Application of humic acid and biofertilizers changes oil and phenolic compounds of fennel and fenugreek in intercropping systems.
The study investigated the effect of organic/biofertilizers in intercropping patterns on seed yield and yield components and essential oil, fatty acid, and phenolic compounds of fennel (Foeniculum vulgare L.) and fenugreek (Trigonella foenum-graecum L.). Experimental treatments included the application of humic acid (HA), biofertilizers (BFS), and the unfertilized control in five planting patterns [1 row fennel + 2 rows fenugreek intercropping (1F:2FG), 2 rows fennel + 2 rows fenugreek intercropping (2F:2FG), 2 rows fennel + 4 rows fenugreek intercropping (2F:4FG), and sole cropping of each species]. Sole cropping with BFS produced the highest seed yields for fennel (2233 kg ha-1) and fenugreek (1240 kg ha-1). In contrast, the 2F:2FG intercropping ratio with BFS yielded the maximum fixed oil content for fennel (17.4%) and fenugreek (8.3%). Application of HA and BFS enhanced oil yields by 66% and 75% in fennel and 40% and 57% in fenugreek, respectively. The 2F:2FG intercropping ratio with BFS produced the maximum essential oil constituents [(E)-anethole, estragole, and fenchone] in fennel. In addition, 2F:4FG with BFS and 1F:1FG with HA produced the highest unsaturated fatty acid (oleic and linoleic acids) concentration in both species. The 2F:2FG intercropping ratio with BFS and HA produced the highest chlorogenic acid and quercetin contents, respectively, in fennel. In contrast, the 2F:4FG intercropping ratio with HA produced the highest chlorogenic acid and caffeic acid contents in fenugreek. Intercropping fennel/fenugreek with BFS or HA improved the essential oil content (fennel only), fixed oil quality and quantity, and phenolic compounds and created a more sustainable cultivation system than sole cropping systems for both species under low-input conditions.


Objectivity for the research worker.
In the last decade, many problematic cases of scientific conduct have been diagnosed; some of which involve outright fraud (e.g., Stapel, 2012) others are more subtle (e.g., supposed evidence of extrasensory perception; Bem, 2011). These and similar problems can be interpreted as caused by lack of scientific objectivity. The current philosophical theories of objectivity do not provide scientists with conceptualizations that can be effectively put into practice in remedying these issues. We propose a novel way of thinking about objectivity for individual scientists; a negative and dynamic approach.We provide a philosophical conceptualization of objectivity that is informed by empirical research. In particular, it is our intention to take the first steps in providing an empirically and methodologically informed inventory of factors that impair the scientific practice. The inventory will be compiled into a negative conceptualization (i.e., what is not objective), which could in principle be used by individual scientists to assess (deviations from) objectivity of scientific practice. We propose a preliminary outline of a usable and testable instrument for indicating the objectivity of scientific practice.


D-amphetamine-induced behavioral sensitization: effect of lesioning dopaminergic terminals in the medial prefrontal cortex, the amygdala and the entorhinal cortex.
The behavioral sensitization produced by the repeated administration of D-amphetamine is known to involve dopaminergic neurons in the mesoaccumbens pathway. Induction of this process is dependent on action of the drug in the ventral tegmental area while its expression involves action in the nucleus accumbens. We studied here the putative involvement of dopaminergic projections other than the mesoaccumbens in this phenomenon. We examined the influence of dopaminergic lesion of the medial prefrontal cortex, the amygdala and the entorhinal cortex in the behavioral sensitization produced by repeated injections of amphetamine either peripherally or directly into the ventral tegmental area of the brain. The repeated administration of amphetamine induced a behavioral sensitization, with the ventral tegmental area a critical site for induction of the process. This sensitization to amphetamine cross-reacted with morphine and was still observed 2 weeks after cessation of the treatment. Bilateral 6-hydroxydopamine lesion of dopaminergic terminals in either the medial prefrontal cortex or the amygdala, but not in the entorhinal cortex, prevented the development of behavioral sensitization to amphetamine and the cross-sensitization with morphine, whether the amphetamine pretreatment was administered peripherally or directly into the ventral tegmental area. In conclusion, these results indicated that behavioral sensitization to amphetamine, which involves dopaminergic neurons of the ventral tegmental area, is also dependent on dopaminergic neurotransmission of the medial prefrontal cortex and amygdala but not of the entorhinal cortex.


A rare case of pulmonary atresia with ventricular septal defect with right-sided aortic arch.
Pulmonary atresia with ventricular septal defect is a congenital heart malformation in which a lack of continuity between ventricles and the pulmonary artery is accompanied by ventricular septal defect. We report a 3-year-old female patient, who presented with a history of shortness of breath and bluish lips. Computed tomography pulmonary angiography showed an absent main pulmonary artery, right pulmonary artery, left pulmonary artery and showed a defect that connects the right ventricle and left ventricle, which concluded a VSD (ventricular septal defect).


Finite element analysis of bone-implant biomechanics: refinement through featuring various osseointegration conditions.
A refinement technique is proposed for developing finite element models capable of simulating peri-implant bone conditions for bone types II, III, and IV at various degrees of osseointegration. The refined models feature a transition region between bone (cortical and cancellous) and implant and designate it partially to fully osseointegrated by assigning corresponding fractions of the bulk bone's elastic properties to this region. Bone is assumed to be transversely isotropic. The refined technique is implemented in a case study, in which osseointegrated (25-100%) peri-implant bone, type II, III, or IV with an implant attached, is loaded with a 100 MPa occlusal load. The biomechanics of this peri-implant bone was simulated and analysed. Results showed that the less dense bone must support higher stress and strain, especially at the cortical region. Higher degree of osseointegration induced higher stress but lower strain. Both the bone type and the osseointegration condition significantly affected the stress-strain relation. For minimum stress and strain, denser and more osseointegrated peri-implant bone is desirable. When bone failure criteria were set, based on the yield strength and strain of the bone, a higher degree of osseointegration was needed for the less dense peri-implant bone to be considered safe.


Hippocampectomy and feature-positive discrimination.
The effects of hippocampal lesions on feature-positive discrimination were investigated using the nictitating membrane response preparation. During training, animals received a simultaneous reinforced compound as the conditioned stimulus (CS+) and a non-reinforced element as the CS-. The compound consisted of a tone and a light, with the tone being more salient than the light. The light and tone served as the CS- in Expts. 1 and 2, respectively. There were no significant differences between hippocampectomized animals and the controls (cortical and sham) when the CS- was the light; however, when the more salient tone stimulus was the CS-, hippocampectomized animals exhibited high levels of responding to both the CS+ and CS- and failed to acquire the discrimination. The results are discussed in terms of attentional and response inhibition theories of hippocampal function.


The lantibiotic mersacidin is a strong inducer of the cell wall stress response of Staphylococcus aureus.
The lantibiotic mersacidin is an antimicrobial peptide of 20 amino acids that is ribosomally produced by Bacillus sp. strain HIL Y-85,54728. Mersacidin acts by complexing the sugar phosphate head group of the peptidoglycan precursor lipid II, thereby inhibiting the transglycosylation reaction of peptidoglycan biosynthesis. Here, we studied the growth of Staphylococcus aureus in the presence of subinhibitory concentrations of mersacidin. Transcriptional data revealed an extensive induction of the cell wall stress response, which is partly controlled by the two-component regulatory system VraSR. In contrast to other cell wall-active antibiotics such as vancomycin, very low concentrations of mersacidin (0.15xMIC) were sufficient for induction. Interestingly, the cell wall stress response was equally induced in vancomycin intermediately resistant S. aureus (VISA) and in a highly susceptible strain. Since the transcription of the VraDE ABC transporter genes was induced up to 1700-fold in our experiments, we analyzed the role of VraDE in the response to mersacidin. However, the deletion of the vraE gene did not result in an increased susceptibility to mersacidin compared to the wild type strain. Moreover, the efficacy of mersacidin was not affected by an increased cell wall thickness, which is part of the VISA-type resistance mechanism and functions by trapping the vancomycin molecules in the cell wall before they reach lipid II. Therefore, the relatively higher concentration of mersacidin at the membrane might explain why mersacidin is such a strong inducer of VraSR compared to vancomycin. In conclusion, mersacidin appears to be a strong inducer of the cell wall stress response of S. aureus at very low concentrations, which reflects its general mode of action as a cell wall-active peptide as well as its use of a unique target site on lipid II. Additionally, mersacidin does not seem to be a substrate for the resistance transporter VraDE.


Effects of 17 beta-oestradiol and 5 alpha-dihydrotestosterone on the expression of the muscle and heart types of lactate dehydrogenase isozymes in the masseter muscle of developing mice.
17 beta-oestradiol (E2) and/or 5 alpha-dihydrotestosterone (5 alpha-DHT) had no effect on the expression of isozymes of lactate dehydrogenase (LDH) in the masseter muscle of intact male mice. However, treatment with E2 restored the level of the muscle (M) type of LDH isozyme, which had been reduced by testectomy, to that found in intact male mice treated with vehicle only. Moreover, 5 alpha-DHT alone was more effective than E2 in increasing the relative level of this isozyme in testectomized mice. 5 alpha-DHT had a more significant effect on the increase in the relative level of the M-type LDH isozyme when combined with E2. These results suggest that androgens promote, in the presence of oestrogens, the postnatal changes in the characteristics of the masseter muscle of developing male animals.


Does BMI affect the clinical efficacy of proton pump inhibitor therapy in GERD? The case for rabeprazole.
Increased BMI is associated with a higher risk of gastroesophageal reflux disease. To investigate whether overweight/obesity (BMI≥25 kg/m(2)) affects rabeprazole clinical efficacy versus omeprazole in patients with erosive esophagitis (EE). Post-hoc analysis of EE healing rate and symptom response stratified by patient BMI was performed on data from a multicenter, double-blind, randomized, 4-to-8-week trial comparing EE healing with rabeprazole (20 mg daily) and omeprazole (20 mg daily). Analysis of variance, two-sample t-test, Blackwelder's test for equivalence, log-rank, and Cochran-Mantel-Haenszel tests were used to analyze comparisons. In the two BMI groups (<25 kg/m(2) and ≥25 kg/m(2) respectively), rabeprazole and omeprazole were equally effective for mucosal healing regardless of patient's BMI (N=542, P>0.05). However, in overweight/obese patients, rabeprazole was significantly faster than omeprazole in inducing heartburn relief during the first treatment week (P<0.0001). Results of this study show that the clinical efficacy of rabeprazole is maintained in overweight/obese patients with gastroesophageal reflux disease and suggest that this subgroup of patients may derive, from rabeprazole, even greater benefit than lean patients.


Separation and detection of the isomeric equine conjugated estrogens, equilin sulfate and delta8,9-dehydroestrone sulfate, by liquid chromatography--electrospray-mass spectrometry using carbon-coated zirconia and porous graphitic carbon stationary phases.
Equilin-3-sulfate and delta8,9-dehydroestrone-3-sulfate are two isomers found in equine conjugated estrogens that differ in structure only by the position of a double bond in the steroid B-ring. These geometric isomers were not resolved on a C18 column during the analysis of conjugated estrogen drug products by LC-MS using acetonitrile-ammonium acetate buffer as the mobile phase. While no separations of these two isomers were observed on C18 or other alkyl-bonded silica based phases using a variety of mobile phase conditions, partial separations were achieved on phenyl bonded silica phases with a resolution of 1.5 on a diphenyl phase, and baseline separations were readily achieved on two carbonaceous phases with resolutions routinely exceeding three on graphitic carbon-coated zirconia (Zr-CARB) and resolutions as high as 19 on porous graphitic carbon (Hypercarb). An examination of a selected few conjugated estrogens in the complex drug substance by LC-MS on Hypercarb is presented.


Robust fetal QRS detection from noninvasive abdominal electrocardiogram based on channel selection and simultaneous multichannel processing.
The purpose of this study is to provide a new method for detecting fetal QRS complexes from non-invasive fetal electrocardiogram (fECG) signal. Despite most of the current fECG processing methods which are based on separation of fECG from maternal ECG (mECG), in this study, fetal heart rate (FHR) can be extracted with high accuracy without separation of fECG from mECG. Furthermore, in this new approach thoracic channels are not necessary. These two aspects have reduced the required computational operations. Consequently, the proposed approach can be efficiently applied to different real-time healthcare and medical devices. In this work, a new method is presented for selecting the best channel which carries strongest fECG. Each channel is scored based on two criteria of noise distribution and good fetal heartbeat visibility. Another important aspect of this study is the simultaneous and combinatorial use of available fECG channels via the priority given by their scores. A combination of geometric features and wavelet-based techniques was adopted to extract FHR. Based on fetal geometric features, fECG signals were divided into three categories, and different strategies were employed to analyze each category. The method was validated using three datasets including Noninvasive fetal ECG database, DaISy and PhysioNet/Computing in Cardiology Challenge 2013. Finally, the obtained results were compared with other studies. The adopted strategies such as multi-resolution analysis, not separating fECG and mECG, intelligent channels scoring and using them simultaneously are the factors that caused the promising performance of the method.


Myeloid-derived suppressor cells promote tumor growth and sorafenib resistance by inducing FGF1 upregulation and fibrosis.
Considerable evidence implicates myeloid-derived suppressor cells (MDSCs) promote tumor progression and drug resistance. Sorafenib is the standard first-line therapy for advanced hepatocellular carcinoma (HCC). Clinical evidence indicates that sorafenib resistance is associated with increased MDSCs, by which MDSCs exerts these effects is obscure. This study aimed to investigate the mechanism of sorafenib resistance mediated by MDSCs. A syngeneic mouse-liver cancer cell line BNL was subcutaneously injected to build a tumor-bearing mouse model, and syngeneic MDSCs were adoptive transferred into the tumor-bearing mouse. Tumor tissue was obtained, and transcriptomic analysis of the tumor was carried out on RNAseq data. A coculture system was used to verify the crosstalk between MDSCs and BNL cells. Adoptive MDSCs transfer into tumor-bearing mice induced an increase of tumor-infiltrating MDSCs, which led to tumor growth and impaired antitumor activity of sorafenib in BNL HCC models. MDSCs transfer contributed to tumor fibrosis and tumor-associated fibroblast (CAF) activation, associated with fibroblast growth factor (FGF1) upregulation. In contrast, MDSC depletion by anti-Ly6G+ reduced fibrosis and increased sorafenib antitumor efficacy. Intriguingly, tumor-infiltrating MDSCs barely expressed FGF1. IL-6 derived from MDSCs increased FGF1 expression in BNL liver cancer cells, and anti-IL-6 attenuated this effect in vitro. MAPK pathway, one of the sorafenib targets, is the downstream signaling of FGF1 and is reactivated by MDSCs-mediated FGF1 upregulation. Our finding demonstrated that MDSCs led to tumor growth and sorafenib resistance via FGF1 upregulation and subsequent indirect CAF activation. We offered a novel mechanism of MDSCs-driven HCC progression and sorafenib resistance.


Activation of endothelial nitric oxide synthase is critical for erythropoietin-induced mobilization of progenitor cells.
The present study aimed to define the ability of erythropoietin (EPO) to mobilize hematopoietic stem cells (c-kit(+)/sca-1(+)/lin-1(-); KSL-cells) and hematopoietic progenitor cells (CD34(+) cells), including vascular endothelial growth factor receptor 2 expressing hematopoietic progenitor cells (CD34(+)/Flk-1(+) cells). We also sought to determine the role of endothelial nitric oxide synthase (eNOS) in EPO-induced mobilization. Wild type (WT) and eNOS(-/-) mice were injected bi-weekly with recombinant erythropoietin (EPO, 1000U/kg, s.c.) for 14 days. EPO increased the number of KSL, CD34(+), CD34(+)/Flk-1(+) cells in circulating blood of wild type mice. These effects of EPO were abolished in eNOS(-/-) mice. Our results demonstrate that, EPO stimulates mobilization of hematopoietic stem and progenitor cells. This effect of EPO is critically dependent on activation of eNOS.


A 61-Year-Old Man With Shortness of Breath, Ascites, and Lower Extremity Edema.
A 61-year-old man presented with an 18-month history of progressive shortness of breath on exertion, fatigue, worsening bilateral lower extremity edema, abdominal swelling, and increased assistance with activities of daily living. Pertinent past medical history included right-sided pneumonia secondary to Streptococcus pneumoniae that was complicated by empyema, requiring right-sided video-assisted thoracoscopic surgery with decortication 2 years earlier. He had a negative cardiac history, no recent travel in the last 3 years, and no known exposure to tuberculosis. His medications included aspirin and daily furosemide. His symptoms appeared to be refractory to diuretic therapy. Previous workup 6 months earlier included an echocardiography (ECHO) showing enlarged left and right atria with a normal ejection fraction, and a catheterization of the left side of the heart with reported normal left ventricular function and unobstructed coronary arteries.


Changes in stroke rehabilitation outcomes after the implementation of Japan's long-term care insurance system: a hospital-based study.
To explore the changes in stroke rehabilitation outcomes after the introduction of Japan's long-term care insurance (LTCI) system. Stroke patients discharged during a 3-yr period before and after the implementation of LTCI were compared (before-LTCI vs. after-LTCI). Outcome measures included onset to admission interval, length of stay, and correlation between discharge site and functional level at discharge. A total of 201 patients in the before-LTCI group and 252 patients in the after-LTCI group were eligible for the study. Shorter mean length of stay (P < 0.01) and higher rates of discharge to a rehabilitation facility (P < 0.01) were found in the after-LTCI group. Logistic regression analysis revealed that the patients with higher activities of daily living scores or ambulatory status at discharge were more likely to be discharged to home after inpatient rehabilitation in both groups (P < 0.01). The rate of discharge to home was similar in both groups. Within this rehabilitation hospital's experience, the mean length of stay was reduced after the implementation of the LTCI. Although it was one of the primary goals of the LTCI, the rate of discharge to home did not significantly increase. Further evaluation and modification of the LTCI and more efforts to improve a patient's activities of daily living and ambulatory status at discharge will be necessary to promote in-home care in Japan.


Facial nerve reconstruction using a muscle flap following resection of parotid gland tumours with thorough recipient bed preparation.
Recent innovations in facial nerve reconstruction procedures or 'restoration of facial expression', extremely important in patients' social activities, have provided some interesting findings. However, there has been little discussion of immediate facial nerve reconstruction following resection of a parotid carcinoma. In this article, details of our techniques and the concepts are presented. Ten patients underwent immediate facial nerve reconstruction following resection of a parotid carcinoma, with thorough 'recipient bed preparation', between October 2003 and October 2009. Postoperative radiotherapy was administered to seven cases, with an average radiation dosage of 55 Gy. Nerve reconstruction was performed using a sural nerve graft and either method 1, using a sternocleidomastoid and platysma muscle flap or method 2, using a pectoralis major muscle flap. Method 1 was used in six cases, and method 2 in four. Postoperative function was House Brackmann (HB) grade II in two cases, grade III in seven, grade IV in one and unassessable in one. Average Sunnybrook facial grading score was 50. No complications, such as contour deformity or Frey syndrome, were detected. We performed immediate facial nerve reconstruction following resection of parotid tumours with the emphasis on recipient bed preparation using a muscle flap, achieving the following objectives: (1) stable facial nerve reconstruction; (2) avoidance of contour deformity; and (3) prevention of Frey syndrome. We believe this is an extremely useful method, technically easy to perform and provides stable results.


Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and matrix metalloproteinase-2 in neoplasms and precursor lesions derived from cutaneous squamous cells: An immunohistochemical study.
Extracellular matrix metalloproteinase inducer (CD147) is a transmembrane glycoprotein involved in the regulation of matrix metalloproteinases (MMPs). The study investigated CD147 and MMP-2 expression in epidermis of cutaneous squamous lesions. CD147 and MMP-2 expressions were evaluated immunohistochemically in 44 specimens: 18 actinic keratoses (AK), 6 squamous cell carcinomas in situ (SCCIS), 13 squamous cell carcinomas (SCC; peritumoral and invasive portions assessed), and 7 normal skins. Patterns of expression were assessed, with MMP-2 in nuclei (MMP-2n) and cytoplasm (MMP-2c) evaluated separately. The expression of each marker was quantified using a calculated immunohistochemical/histologic score (H-score). Correlations were analyzed for the marker H-scores in each study group. Associations between H-scores and histopathologic parameters were also evaluated. CD147 H-score was the highest in SCC (invasive islands), followed by AK, SCCIS, and control specimens, respectively. MMP-2n and MMP-2c H-scores were the highest in AK, followed by SCCIS, SCC, and control specimens, respectively. MMP-2c and MMP-2n H-scores were significantly higher in peritumoral epidermis than in invasive islands of SCC. MMP-2c and CD147 H-scores were positively correlated in the peritumoral SCCs. CD147 H-score was positively correlated with tumor differentiation in SCC. The findings suggest that overexpression of CD147 plays a role in the development of SCC.


Second operation for repair of biliary atresia.
In our experience with biliary atresia, there are few cases amenable to reoperation for recurrent jaundice. All authors would agree that specific conditions such as complete bile flow recovery from the first operation followed by early recurrence should be an unquestionable case for revision of the anastomosis, inasmuch as no biologic signs of ongoing cholangitis can be traced. The same decision would apply to the problem of bile leakage after hepatoportocholecystostomy. In other cases, however, one should be aware that these reoperations expose the child to ascitis, poor healing of the abdominal wound, liver failure, and also bring with the decision to reoperate undue hopes to the parents of the child. Moreover, if the child should be a future candidate for liver transplantation, it may be wiser to avoid useless laparotomies and abdominal dissections that are known to complicate the task of hepatectomy.


Structure of ribosomal genes of mammalian cells in situ.
The structural and functional organization of ribosomal genes was investigated in situ in human circulating lymphocytes and a human tumour cell line, TG cells, Stereo-pair electron micrographs revealed that this ribosomal chromatin is not structured into nucleosomes, but composed of completely extended filaments, 2-3 nm thick. Despite its homogeneous morphological structure only a small portion of ribosomal chromatin present in the dense fibrillar component is transcriptionally active. This was demonstrated in TG cells by exclusive autoradiographic labelling on serial sections of the dense fibrillar component with 3H-uridine and by the distribution of RNase-gold particles in all the ribonucleoprotein (RNP) structures but not in the fibrillar centres. The extended, non-nucleosomal configuration of both transcriptionally inactive and active ribosomal chromatin could be explained by the peculiar protein composition of this chromatin. Staining with the acrolein-silver-methenamine technique for basic proteins indicated that all the completely extended ribosomal chromatin is devoid of histones, even after inactivation of transcription by actinomycin D. Stereo-electron-microscopical visualisation of the Ag-NOR proteins revealed a thread-like structural organization of these proteins with a spatial distribution superimposable on that of the ribosomal chromatin filaments.


Experimental and Computational Investigations of the Reactions between α,β-Unsaturated Lactones and 1,3-Dienes by Cooperative Lewis Acid/Brønsted Acid Catalysis.
The reactions of α,β-unsaturated δ-lactones with activated dienes such as 1,3-dimethoxy-1-[(trimethylsilyl)oxy]-1,3-butadiene (Brassard's diene) are barely known in literature and show high potential for the synthesis of isocoumarin moieties. An in-depth investigation of this reaction proved a stepwise mechanism via the vinylogous Michael-products. Subsequent cyclisation and oxidation by LHMDS and DDQ, respectively, provided six mellein derivatives (30-84 %) and four angelicoin derivatives (40-78 %) over three steps. DFT-calculations provide insights into the reaction mechanism and support the theory of a stepwise reaction.


Postural sway changes in genu recurvatum deformity during standing with manipulation of visual and proprioceptive systems.
Genu recurvatum deformity shifts the mechanical axis of lower extremity posteriorly which may disturb the balance and lead to injury. The aim of this research was to compare postural sways in genu recurvatum subjects with healthy controls while manipulating visual and proprioceptive systems. 10 female subjects with genu recurvatum (20.04 ± 4.64 years) and 11 female healthy controls (20.11 ± 4.64 years) participated in the study. The back knee angle was measured using a goniometer. Dynamic BIODEX balance system was used to measure the total, anteroposterior, and mediolateral postural sways while manipulating the stability of the base of support (stable versus unstable) and visual system (open versus closed eyes). During standing on the stable level, in both visual conditions, genu recurvatum subjects demonstrated greater total and anteroposterior postural sways than controls in both standing on the right and left foot (p<0.05). Similarly, when standing on the unstable base of support, in all conditions, the postural sways of genu recurvatum subjects were significantly greater than controls in both right and left foot (p<0.05). The vision had a main effect on postural control of genu recurvatum group (p=0.0001). There was a significant interaction between vision, the stability of the base of support and group factors (p=0.003). The results indicated that genu recurvatum subjects have a proprioceptive deficiency and they mainly rely on visual system inputs to control and maintain their balance. Thus, the proprioceptive system and balance control should be considered in assessment and designing an appropriate treatment regimen for genu recurvatum.


Imaging of cystic or cyst-like neck masses.
Cystic or cyst-like neck masses form a unique category within head and neck radiology with unique differential diagnoses. The precise anatomical location and imaging appearances are important for accurate diagnosis and formulating the differential diagnoses of cystic lesions in the neck. In vast majority of cases ultrasound, sometimes supplemented by fine-needle aspiration cytology (FNAC), is adequate for pre-treatment assessment. For large, deep-seated lesions assessment using magnetic resonance imaging (MRI) or computed tomography (CT) often provides useful supplementary information. Radiologists should be aware of imaging findings of common cystic neck masses to help in their appropriate management.


The attitudes of student nurses towards obese patients: A questionnaire study exploring the association between perceived causal factors and advice giving.
Nurses acting in primary care roles are central in addressing obesity as a public health priority. Nurses with a lower Body Mass Index have been shown to have negative attitudes towards obesity. Additionally, where the patient is perceived as being responsible for their excess weight, a negative attitude may also be held. The extent to which negative attitudes may influence the advice provided by nurses to obese patients is unknown. The present paper sought to examine whether the level of advice offered to obese patients by student nurses is associated with (i) the perceived causal factors of obesity, (ii) attitudes towards obesity and (iii) body mass index of the nurse. Participants were 92 student nurses from a university in the Midlands, UK. Participants received one of four patient vignettes; three were affected by obesity, with reference to either a behavioural, social, or medical cause; and the fourth was normal weight. Student nurses elected advice they would offer from five staged options (from no active involvement in advising the patient, through to discussing dietary advice). Attitudes towards obesity and social desirability were measured using validated questionnaires. No association was found between the level of advice offered and either the causal factor of obesity, the student nurses' attitude towards obesity, or the nurses' Body Mass Index. Most students endorsed the highest level of advice-a patient centred discussion. Findings show that advice giving by student nurses was not associated with perceived cause of obesity, or attitude, but is in line with the current Nursing and Midwifery Council (2015) recommendations. That is, most students endorsed a patient centred discussion. This suggests that professional training guidelines for the non-judgemental treatment of obese patients are not only being recognised, but implemented.


Synthesis of a magnetic SBA-15-NH2@Dual-Template Imprinted Polymer for solid phase extraction and determination of Pb and Cd in vegetables; Box Behnken design.
In this study, a simple one-step method was applied for extraction and determination of lead and cadmium. The significant variables in extraction and pre-concentration were identified using analysis of variance and their behavior was modeled. Dual-template imprinted polymer was synthesized on modified Mesoporous silica structures coated with Fe3O4 magnetic nanoparticles. The optimum condition was 6.12 for pH, 40.62 mg for the polymer amount and 17.38 for the ultrasonic time. Concentration range, correlation coefficient, limit of detection and relative standard deviation for lead were reported to be 0.5-950, 0.9988, 0.35 μg L-1 and 3.5%, respectively. For cadmium the above mentioned figure of merits were 0.3-980, 0.9969, 0.15 μg L-1 and 2.4%, respectively. The adsorption capacities for lead and cadmium were reported to be 10.28 and 10.38, while their imprinting factors were 5.89 and 6.36, respectively.


Pityriasis versicolor in school children in Cross River State of Nigeria.
Out of 2,353 primary school children aged 4-16 years in Cross River State of Nigeria examined, 88 (3.7%) showed lesions mycologically proven to be pityriasis versicolor. Incidence was highest (6.3%) in children aged 12-16. Lesions were much more common on the face than on other sites.


Morphology of rat gastric mucosal damage, defense, and restitution in the presence of luminal ethanol.
The morphology of ligated rat stomachs filled with absolute ethanol for 1, 7, 15, 30, and 60 min was studied. With interrupted blood circulation, the entire mucosa was destroyed within minutes. With intact circulation, the mucosae remained macroscopically normal or developed visible lesions. Areas with lesions had extensive surface and gland cell disruption and were hemorrhagic and hyperemic. Histologically, nonlesion sites had about 92% of the mucous cells on the surface and upper gastric pits destroyed within 1 min. Detached necrotic cells and an accumulation of an exudate with fibrin fibers formed a thick layer over the damaged mucosal surface. Intact cells from the gastric pits started migrating over the denuded basal lamina and after 7 min about 4% of the surface was reepithelialized. Within the next 8 min there was a sharp increase in mucosal restitution to about 54%. After 30 min 84% of the mucosa was restituted and there was only a slight increase to about 87% after 1 h of continuous exposure to ethanol. After 30 min the ethanol was diluted to about 40% vol/vol. Focal geyserlike eruptions of plasma containing polymerized fibrin were visible at sites of epithelial discontinuity. Restitution of the mucosal surface in the presence of luminal ethanol may be facilitated by the favorable microenvironment created by the thick unstirred layer formed by the mucoid coat of necrotic cells, fibrin, and continued plasma shedding.


Systematic review: Clinical outcomes of discontinuation of oral antivirals in hepatitis B-related liver cirrhosis.
Discontinuation of Nucleos(t)ide analogs (NAs) remains one of the most controversial topics in the management of hepatitis B-related liver cirrhosis. However, clinical outcomes after NAs discontinuation have not been studied. The aim of this systematic review is to evaluate existing data on clinical outcomes of NAs withdrawal in chronic hepatitis B (CHB) patients with cirrhosis. A literature search (until May 2022) was performed in order to identify all published studies including hepatitis B-related cirrhotic patients who discontinued NAs in virological remission with off-therapy follow-up >12 months. Nineteen studies with 1,287 hepatitis B-related cirrhotic patients were included. Most cirrhotic patients were compensated and achieved complete virological suppression when they stopped the antiviral therapy. The pooled proportions of virological relapse and clinical relapse after NAs discontinuation in cirrhotic patients were 55.23 (95% CI: 40.33-69.67) and 43.56% (95% CI: 26.13-61.85), respectively. HBsAg loss was observed in 56 of 500 (pooled proportion = 13.68%, 95% CI: 5.82-24.18) cirrhotic patients. And the pooled proportions of HCC development, hepatic decompensation and overall mortality were 8.76 (95% CI: 2.25-18.95), 3.63 (95% CI: 1.31-7.03), and 0.85% (95% CI: 0.35-1.57), respectively, after NAs discontinuation in cirrhotic patients. In hepatitis B-related compensated cirrhosis, who have achieved complete virological suppression, discontinuation of oral antivirals still carries a high relapse rate, but the incidence of adverse events is generally low and controlled during follow-up of at least 12 months. Of attention is that discontinuation of NAs can achieve a high rate of HBsAg seroclearance. This study may be helpful in the management of NAs in cirrhotic patients. http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020170103.


Effect of storage temperature on sperm cryopreservation.
To evaluate the influence of cryopreservation temperature on human sperm motility and morphology. Controlled study, investigator was blinded to the type of cryopreservation. University-based andrology laboratory. Sixteen semen samples with normal motility and sperm count from men after a fertility work up. Semen aliquots were either stored in a mechanical freezer at -70 degrees C or in liquid nitrogen at -196 degrees C for 7 days or 3 months. Test yolk buffer was used as a cryoprotectant. With use of a programmable freezing unit, all samples were cooled at a controlled rate. Sperm motility and morphology. After 7 days of cryopreservation, there was a greater decrease in sperm motility among specimens maintained at -70 degrees C than among those maintained at -196 degrees C (47% versus 39% decrease). The difference in sperm motility was even greater after 3 months of cryopreservation (72% versus 39% decrease). No difference in postthaw sperm morphology was detected among sperm preserved at -70 degrees C versus -196 degrees C. Sperm cryopreservation at -196 degrees C is superior to cryopreservation at -70 degrees C. Sperm can be stored at -70 degrees C for a short period of time with a relatively modest loss of motility.


Estimating changes in flood risks and benefits of non-structural adaptation strategies - a case study from Tyrol, Austria.
Flood damage has increased significantly and is expected to rise further in many parts of the world. For assessing potential changes in flood risk, this paper presents an integrated model chain quantifying flood hazards and losses while considering climate and land use changes. In the case study region, risk estimates for the present and the near future illustrate that changes in flood risk by 2030 are relatively low compared to historic periods. While the impact of climate change on the flood hazard and risk by 2030 is slight or negligible, strong urbanisation associated with economic growth contributes to a remarkable increase in flood risk. Therefore, it is recommended to frequently consider land use scenarios and economic developments when assessing future flood risks. Further, an adapted and sustainable risk management is necessary to encounter rising flood losses, in which non-structural measures are becoming more and more important. The case study demonstrates that adaptation by non-structural measures such as stricter land use regulations or enhancement of private precaution is capable of reducing flood risk by around 30 %. Ignoring flood risks, in contrast, always leads to further increasing losses-with our assumptions by 17 %. These findings underline that private precaution and land use regulation could be taken into account as low cost adaptation strategies to global climate change in many flood prone areas. Since such measures reduce flood risk regardless of climate or land use changes, they can also be recommended as no-regret measures.


Refractory period impairment in sural nerves of diabetics.
Polyneuropathy is a frequent complication in diabetics. In a non-selected group of 65 diabetics, 30 patients had clinical signs of neuropathy. These patients had more significant changes in electrophysiological parameters than patients without clinically evident polyneuropathy. Significant reduction of sural nerve conduction velocity was observed in 16 of 30 patients with and in 4 of 35 diabetics without clinical signs of polyneuropathy. Additional information was obtained when paired stimuli were applied and the test response latency was measured. Stimulus intervals of 3 ms gave the highest quota of information about involvement of the sural nerve. Significant prolongation of the test response in paired stimulation at intervals of 3 ms was found in 21 of 30 patients with clinically apparent diabetic polyneuropathy and in 16 of 35 diabetics without clinical signs of polyneuropathy.


Pleural pressure from abdominal to pulmonary rib cage: sweep of the lung border.
Pleural pressure was measured by a capsule placed in the superior part of right 8th or 9th intercostal space of dogs in left lateral posture. Transit of lung border was observed through endothoracic fascia at sides of the capsule. During inspiration the capsule membrane faced sequentially: diaphragm, lung border, lung; vice versa during expiration. Pressure on the diaphragm at end expiration was -5.3 +/- 0.5 cm H2O, reflecting outward recoil of the rib cage. At transit of lung border during inspiration (bor. I) a marked negative pressure spike occurred; a smaller spike occurred at expiratory transit (bor. E). These spikes should reflect pleural liquid pressure at lung border. At bor. I lung volume and radial displacement of rib 9 or 10 were greater during active than passive ventilation, whereas at bor. E they were similar under both conditions. Hence, during spontaneous inspiration displacement of lung border lags behind lung and rib expansion. Speed of lung border (assessed from duration of negative spike) ranged from 0.8 to 2.3 cm/sec during spontaneous breathing. On average it was similar at bor. I and bor. E, while air flow was greater at bor. I.


Tuberculous altantoaxial subluxation: a case report with review of literature.
Involvement of upper cervical and craniovertebral junction is rare but might lead to lethal consequences if the diagnosis is delayed. We present a case of atlantoaxial joint tuberculosis, resulting in gross instability of the joint. The patient was treated with antitubercular medication combined with posterior decompression and transarticular screw fixation. Patient improved neurologically, and clinical and radiological improvements were maintained at the latest follow-up of 2 years.


Lyotropic liquid crystal as a real-time detector of microbial immune complexes.
To design a simple method for the detection of microbe-immune complexes exploiting the optical and elastic properties of a biocompatible liquid crystalline material. Aqueous solution of disodium cromoglycate (DSCG), a lyotropic chromonic liquid crystal (LCLC), was aligned in a glass cell so as to be optically dark in polarized light. Immune complexes of at least three to four organisms altered the DSCG alignment such that polarized light was subsequently transmitted to reveal the presence of pathogens as optically bright regions around the immune complexes. This work describes the first method to detect viable micro-organisms in real time using LCLC. This technique provides a powerful tool for the detection of microbes in minutes, exploiting the optical and elastic properties of LC.


Management of helical adhesion malformation.
Congenital auricular anomalies are common, however very few articles in the English literature address helical adhesion malformation, whereby the helix is adhered to the scapha. We describe a surgical approach to correct helical adhesion malformation which, unlike previously described methods, is simpler and results in an inconspicuous scar on the back of the ear. We illustrate our technique with an 11-year-old girl with bilateral helical adhesion malformations. Satisfactory ear shape was achieved bilaterally without complication. Meticulous dissection over the helix and exposure beyond the adhesion is of paramount importance in successfully correcting this malformation. Through a posterior auricular incision, this wide exposure and visualisation of the helix can be attained, with the added benefit of a scar hidden on the back of the ear.


Mycophenolate mofetil strongly potentiates the anti-herpesvirus activity of acyclovir.
We demonstrate that the novel immunosuppressive agent mycophenolate mofetil (MMF), that has been approved for use in kidney transplant recipients, strongly potentiates the antiviral activity of acyclovir in murine models for herpesvirus infections. Hairless mice that were infected intracutaneously with herpes simplex virus type 1 were treated systemically with ACV (20 mg/kg per day) and topically with 5% MMF. Combined use of both drugs resulted in an almost complete protection, whereas single use of either compound had virtually no effect. When athymic-nude mice were infected with an ACV-resistant (ACVr)-thymidine kinase-deficient (TK-) HSV-2 strain, combined use of systemically administered ACV (100 mg/kg per day) and topically applied MMF (5%) protected 60% of the animals against the infection, whereas all mice treated with either drug alone succumbed. Since transplant recipients under MMF therapy may develop opportunistic herpesvirus infections, requiring treatment with acyclovir (or valaciclovir), our findings have important implications for the treatment of these herpesvirus infections.


Multi-target plasmid controls for conventional and real-time PCR-based serotyping of Streptococcus pneumoniae.
Serotyping of Streptococcus pneumoniae is an integral part of disease surveillance, with over 92 serotypes characterized to date using traditional serotyping. To identify the most predominant disease causing serotypes, molecular serotyping methods are now increasingly being used, like conventional and real-time multiplex PCR (cmPCR and rmPCR, respectively). Given that cmPCR consists of eight reactions spanning 41 targets, and rmPCR consists of seven triplex reactions, standardizing positive controls for these assays is challenging. As such, a 43-target plasmid for cmPCR (pSpn-CM1) and a 23 target plasmid for rmPCR (pSpn-RM1) were designed and validated. Plasmid pSpn-RM1 was designed and synthesized as chimeric DNA sequences to include all PCR target primer binding sites sequences for cmPCR. Plasmid pSpn-RM1 consisted of all primer and probe sequences required for rmPCR. Additional targets (lytA and cpsA) were included in both plasmids for quantification, following their propagation and purification from Escherichia coli. When tested using the cmPCR reactions, all targets could be reproducibly be detected using pSpn-CM1 as template, with good amplicon visibility at a concentration of 1.4 (± 0.3) × 105 copies/ml was used. For the rmPCR reactions, all targets were reproducibly amplified with a concentration of 1.1 (± 0.2) × 104 copies/ml of pSpn-RM1, and the PCR efficiency for each target was equivalent to DNA extracted from representative S. pneumoniae serotypes. These quantifiable multi-target plasmids simplify the preparation of controls for PCR-based serotyping of S. pneumoniae, and methods herein could be extended to other highly multiplexed PCR assays.


A pilot study of the feasibility of empagliflozin in recent-onset type 1 diabetes.
Sodium-glucose linked transporter (SGLT) inhibitors could improve glycaemia and simplify insulin regimens in recent-onset type 1 diabetes (T1D), provided they were well-tolerated and safe. This study aimed to determine the feasibility and safety of a SGLT inhibitor for the treatment of recent-onset T1D. An open label, prospective pilot study in adults with recent-onset T1D was performed. Empagliflozin, 25 mg orally daily, was given in combination with insulin and multidisciplinary care during a 24-week treatment phase, followed by wash-out visits at weeks 30 and 36. Fourteen participants (4 women; median age 26 years) began and 13 completed the study. No treatment-emergent serious adverse events were observed, with fatigue and genital infection the most common side-effects. Four participants stopped mealtime insulin for at least one month when taking empagliflozin. At week 24, median weight, HbA1c and insulin dose decreased by 4.4 kg, 1.5% (17 mmol/mol) and 0.03 units/kg/day, respectively. Meal-stimulated C-peptide was maintained during the treatment phase and then decreased at 36 weeks. Treatment of adults with empagliflozin within 100 days of T1D diagnosis appeared safe and was associated with improved clinical outcomes. These findings justify a definitive trial to determine if SGLT inhibitors simplify treatment regimens and improve clinical outcomes in recent-onset T1D. ACTRN12617000016336.


An automated method for high-throughput protein purification applied to a comparison of His-tag and GST-tag affinity chromatography.
Functional Genomics, the systematic characterisation of the functions of an organism's genes, includes the study of the gene products, the proteins. Such studies require methods to express and purify these proteins in a parallel, time and cost effective manner. We developed a method for parallel expression and purification of recombinant proteins with a hexahistidine tag (His-tag) or glutathione S-transferase (GST)-tag from bacterial expression systems. Proteins are expressed in 96-well microplates and are purified by a fully automated procedure on a pipetting robot. Up to 90 microgram purified protein can be obtained from 1 ml microplate cultures. The procedure is readily reproducible and 96 proteins can be purified in approximately three hours. It avoids clearing of crude cellular lysates and the use of magnetic affinity beads and is therefore less expensive than comparable commercial systems. We have used this method to compare purification of a set of human proteins via His-tag or GST-tag. Proteins were expressed as fusions to an N-terminal tandem His- and GST-tag and were purified by metal chelating or glutathione affinity chromatography. The purity of the obtained protein samples was similar, yet His-tag purification resulted in higher yields for some proteins. A fully automated, robust and cost effective method was developed for the purification of proteins that can be used to quickly characterise expression clones in high throughput and to produce large numbers of proteins for functional studies.His-tag affinity purification was found to be more efficient than purification via GST-tag for some proteins.


Late presentation to care for HIV infection in Croatia and the effect of interventions during the Croatian Global Fund Project.
There are limited data on how HIV prevention interventions affect individuals presenting to care in settings with a low-level HIV epidemic. We examined whether interventions undertaken during the Croatian Global Fund Project in 2004-2006 had an influence on patients entering care. The number of men who have sex with men (MSM) presenting in 2004-2006 (n = 86) was 59% higher than in 2001-2003 (n = 54); in heterosexual patients the increase was 14% (n = 51 in 2001-2003; n = 58 in 2004-2006). MSM presented at a younger age (median 32 years) in 2004-2006 than in 2001-2003 (median 36 years). Late presentation to care was found in 28% of MSM and in 59% of heterosexual patients in 2004-2006. MSM were less frequently late presenters in 2004-2006 compared with 2001-2003 (odds ratio, 0.48; 95% confidence interval, 0.24 to 0.99; P = 0.046). Additional strategies for earlier initiation of care must be developed for MSM and particularly for heterosexual patients.


Acute acral pustulosis.
We report a patient with a pustular eruption in an acral distribution that developed abruptly 4 days after a streptococcal pharyngitis. The histology showed an intraepidermal vesicle filled with neutrophils with an underlying lymphocytic vasculitis. Direct immunofluorescence demonstrated heavy deposition of C3 within the vessel walls. In addition, circulating immune complexes were found.


Applying network analysis to understand the relationships between impulsivity and social media addiction and between impulsivity and problematic smartphone use.
Prior studies have revealed the relationships between impulsivity and social media addiction (SMA) and between impulsivity and problematic smartphone use (PSU) based on total scores on standardized self-report scales. However, there has been a lack of studies exploring how the dimensions of impulsivity and components of SMA or PSU are interrelated. The present study aimed to investigate the structural relationships between the dimensions of impulsivity and components of SMA and PSU and determine the critical bridge node using network analysis. A total of 325 healthy adults aged 18-36 years participated in the study. SMA and PSU were assessed using the Bergen Social Media Addiction Scale (BSMAS) and Smartphone Application-Based Addiction Scale (SABAS), respectively. Impulsivity was measured by the Barratt Impulsiveness Scale Version 11 (BIS-11). Network analysis was used to construct an SMA-Impulsivity network and a PSU-Impulsivity network. Bridge centrality (bridge expected influence, BEI) was estimated to identify influential bridge nodes. In addition to relationships within each community, network analysis revealed that the dimensions of impulsivity were closely associated with the components of SMA and PSU. Particularly, I2 "motor impulsivity" had a relatively strong connection with SMA3 "mood modification" and SMA4 "relapse" in the SMA-Impulsivity network, and with PSU2 "conflict" and PSU5 "withdrawal" in the PSU-Impulsivity network. Moreover, I2 "motor impulsivity" was identified as the most critical bridge node in both networks. These findings demonstrate potential pathways between different dimensions of impulsivity and the components of SMA and PSU, providing new evidence relevant to understanding the underlying mechanisms that account for how highly impulsive individuals develop SMA and PSU, and highlight the critical bridge node-motor impulsivity-that may be a promising and effective target for the prevention and treatment of SMA and PSU.


Suppression of transformed phenotypes in intraspecific somatic cell hybrid clones between the c-myc activating mouse plasmacytoma line and normal cells.
The role of normal-cell-derived chromosome 15 in suppressing transformed phenotypes was studied in intraspecific hybrid clones between the c-myc oncogene activating BALB/c mouse plasmacytoma (S194) cells and normal spleen cells or fibroblasts from CBA/H-T6 mice. All the hybrid clones between S194 and normal spleen cells grew very rapidly in suspension and formed colonies in soft agar. In contrast, the hybrid clones between S194 and normal fibroblasts grew slowly in an attached form. They were divided into 2 groups on the basis of their morphology and growth properties: most clones showed flat type morphology, and no colony formation was seen in soft agar, while some clones grew in a piled-up fashion and formed colonies in soft agar. The hybrid clones between S194 and normal spleen cells lost some normal-cell-derived chromosomes but retained most tumor-derived marker chromosomes including the t(12;15) chromosome which carried the activated c-myc oncogene. On the other hand, hybrid clones between S194 cells and normal fibroblasts retained almost all chromosomes from both parental cells. With respect to retention of normal-cell-derived chromosome 15, both the flat and piled-up type clones retained 2 copies each of the t(14;15) and T6 marker chromosomes, the normal counterparts of the t(12;15) chromosomes. Our results suggest that the transformed phenotypes of the hybrid clones between S194 cells and normal fibroblasts are negatively modulated by normal-cell-derived chromosomes but not by normal-cell-derived chromosome 15 alone.


Interaction of methemoglobin with GDA/n-C5H11OH/water assemblies.
In the present paper, we studied the interaction between n-dodecylammonium alpha-glutamate (GDA)/n-C5H11OH/H2O assemblies and methemoglobin by UV-vis spectroscopy, X-ray diffraction, electron spin resonance (ESR), rheology, and freeze-fractured transmission electron microscopy (FF-TEM). It is found that W/O microemulsion forms at a lower n-pentanol content and O/W microemulsion forms at a lower water content with the addition of methemoglobin. The existence of methemoglobin reduces the hexagonal liquid crystal region, while the lamellar liquid crystal region is little changed in the presence of methemoglobin. Moreover, methemoglobin and GDA/n-C5H11OH/H2O assemblies can affect their structures and properties and the change in behavior is dependent on the content of methemoglobin and the composition and structure of the GDA/n-C5H11OH/H2O system. The relationship among the changes in the structure and properties of GDA/n-C5H11OH/H2O assemblies, the content of methemoglobin, and the composition and structure of GDA/n-C5H11OH/H2O assemblies may provide some important theoretical information for elucidation of the interaction between methemoglobin and blood cell membrane and may also be helpful for the cure of some blood diseases.


Abnormal Bursting as a Pathophysiological Mechanism in Parkinson's Disease.
Despite remarkable advances in Parkinson's disease (PD) research, the pathophysiological mechanisms causing motor dysfunction remain unclear, possibly delaying the advent of new and improved therapies. Several such mechanisms have been proposed including changes in neuronal firing rates, the emergence of pathological oscillatory activity, increased neural synchronization, and abnormal bursting. This review focuses specifically on the role of abnormal bursting of basal ganglia neurons in PD, where a burst is a physiologically-relevant, transient increase in neuronal firing over some reference period or activity. After reviewing current methods for how bursts are detected and what the functional role of bursts may be under normal conditions, existing studies are reviewed that suggest that bursting is abnormally increased in PD and that this increases with worsening disease. Finally, the influence of therapeutic approaches for PD such as dopamine-replacement therapy with levodopa or dopamine agonists, lesions, or deep brain stimulation on bursting is discussed. Although there is insufficient evidence to conclude that increased bursting causes motor dysfunction in PD, current evidence suggests that targeted investigations into the role of bursting in PD may be warranted.


JP-1366: A novel and potent potassium-competitive acid blocker that is effective in the treatment of acid-related diseases.
The global prevalence of GERD is substantially increasing each year, and GERD is a chronic disease that reduces the quality of life of patients. The efficacy of conventional drugs is diverse, and most require long-term or lifetime administration; thus, the development of more effective therapeutic agents is needed. Herein, a more effective treatment for GERD was tested. We investigated whether JP-1366 affected gastric H+/K+-ATPase activity and used the Na+/K+-ATPase assay to confirm the selectivity of H+/K+-ATPase inhibition. To clarify the mechanism of enzyme inhibition, JP-1366 and TAK-438 were analyzed by Lineweaver-Burk. Also, we investigated the effects of JP-1366 in various models involving reflux esophagitis. We found that JP-1366 mediates strong, selective, and dose-dependent inhibition of H+/K+-ATPase. We found that JP-1366 significantly suppressed gastric acid secretion in histamine-treated pylorus-ligated rats in a dose-dependent manner. Additionally, we confirmed that JP-1366 inhibited histamine-stimulated gastric acid secretion in the HPD model. JP-1366 exhibited a more than 2-fold higher inhibitory effect on esophageal injury than TAK-438 in GERD lesions and had a more potent inhibitory effect in indomethacin- or aspirin-induced gastric ulcer rat models than TAK-438. Additionally, JP-1366 inhibited gastric ulcers. These results support the possibility that JP-1366 is a good candidate drug for treating acid-related diseases.


Why lose an in vitro fertilization cycle when stimulation fails?
Different protocols using agonists of GnRH-a have been proposed for the ovarian stimulation in IVF cycles. In case of stimulation failure with the flare-up protocol, we have investigated whether an immediate switch to pituitary blockade by the long-acting analog may avoid the cycle to be canceled. This procedure allows a rescue of cycles among poor responders and does not have any deleterious effect on the recruitment of follicles, oocyte quality, fertilization, and pregnancy rates.


A forgotten disease reminds itself with a rare complication.
Diagnosed cases of sexually transmitted diseases (STD) represent tip of the iceberg and Donovanosis in one of them. Donovanosis, in most cases is obvious clinically, but rely for its confirmation on the demonstration of donovan bodies in histological sections and cytological preparation. In an extremely rare setting, this disease may get complicated by the development of squamous cell carcinoma. We report this occurrence in an 18-year-old girl to review the currently forgotten status of donovanosis amongst the STDs and the poor outcome of the disease if left untreated.


Ancyronyx Erichson, 1847 (Coleoptera, Elmidae) from Mindoro, Philippines, with description of the larvae and two new species using DNA sequences for the assignment of the developmental stages.
Ancyronyx buhid sp. n. and Ancyronyx tamaraw sp. n. are described based on adults and larvae, matched using their cox1 or cob DNA sequence data. Additional records of Ancyronyx schillhammeri Jäch, 1994 and Ancyronyx minerva Freitag & Jäch, 2007 from Mindoro are listed. The previously unknown larva of Ancyronyx schillhammeri is also described here, aided by cox1 data. The new species and larval stages are described in detail and illustrated by SEM and stacked microscopic images. Keys to the adult and larval Ancyronyx species of Mindoro and an updated checklist of Philippine Ancyronyx species are provided. The usefulness as bioindicators, the phylogenetic relationships and biogeographic aspects affecting the distribution patterns are briefly discussed.


Finding effective strategies for teaching ethics: a comparison trial of two interventions.
To compare the effects of two teaching methods (written case analyses and written case analyses with group discussion) on students' recognition and assessment of common ethical dilemmas. In 1999-2000, all third-year students at the University of Washington School of Medicine on a pediatrics clinical rotation participated in the study. Eighty students were based in Seattle and 66 were in community sites in a five-state area. All students received three scenarios with written instructions for ethical analysis, submitted written answers, and received written feedback from a single evaluator. The Seattle students also participated in an hour-long, one-time discussion group about the cases. All students submitted a final case analysis. Four components of the case analyses were evaluated: ability to identify ethical issues, see multiple viewpoints, formulate an action plan, and justify their actions. One investigator evaluated a masked subset of the case analyses from both groups to assess whether teaching method affected the students' ability to recognize and assess ethical problems. Forty-eight of 146 available case analysis sets (each set included three initial analyses plus one final analysis) were masked and coded. Performances on the initial analyses were similar in both groups (p >.2-.8). The discussion group had a higher absolute increase in total score (p =.017) and in ability to formulate a plan (p =.013) on the final case analysis. Performances otherwise remained largely similar. Students' recognition and assessment of ethical issues in pediatrics improves following a case-based exercise with structured feedback. Group discussion may optimize the learning experience and increase students' satisfaction.


Use of a plate-rod construct and principles of biological osteosynthesis for repair of diaphyseal fractures in dogs and cats: 47 cases (1994-2001).
To determine outcome for dogs and cats with diaphyseal fractures in which a plate-rod construct was used for fracture repair. Retrospective study. 35 dogs and 12 cats. Medical records and radiographs were reviewed to obtain information concerning signalment, fracture severity, construct design, time to radiographic union, complications, and outcome. Clients were contacted by telephone to obtain information on complications, limb usage, and overall satisfaction with the procedure. 31 femoral, 9 humeral, and 7 tibial fractures were assessed. Thirteen fractures consisted of 2 fragments, 22 consisted of 3 to 5 fragments, and 12 consisted of > 5 fragments. Forty-six of 47 (98%) fractures reached union. Mean +/- SD times to radiographic union were 7.5 +/- 2.7 weeks for the dogs and 4.8 +/- 1.3 weeks for the cats. There were 4 short-term, minor complications and 15 long-term complications (2 major and 13 minor). Owners of 21 of 30 dogs (70%) and 9 of 12 cats reported that their animals had normal limb function. Twenty-six of 28 dog owners (93%) and 12 of 12 cat owners indicated that they were satisfied with results of the procedure. As surgery time increased, time to union also increased. Time to union for fractures with > 5 fragments was significantly shorter than time to union for fractures with < or = 5 fragments. Results suggest that plate-rod constructs can successfully be used for repair of diaphyseal fractures of a wide range of severity in dogs and cats.


Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP/LOXL2 pathway.
Lysyl oxidase-like 2 (LOXL2) is an extracellular copper-dependent enzyme that plays a central role in fibrosis by catalyzing the crosslinking and deposition of collagen. Therapeutic LOXL2 inhibition has been shown to suppress liver fibrosis progression and promote its reversal. This study investigates the efficacy and underlying mechanisms of human umbilical cord-derived exosomes (MSC-ex) in LOXL2 inhibition of liver fibrosis. MSC-ex, nonselective LOX inhibitor β-aminopropionitrile (BAPN), or PBS were administered into carbon tetrachloride (CCl4)-induced fibrotic livers. Serum LOXL2 and collagen crosslinking were assessed histologically and biochemically. MSC-ex's mechanisms on LOXL2 regulation were investigated in human hepatic stellate cell line LX-2. We found that systemic administration of MSC-ex significantly reduced LOXL2 expression and collagen crosslinking, delaying the progression of CCl4-induced liver fibrosis. Mechanically, RNA-sequencing and fluorescence in situ hybridization (FISH) indicated that miR-27b-3p was enriched in MSC-ex and exosomal miR-27b-3p repressed Yes-associated protein (YAP) expression by targeting its 3' untranslated region in LX-2. LOXL2 was identified as a novel downstream target gene of YAP, and YAP bound to the LOXL2 promoter to positively regulate transcription. Additionally, the miR-27b-3p inhibitor abrogated the anti-LOXL2 abilities of MSC-ex and diminished the antifibrotic efficacy. miR-27b-3p overexpression promoted MSC-ex mediated YAP/LOXL2 inhibition. Thus, MSC-ex may suppress LOXL2 expression through exosomal miR-27b-3p mediated YAP down-regulation. The findings here may improve our understanding of MSC-ex in liver fibrosis alleviation and provide new opportunities for clinical treatment.


Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase).
The participation of a multifunctional enzyme (a single polypeptide with multiple catalytic activities (14)) has been demonstrated in the conversion of agmatine to putrescine in Lathyrus sativus seedlings. This enzyme (putrescine synthase) with inherent activities of agmatine iminohydrolase, putrescine transcarbamylase, ornithine transcarbamylase, and carbamate kinase has been purified to homogeneity and has Mr = 55,000. In the presence of inorganic phosphate, the enzyme catalyzed the stoichiometric conversion of agmatine and ornithine to putrescine and citrulline, respectively. The different activities associated with the enzyme copurified with near constancy in their specific activity. The enzyme catalyzed phosphorolysis and arsenolysis of N-carbamyl putrescine. The multifunctionality of putrescine synthase was also supported by 1) activity staining, 2) intact transfer of the ureido-14C group from labeled NJ-carbamyl putrescine to ornithine to form citrulline, and 3) the affinity of the enzyme toward structurally and functionally related affinity matrices. An agmatine cycle is proposed wherein N-carbamyl putrescine arising from the agmatine iminohydrolase reaction is converted to putrescine and citrulline, with the ureido group of N-carbamyl putrescine being transferred intact to ornithine. Preliminary results indicate that this series of reactions is also present in other plants.


Adenosine inhibits the release of interleukin-1beta in activated human peripheral mononuclear cells.
The effects of adenosine and subtype-specific activators of adenosine receptors (A1, A2A, A2B and A3) were studied on the release of interleukin-1beta (IL-1beta) from peripheral mononuclear cells, monocytes and lymphocytes. In the cells activated by the protein kinase C specific phorbol ester (phorbol 12-myristate 13-acetate) and Ca(2+) ionophore (A23187) both adenosine and the subtype-specific receptor agonists, CPA (A1), CGS 21680 (A2A) and IB-MECA (A3) induced a concentration-dependent inhibition of IL-1beta release. The rank order of potency in the inhibition of IL-1beta release was CPA=CGS 21680>IB-MECA>adenosine>NECA (in the presence of A1, A2A and A3 receptor inhibitors). The inhibitory actions of CPA, CGS 21680 or IB-MECA were significantly reduced in the presence of DPCPX, ZM 243185 or MRS 1191 as subtype-specific antagonists on A1, A2A and A3 adenosine receptors, respectively. It can be concluded that adenosine inhibits the release of IL-1beta from the activated human peripheral mononuclear cells. In this process A1, A2A and A3 receptors are involved.


Thyroid hormone autoantibodies (THAA) in three sisters: a four-year follow up.
We have found three sisters who had thyroid hormone autoantibodies (THAA) in serum. Two of them were hypothyroid due to Hashimoto's thyroiditis. They were treated with synthetic thyroxine (T4) (Case 1) or T4 and triiodothyronine (T3) (Case 2). The other sister (Case 3) was euthyroid throughout the investigation period. Changes in the titers of THAA, antithyroglobulin (Tg) antibodies as well as in the concentrations of thyrotropin (TSH), and total and free thyroid hormones (T3, T4, FT3, and FT4) in sera from each patient were examined for four years. A significant positive correlation was observed between titers of THAA and anti-Tg antibodies in both Case 1 (anti-T3 and anti-T4) and 2 (anti-T4). On the other hand, a significant negative correlation between titers of anti-T3 and anti-Tg antibodies was observed in Case 3. These results suggest that antigen of THAA might be Tg in Case 1 and 2 and mechanism(s) of the production of THAA of Case 1 might be different from that of Case 1 and 2 in terms of their antigen or immune recognition of Tg.


Evidence for the involvement of substance P in the atropine-resistant peristalsis of the guinea-pig ileum.
In the isolated, vascularly perfused guinea-pig ileum, peristalsis could be induced by raising the intraluminal pressure in the presence of atropine. Atropine-resistant peristalsis was greatly inhibited or abolished by the substance P antagonist (D-Pro2, D-Trp7.9)-substance P, substance P desensitization, hexamethonium and by the enkephalin analogue FK 33-824. It is concluded that substance P neurones of the intestine play an important role in the atropine-resistant peristalsis of the guinea-pig ileum.


Magnetic ordering temperature of nanocrystalline Gd: enhancement of magnetic interactions via hydrogenation-induced "negative" pressure.
Gadolinium is a nearly ideal soft-magnetic material. However, one cannot take advantage of its properties at temperatures higher than the room temperature where Gd loses the ferromagnetic ordering. By using high-purity bulk samples with grains ~200 nm in size, we present proof-of-concept measurements of an increased Curie point (TC) and spontaneous magnetization in Gd due to hydrogenation. From first-principles we explain increase of TC in pure Gd due to the addition of hydrogen. We show that the interplay of the characteristic features in the electronic structure of the conduction band at the Fermi level in the high-temperature paramagnetic phase of Gd and "negative" pressure exerted by hydrogen are responsible for the observed effect.


Composition characterization and biotransformation of dissolved, particulate and algae organic phosphorus in eutrophic lakes.
Characteristics and transformation of organic phosphorus in water are vital to biogeochemical cycling of phosphorus and support of blooms of phytoplankton and cyanobacteria. Using solution 31P nuclear magnetic resonance (NMR), combined with field surveys and lab analyses, composition and structural characteristics of dissolved phosphorus (DP), particulate phosphorus (PP) and organic P in algae were studied in two eutrophic lakes in China, Tai Lake and Chao Lake. Factors influencing migration and transformation of these constituents in lake ecosystems were also investigated. A method was developed to extract, flocculate and concentrate DP and PP from lake water samples. Results showed that orthophosphate (Ortho-P) constituted 32.4%-81.3% of DP and 43.7%-54.9% of PP, respectively; while monoester phosphorus (Mono-P) was 13.2%-54.0% of DP and 32.9%-43.7% of PP, respectively. Phosphorus in algae was mostly organic P, especially Mono-P, which was ≥50% of TP. Environmental factors and water quality parameters such as temperature (T), electrical conductivity (EC), pH, secchi depth (SD), dissolved oxygen (DO), chemical oxygen demand (CODcr), chlorophyll-a (Chl-a), affected the absolute and relative concentrations of various P components in the two lakes. Increased temperature promoted bioavailable P (Ortho-P and Mono-P) release to the lake waters. The results can provide an important theoretical basis for the mutual conversion process of organic P components between various media in the lake water environment.


The National Health and Medical Research Council Road Map: a strategic framework for improving Aboriginal and Torres Strait Islander health through research.
What impact has the NHMRC Road Map had on Aboriginal and Torres Strait Islander health? A review process now underway aims to find out.


IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells.
The biomaterial integration depends on its interaction with the host immune system. Monocyte-macrophage lineage cells are immediately recruited to the implant site, polarized into different phenotypes, and fused into multinucleated cells, thus playing roles in tissue regeneration. IL-1R-associated kinase 4 (IRAK4) inhibition was reported to antagonize inflammatory osteolysis and regulate osteoclasts and foreign body giant cells (FBGCs), which may be a potential target in implant osseointegration. In in-vitro experiments, we established simulated physiological and inflammatory circumstances in which bone-marrow-derived macrophages were cultured on sand-blasted and acid-etched (SLA) titanium surfaces to evaluate the induced macrophage polarization, multinucleated cells formation, and biological behaviors in the presence or absence of IRAK4i. Then, bone marrow stromal stem cells (BMSCs) were cultured in the conditioned media collected from the aforementioned induced osteoclasts or FBGCs cultures to clarify the indirect coupling effect of multinucleated cells on BMSCs. We further established a rat implantation model, which integrates IRAK4i treatment with implant placement, to verify the positive effect of IRAK4 inhibition on the macrophage polarization, osteoclast differentiation, and ultimately the early peri-implant osseointegration in vivo. Under inflammatory conditions, by transforming the monocyte-macrophage lineage cells from M1 to M2, IRAK4i treatment could down-regulate the formation and activity of osteoclast and relieve the inhibition of FBGC generation, thus promoting osteogenic differentiation in BMSCs and improve the osseointegration. This study may improve our understanding of the function of multinucleated cells and offer IRAK4i as a therapeutic strategy to improve early implant osseointegration and help to eliminate the initial implant failure.


Direct fluorescent labelling of clones by DOP PCR.
Array Comparative Genomic Hybridisation (array CGH) is a powerful technique for the analysis of constitutional chromosomal anomalies. Chromosomal duplications or deletions detected by array CGH need subsequently to be validated by other methods. One method of validation is Fluorescence in situ Hybridisation (FISH). Traditionally, fluorophores or hapten labelling is performed by nick translation or random prime labelling of purified Bacterial Artificial Chromosome (BAC) products. However, since the array targets have been generated from Degenerate Oligonucleotide Primed (DOP) amplified BAC clones, we aimed to use these DOP amplified BAC clones as the basis of an automated FISH labelling protocol. Unfortunately, labelling of DOP amplified BAC clones by traditional labelling methods resulted in high levels of background. We designed an improved labelling method, by means of degenerate oligonucleotides that resulted in optimal FISH probes with low background. We generated an improved labelling method for FISH which enables the rapid generation of FISH probes without the need for isolating BAC DNA. We labelled about 900 clones with this method with a success rate of 97%.


Effects of physicochemical properties of TiO2 nanomaterials for pulmonary inflammation, acute phase response and alveolar proteinosis in intratracheally exposed mice.
Nanomaterial (NM) characteristics may affect the pulmonary toxicity and inflammatory response, including specific surface area, size, shape, crystal phase or other surface characteristics. Grouping of TiO2 in hazard assessment might be challenging because of variation in physicochemical properties. We exposed C57BL/6 J mice to a single dose of four anatase TiO2 NMs with various sizes and shapes by intratracheal instillation and assessed the pulmonary toxicity 1, 3, 28, 90 or 180 days post-exposure. The quartz DQ12 was included as benchmark particle. Pulmonary responses were evaluated by histopathology, electron microscopy, bronchoalveolar lavage (BAL) fluid cell composition and acute phase response. Genotoxicity was evaluated by DNA strand break levels in BAL cells, lung and liver in the comet assay. Multiple regression analyses were applied to identify specific TiO2 NMs properties important for the pulmonary inflammation and acute phase response. The TiO2 NMs induced similar inflammatory responses when surface area was used as dose metrics, although inflammatory and acute phase response was greatest and more persistent for the TiO2 tube. Similar histopathological changes were observed for the TiO2 tube and DQ12 including pulmonary alveolar proteinosis indicating profound effects related to the tube shape. Comparison with previously published data on rutile TiO2 NMs indicated that rutile TiO2 NMs were more inflammogenic in terms of neutrophil influx than anatase TiO2 NMs when normalized to total deposited surface area. Overall, the results suggest that specific surface area, crystal phase and shape of TiO2 NMs are important predictors for the observed pulmonary effects of TiO2 NMs.


Adaptive response to hypoxia and remote ischaemia pre-conditioning: a new hypoxia-inducible factors era in clinical medicine.
Transient ischaemia leads to tolerance to subsequent protracted ischaemia. This 'ischaemia pre-conditioning' results from the induction of numerous protective genes, involved in cell metabolism, proliferation and survival, in antioxidant capacity, angiogenesis, vascular tone and erythropoiesis. Hypoxia-inducible factors (HIF) play a pivotal role in this transcriptional adaptive response. HIF prolyl hydroxylases (PHDs), serving as oxygen sensors, control HIFα degradation. HIF-mediated ischaemic pre-conditioning can be achieved with the administration of PHD inhibitors, with the attenuation of organ injury under various hypoxic and toxic insults. Clinical trials are currently under way, evaluating PHD inhibitors as inducers of erythropoietin. Once their safety is established, their potential use might be further tested in clinical trials in various forms of acute ischaemic and toxic organ damage. Repeated transient limb ischaemia was also found to attenuate ischaemic injury in remote organs. This 'remote ischaemic pre-conditioning' phenomenon (RIP) has been extensively studied recently in small clinical trials, preceding, or in parallel with an abrupt insult, such as myocardial infarction, cardiac surgery or radiocontrast administration. Initial results are promising, suggesting organ protection. Large-scale multi-centre studies are currently under way, evaluating the protective potential of RIP in cardiac surgery, in the management of myocardial infarction and in organ transplantation. The mechanisms of organ protection provided by RIP are poorly understood, but HIF seemingly play a role as well. Thus, Inhibition of HIF degradation with PHD inhibitors, as well as RIP (in part through HIF), might develop into novel clinical interventions in organ protection in the near future.


A non-targeted approach for extended liquid chromatography-mass spectrometry profiling of free and esterified jasmonates after wounding.
Upon wounding or herbivory, plants quickly react by activating various defense mechanisms. A major part of these defenses is thought to be regulated by the jasmonate pathway through the induction of jasmonic acid and its biologically active jasmonoyl-isoleucine conjugate. Yet, these well-known phytohormones are only two among the numerous compounds that compose the jasmonate family. Here, we describe a method based on ultrahigh-pressure liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry that can potentially profile the full range of known free and esterified jasmonates in a non-targeted manner. The developed approach is illustrated by the analysis of Arabidopsis thaliana leaves after mechanical wounding.


Accuracy of Holladay 2 formula using IOLMaster parameters in the absence of lens thickness value.
The accuracy of the Holladay 2 (H2) formula is well-documented. This formula requires seven variables to estimate effective lens position (ELP) for the IOL power calculation. The lens thickness (LT) value is one of the required variables. Interestingly, the IOLMaster, which is one of the most commonly used optical biometers, can provide all the required ocular variables except LT value. It has become a pertinent issue to evaluate the accuracy of theH2 formula when it is used without the LT value. The purpose of this study was to evaluate the results when using the H2 formula, without the LT value, and compare such results to those obtained using the Haigis formula and the Hoffer Q formula. The Institutional review board (IRB) gave their approval for the conduct of this prospective comparative study. One hundred and sixty-three eyes of 143 cataract patients from the Ophthalmology Department, Siriraj Hospital, Thailand were recruited. All eyes were measured using the IOLMaster (Carl Zeiss Meditec, Jena, Germany) for keratometry (K), axial length (AL), anterior chamber depth (ACD), and horizontal white-to-white (WTW) corneal diameter. Then, the LT measurement was obtained by A-scan ultrasonography (Quantel Axis-II, Quantel Medical, USA). Every patient underwent uncomplicated phacoemulsification by a single surgeon (NC) with a single technique using a single IOL model. Post-operative refraction was obtained at 3 months. The mean absolute errors (MAEs), median absolute errors (MedAEs) and percentage of the eyes within ±0.25, ±0.50, and ±1.00 D of predicted refraction was calculated for H2 formula both with and without LT input, Haigis, and Hoffer Q formula. The results were also classified into a group of short AL (<22.0 mm), average AL (22.0 to 24.5 mm) and long AL (>24.5 mm). There was no statistically significant difference in either MAEs or MedAEs of all formulas in all AL groups including the H2 with and without LT. There was a trend toward lower MAEs and MedAEs for H2 in the long AL group. Percentage of the eyes within ±0.25, ±0.50, and ±1.00 D of predicted refraction were similar in all AL groups. The preliminary results of this study showed that the H2 formula performed well even without the LT value. It was comparable to the Haigis and Hoffer Q formulas.


Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: a comparison of selective and combined endothelin receptor blockade.
Endothelin (ET) is implicated in the pathophysiology of chronic renal failure (CRF). We therefore studied the systemic and renal hemodynamic effects of ET receptor antagonists in CRF and examined differences between selective ETA, selective ETB, and combined ETA/B receptor blockade. We conducted a randomized, placebo-controlled, double-blind, 4-way crossover study comparing selective ET receptor antagonists BQ-123 (ETA) and BQ-788 (ETB), given alone and in combination, in acute studies in 8 hypertensive CRF patients and 8 matched healthy controls. BQ-123, alone and in combination with BQ-788, reduced blood pressure in CRF, particularly with BQ-123 alone (mean arterial pressure: controls -4+/-2%, CRF -13+/-2%, P<0.01 versus placebo). In CRF, in the face of this fall in blood pressure, BQ-123 substantially increased renal blood flow (38.8+/-23.9%, P<0.01 versus placebo) and reduced renal vascular resistance (-44.5+/-11.3%, P<0.01 versus placebo) when given alone but not when combined with BQ-788. These changes were accompanied by a reduction in effective filtration fraction. BQ-123, alone or in combination with BQ-788, had minimal effects on the renal circulation in healthy controls, and BQ-788 alone produced both systemic and renal vasoconstriction in CRF and healthy controls. ETA receptor antagonism was highly effective in lowering blood pressure in CRF patients currently treated for hypertension. In addition, there were effects consistent with a renoprotective action. However, because the ETB receptor appears to play a key role in the maintenance of tonic renal vasodilation, combined ETA/B receptor antagonism, although it lowered blood pressure, did not confer these renal benefits.


Melatonin administration acutely decreases the diffusing capacity of carbon monoxide in human lungs.
Most physiological measurements of the pulmonary diffusing capacity use carbon monoxide (CO) as a tracer gas. Similar to CO, melatonin binds the hemoglobin in the blood. The present study was designed to assess the effect of exogenous melatonin administration on pulmonary functions including diffusing capacity for carbon monoxide (DL(CO)) in healthy subjects. The study was performed in a randomized, double-blind, placebo-controlled manner. DL(CO) was measured in 22 healthy male volunteers (age 18-25 years) who were randomized to melatonin (n = 11) and placebo administration (n = 11). At baseline, DL(CO), alveolar volume (V(A)) and other spirometric parameters such as forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), peak expiratory flow (PEF) and maximal voluntary ventilation (MVV) were measured. DL(CO) was then corrected for the hemoglobin concentration. Measurements were repeated in a double-blind fashion 60 min after the administration of melatonin (1 mg) or placebo. DL(CO) was significantly decreased (39.31 +/- 4.75 vs. 34.82 +/- 6.18 ml/min/mm Hg) 60 min after the melatonin administration (p = 0.01), while FEV(1), FVC, FEV(1)/FVC, PEF and MVV values did not demonstrate significant differences. Placebo administration did not result in significant alteration in any of these parameters. In healthy subjects, oral administration of melatonin acutely influences the DL(CO) without affecting other pulmonary function test results. We conclude that melatonin may have a reducing effect on the DL(CO) in the lungs.


Preoperative Prediction of Type 2 Diabetes Remission After Gastric Bypass Surgery: a Comparison of DiaRem Scores and ABCD Scores.
Gastric bypass surgery has been well accepted as a novel treatment modality for type 2 diabetes mellitus (T2DM) in obese patients. Some scoring systems have been proposed for the selection of T2DM patients who are eligible for gastric bypass surgery. This study compares two scoring systems with regard to remission of T2DM after gastric bypass surgery. This retrospective cohort study included 245 patients (150 females and 95 males) who had undergone gastric bypass surgery for the treatment of T2DM with 1 year follow-up. We examined the predictive power of complete remission of two scoring systems, the DiaRem score, and the ABCD score. The DiaRem score includes the factors of age, HbA1c, medication, and insulin usage. The ABCD score includes the factors of age, BMI, C-peptide level, and duration of T2DM. The rate of remission of T2DM after gastric bypass surgery was evaluated using both scoring systems. At 1 year after surgery, the percent weight loss was 26.5 % and the mean BMI decreased from 35.7 to 26.2 kg/m(2). The mean HbA1c decreased from 8.8 to 6.2 %. A significant number of patients showed improvement in glycemic control, including 130 (53.1 %) patients with complete remission (HbA1c < 6.0 %), 36 (14.7 %) patients with partial remission (HbA1c < 6.5 %), and 26 (10.6 %) patients with improvement (HbA1c < 7 %). Both the DiaRem score and the ABCD score predicted the success of the gastric bypass surgery, but the ABCD score was better at differentiating patients with poorer score (27.9 vs. 9.1 %, p < 0.001). Gastric bypass surgery is a treatment option for obese T2DM patients. The ABCD score is better at predicting T2DM remission at 1 year after gastric bypass surgery than the DiaRem score.


The cation selectivity of the ZIP transporters.
Zinc is a required micronutrient for cellular homeostasis and is essential for the structure and/or function of 100s of biological processes. Despite the central importance of zinc in physiology, the mechanism by which this transition metal is transported into cells is not well understood. The first human zinc importer was identified in 2000. Since that time, a new family of proteins, named ZIP, for Zrt-, Irt-like proteins, has been shown to be expressed in a tissue-specific manner in humans. There are a total of 14 members of this family, which can be further divided into four subfamilies based on sequence similarities: ZIPI, ZIPII, gufA and LIV-1. It has been shown that these proteins are expressed on the plasma membrane as well as on intracellular organelles and each function or are proposed to function to increase the cytosolic concentration of zinc. While the subcellular localization of most of the ZIP family of proteins has been elucidated, the mechanistic details of these proteins including the driving force of cation translocation, residues essential for transport and the molecular determinants which define the differing cation selectivity between the ZIP family of proteins have not been well resolved. The objective of this review is to describe the current understanding of cation transport, mediated by the mammalian family of ZIP proteins and to present some molecular determinants that may contribute to the differing substrate specificity for this family of proteins.


The effects of ageing on the meiotic chromosomes of male and female mice.
The effects of age on the chiasma frequencies, chiasma position and numbers of univalents at MI in males and females of three strains of mouse were examined. Males showed a slight but non significant rise in chiasma frequency in age due to an increase in bivalents with two chiasmata at the expense of single chiasmata bivalents. In contrast, females exhibited a significant decrease in chiasma frequency with age due to the loss of two chiasma bivalents with a corresponding increase in single terminal chiasmata bivalents. In both males and females there was no significant increase in univalents with age in the strains studied. Of interest was the finding of a greater degree of contraction of the MI chromosomes in the oocytes of old relative to young females, a differential contraction that was independent of culture time. This finding is discussed with regard to the "production line theory" and non disjunction at Anaphase in other strains of mice.


Unitary properties of potassium channels activated by 5-HT in acutely isolated rat dorsal raphe neurones.
1. Single inwardly rectifying K+ channel currents were recorded from acutely isolated adult serotonergic dorsal raphe (DR) neurones using the cell-attached and outside-out patch clamp configuration. 2. Four equally spaced conductance levels were observed in both outside-out and cell-attached patch recordings with conductance levels averaging 11, 21, 30 and 40 pS. Larger conductance openings (50-120 pS) were seen less frequently. 3. When using 136 [K+]0 the single channel I-V relation was linear in the range 0 mV to -100 mV in all cases. 4. Transitions between the various conductance levels were observed, as were apparent direct opening and closing to each individual conductance level. Furthermore openings of 11, 21 and 30 pS were observed in almost all the patches. These results suggest that the different-sized events result from substrates of a single channel rather than several different channels with different conductances. 5. Unitary K+ channel current probability of opening, recorded in cell-attached patch, was unchanged after 5-hydroxytryptamine (5-HT) was added to the bath outside the patch pipette which suggests that no easily diffusible second messenger was involved. 6. The single K+ channel activity, however, was increased on average by 670% following the addition of 5-HT to the bath when recording channel activity in the outside-out configuration. Usually all K+ channel subconductance levels increased in activity but the largest increases occurred in the events with 30 and 40 pS conductance. 7. These results suggest that 5-HT enhances the probability of opening of the resting K+ channel activity, which can open to several levels of conductance, and that no new channel or freely diffusible second messenger is involved in the response.


Therapeutic effects of Ag85B and MPT64 DNA vaccines in a murine model of Mycobacterium tuberculosis infection.
A new improved therapeutic strategy for tuberculosis is urgently needed. In our previous work DNA vaccines encoding secreted proteins Ag85B and MPT64 have been reported to protect mice from following H37Rv challenge by prompting the Th1 response and we consider whether these vaccines have the therapeutic effect through the same mechanism. In the present study these two DNA vaccines were tested in a mouse tuberculosis model to confirm their immunotherapeutic effect. C57BL/6 mice infected with Mycobacterium tuberculosis were treated with pCDNA3.1, pcD85B, pcDMPT64, pcD85B plus pcDMPT64, respectively. The numbers of viable bacteria in lung and spleen were counted as log(10)CFU/g. The level of IFN-gamma, IL-4 and TNF-alpha released by spleen lymphocytes stimulated with PPD was detected with ELISA. Lungs and spleens were harvested for pathological analysis. The pcD85B group reduced the pulmonary and splenic bacterial loads of 1.2 and 0.7 logs, respectively compared with that of control mice, but the difference between pcDMPT64 group and control mice was not significant. Vaccination with pcD85B induced high level of IFN-gamma and TNF-alpha. No change of IL-4 level was found in all groups. The pathological change in lung in pcD85B group was slight, alveolar wall structure is clear and the lesions are constrained, while that in control group was extensive, alveoli and interalveolar septae are effaced. And there was no special change in spleen in all groups. In conclusion, Ag85B DNA vaccination has immunotherapeutic effects, and the effects may be associated with a switch to Th1 response and prompting production of cytokine TNF-alpha and INF-gamma synchronously. Therefore, MPT64 DNA vaccination has no immunotherapeutic effect on mice tuberculosis. Rather, the effects may be associated with its disability in switching improper immune status and with recalling a strong and early specific memory immune response against tuberculosis.


Altered modulatory actions of serotonin on dentate granule cells of aged rats.
The effects of serotonin (5-HT) on dentate granule (DG) neurons in hippocampal slices taken from young mature (6-8 months) and old (25-29 months) rats were compared. Intracellular measurements of membrane potential, cell input resistance and slow postspike afterhyperpolarization did not differ significantly between young and old neurons. Neurons recorded in slices taken from old animals responded with less hyperpolarization to increasing doses of the drug, and their responses were significantly reduced after repeated applications of 5-HT. Serotonin-mediated reduction of the slow afterhyperpolarization in young DG neurons was less prominent or totally absent in the old cells. It is concluded that serotonergic postsynaptic actions are impaired in old age.


Experiences of Healthcare in Australia's Workers' Compensation Schemes: A Cross-Sectional Study.
To determine personal, injury, and scheme factors are associated with experiencing stressful healthcare provider (HCP) interactions, and to determine impact of stressful HCP interactions on return to work (RTW). Using the 2018 National RTW Survey of 4574 injured workers that submitted a workers' compensation claim, multivariable logistic regression determined factors associated with stressful HCP interactions (recorded as "a bit stressful" to "extremely stressful") and RTW (self-reported yes/no at interview). Workers claiming for mental illness, who found healthcare difficult to access, who consulted with multiple HCPs, and who experienced psychological or financial stress, were significantly more likely to experience stressful HCP interactions. Stressful HCP interactions were associated with lower odds of RTW. Findings provide impetus to investigate why HCP interactions are stressful to enable efforts to reduce stress, possibly improving RTW outcomes.