2%, respectively. The proportion of patients who successfully tapered CSs at EOS was 66.7% (12/18), of which 10 patients were steroid-free. The most common adverse events were infections (238.3 events/100 patient-years). Serious adverse events were observed in 52.6%. The event (n=1) adjudicated as possible macrophage activation syndrome was preceded by sJIA flare. No deaths were reported. Canakinumab treatment resulted in a sustained treatment response in sJIA patients over 48 weeks and was associated with CS tapering in majority of patients. No new safety findings were reported.


Impact of preoperative biopsy sampling on severe submucosal fibrosis on endoscopic submucosal dissection for colorectal laterally spreading tumors: a propensity score analysis.
It is believed that preoperative biopsy sampling for superficial-type colorectal tumors should be avoided because submucosal fibrosis caused by biopsy sampling makes EMR impossible. However, few studies have reported the influence of biopsy sampling on colorectal endoscopic submucosal dissection (ESD). This study aimed to examine the effect of biopsy sampling on submucosal fibrosis and treatment outcomes of ESD for laterally spreading tumors (LSTs). Between April 2005 and September 2015, 441 consecutive patients underwent colorectal ESD in Osaka City University Hospital. Using propensity score matching and inverse probability of treatment weighting (IPTW), we retrospectively evaluated risk factors for severe submucosal fibrosis and treatment outcomes for patients with LSTs, with or without preoperative biopsy sampling. A total of 428 LSTs resected using ESD were enrolled. After matching, there were 136 matched pairs of lesions that did or did not undergo biopsy sampling. Preoperative biopsy sampling increased severe fibrosis compared with that in the non-biopsy sampling group (20.6% vs 11.0%; P = .03) and was significantly associated with severe fibrosis after matching (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.07-4.10; P = .03). After adjustment with IPTW, biopsy sampling also increased the risk of severe fibrosis (OR, 2.33; 95% CI, 1.17-4.63; P = .02). However, no significant differences were observed between the 2 groups in treatment outcomes. Preoperative biopsy sampling for colorectal LSTs might cause severe submucosal fibrosis but has no adverse influence on clinical outcomes of ESD.


Recent progress of gene circuit designs in immune cell therapies.
The success of chimeric antigen receptor (CAR) T cell therapy against hematological cancers has convincingly demonstrated the potential of using genetically engineered cells as therapeutic agents. Although much progress has been achieved in cell therapy, more beneficial capabilities have yet to be fully explored. One of the unique advantages afforded by cell therapies is the possibility to implement genetic control circuits, which enables diverse signal sensing and logical processing for optimal response in the complex tumor microenvironment. In this perspective, we will first outline design considerations for cell therapy control circuits that address clinical demands. We will compare and contrast key design features in some of the latest control circuits developments and conclude by discussing potential future directions.


Outcome in elderly patients undergoing definitive surgery and radiation therapy for supratentorial glioblastoma multiforme at a tertiary care institution.
To determine the efficacy of definitive surgery and radiation in patients aged 70 years and older with supratentorial glioblastoma multiforme. We selected elderly patients (> or = 70 years) who had primary treatment for glioblastoma multiforme at our tertiary care institution from 1977 through 1996. The study group (n = 102) included 58 patients treated with definitive radiation, 19 treated with palliative radiation, and 25 who received no radiation. To compare our results with published findings, we grouped our patients according to the applicable prognostic categories developed by the Radiation Therapy Oncology Group (RTOG): RTOG group IV (n = 6), V (n = 70), and VI (n = 26). Patients were retrospectively assigned to prognostic group IV, V, or VI based on age, performance status, extent of surgery, mental status, neurologic function, and radiation dose. Treatment included surgical resection and radiation (n = 49), biopsy alone (n = 25), and biopsy followed by radiation (n = 28). Patients were also stratified according to whether they were optimally treated (gross total or subtotal resection with postoperative definitive radiation) or suboptimally treated (biopsy, biopsy + radiation, surgery alone, or surgery + palliative radiation). Patients were considered to have a favorable prognosis (n = 39) if they were optimally treated and had a Karnofsky Performance Status (KPS) score of at least 70. The median survival for patients according to RTOG groups IV, V, and VI was 9.2, 6.6, and 3.1 months, respectively (log-rank, p < 0.0004). The median overall survival was 5.3 months. The definitive radiation group (n = 58) had a median survival of 7.3 months compared to 4.5 months in the palliative radiation group (n = 19) and 1.2 months in the biopsy-alone group (p < 0.0001). Optimally treated patients had a median survival of 7.4 months compared to 2.4 months in those suboptimally treated (p < 0.0001). The favorable prognosis group had an 8.4-month median survival compared to 2.4 months in the unfavorable group (p < 0.0001). On multivariate analysis, the KPS, RTOG group, favorable/unfavorable prognosis, and optimal treatment/suboptimal treatment were significant predictors of survival. Elderly patients with good performance status (> or = 70 KPS) when treated aggressively with maximal resection and definitive radiation had longer survival than those treated with palliative radiation and biopsy. Aggressive treatment in such patients should be considered.


Infectious Diseases of Poverty in Children: A Tale of Two Worlds.
"Infectious diseases of poverty" (IDoP) describes infectious diseases that are more prevalent among poor and vulnerable populations, namely human immunodeficiency virus (HIV) infection, tuberculosis (TB), malaria, and neglected tropical diseases (NTDs). In 2013, 190,000 children died of HIV-related causes and there were 550,000 cases and 80,000 TB deaths in children. Children under age 5 account for 78% of malaria deaths annually. NTDs remain a public health challenge in low- and middle-income countries. This article provides an overview of the major IDoP that affect children. Clinicians must be familiar with the epidemiology and clinical manifestations to ensure prompt diagnosis and treatment.


Novel targets in rectal cancer by considering lncRNA-miRNA-mRNA network in response to Lactobacillus acidophilus consumption: a randomized clinical trial.
We aimed to explore the lncRNA-miR-mRNA network in response to Lactobacillus acidophilus (L. acidophilus) consumption in rectal cancer patients. The candidate miRs were first taken from the GEO and TCGA databases. We constructed the lncRNA-miR-mRNA network using the high-throughput sequencing data. At last, we created a heatmap based on the experimental data to show the possible correlation of the selected targets. The expression levels of selected targets were measured in the samples of 107 rectal cancer patients undergoing placebo and probiotic consumption and 10 noncancerous subjects using Real-Time PCR. Our analysis revealed a group of differentially expressed 12 miRs and 11 lncRNAs, and 12 genes in rectal cancer patients. A significant expression increase of the selected tumor suppressor miRs, lncRNAs, and genes and a substantial expression decrease of the selected oncomiRs, onco-lncRNAs, and oncogenes were obtained after the probiotic consumption compared to the placebo group. There is a strong correlation between some network components, including miR-133b and IGF1 gene, miR-548ac and MSH2 gene, and miR-21 and SMAD4 gene. In rectal cancer patients, L. acidophilus consumption was associated with improved expression of the lncRNA-miR-mRNA network, which may provide novel monitoring and therapeutic approaches.


Improvement of lipid profile and antioxidant of hypercholesterolemic albino rats by polysaccharides extracted from the green alga Ulva lactuca Linnaeus.
Sulfated polysaccharides from Ulva lactuca were extracted in hot water and precipitated by ethanol then orally gavaged to rats fed on a hypercholesterolemic diet for 21 days to evaluate the antihypercholesterolemic and antioxidant actions. Atorvastatine Ca (Lipitor) was used as a reference drug. The intragastric administration of U. lactuca extract to hypercholesterolemic rats caused significant decrease of serum total lipids, triglycerides, total cholesterol, LDL-cholesterol and vLDL-cholesterol levels. Whereas, HDL-cholesterol concentration was markedly increased by 180%. Aqueous extract showed a significant ameliorative action on elevated atherogenic index, creatine kinase and lactate dehydrogenase activities of hypercholesterolemic group. Furthermore, serum activities of transaminases and alkaline phosphatase were also improved. High fat diet intake caused a highly significantly elevated serum urea, creatinine concentration. These effects were reversed by oral administration of U. lactuca extract. Sulfates polysaccharides extract of U. lactuca ameliorate hepatic enzymatic (catalase, glutathione peroxidase and superoxide dismutase), non-enzymatic (reduced glutathione & total thiol) antioxidant defenses and thiobarbituric acid reactive substances. In conclusion, the tested U. lactuca polysaccharides extract has potent hypocholesterolemic and antioxidant effects in experimentally-induced hypercholesterolemic animal model.


European Working Time Directive and the use of simulators and models in Irish orthopaedics.
To report on the perceptions of a group of orthopaedic trainees and trainers on perceived effects of the proposed introduction of European Working Time Directive (EWTD) restrictions into Ireland and on the use of simulators in training orthopaedic skills. A structured questionnaire was developed to evaluate the opinions of a group of orthopaedic surgeons and trainees at the annual national orthopaedic conference. There were 44 participants [12 consultants, 32 trainees (15 specialist registrars, 8 registrars, 9 senior house officers)]. Seventy-five percent of participants felt that both the quality of patient care and training would be negatively affected. A higher proportion of consultants than trainees felt that quality of life would be affected. A high proportion of participants (81.8%) had used a simulator or model to learn a surgical skill and 100% would consider using them again. While we wait for the full introduction of the EWTD hours the perception is that both quality of patient care and training will be affected. Models and simulators are well perceived as a method of training.


Relationship between the phase value of ESWAN and fractional anisotropy of diffusion tensor imaging in patients with cerebral microbleeds: preliminary results.
The purpose of the present study was to measure phase values (PVs) and fractional anisotropy (FA) of cerebral microbleeds (CMBs) using phase and FA map, and to investigate the potential relationship between PVs and FAs in CMBs in vivo. We retrospectively analyzed 30 patients with CMBs using enhanced T2*-weighted angiography and diffusion tensor imaging. The PVs and FAs of CMBs were measured and documented, and the mean FAs were compared between CMBs and the corresponding normal brain tissue. The mean PVs were correlated with FAs in CMBs in seven different brain regions. A total of 106 CMBs were defined, and the mean FA of the CMBs in white matter, EC/IC/CR, thalamus, and cerebellum were significantly lower than that of normal brain tissue in the control group (p<0.05). Positive correlations were observed between the PV and FA of CMBs in white matter, external capsule, internal capsule and corona radiata (r=0.70, 0.38). Enhanced T2*-weighted angiography and diffusion tensor imaging sequence may be useful neuroimaging sequences that could reflect the severity of damage of white matter by measuring the FA of CMBs and provide useful reference data for the quantitative assessment of CMBs.


Angiotomography for aneurysms and arteriovenous malformations of the head and neck.
Angiotomographic studies were performed preoperatively on 201 arterial aneurysms and arteriovenous malformations (AVMs) of the head and neck. There were two extracranial aneurysms, 186 intracranial aneurysms and 13 intracranial AVMs. The equipment used was the Philips NeuroDiagnost, either armed with a single multisection cassett for single-phase angiotomography or a triple cassette system on a motor-driven prism for serial amgiotomography. Angiotomography was limited to lesions where its use promised to add significantly to the information already obtained from conventional angiograms. Angiotomography was found to be of particular value for the differentiation of small aneurysms from normal vascular structures, for the study of morphology and topography of more or less spherical aneurysms in close proximity to a number of neighboring arteries, for the study of giant aneurysms, for the demonstration of very small AVMs (microangiomas) and for the evaluation of feeding and draining vessels of midline AVMs.


Breathing in danger: how particulate matter pollution is putting the public at risk of lung cancer†.
We are constantly exposed to chemicals and other agents in our environment that can influence our risk of tumorigenesis, but exactly how these factors contribute to cancer development is largely unknown. Fine particulate matter measuring ≤2.5 μm (PM2.5 ) from air pollution can accumulate in alveoli, contributing to inflammation and tissue damage. Despite prior correlative studies highlighting the mortality risk, there has been a historical reluctance to lower national standards for safe PM2.5 exposure. A recent publication further highlights the attributable risk of PM2.5 exposure with lung cancer - particularly in 'never-smokers' with EGFR-driven non-small cell lung cancer. Importantly, it also elucidates a mechanistic link between PM2.5 exposure and tumorigenesis using in vivo models of EGFR non-small cell lung cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Exploring the relationship between race/ethnicity, age of first school-based services utilization, and age of first specialty mental health care for at-risk youth.
This study investigated race/ethnic variations in age of entry into school-based services and specialty mental health outpatient services among 1552 high-risk youths served in a publicly funded system of care. Non-Hispanic White youths were more likely to receive school-based services as compared to ethnic minority groups, and to begin use at an earlier age. In addition, the earlier a child was identified for school-based services, the earlier the child first utilized specialty outpatient mental health services. Multiple regression models showed that inclusion of race/ethnicity as a predictor significantly increased the overall variance explained in the model predicting age of first school-based services, and both race/ethnicity and first use of school-based services increased the overall variance explained in the model predicting age of first specialty mental health outpatient service use. The results suggest that involvement in school-based services may play an important role in facilitating specialty outpatient mental health service use for youths.


Effects of insulin and IGF-I on RNA synthesis in isolated soleus muscle.
The effects of insulin and insulin-like growth factor I (IGF-I) on RNA synthesis and the effect of IGF-I on polypeptide chain initiation have been studied in the isolated mouse soleus muscle. Both peptides after a 3 h incubation enhanced net incorporation of the labelled uridine into RNA to a similar extent (40% increase over basal). The maximally effective concentrations were 66 nM and 100 nM for insulin and IGF-I respectively. Actinomycin D prevented the peptides' effect on RNA synthesis without modifying their effect on protein synthesis. Furthermore IGF-I increased the rate of initiation of polypeptide chains. It is suggested that in muscle, IGF-I and insulin stimulate protein synthesis by a dual mechanism: a rapid effect on the rate of polypeptide chain initiation; a slower effect on RNA synthesis.


Functionality improvement of fungal lignin peroxidase by DNA shuffling for 2,4-dichlorophenol degradability and H2O2 stability.
One of the major problems of wild-type lignin peroxidase (LiP) is its inactivity at the presence of excess H(2)O(2) and high concentration of aromatic compounds. Little is known about the substrate-binding site of LiP, and functionality improvement of LiP was not actively tried by genetic engineering and directed evolution. In order to improve LiPs functionality, we performed directed evolution with a colorimetric screening method. Finally, three types of LiP mutants were screened. The catalytic efficiency of the variants toward 2,4-dichlorophenol (DCP) degradation activity and the stability against H(2)O(2) was increased over the wild type. The K(m) value of the variants toward H(2)O(2) was increased, but K(m) value toward 2,4-DCP degradation was reduced. Overall, The K(cat)/K(m) values of the mutants toward 2,4-DCP was increased ca. 4-fold, and that toward H(2)O(2) was increased ca. 89-fold. Amino acid sequence analysis indicated that the most of the mutations were located on the enzyme surface. We expect that these results coupled with recombining mutation can be successfully applied to the molecular evolution cycles for screening of LiPs and other oxidative enzymes with improved functionality and stability.


Contribution of the corneal epithelium to anterior corneal topography in patients having myopic photorefractive keratectomy.
To assess the variations in corneal topographic characteristics after removal of the epithelium in patients having myopic photorefractive keratectomy (PRK). Rothschild Foundation, Paris, France. Forty-four eyes of 25 patients with myopia had corneal topography examination with the Orbscan II device (Bausch & Lomb) before removal of the corneal epithelium preoperatively and after removal of the corneal epithelium during PRK. On each examination, elevation, curvature, and pachymetry parameters were recorded and analyzed (paired 2-sided Student t test). The mean difference in central pachymetry between preoperative and epithelial removal was 37.84 mum +/- 9.82 (SD) (range 19 to 58 mum). The mean best-fit spherical surface radius was 7.75 +/- 0.28 mm (range 7.25 to 8.42 mm) before removal of the epithelium and 7.92 +/- 0.29 mm (range 7.39 to 9.16 mm) after removal of the epithelium (P<.0001). The mean simulated K-value difference increased from 0.75 +/- 0.55 diopter (D) (range 0.1 to 4.7 D) before removal to 1.21 +/- 0.66 D (range 0.2 to 4.7 D) after removal (P<.0001). The mean simulated value decreased from 43.77 +/- 1.83 D (range 40.25 to 47.00 D) to 42.44 +/- 1.73 D (range 37.05 to 45.50 D), respectively. The mean power (3.0 mm) decreased from 44.42 +/- 1.59 D (range 40.4 to 47.2 D) before removal to 43.46 +/- 1.37 D (range 39.7 to 46.9 D) after removal. The mean irregularity index increased from 1.07 +/- 0.35 D (range 0.5 to 2.5 D) to 2.03 +/- 0.38 D (range 1.3 to 3.3 D), respectively (P<.0001). The mean asphericity value (Q) changed from -0.44 +/- 0.14 (range -0.72 to -0.20) to -0.65 +/- 0.46 (range -1.04 to 0.14), respectively (P = .003). The epithelium affected the topographic properties of the cornea by significantly reducing corneal topographic astigmatism and irregularity. This might prove to be important in the assessment of patient candidacy for and treatment planning in refractive surgery.


Insulinoma cells in culture show pronounced sensitivity to alloxan-induced oxidative stress.
In a model system of cultured J-774 cells we have previously shown that alloxan in moderate concentration is toxic only in the presence of a reducing agent with the production of hydrogen peroxide. The cytotoxicity was found to involve lysosomal destabilization. In the present study the cytotoxic effects of (i) alloxan alone, (ii) a combination of alloxan and cysteine or (iii) hydrogen peroxide were investigated in two established insulinoma cell lines (HIT-T15 and RINm5F), and compared with the effects on J-774 cells. The protective effects of desferrioxamine and catalase, and the intracellular levels of reduced glutathione and activities of the enzymes glutathione peroxidase, glutathione reductase and catalase were also studied. HIT and RIN cells showed about 10 times greater sensitivity than J-774 cells against exposure to either alloxan and cysteine, or hydrogen peroxide. All cell types were relatively insensitive to alloxan alone. Preincubation with desferrioxamine and addition of catalase provided efficient protection against cytotoxicity and lysosomal destabilization. HIT and RIN cells has less capacity to degrade hydrogen peroxide and lower levels of glutathione peroxidase than J-774 cells. The lysosomal stability in all three cell lines was directly correlated to their viability. We conclude that HIT and RIN cells have weak antioxidative defence systems resulting in enhanced lysosomal vulnerability when they are exposed to alloxan and cysteine, which produce hydrogen peroxide extracellularly. The degree of cytotoxicity seems to be dependent on cellular capacity to degrade hydrogen peroxide and the lysosomal content of reactive iron.


Self-efficacy, organizational commitment, workload as predictors of life satisfaction in elementary school teachers: the mediating role of job satisfaction.
Life satisfaction as well as job satisfaction of teachers has a significant impact on educational outcomes. To evaluate a model of factors predicting life satisfaction through the mediating role of job satisfaction. This was a cross-sectional study, with a sample of 300 primary school teachers of both sexes (68% female, 32% male) and with a mean age of 42.52 years (SD = 10.04). They were administered the General Self-Efficacy Scale, the Satisfaction with Life Scale (SWLS), the Workload Scale (ECT), the Generic Job Satisfaction Scale, and the Organizational Commitment Questionnaire (OCQ). Structural equation modeling (SEM) was used for data analysis. The SEM analysis found significant goodness-of-fit indices: (χ2 = 13.739; df = 5; p = <0.001; CFI = 0.99, TLI = 0.98, RMSEA = 0.05, SRMR = 0.04). Specifically, self-efficacy and organizational commitment were positive predictors of job satisfaction, while workload was a negative predictor of job satisfaction. The mediating effect of job satisfaction between self-efficacy, life satisfaction, workload, and overall life satisfaction was confirmed. The results confirm the importance of self-efficacy, organizational commitment, and workload in job satisfaction and overall life satisfaction of elementary education teachers. Job satisfaction acts as a mediator in this relationship. It is important to reduce workload and promote self-efficacy and organizational commitment to improve the well-being and satisfaction of teachers.


[Transportation processes and rates of heavy metals in an artificial rainstorm runoff under different land use types].
Studies on the transportation and flux of various kinds of heavy metals in runoff and sediment of five typical landuse types in West Tiaoxi catchment showed that the losses of Cu (0.21 mg.m-2.min-1), Zn (0.45 mg.m-2.min-1), and Pb (0.15 mg.m-2.min-1) in mulberry and that of Cr (0.06 mg.m-2.min-1) in paddy field were larger in surface runoff, while their losses in pinery were very small. Suspended thin particles played the main role on transporting heavy metals in surface runoff under all kinds of land uses. The losses from runoff were much lower than that from sediment, which only occupied 0.1%-4.9%, and the loss rate of Cu from runoff and sediment was higher than that of Cr, Pb and Zn.


Similarities and Differences Between Yoruba Traditional Healers (YTH) and Native American and Canadian Healers (NACH).
Indigenous people of the world have used the services of medicine men and traditional healers from time immemorial. According to the World Health Organization, 80 % of the world's populations consult traditional healers. With an emerging globalization of health services in the world, there is a need for western mental health practitioners to learn and understand the practices of indigenous healers across the globe. This paper will not only highlight the similarities and differences between Yoruba traditional healers of Western Nigeria and Native American and First Nation Canadian traditional healers, but it will also allow practitioners to gain clearer perspectives of indigenous clients from Yoruba land and those from the United States of America and Canada. This ultimately will inform culturally sensitive clinical practice with these populations.


Glycine modulates cytokine secretion, inhibits hepatic damage and improves survival in a model of endotoxemia in mice.
There is substantial experimental evidence that the amino acid glycine may have a role in protecting tissues against insults such as ischemia, hypoxia and reperfusion. Our aim was to investigate the ability of the amino acid glycine to prevent hepatic damage induced by injection of lipopolysaccharide and d-galactosamine (d-Gal), to modulate pro- and anti-inflammatory cytokine levels, and to improve survival. Mice were challenged with an intraperitoneal injection of d-Gal (16 mg/mouse) and lipopolysaccharide (LPS, 1 microg/mouse). The intervention group also received an intraperitoneal injection of glycine (150 mg/kg) in two doses: 24 h before and just after LPS challenge. Serum cytokine levels were measured 2 h after challenge, and liver enzymes and histology were determined 16 h after LPS. Separate groups of mice received the same treatment and the survival rate was determined 24 h and ten days after endotoxin administration. In in vitro experiments, cultured mononuclear cells were stimulated by LPS, and TNF-alpha and IL-10 secretion were measured, in the presence or absence of glycine. In the glycine-treated mice, the serum levels of liver enzymes and TNF-alpha, the histologic necroinflammation score and the mortality rate were significantly reduced compared to control mice (P<0.001). Serum IL-10 levels in the glycine-treated mice were increased (P<0.01). In vitro studies in cultured lymphocytes isolated from either normal or glycine pretreated mice, demonstrated a significant and dose-dependent inhibition of LPS-induced TNF-alpha secretion and increase in IL-10 response after treatment with glycine (P<0.01). In conclusion, glycine reduces hepatic damage and improves survival rate in this mouse model of endotoxemia. The protective effect of glycine is associated with modulation of TNF-alpha and IL-10 secretion.


Warming has stronger direct than indirect effects on benthic microalgae in a seaweed system in spring.
Using outdoor mesocosms we investigated the relative importance of the direct and indirect (here: altered grazing) effects of seawater warming on benthic microalgae in a Baltic Sea Fucus vesiculosus (Phaeophyceae) system during the spring season. Seawater warming had a positive main effect on microalgal total biomass accrual and growth rate and on total mesograzer abundance and biomass. Moreover, under the existing resource-replete conditions in spring the direct positive effect of warming on microalgae was stronger than its indirect negative effect through enhanced grazing. The outcome of this study contrasts previous observations from the summer and winter season, where indirect effects of warming mediated by altered grazing were identified as an important driver of primary biomass in the Fucus system. In this context, the results from the spring season add mechanistic information to the overall understanding of the seasonal variability of climate change effects. They suggest that the relative importance of the underlying direct and indirect effective pathways of warming and the overall effect on the balance between production and consumption are influenced by the trophic state of the system, which in temperate regions is related to season.


Does a high-fat diet affect the circadian clock, or is it the other way around? A systematic review.
This paper reviews studies that addressed the influence of diet on circadian rhythmicity in mice and, in turn, circadian clock chronodisruption and its role in the development of metabolic disorders. Studies from the past 14 years were selected via a systematic search conducted using the PubMed electronic database. After applying the inclusion and exclusion criteria, 291 studies were selected, of which 13 were chosen using the following inclusion criteria: use of a high-fat diet for mice, evaluation of clock gene expression, and the association between chronodisruption and lipid metabolism disorders. These studies reported changes in animals' biological clock when they developed metabolic disorders by consuming a high-fat diet. It was also evident that some clock gene mutations or deletions triggered metabolic changes. Disturbances of clock gene machinery may play important roles in lipid metabolism and the development of atherosclerotic processes. However, many metabolic processes also affect the function of clock genes and circadian systems. In summary, this review's results may provide new insights into the reciprocal regulation of energy homeostasis and the biological clock.


UV survival of human mycoplasmas: evidence of dark reactivation in Mycoplasma buccale.
The inactivation by ultraviolet (UV) light irradiation of mycoplasma cells of five human strains was monitored by investigating the colony-forming ability. The survival curves of five strains tested indicated that the cells of Mycoplasma buccale only are single and homogenously susceptible to UV light. The effect of the repair inhibitor, caffeine, on the colony-forming ability of UV-irradiated cells was investigated with M. buccale because of its homogenous susceptibility to UV light. The colony formation of irradiated cells was markedly depressed by post-irradiation treatment with caffeine at concentrations that had little or no effect on the colony formation of unirradiated cells. The colony-forming units (CFU) of UV-irradiated cells which were kept in broth without caffeine in the dark increased without a lag as the time in the dark increased. The colony-forming ability of the irradiated cells completely recovered after 3 hr in the dark. However, when irradiated cells were kept in the presence of caffeine, no increase in their CFU was observed. The mode of action of caffeine on UV-irradiated cells closely resembles that described for other organisms which possess dark reactivation systems for UV-induced damage in deoxyribonucleic acid (DNA). Thus, the results obtained provide evidence for the existence of a dark repair function in M. buccale.


Adjuvant chemoradiation for gastric cancer: multicentric study of the Anatolian Society of Medical Oncology.
The aims of this study were to report the clinical outcomes of adjuvant chemo-radiotherapy after curative resection in 637 patients with gastric cancer. The retrospective analysis included 637 patients with resectable gastric cancer and stage IB-IV (M0) from 8 medical centers between 2003 and 2010. The patients were treated with 5FU-leucovorin and radiotherapy according to Schema for INT-0116. Of the 637 patients, the median of overall survival (OS) was 43.7 months and relapse free survival (RFS) was 36.6 months. OS rates were 84%, 45%, 40% while RFS rates were 81%, 45% and 35% at 1, 3 and 5-years, respectively. Hematological and gastrointestinal toxicities (grade 1-4) were observed in 35% and 36.5% of patients, respectively. In univariate analysis, according to the Lauren classification, tumor grade, T stage, N stage, type of operation (total gastrectomy or subtotal) and surgery resection margin (R0 or R1) were found as prognostic factors on RFS and OS (p<0.05). In multivariate analysis, T stage, N stage and surgical margins were found as effective factors on OS. T stage, N stage and Lauren classification were factors affecting RFS. Adjuvant chemo-radiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities in the Turkish population.


[Principles of epidemic emergency preparedness planning: the example of the German Influenza Pandemic Preparedness Plan].
Despite significant medical progress, recent events have shown that infectious diseases have not lost significance. Indeed, the threat of worldwide epidemics has increased. Due to their high infectious ness and rapid person-to-person transmissibility, the emergence of new influenza viruses with pandemic potential poses an especially alarming situation in this regard. The world population would be "immunologically naïve" to a new pandemic virus, permitting explosive spread of the disease. During the last century, three influenza pandemics have demonstrated that this is not merely a hypothetical risk. Currently it is feared that the possible human adaptation of avian influenza viruses that have recently become endemic in birds in Southeast Asia could result in a new pandemic strain. With the publication of the German Influenza Pandemic Preparedness Plan, preparation for this potential threat has reached an important stage in Germany. The implementation of the plan, which includes measures that go beyond the scope of public health, must now proceed swiftly. The long-term goal of pandemic preparedness planning is to be better equipped to deal with potential health threats in general, in particular those ensuing from the emergence of new infectious diseases under conditions of a growing global network.


The Role of a Gut Microbial-Derived Metabolite, Trimethylamine N-Oxide (TMAO), in Neurological Disorders.
Trimethylamine lyases are expressed in a wide range of intestinal microbiota which metabolize dietary nutrients like choline, betaine, and L-carnitine to form trimethylamine (TMA). Trimethylamine N-oxide (TMAO) is an oxidative product of trimethylamine (TMA) catalyzed by the action of flavin monooxygenases (FMO) in the liver. Higher levels of TMAO in the plasma and cerebrospinal fluid (CSF) have been shown to contribute to the development of risk factors and actively promote the pathogenesis of metabolic, cardiovascular, and cerebrovascular diseases. The investigations on the harmful effects of TMAO in the development and progression of neurodegenerative and sleep disorders are summarized in this manuscript. Clinical investigations on the role of TMAO in predicting risk factors and prognostic factors in patients with neurological disorders are also summarized. It is observed that the mechanisms underlying TMAO-mediated pathogenesis include activation of inflammatory signaling pathways such as nuclear factor kappa B (NF-κβ), NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, and MAPK/JNK in the periphery and brain. Data suggests that TMAO levels increase with age-related cognitive dysfunction and also induce mitochondrial dysfunction, oxidative stress, neuronal senescence, and synaptic damage in the brain. Further research into the relationships between dietary food consumption and gut microbiota-dependent TMAO levels could provide novel therapeutic options for neurological illnesses.


A cluster analysis of personality style in adults with ADHD.
The purpose of this study was to use hierarchical linear cluster analysis to examine the normative personality styles of adults with ADHD. A total of 311 adults with ADHD completed the Millon Index of Personality Styles, which consists of 24 scales assessing motivating aims, cognitive modes, and interpersonal behaviors. The sample was randomly divided into half, and independent hierarchical linear cluster analyses were performed on each half to identify replicable clusters. A three-cluster solution was selected, and two of the clusters were replicated across the independent analyses. Participants in Cluster 1 manifested more polarized, negative motivating aims, cognitive modes, and interpersonal behaviors than participants in Cluster two. Hierarchical linear cluster analyses identified two very different personality styles in a sample of adults with ADHD, with implications for clinicians and future research.


[Surface modification of vascular tissue engineering biomaterial by low temperature plasma with NH3, CO2 and O2].
To study the biocompatibility of poly (hydroxybutyrate-hydroxyvalerate) (PHBV) modified by low temperature plasma with NH3, CO2, and O2 with canine Endothelial cells (ECs) and provide the better materials for blood vessel tissue engineering via surface modification. PHBV was modified by low temperature plasma with NH3, CO2, and O2, for 0, 5, 10, 20, and 30 min respectively, PHBV not modified was used as control group. The contact angle was measured. X-ray photoelectron spectroscopy was used to detect the surface elements. Canine endothelial cells (ECs) were cultured on the surface of PHBV and were stained with fluorescence isothiocyanate (FITC). Their morphological characteristics were observed with fluorescence microscopy, and the cell proliferation was detected with MTT assay. The surface contents of carbon of the PHBV modified by low temperature plasma with O2 and CO2 were 63.75% and 69.72%, both lower than that before modification (77.97%). The surface contents of oxygen of the PHBV modified by low temperature plasma with O2 and CO2 were 30.72% and 28.48%, both higher than that before modification (21.74%). The surface content of nitrogen of the PHBV modified by low temperature plasma with NH3 was 3.25%, remarkably higher than that before modification (0). The contact angles of different modification groups, especially those of the 5 min groups, were all significantly smaller than that of the unmodified group (P < 0.05 or P < 0.01). Compared with the control group, the cytocompatibility was better in the low temperature plasma modified groups. The surface of PHBV modified by low temperature plasma with NH3, CO2, and O2 has active groups and good biocompatibility, so the surface modification of low temperature plasma with NH3, CO2, and O2 can be a kind of effective method for the tissue engineering blood vessel.


The Continuing SAGA of TFIID and RNA Polymerase II Transcription.
Using improved techniques, Baptista et al. (2017) and Warfield et al. (2017) revisit fundamental questions about SAGA and TFIID function in yeast. They conclude that each complex independently contributes to the expression of all genes transcribed by RNA polymerase II.


An Evaluation of Primary Studies Published in Predatory Journals Included in Systematic Reviews From High-Impact Dermatology Journals: Cross-sectional Study.
Predatory publishing is a deceptive form of publishing that uses unethical business practices, minimal to no peer review processes, or limited editorial oversight to publish articles. It may be problematic to our highest standard of scientific evidence-systematic reviews-through the inclusion of poor-quality and unusable data, which could mislead results, challenge outcomes, and undermine confidence. Thus, there is a growing concern surrounding the effects predatory publishing may have on scientific research and clinical decision-making. The objective of this study was to evaluate whether systematic reviews published in top dermatology journals contain primary studies published in suspected predatory journals (SPJs). We searched PubMed for systematic reviews published in the top five dermatology journals (determined by 5-year h-indices) between January 1, 2019, and May 24, 2021. Primary studies were extracted from each systematic review, and the publishing journal of these primary studies was cross-referenced using Beall's List and the Directory of Open Access Journals. Screening and data extraction were performed in a masked, duplicate fashion. We performed chi-square tests to determine possible associations between a systematic review's inclusion of a primary study published in a SPJ and particular study characteristics. Our randomized sample included 100 systematic reviews, of which 31 (31%) were found to contain a primary study published in a SPJ. Of the top five dermatology journals, the Journal of the American Academy of Dermatology had the most systematic reviews containing a primary study published in an SPJ. Systematic reviews containing a meta-analysis or registered protocol were significantly less likely to contain a primary study published in a SPJ. No statistically significant associations were found between other study characteristics. Studies published in SPJs are commonly included as primary studies in systematic reviews published in high-impact dermatology journals. Future research is needed to investigate the effects of including suspected predatory publications in scientific research.


Volatile oil comparison of cotyledon leaves of chemotypes of Melaleuca alternifolia.
Oil quantity and quality were measured for the cotyledon leaves of the commercial terpinen-4-ol chemical variety of Melaleuca alternifolia. Oil yield obtained by ethanolic extraction was 3.8 micrograms per leaf or 2.6% (dry weight basis). The major components of the oil were alpha-pinene (7.4%), beta-pinene (12.0%) and terpinolene (27.3%). The non-commercial terpinolene chemical variety was found to be rich in 1,8-cineole (12.5%) and terpinolene (25.4%). The non-commercial 1,8-cineole chemical variety was rich in 1,8-cineole (37%) with significant quantities of alpha-pinene (15.5%), beta-pinene (23.3%) and terpinolene (10.9%). The cotyledon leaf composition, when compared with that of mature leaf from the same chemical variety, was found to be biased toward pinene and terpinolene biogenetic pathway constituents and hence not a good indicator of mature tree quality especially for the commercial terpinen-4-ol chemical variety. The implications of these analyses for the determination of M. alternifolia plantation quality and the understanding of oil formation, are discussed.


Deprenyl enhances the striatal neuronal damage produced by quinolinic acid.
We have tested the effect of deprenyl on the neurotoxicity induced by the injection of quinolinic acid within the striatum. Deprenyl was unable to prevent these quinolinic acid-induced damages, but enhanced the loss of several gamma-aminobutyric acid (GABA) positive subpopulations, the loss of the astroglial population and the activation of microglia produced by quinolinic acid. These effects are produced by deprenyl potentiation of dopamine actions since dopamine depletion produced by previous injection of the dopaminergic toxin 6-hydroxydopamine within the medial forebrain bundle overcomes deprenyl effects and the involvement of dopamine in the quinolinic acid-induced toxicity in striatum. In these conditions, quinolinic acid toxic action in striatum is significantly lower and similar in the animals treated with or without deprenyl. All these data justify why deprenyl worsen some pathological signals of disorders involving excitotoxicity. This also may be involved in other secondary effects described for deprenyl.


Earning opportunities and informal payment as influencing factors in medical students' speciality choice.
The Hungarian primary care system faces a severe shortage of family physicians. Medical students' perceptions of family medicine need to be known and medical students need to be given appropriate and comprehensible information about this speciality. The expected future salary is an important factor in career choice. Most of the family doctors are self-employed and the practices have a corrected capitation-type financing. Although the majority of health care services are covered by social health insurance and are provided for the insured patients free of charge, informal payment is an existing phenomenon with different motivations and consequences. This study aimed to investigate medical students' knowledge about their future earning opportunities and their attitudes towards informal payment. A cross sectional survey with a self-administered questionnaire was conducted. Each of the four Hungarian medical universities were represented by their medical students who attended family medicine lectures in person from December 2019 to April 2020. The students were asked about their career plans, about their estimations of current and ideal expected salaries and about the effect of expected income for the choice of specialisation. Their attitudes towards informal payment were assessed. Response rate was 67.3% (N = 465/691). Almost two-thirds of the participants were women. Only 5% of the respondents (N = 23/462) plan to work as a family doctor in the future. The vast majority (91.9%) of the students had already thought about their future income. On a 10-point Likert scale (1 = 'no influence', 10 = 'very big influence') 76% answered that the expected future income exerts a considerable (≥5 Likert points) influence on their career choice in general. The mean of the ideal expected monthly income of the residents, GPs and other specialists was €1154 ± 648, €1696 ± 904 and €2174 ± 1594, respectively. The mean of the monthly income for a GP, as estimated by the studenst, was €1140 in rural and €1122 in urban settings. More than four-fifths of the students (N = 375/453) rejected the practice of informal payment. Expected salaray is one important aspect in the career choice of medical students, students wish to have more information on this topic. The reported ideal incomes are higher than those expected. This points to a relevant gap. However, most of the students do not accept informal payment as a possibility to close this gap. The expected and the ideal income differ from the real incomes of Hungarian GPs - this indicates the need of bringing objectoive information to the students to enhance attractivity of GP as a carer choice.


Graded or threshold response of the tet-controlled gene expression: all depends on the concentration of the transactivator.
Currently, the step-wise integration of tet-dependent transactivator and tet-responsive expression unit is considered to be the most promising tool to achieve stable tet-controlled gene expression in cell populations. However, disadvantages of this strategy for integration into primary cells led us to develop an "All-In-One" vector system, enabling simultaneous integration of both components. The effect on tet-controlled gene expression was analyzed for retroviral "All-In-One" vectors expressing the M2-transactivator either under control of a constitutive or a new type of autoregulated promoter. Determination of luciferase activity in transduced cell populations indicated improvement of the dynamic range of gene expression for the autoregulated system. Further differences were observed regarding induction kinetics and dose-response. Most notably, introduction of the autoregulated system resulted in a threshold mode of induction, whereas the constitutive system exhibited pronounced effector-dose dependence. Tet-regulated gene expression in the applied autoregulated system resembles a threshold mode, whereby full induction of the tet-unit can be achieved at otherwise limiting doxycycline concentrations.


Real-time PCR based HLA-B*27 screening directly in whole blood.
The linkage between the occurrence of human leucocyte antigen B*27 (HLA-B*27) and ankylosing spondylitis or other related spondyloarthritides is well documented. PCR based methods are widely used for HLA-B*27 screening. To refine HLA-B*27 testing we aimed at establishing a real-time PCR protocol to detect the HLA-B*27 allele directly in blood samples, without DNA extraction. HLA-B*27 analysis was performed by two real-time PCRs using TaqMan primer-probe assays for B*27 specific amplification of exon 2 or exon 3 of the HLA-B gene together with a mutant of Taq polymerase for direct blood PCR. Conditions for direct blood PCR were optimized and the reliability of the direct blood PCR protocol was evaluated by re-genotyping over 200 blood samples from patients who previously underwent routine DNA-based HLA-B*27 testing. Heating blood samples at 95°C for 10 minutes significantly improved PCR performance. Results from real-time PCR based HLA-B*27 testing directly in blood of over 200 patients were in 100% concordance with results obtained by routine DNA-based HLA-B*27 genotyping. In summary, we present a reliable real-time PCR protocol for HLA-B*27 screening directly in whole blood supporting fast clarification of the presence of ankylosing spondylitis or other spondyloarthritides in suspected cases.


[Effect of administration of alpha-amanitine on Mn2+ - dependent poly-A-polymerase in rat liver nuclei].
Mn2+-dependent poly(A) polymerase activity tested in isolated rat liver nuclei is unchanged both in the absence and presence of exogenous poly(A) 30 min. after administration of a dose of alpha-amanitin that inhibits DNA-dependent RNA polymerase B. Longer times of treatment cause poly(A) polymerase to drop to 50% in the absence of poly(A) and to increase almost twice in its presence.