Occult infection of old nonfunctioning arteriovenous grafts: a novel cause of erythropoietin resistance and chronic inflammation in hemodialysis patients.
Occult infection of old nonfunctioning arteriovenous grafts (AVGs) is frequent among hemodialysis patients. It is a recognized cause of bacteremia and other infectious complications. Additionally, old nonfunctioning AVGs may be harbingers of other noninfectious complications. The aim of this study was to investigate whether occult infection of old nonfunctioning AVGs is a cause of a chronic inflammatory state in hemodialysis patients. This study was performed in two phases: In the first phase (study 1), 22 patients with clinically proven occult infection of old nonfunctioning AVG were identified, and data on hemoglobin, weekly erythropoietin dose, and albumin levels were collected retrospectively. Comparisons were made between values obtained pre- and post-AVG resection. In the second phase (study 2), we examined whether the presence of a chronic inflammatory state is associated with occult AVG infection in old nonfunctioning AVGs. Twenty hemodialysis patients were identified with chronic inflammatory state based on erythropoietin dose (units/wk)/hematocrit ratio>470, serum albumin <3.3 g/dL, and CRP>25 mg/L. Among these patients, we found eight with old nonfunctioning AVGs. We then performed indium-labeled white blood cell (WBC) scans on the eight patients to screen for occult infection of old nonfunctioning AVGs. The AVGs with positive indium scan were resected and cultured. Data on hematocrit, erythropoietin dosing, serum albumin, ferritin, and CRP were obtained at 2 months following AVG resection and compared to pre-resection values. In study 1, the 22 patients with occult infection of old nonfunctioning AVG exhibited profound anemia and hypoalbuminemia. Their mean hemoglobin was 9.2 +/- 1.2 g/dL which improved to 11.6 +/- 0.8 g/dL (P < 0.05) 3 months after AVG resection. Their mean serum albumin was 3.3 +/- 0.5 g/dL which improved to 3.8 +/- 0.2 g/dL (P < 0.05) 3 months after AVG resection. Their mean erythropoietin dosages (units/patient/wk) fell from 14,240 +/- 350 to 6,675 +/- 455 (P < 0.05). In study 2, among the 8 patients with chronic inflammatory state and old nonfunctioning AVG, 6 (75%) had positive indium scans and underwent surgical resection that proved bacterial infection. Upon follow-up, the 2-month data showed a remarkable improvement in the following parameters: weekly erythropoietin dose/hematocrit ratio from 622 +/- 137 to 254 +/- 28 (P < 0.05), plasma ferritin values from 690 +/- 126 ng/mL to 247 +/- 42 ng/mL (P < 0.01), and plasma CRP from 56.7 +/- 9.0 to 14.5 +/- 3.8 mg/L (P < 0.01). Serum albumin values also improved from 3.07 +/- 0.08 g/dL to 3.34 +/- 0.14 g/dL (P = 0.13). Percent plasma iron saturation did not appreciably differ from baseline (20.5% +/- 4.4% to 19.8 +/- 1.9%, P = 0.89). Occult infection of old nonfunctioning AVG is a common cause of erythropoietin resistance and chronic inflammatory state among hemodialysis patients. Resection of old nonfunctioning AVGs with occult infection is associated with resolution of markers of chronic inflammatory state.


Retraction: Oroxylin a Inhibits the Protection of Bone Marrow Microenvironment on CML Cells Through CXCL12/CXCR4/P-gp Signaling Pathway.
[This retracts the article DOI: 10.3389/fonc.2019.00188.].


PROPHYLACTIC n CMT-3 ATTENUATES SEPSIS-INDUCED ACUTE KIDNEY INJURY IN ASSOCIATION WITH NLRP3 INFLAMMASOME ACTIVATION AND APOPTOSIS.
Background: The kidney is the most common extrapulmonary organ injured in sepsis. The current study examines the ability of aerosolized nanochemically modified tetracycline 3 (nCMT-3), a pleiotropic anti-inflammatory agent, to attenuate acute kidney injury (AKI) caused by intratracheal LPS. Methods: C57BL/6 mice received aerosolized intratracheal nCMT-3 (1 mg/kg) or saline, followed by intratracheal LPS (2.5 mg/kg) to induce acute lung injury-induced AKI. Tissues were harvested at 24 h. The effects of nCMT-3 and LPS on AKI were assessed by plasma/tissue levels of serum urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and renal histology. Renal matrix metalloproteinase (MMP) level/activity, cytochrome C, Bax, Bcl-2, caspase-3, p38 mitogen-activated protein kinase activation, NLRP3, and caspase-1 were also measured. Apoptotic cells in kidney were determined by TUNEL assay. Renal levels of IL-1β and IL-6 were measured to assess inflammation. Results: Acute lung injury-induced AKI was characterized by increased plasma blood urea nitrogen, creatinine, injury biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule 1), and histologic evidence of renal injury. Lipopolysaccharide-treated mice demonstrated renal injury with increased levels of inflammatory cytokines (IL-1β, IL-6), active MMP-2 and MMP-9, proapoptotic proteins (cytochrome C, Bax/Bcl-2 ratio, cleaved caspase-3), apoptotic cells, inflammasome activation (NLRP3, caspase-1), and p38 signaling. Intratracheal nCMT-3 significantly attenuated all the measured markers of renal injury, inflammation, and apoptosis. Conclusions: Pretreatment with aerosolized nCMT-3 attenuates LPS-induced AKI by inhibiting renal NLRP3 inflammasome activation, renal inflammation, and apoptosis.


Doing mini-health technology assessments in hospitals: a new concept of decision support in health care?
The purpose of this project was to evaluate local decision support tools used in the Danish hospital sector from a theoretical and an empirical point of view. The use of local decision support was evaluated through questionnaires sent to all county health directors, all hospital managers, and all heads of clinical departments in cardiology, orthopedic surgery, and intensive care. In addition, respondents were asked to submit whatever decision support tools they were using (including mini-HTAs, other forms or checklists, and special procedures for decision making concerning new health technologies). A theoretical analysis of the decision support tools (decision theory) was performed as well as a comparison with the business case method used in private companies. Finally, the Danish mini-HTA was compared with foreign production and use of HTA and HTA-like assessments as local decision support. The response rate was high (87 percent, 94 percent, 85 percent, respectively). We collected sixty different forms (of which forty-nine were mini-HTAs) and twenty variants of written procedures. We found theoretical and empirical evidence that local involvement in the process of making the HTA could be important for the use of the results from the HTA and for the process of implementing the new technology. Doing mini-HTA in hospitals seems to balance the need for quality and depth with the limited time and resources for assessment.


Rhamnetin induces apoptosis in human breast cancer cells via the miR-34a/Notch-1 signaling pathway.
The present study aimed to investigate whether rhamnetin induced apoptosis in human breast cancer cells and the underlying molecular mechanism of this anti cancer effect. The treatment of MCF-7 cells with rhamnetin was able to significantly inhibit cell proliferation and induce caspase-3/9 activity in a dose- and time-dependent manner, compared with untreated cells. In addition, treatment with rhamnetin was able to significantly promote the expression of p53 protein and microRNA (miR-)34a compared with untreated cells. The treatment with rhamnetin also suppressed the expression of Notch1 protein in MCF-7 cells compared with untreated cells. Subsequently, miR-24a expression was promoted in rhamnetin-treated MCF-7 cells using a miR-34a plasmid. The overexpression of miR-34a was able to significantly inhibit cell viability and induce caspase-3/9 activity in MCF-7 cells following treatment with rhamnetin. Furthermore, the overexpression of miR-34a was able to significantly promote the expression of p53 protein and miR-34a, and suppress the expression of Notch1 protein in rhamnetin-treated MCF-7 cells. Therefore, the results of the present study demonstrated that rhamnetin induced apoptosis in human breast cancer cells via the miR-34a/Notch-1 signaling pathway.


Exploring the Molecular Aspects of Glycosylation in MOG Antibody Disease (MOGAD).
Myelin Oligodendrocyte Glycoprotein-antibody disease (MOGAD) is an immune-mediated disorder that mainly targets the central nervous system of the patient. The pattern of inflammation caused by MOGAD mainly targets the brain stem, spinal cord, and optic nerve, and the symptoms vary from person to person. Its clinical features often overlap with Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) which makes the accurate diagnosis of this rare neurodegenerative disease quite difficult. Hence, this review was attempted not only to understand MOGAD but also to comprehend the differences between MOGAD and MS with the help of a brief overview of the similarities and contrasting features. Here we highlight the mechanism and importance of MOG in myelination and demyelination. Glycosylation has a serious impact on the myelination of neurons as N-glycan helps in the proper folding of MOG. On transforming into an autoantigen, MOG can activate the classical complement pathway by triggering the activation of proteins associated with the complement cascade. Patients with persistently positive antibodies to MOG are at risk for recurrent episodes of MOGAD. In the current scenario, there is an urgent need to develop therapeutic interventions that induce remyelination. Remyelination in terms of MOG glycosylation is hypothesized as a possible strategy to treat patients diagnosed with MOGAD. On the whole, the article aims to provide a clear insight into the disease and the structural aspects associated with it.


Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice.
Circulating alpha 1-antitrypsin is synthesized primarily in the liver and secreted into the bloodstream, where it serves as the major protease inhibitor. The PiZ variant of alpha 1-antitrypsin is associated with decreased levels of the protein in sera as a result of its retention within hepatocytes. Homozygosity for the variant allele predisposes individuals to the development of pulmonary emphysema and an increased risk for liver disease. We and others have previously demonstrated that the normal PiM human alpha 1-antitrypsin gene can be properly expressed in the livers of transgenic mice. The PiZ variant of the human alpha 1-antitrypsin gene was introduced into the germline of mice to determine whether the mutant protein would accumulate in mouse hepatocytes and if such accumulation would result in the development of liver damage in an animal model. As expected, the mutant human protein was abundantly synthesized in the livers of the transgenic animals and accumulated within the rough endoplasmic reticulum of hepatocytes as it does in human patients. PiZ mice developed significantly more liver necrosis and inflammation than PiM transgenic mice or control littermates. The degree of liver damage was correlated with the amount of PiZ alpha 1-antitrypsin accumulated in the liver of the different pedigrees of mice. Although 40% of PiZ mice tested were seropositive for mouse hepatitis virus (MHV), the degree of liver damage was not influenced by the MHV seropositivity; rather, it was related only to the presence of accumulated PiZ protein.


Elimination of error induced by a beam splitter substrate for a dispersion-compensated polarization Sagnac interferometer.
A wire grating beam splitter (WGBS) substrate in a dispersion-compensated polarization Sagnac interferometer (DCPSI) may introduce an additional shear distance in the shear distance generated by the DCPSI, thereby causing poor adaptability of the DCPSI to white light. This work applies a compensation scheme of an optical flat with the same material and thickness as the WGBS and parallel to the WGBS introduced in the other arm of the DCPSI. Theoretically, this method can decrease the additional shear distance approaching 0. The ideal shear distance in the simulation experiment is 5.86 mm, and the shear distance before and after compensation is 5.40 and 5.86 mm, respectively. The theoretical value of the additional shear distance in this experiment is -0.6625 mm, and the average compensation value is 0.66 mm. Overall, experiment and simulation results indicate that the above method can effectively eliminate the additional shear distance.


Role of gallium SPECT-CT in the diagnosis of left ventricular assist device infections.
Infection remains a well-established complication after the placement of left ventricular assist devices (LVADs). Defining the extent of infection is a challenging task as there are few effective imaging modalities and no standardized guidelines regarding imaging in the diagnosis of device-related infections (DRIs). The use of gallium with single photon emission tomography-computed tomography (Ga-SPECT-CT) has not been previously reported in localizing DRIs. We reviewed the charts and images of five patients with LVADs who underwent Ga-SPECT-CT for the diagnosis of various types of DRIs. Gallium SPECT-CT further clarified the extent of infections among LVAD patients, allowing for patient-specific tailored treatments including surgical debridement. Gallium SPECT-CT is a useful tool when diagnosing LVAD infections and could potentially be the imaging modality of choice in the near future. With improved imaging studies, such as Ga-SPECT-CT, allowing for earlier and more accurate diagnoses of DRIs, the outcome of such infections is likely to improve.


Effects of a Porphyromonas gingivalis infection on inflammatory mediator response and pregnancy outcome in hamsters.
This study examines the effects of various localized, nondissemination challenges of Porphyromonas gingivalis on inflammatory mediator production and pregnancy outcome in the golden hamster. Live or heat-killed (HK) organisms were inoculated into a previously implanted subcutaneous tissue chamber on the 8th day of gestation to determine the effects on fetal weight, viability, and resorption. In one group of animals, HK organisms were inoculated prior to mating to determine the effects of previous exposure on day-8 gestational challenges. Chamber contents were assayed at 1 and 5 days after challenge for prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF-alpha). All P. gingivalis challenges caused a significant increase in chamber PGE2 and TNF-alpha at P < 0.01 in the following order of potency: HK < Live < HK+Live. For example, following the HK+Live challenge, PGE2 levels increased from 4.7 pg/ml at baseline to 362 pg/ml at day 5 and TNF-alpha increased from 26.4 pg/ml to 724 pg/ml at day 5. The same order of potency of the various challenges was maintained with regard to the toxic effects of P. gingivalis on pregnancy outcome. For the HK+Live challenge, fetal weight was decreased 24%; embryolethality increased to 26.5% and the percent fetal resorption increased to 10.6% compared with control animal levels. There was a statistically significant association between increasing levels of both PGE2 and TNF-alpha and fetal growth retardation and embryolethality at P < 0.001. These data suggest that infections with gram-negative periodontal pathogens can elicit adverse pregnancy outcomes and that the levels of PGE2 and TNF-alpha produced as a result of challenge are associated with the severity of fetal effect.


[The effect of Gynostemma pentaphyllum (GP) on plasma lipoprotein metabolism and lipoperoxidation lipoprotein in the experimental hyperglycemia rats].
To study the regulation mechanism of GP on plasma lipoprotein metabolism and To explore its mechanism of anti-lipoperoxidation in the experimental hyperglycemia rats. The rats were raised with high fat diet for six weeks,and the model of hyperglycemia was then established. After that, those rats were treated with high or low dose of GP and xuezhikang as a masculine comparison for four weeks. Then, those rat were executed, and detected the plasma TC, TG, LDL-C, HDL-C, GSH-Px, at the same time the SOD, CAT and MDA concentration also be mensurated. The results showed that high and low dose of GP could decrease the concentration of serum LDL-C, cholesterol and triglyceride remarkably and raise the concentration of HDL-C. The activity of GSH-Px, SOD and CAT in GP groups were promoted and the level of MDA was decreased distinctly. The GP can therapy the abnormity of serum lipid and has obviously anti-lipoperoxidation affection.


Should I eXtract Every Six dental trial (SIXES): study protocol for a randomized controlled trial.
Extraction of lower first permanent molars in children is common. There is uncertainty among clinicians as to whether a 'compensating extraction' (removal of the upper first permanent molar to prevent it over erupting) is necessary despite current guidelines recommending this. As a result, unnecessary dental extractions may be carried out or children may be failing to receive extractions required to achieve optimal long-term oral health. In addition, the decision to extract fewer or more teeth affects management options (local anesthetic injections alone, inhalation sedation or general anesthesia) needed to support the child with the surgical procedure(s).The SIXES (Should I eXtract Every Six) dental trial investigates clinical effectiveness and quality of life for conventional treatment (following the guideline of compensation extraction of the upper first permanent molar) compared with the alternative intervention (removal of lower first permanent molars but no extraction of the upper). This is a multicenter, two-arm parallel group randomized clinical trial. Allocation will be web-based randomization. Practitioners in primary and secondary care settings, reflecting the points of presentation and treatment of eligible patients, will recruit 400 children, aged 7 to 11 years requiring extraction of lower first permanent molars but who have upper first permanent molars of good prognosis. Baseline measures (prior to treatment) and outcome data (at one and five years, or when the patient reaches 14 years of age) will be assessed through study models and child/parent questionnaires.The primary outcome measure is degree of tipping of the lower second permanent molar, (favorable outcome is tipping less than 15°).The secondary outcomes are type of anesthetic/sedation used, residual spacing (between lower second premolar and second permanent molar), orthodontic treatment requirement, quality of life, and over-eruption in the intervention group. Assessors will be blinded where possible. SIXES dental trial investigates whether compensating extraction of upper first permanent molars should be carried out following loss of lower first permanent molars. Currently dentists and orthodontists face a dilemma in clinical decision-making, relying on the lowest level of evidence - expert opinion. SIXES will provide evidence to support decision-making and inform practices and may result in reduced tooth extractions. Clinical Trials.gov Identifier: NCT01591265.


Identification of a cell-specific transcriptional enhancer in the first intron of the mouse alpha 2 (type I) collagen gene.
A transcriptional enhancer has been identified in the first intron of the mouse alpha 2 (type I) collagen gene in a region between +418 and +1524 base pairs from the transcriptional start site. The enhancer functions both when it is located 5' and 3' to the promoter that it activates and is independent of the orientation of the element. The enhancer stimulates both the homologous alpha 2 type I [alpha 2(I)] collagen promoter and the heterologous early simian virus 40 promoter. In transient expression experiments, enhancer-dependent transcription from the alpha 2(I) collagen promoter utilizes the same transcriptional start site as the one used in the endogenous alpha 2(I) collagen gene. The enhancer activates transcription at a distance of at least 3 kilobase pairs from the transcriptional start site. The alpha 2(I) collagen enhancer displays cell specificity, since it is functional in NIH 3T3 fibroblasts but completely inactive in a lymphoid cell line, in contrast to two immunoglobulin gene enhancers that show the opposite behavior. We find several areas of sequence homology with viral enhancers, particularly the enhancer of simian virus 40.


Effect of intensified training on muscle ion kinetics, fatigue development, and repeated short-term performance in endurance-trained cyclists.
The effects of intensified training in combination with a reduced training volume on muscle ion kinetics, transporters, and work capacity were examined. Eight well-trained cyclists replaced their regular training with speed-endurance training (12 × 30 s sprints) 2-3 times per week and aerobic high-intensity training (4-5 × 3-4 min at 90-100% of maximal heart rate) 1-2 times per week for 7 wk and reduced training volume by 70% (intervention period; IP). The duration of an intense exhaustive cycling bout (EX2; 368 ± 6 W), performed 2.5 min after a 2-min intense cycle bout (EX1), was longer (P < 0.05) after than before IP (4:16 ± 0:34 vs. 3:37 ± 0:28 min:s), and mean and peak power during a repeated sprint test improved (P < 0.05) by 4% and 3%, respectively. Femoral venous K(+) concentration in recovery from EX1 and EX2 was lowered (P < 0.05) after compared with before IP, whereas muscle interstitial K(+) concentration and net muscle K(+) release during exercise was unaltered. No changes in muscle lactate and H(+) release during and after EX1 and EX2 were observed, but the in vivo buffer capacity was higher (P < 0.05) after IP. Expression of the ATP-sensitive K(+) (KATP) channel (Kir6.2) decreased by IP, with no change in the strong inward rectifying K(+) channel (Kir2.1), muscle Na(+)-K(+) pump subunits, monocarboxylate transporters 1 and 4 (MCT1 and MCT4), and Na(+)/H(+) exchanger 1 (NHE1). In conclusion, 7 wk of intensified training with a reduced training volume improved performance during repeated intense exercise, which was associated with a greater muscle reuptake of K(+) and muscle buffer capacity but not with the amount of muscle ion transporters.


Variation in soft-tissue thicknesses on the human face and their relation to craniometric dimensions.
The average thickness of soft tissues on parts of the face is known, but its variation has not been related to cranial morphology. To investigate this relationship, measurements of facial soft-tissue depths and craniometric dimensions were taken on adult, white Australian cadavers (17 male and 23 female). Significant correlations between many soft-tissue depths and craniometric dimensions were found, suggesting a relationship between the amount of soft tissue present on the face and the size of the underlying bony skeleton. Soft-tissue depths were highly positively correlated with each other; craniometric dimensions were correlated but to a lesser extent. Males had thicker soft tissues and larger craniometric dimensions than females; considerable overlap of ranges was also noted. Multiple regression analysis was used to produce equations predicting the soft-tissue depth at specified areas of the face from craniometric dimensions. A subsample of nine cadavers was examined for the effects of tissue embalming. Embalming caused significant initial increases in facial soft-tissue depths. Cadavers embalmed for less than 6 months had soft-tissue depths significantly greater than for fully embalmed cadavers. The evidence that facial soft-tissue thicknesses vary with craniofacial dimensions has implications for forensic identification, facial aesthetic surgery, and approximation of the facial features of extinct individuals.


Effect of osmotic lysis and resealing on red cell structure and function.
We have recently modified the dialysis tubing osmotic lysis and resealing method to examine the role of intracellular red blood cell (RBC) antioxidants. However, the potential effect of resealing on the RBC was not fully investigated. This study examined a number of cellular characteristics to determine the effects of physical lysis and resealing on the RBC. Following resealing, RBC exhibited normal morphology and at most only slight alterations in mean cell volume and mean cell hemoglobin concentration. RBC density distribution was significantly affected by resealing with increased populations of both light and dense cells, though the mean cell density was similar to that of control cells. Endogenous enzyme activities and adenosine triphosphate (ATP) concentration were unaffected by the resealing procedure. While reduced glutathione (GSH) concentration was decreased by 15%, RBC oxidant sensitivity was found to be unaltered. Cellular deformability of the resealed RBC was 80% to 90% that of the control cells. Membrane phospholipid and fatty acyl composition of the resealed RBC were unaffected when compared with matched control samples. Membrane transport, permeability, and Ca2(+)-mediated cellular vesiculation were minimally altered by resealing. Finally, entrapment of fluorescent compounds demonstrated that greater than 95% of the resealed RBC had incorporated exogenous agents. In summary, the osmotic lysis and resealing method described resulted in only minor changes in cellular characteristics while allowing for the efficient loading of compounds to which the RBC membrane is normally impermeable. Consequently, this method provides great potential for the selective modification of erythrocyte constituents in order to further define their roles within the RBC.


[Indications for oral implantology in a referral clinic. A three-year retrospective analysis of 737 patients with 1176 implants].
The following study reviews patients from the Department of Oral Surgery and Stomatology at the University of Berne undergoing implant therapy. Between 2000 and 2002, 737 patients received 1176 ITI screw-type implants. At least 70% of these patients were 50 years or older. The main reason for tooth loss in this group was often periodontitis, followed by carious, periapical infection and root fractures. Only 15% of the patients were younger than 30 years. They had lost their teeth mainly due to trauma or agenesis of teeth. This study reports a trend towards treatment of partially edentulous patients (>90%), with single tooth gaps (>50%) being the most frequent indication for implant therapy. The analysis also demonstrated the importance of augmentation procedures prior to implant placement. Almost 40% of the implant cases required either ridge augmentation or sinus lift procedures. The GBR technique was frequently utilized in the anterior maxilla, especially with bone defects resulting from dental trauma. Data also showed that with these augmentation procedures more implants were inserted in the maxilla (53%) than in the mandible. During the healing or early loading phase only six implants out of 1176 were lost, resulting in an early failure rate of 0.51%. Our study has demonstrated that a high level of implant success can be achieved with the ITI system when using a strict selection criteria and stringent operating protocols.


Factors predicting smoking behavior through multilevel interventions in the Royal Thai Army conscripts.
To determine factors predicting smoking behavior through multilevel interventions in the Royal Thai Army Conscripts. The present study was apart ofquasi-experimental research designed to evaluate the effectiveness of smoking cessation program based on ecological model for improving smoking behavior among the conscripts in the three levels ofbehavior change interventions; intrapersonal level, interpersonal level and organizational level. The 89 participants were purposively selected from the first infantry regiment of conscripts who were current smokers from the King's Royal Guards recruited into the Army in the first section of the year 2009 and put into a trial run-through of the three influential factors process throughout the first six months. The instruments used to collect data was a self-dministered questionnaire used between May 2009 and November 2009. In addition, the individual interviews and checklists of observations were employed to collect data related to organizational intervention. Data mining classification was used to predict the influential factors improving smoking behavior after the end of smoking cessation program at six months. The conscripts were able to change their smoking behaviors. 62.9% ofparticipants reduced smoking, and 4.5% could quit smoking. Data mining analysis showed self-efficacy in intrapersonal level was the crucial variable to predict smoking behavior which correctly classified in the model 77.78%, subsequently, behavioralfactors, e.g., duration of smoking and the number of cigarettes smoked per day. Additionally, organizational intervention also had an influence on the change of smoking behavior by strengthening the policy related to tobacco control, settingsmoke free workplace and supportingfrom the commander. For interpersonal intervention, family support alone did not improve their smoking behaviors. Self-efficacy and organizational intervention can help the conscripts improve their smoking behaviors during service in the army.


A Comparison of Mindfulness-Based Group Training and Skills Group Training in Adults With ADHD.
To compare a novel "third wave" mindfulness-based training program with an established skills training derived from dialectical behavior therapy, to reduce ADHD symptoms and improve mindfulness and self-efficacy. Ninety-one adults with ADHD (combined and inattentive type, mainly medicated) were non-randomly assigned to and treated within a mindfulness-based training group (MBTG, n = 39) or a skills training group (STG, n = 52), each performed in 13 weekly 2-hr sessions. General linear models with repeated measures revealed that both programs resulted in a similar reduction of ADHD symptoms, and improvement of mindfulness and self-efficacy. However, the effect sizes were in the small-to-medium range. A decrease in ADHD symptoms ≥30% was observed in 30.8% of the MBTG participants and 11.5% of the STG participants. The comparatively weak results may be due to limitations such as the absence of randomization, the lack of a control group without intervention, and the lack of matching groups for borderline, depression, and anxiety status. Moreover, audio instructions for home exercises and more stringent monitoring of participants' progress and eventual absence from sessions might have improved the outcome.


Transcranial sonography in differential diagnosis of Parkinson disease and other movement disorders.
Reports evaluating the efficacy of transcranial sonography (TCS) for the differential diagnosis of Parkinson disease (PD) and other movement disorders in China are scarce. Therefore, this study aimed to assess the application of TCS for the differential diagnosis of PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and essential tremor (ET) in Chinese individuals. From 2017 to 2019, 500 inpatients treated at the Department of Dyskinesia, Beijing Tiantan Hospital, Capital Medical University underwent routine transcranial ultrasound examination. The cross-sections at the midbrain and thalamus levels were scanned, and the incidence rates of substantia nigra (SN) positivity and the incidence rates of lenticular hyperechoic area were recorded. The echo of the SN was manually measured. Of the 500 patients, 125 were excluded due to poor signal in temporal window sound transmission. Among the 375 individuals with good temporal window sound transmission, 200 were diagnosed with PD, 90 with ET, 50 with MSA, and 35 with PSP. The incidence rates of SN positivity differed significantly among the four patient groups (χ2 = 121.061, P < 0.001). Between-group comparisons were performed, and the PD group showed a higher SN positivity rate than the ET (χ2 = 94.898, P < 0.017), MSA (χ2 = 57.619, P < 0.017), and PSP (χ2 = 37.687, P < 0.017) groups. SN positivity showed a good diagnostic value for differentiating PD from the other three movement diseases, collectively or individually. The incidences of lenticular hyperechoic area significantly differed among the four patient groups (χ2 = 38.904, P < 0.001). Next, between-group comparisons were performed. The lenticular hyperechoic area was higher in the PD group than in the ET (χ2 = 6.714, P < 0.017) and MSA (χ2 = 18.680, P < 0.017) groups but lower than that in the PSP group (χ2 = 0.679, P > 0.017). SN positivity could effectively differentiate PD from ET, PSP, and MSA in a Chinese population.


The use of trans-applicator intracavitary ultrasonography in brachytherapy for cervical cancer: phantom study of a novel approach to 3D image-guided brachytherapy.
To assess the feasibility of applying trans-applicator intracavitary ultrasonography to image-guided brachytherapy for cervical cancer. For this experiment, a phantom was created and included a polyethylene tube, intended to simulate a tandem applicator, which was inserted into chicken meat and embedded in agar, along with magnetic resonance imaging (MRI)-compatible ovoid applicators. Three-dimensional images of the phantom were obtained using computed tomography (CT), MRI (T2-weighted), and intracavitary ultrasonography sectional images acquired at 1 mm slice intervals. Intracavitary ultrasonography images were acquired from within the simulated tandem applicator using a radial transducer. Magnetic resonance imaging and intracavitary ultrasonography images were manually registered onto CT images. The chicken meat was contoured as the target volume independently on the CT, MRI, and intracavitary ultrasonography images, and the Dice similarity coefficient was used to compare the target volumes. The dose distributions of a sample brachytherapy plan were also evaluated. Computed tomography, MRI, and intracavitary ultrasonography all visualized the three-dimensional phantom volumes. Intracavitary ultrasonography images depicted the meat with high echoic signals and a border clearly distinguishable from the surrounding agar. The Dice similarity coefficient values for the target volumes on CT vs. MRI, CT vs. intracavitary ultrasonography, and MRI vs. intracavitary ultrasonography were 0.966, 0.965, and 0.971, respectively, indicating similar contouring with the three modalities. Among the modalities, the differences in D50, D90, D98, and D100 values were 1.8%, 2.9%, 3.7%, and 2.9%, respectively. Three-dimensional reconstructed trans-applicator intracavitary ultrasonographic images clearly depicted meat tissue within the phantom, and could thus be used for brachytherapy planning. This study proves the concept of trans-applicator intracavitary ultrasonography for intracavitary brachytherapy. Further research such as development of intracavitary ultrasonography system, 3D reconstruction method, ultrasonography-compatible applicators, and ultrasonography-based target concept is warranted to assess the potential clinical application.


Self-assembly of J-aggregate nanotubes and their applications for sensing dopamine.
J-aggregates are an attractive supramolecular structure with interesting excitation properties found in the light-harvesting antenna of green sulfur bacteria. To structurally mimic the light-harvesting antenna, we synthesize J-aggregate nanotubes with a sharp and intense absorption band (J-band) by the coassembly of lithocholic acid (LCA) and 3,3'-dipropylthiadicarbocyanine iodide (DiSC3(5)) in aqueous solution. We show that the J-aggregate nanotubes can be used as a supramolecular probe for the sensitive and selective detection of dopamine (DA) in phosphate buffered saline (PBS) solution with the detection limit of ∼0.4 nM by simply observing the intensity change of the J-band due to the efficient photoinduced electron transfer from the J-aggregate nanotubes to the adsorbed DA.


Myc genes linked to viral promoters can collaborate with a transformation-deficient simian virus 40 early gene mutant to transform established rat cells.
Cotransfection of a transformation-deficient and immortalization-positive SV40 early gene mutant with various constructs of viral promoter-linked myc genes induced dense foci in 3Y1 cells, an established cell line derived from rat embryo fibroblasts, whereas transfections with either species alone did not. Four cell clones were isolated from colonies grown in soft agar medium, and found to contain at least a single copy of both DNA species and to express both sequences at relatively high levels. These results indicate that the two immortalizing genes used in the present study collaborate to transform 3Y1 cells.


[Hepatic distomatosis of tumor form after prolonged treatment with corticoids].
A 49-year woman, living in Cameroun and treated by steroids for connective tissue disease, was admitted for a liver mass and epigastric pain. An increase in blood count of eosinophils (1,590.10(9)/L) was observed. Imaging examination showed the presence of a voluminous, multilocular, and heterogeneous hepatic lesion. Pathological examination of the liver showed no evidence of tumor but revealed a rounded cuticle remnant, compatible with bilharziosis eggs or loase transversal section, and Charcot-Leyden's crystals. Due to the uncertainty of diagnosis, a right hepatectomy was performed. Pathological and parasitological examination of the surgical specimen confirmed the diagnosis of hepatic distomatosis, with typical eggs of Fasciola hepatica within necrotic tissue, surrounded by eosinophilic inflammatory infiltrates. Specific serology was positive. The presence of intraparenchymatous eggs was unusual and reflected the ectopic migration of a mature fluke into the hepatic parenchyma, even though the worm was not found in the surgical specimen. Serology for fascioliasis should be performed in any patient suffering from hepatic lesions with eosinophilia.


Isotopic criteria in the characterization of aromatic molecules. 1. Hydrogen affiliation in natural benzenoid/phenylpropanoid molecules.
The site-specific isotope ratios of several families of aromatic molecules are analyzed in terms of hydrogen affiliation and discriminating potential. Among the aromatic molecules produced by plants, many are biosynthesized by the shikimate pathway, but the terpenic pathway also forms some compounds with a benzenic ring. In compounds of the phenylpropanoid family, specific hydrogen connections are determined with cinnamic acid, a key intermediate in the formation of a large number of aromatic molecules. Then affiliations through the phenylalanine precursor, back to the parent d-erythrose 4-phosphate and phosphoenolpyruvate molecules and finally to glucose, are considered. Typical isotopic profiles of the benzenic ring in natural, as compared to non-natural, molecules are defined. The dispersion observed in the (D/H)i ratios of the lateral chains is illustrative of diverse mechanistic responses and the role of exchange phenomena. The isotopic patterns of aromatic molecules pertaining to the terpenic family are drastically different from those of the shikimate descendants, and they exhibit much less variability. They enable the stereochemical affiliation of individual hydrogen atoms to be traced back first to the parent atoms in the common intermediate, geranyl diphosphate, then to the glyceraldehyde 3-phosphate and pyruvate couple involved in the DOXP pathway, and ultimately to the glucose precursor. The results illustrate the aptitude of the site-specific isotope ratios not only to authenticate natural with respect to chemical molecules but also to characterize different metabolic pathways and to reveal differences associated with the nature of the plant precursor.


Aberrant DNA methylation associated with Alzheimer's disease in the superior temporal gyrus.
Abnormal DNA methylation patterns have been demonstrated to be associated with the pathogenesis of Alzheimer's disease (AD). The present study aimed to identify differential methylation in the superior temporal gyrus (STG) of patients with late-onset AD based on epigenome-wide DNA methylation data by bioinformatics analysis. The genome-wide DNA methylation data in the STG region of 34 patients with late-onset AD and 34 controls without dementia were recruited from the Gene Expression Omnibus database. Through systemic quality control, differentially methylated CpG sites were determined by the Student's t-test and mean methylation value differences between the two conditions. Hierarchical clustering analysis was applied to assess the classification performance of differentially methylated CpGs. Functional analysis was performed to investigate the biological functions of the genes associated with differentially methylated CpGs. A total of 17,895 differentially methylated CpG sites were initially identified, including 11,822 hypermethylated CpGs and 6,073 hypomethylated CpGs. Further analysis examined 2,211 differentially methylated CpGs (covering 1,991 genes). AD subjects demonstrated distinctive DNA methylation patterns when compared with the controls, with a classification accuracy value of 1. Hypermethylation was mainly detected for genes regulating the cell cycle progression, whereas hypomethylation was observed in genes involved in transcription factor binding. The present study demonstrated widespread and distinctive DNA methylation alterations in late-onset AD. Identification of AD-associated epigenetic biomarkers may allow for the development of novel diagnostic and therapeutic targets.


Ligand 5,10,15,20-tetra(N-methyl-4-pyridyl)porphine (TMPyP4) prefers the parallel propeller-type human telomeric G-quadruplex DNA over its other polymorphs.
The binding of ligand 5,10,15,20-tetra(N-methyl-4-pyridyl)porphine (TMPyP4) with telomeric and genomic G-quadruplex DNA has been extensively studied. However, a comparative study of interactions of TMPyP4 with different conformations of human telomeric G-quadruplex DNA, namely, parallel propeller-type (PP), antiparallel basket-type (AB), and mixed hybrid-type (MH) G-quadruplex DNA, has not been done. We considered all the possible binding sites in each of the G-quadruplex DNA structures and docked TMPyP4 to each one of them. The resultant most potent sites for binding were analyzed from the mean binding free energy of the complexes. Molecular dynamics simulations were then carried out, and analysis of the binding free energy of the TMPyP4-G-quadruplex complex showed that the binding of TMPyP4 with parallel propeller-type G-quadruplex DNA is preferred over the other two G-quadruplex DNA conformations. The results obtained from the change in solvent excluded surface area (SESA) and solvent accessible surface area (SASA) also support the more pronounced binding of the ligand with the parallel propeller-type G-quadruplex DNA.


Airy-Talbot plasmon: an accelerating self-imaging surface wave.
In this Letter, a new class of an accelerating self-imaging surface plasmonic wave, the Airy-Talbot plasmon, is introduced for the first time, to the best of our knowledge. Our research shows that such a surface wave propagates at the interface between metal (silver) and a dielectric material (air) and causes a strong interference along curved trajectories, which generates the Talbot effect in the surface. The propagation properties have potential value in nanoscale plasmonic devices. A scheme for generating this novel plasmon theoretically is proposed, and we prove it by finite difference time-domain numerical simulations.


Biomechanics of predator-prey arms race in lion, zebra, cheetah and impala.
The fastest and most manoeuvrable terrestrial animals are found in savannah habitats, where predators chase and capture running prey. Hunt outcome and success rate are critical to survival, so both predator and prey should evolve to be faster and/or more manoeuvrable. Here we compare locomotor characteristics in two pursuit predator-prey pairs, lion-zebra and cheetah-impala, in their natural savannah habitat in Botswana. We show that although cheetahs and impalas were universally more athletic than lions and zebras in terms of speed, acceleration and turning, within each predator-prey pair, the predators had 20% higher muscle fibre power than prey, 37% greater acceleration and 72% greater deceleration capacity than their prey. We simulated hunt dynamics with these data and showed that hunts at lower speeds enable prey to use their maximum manoeuvring capacity and favour prey survival, and that the predator needs to be more athletic than its prey to sustain a viable success rate.


[Neuropsychological findings on memory and learning disabilities in children using the BASIC-MLT].
Unrecognized memory and learning disabilities can affect children's general development and limit therapy success. Differentiated assessment of specificities and severity of the disorder is thus essential for specific interventions. This study makes a case for development-related divergences in coping with modality-specific memory and learning tasks. Divergences have been assumed for auditory tasks. Subtest achievements of 403 children in the memory and learning test battery BASIC-MLT were examined by analysis of variance for the factor age (11 age groups from 6-16 years). Results show significant effects for the auditory subtests "Sound series" and "Word learning delay"; respective pairwise comparisons reveal that achievements of 10-year-olds and 12-year-olds deviate from those of most other age groups. These results support the assumption that changes can be shown especially for auditory memory and learning and do correspond with findings on a comparatively later maturation of phonological memory and preference of picture-based strategies in children up to ten years old. Recent studies suggest an increasing activation of left temporal structures up to adulthood, which goes along with reinforced use of verbal strategies.


Interpretation of synovial fluid data.
The routine battery of tests for synovial fluid analysis includes culture and Gram staining, polarizing microscopy, and total WBC and differential counts. If the volume of fluid collected is low, culture and polarizing microscopy have highest priority. Synovial fluid data are diagnostic in only two diseases: septic arthritis and crystal-induced arthritis. In traumatic arthritis, degenerative joint disease, rheumatoid arthritis, and systemic lupus erythematosus, synovial fluid data may provide evidence supporting the diagnosis.


Three-Component Photochemical 1,2,5-Trifunctionalizations of Alkenes toward Densely Functionalized Lynchpins.
Radical remote 1,n-difunctionalization reactions (n > 2) of alkenes are powerful tools to efficiently introduce functional groups with selected distances into target molecules. Among these reactions, 1,5-difunctionalizations are an important subclass, leading to sought-after scaffolds, but typically suffer from tailored starting materials and strict limitations for the formed functional group in 2-position. Seeking to address these issues and to make radical 1,5-difunctionalizations of alkenes more applicable, we report a novel three-component 1,2,5-trifunctionalization reaction between imine-based bifunctional reagents and two distinct alkenes, driven by visible light energy transfer-catalysis. Key to achieving this selective one-step installation of three different functional groups via the choreographed formation of four bonds was the utilization of a 1,2-boron shift and the rigorous capitalization of radical polarities and stabilities. Thorough mechanistic studies were carried out, and the synthetic utility of the obtained products was demonstrated by various downstream modifications. Notably, in addition to the functionalization of individual functional groups, their interplay gave rise to a unique array of cyclic products.


Vibration upshot of operating mechanical sewing machine: an insight into common peroneal nerve conduction study.
Most of the people associated with tailoring occupation in Nepal are still using mechanical sewing machine as an alternative of new technology for tailoring. Common peroneal nerves of both right and left legs are exposed to strenuous and chronic stress exerted by vibration and paddling of mechanical sewing machine. The study included 30 healthy male tailors and 30 healthy male individuals. Anthropometric variables as well as cardio respiratory variables were determined for each subject. Standard Nerve Conduction Techniques using constant measured distances were applied to evaluate common peroneal nerve (motor) in both legs of each individual. Data were analyzed and compared between study and control groups using Man Whitney U test setting the significance level p ≤ 0.05. Anthropometric and cardio respiratory variables were not significantly altered between the study and control groups. The Compound muscle action potential (CMAP) latency of common peroneal nerves of both right [(11.29 ± 1.25 vs. 10.03 ± 1.37), P < 0.001] and left [(11.28 ± 1.38 vs. 10.05 ± 1.37), P < 0.01] legs was found to be significantly prolonged in study group as compared to control group. The Amp-CMAP of common peroneal nerves of both right [(4.57 ± 1.21 vs. 6.22 ± 1.72), P < 0.001] and left [(4.31 ± 1.55 vs. 6.25 ± 1.70), P < 0.001] legs was found significantly reduced in study group as compared to control group. Similarly, the motor nerve conduction velocity (MNCV) of common peroneal nerves of both right [(43.72 ± 3.25 vs. 47.49 ± 4.17), P < 0.001] and left [(42.51 ± 3.82 vs. 46.76 ± 4.51), P < 0.001] legs was also found to be significantly reduced in study group in comparison to control group. Operating mechanical sewing machine by paddling chronically and arduously could have attributed to abnormal nerve conduction study parameters due to vibration effect of the machine on right and left common peroneal nerves. The results of present study follow the trend towards presymptomatic or asymptomatic neuropathy similar to subclinical neuropathy.


Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom.
Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D) is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP). Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.


Back pain in mothers of cerebral palsied children.
Cerebral palsy (CP) leads to varying degrees of movement restrictions, imposing on the parents (especially mothers) a number of additional responsibilities. The burden of long-term care for a disabled child can lead to severe pain in various locations and of various intensity. Therefore, it is important to identify their risk factors and provide training for parents of CP children to educate them how to offer care not only to aid rehabilitation of their child, but also to avoid hazards to their own health. The aim of this study was to evaluate the prevalence of back pain and its underlying causes in mothers of children with cerebral palsy. The study enrolled 179 mothers of CP children aged 3-18 years. The intensity, frequency and functional consequences of the pain were described according to the criteria formulated by Jackson and Moskowitz. The children's functional status was assessed on the basis of their medical records, the GMFCS (Gross Motor Function Classification System) scale and an interview with their mothers. Pain intensity in the mother was compared with the functional status of the child and the level of his/her independence as well as other factors related to the daily care of a child with cerebral palsy. The nonparametric chi-square (x2) test was used for the statistical analyses, with the level of significance at p <0.05. Most of the mothers caring for a CP child on a daily basis suffered from back pain of various location and intensity. The intensity of the pain was determined by the child's locomotor skills and independence level, the necessity of lifting the child several times a day, the number of additional tasks performed by the mother and the age and body weight of the child. At the same time, pain intensity was independent of maternal age, the possibility of having a replacement caregiver and (lack of) prior instruction on appropriate behaviours in their daily care for the disabled child. 1. Long-term daily care of children with cerebral palsy promotes the development of back pain in their mothers. 2. The incidence and intensity of pain depends primarily on the child's functional status and independence level, body weight, age, the need for repeatedly lifting the disabled child throughout the day and the number of additional tasks performed by the mother.


Toward regulating biodegradation in stages of polyurethane copolymers with bicontinuous microphase separation.
For typical biodegradable polymers, their overall performance almost declines exponentially to the degradation degree, which inevitably leads to a dilemma between the requirements of service life and retention time in the environment (both in vitro and in vivo). It is a great challenge to develop a biodegradable polymeric device with relatively stable performance in service while rapidly degrading out of service. Herein, we demonstrate an effective strategy to control degradation of biodegradable polymers in stages by constructing separated bicontinuous microphases with very different microphase degradation rates. First, polyurethane copolymers (PCL-b-CrP-U) containing two blocks, i.e., semicrystalline poly(ε-caprolactone) (PCL) blocks and amorphous random copolymer blocks (CrP) based on ε-CL and p-dioxanone (PDO), were synthesized. The microscopic morphology of PCL-b-CrP-U is investigated by an alkali-accelerated degradation experiment, which also demonstrates that the chain cleavage-induced crystallization during degradation resulted in a self-reinforcement by forming degradation residues with a scaffold-like morphology. The tensile test shows that PCL-b-CrP-U has excellent mechanical properties (1500% of elongation at break, a tensile strength of about 7.5 MPa, and an elastic modulus of 40.0 MPa). The degradation experiments with artificial pancreatic juice as a working medium reveal that PCL-b-CrP-U samples containing relatively high PDO units exhibit a three-stage degradation, i.e. an induction stage, a steady degradation stage and an accelerated degradation stage. The CrP phase preferentially hydrolyzes to form some microchannels due to its amorphous nature and relatively high hydrophilicity, effectively accelerating the entry of water and enzymes into the inner parts of the sample. Meanwhile, at this stage, those originally amorphous PCL segments gradually crystalize owing to their enhanced chain mobility induced by the chain cleavage, forming a "scaffold"-like structure, which effectively reinforces the sample to resist the damage from external force and therefore guarantees a relatively stable mechanical performance of PCL-b-CrP-U during service. With the further depletion of the CrP phase, the intermediate "scaffold"-like structure is also very beneficial to accelerate the degradation of residues owing to its large specific surface area, which is expected to be beneficial for preventing long-term retention of the implantation devices.


Luteolin: A promising natural agent in management of pain in chronic conditions.
Pain due to chronic conditions is a frequent and insufficiently addressed problem. Current drug options for pain management (either in cases of chronic inflammatory conditions or neuropathy) do not adequately treat pain. Moreover, they are associated with important adverse events in long term use. Luteolin is a flavonoid widely present in the plant kingdom and its sources have been assembled in a comprehensive list of this paper. Luteolin has shown in several research studies a range of pharmacological properties; anti-inflammatory, antioxidant, neuroprotective, and analgesic. In this article, we summarize the effects and potential benefits from introducing luteolin as an adjuvant agent in established protocols for pain management. We review the most indicative in vivo and in vitro evidence of how luteolin can target the molecular pathways involved in pathogenesis of chronic inflammatory and neuropathic pain. The data reviewed strongly support luteolin's promising benefits in pain management and raise the need for further clinical trials that can establish its role in clinical practice.


Related functional domains in virus DNA polymerases.
Analysis of the lesions in several drug-resistant DNA polymerase mutants of herpes simplex virus along with comparative analysis of the published polymerase sequences of other human herpesviruses has shown that most lesions (five out of six) are substitutions at amino acid residues conserved in all four polymerases. Furthermore, the majority of lesions are in regions of the polypeptide where there are marked clusterings of conserved residues. On the basis of these data we have identified several domains within the polypeptide which we believe may have important functional roles in the action of the enzyme. The apparent restriction in the potential sites of lesions conferring drug resistance may explain the difficulty in selecting such mutants using acyclovir (ACV) in culture and their failure to emerge so far during ACV therapy. Extension of the comparative analysis to the polymerases of adenovirus type 2, vaccinia virus and phage phi 29 suggests that these enzymes also possess domains homologous to those most conserved in the herpes polymerases (regions I-III) and that these domains have a similar linear spatial distribution on the polypeptides. The results are discussed in relation to the known function of the DNA polymerases.


Multicystic renal dysplasia: a diagnostic dilemma.
A 3-year-old male child had left-sided abdominal lump for 4 months. Radiological examination revealed a cystic mass in the left kidney. A tentative diagnosis of multicystic nephroma was made on clinical and radiological examination. Cytology was inconclusive. Nephrectomy was done. A final diagnosis of multicystic dysplasia was made on histological examination.


Dose-dependent effect of silver nanoparticles (AgNPs) on fertility and survival of Drosophila: An in-vivo study.
Silver nanoparticles (AgNPs) containing consumer products have been proliferating in the market due to its unique antimicrobial property, however, lack of in-depth knowledge about their potential effect on human health in a longer run is of great concern. Therefore, we investigated dose-dependent in vivo effect of AgNPs using Drosophila as a model system. Drosophila, a genetically tractable organism with distinct developmental stages, short life cycle and significant homology with human serves as an ideal organism to study nanomaterial-mediated toxicity. Our studies suggest that ingestion of AgNPs in Drosophila during adult stage for short and long duration significantly affects egg laying capability along with impaired growth of ovary. Additionally, dietary intake of AgNPs from larval stage has more deleterious effects that result in reduced survival, longevity, ovary size and egg laying capability at a further lower dosage. Interestingly, the trans-generational effect of AgNPs was also observed without feeding progeny with AgNPs, thereby suggesting its impact from previous generation. Our results strongly imply that higher doses of AgNPs and its administration early during development is detrimental to the reproductive health and survival of Drosophila that follows in generations to come without feeding them to AgNPs.


Solvent-free method for the determination of lignin-derived phenols in sediments.
A solvent-free method that uses headspace solid-phase microextraction and gas chromatography with flame ionization detection is proposed for the determination of lignin-derived phenols in sediments. The extraction and derivatization conditions for the simultaneous analysis of acetosyringone, acetovanillone, syringaldehyde, vanillin, ferulic acid, syringic acid, vanillic acid, p-hydroxybenzoic acid, and p-coumaric acid were optimized using a central composite design. After optimization, the best results were obtained with the following conditions: exposure of the polyacrylate fiber to the headspace with 60 μL of N,O-bis(trimethylsilyl)trifluoroacetamide as a derivatizing agent for 15 min and then extraction in the headspace of 100 mg of sediment (previously spiked with lignin-derived phenols) for 35 min. The accuracy of the method was estimated based on recovery tests at two concentration levels and by comparison with a high-performance liquid chromatography method reported in the literature. Based on the t-test with a confidence level of 95%, no statistical differences were observed. The detection and quantification limits for the target compounds varied according to their characteristics: values at the microgram per gram level for nonacid compounds and milligram per gram level for phenolic acids, due to the lower volatility of the derivatives.


Flower pollination algorithm-based I/Q phase imbalance compensation strategy.
For wideband receiver systems, it is challenging to compensate the in-phase/quadrature (I/Q) phase mismatch by traditional methods, especially with a time delay deviation (TDD) between the I/Q channels. Considering the above situation, this paper proposes a full-scale I/Q phase imbalance model concerning TDD. The model divides phase mismatch into two parts, i.e., the linear phase (LP) part and the nonlinear phase part, and compensates each part with the corresponding compensation module separately. The design strategy of the compensation module is innovatively transformed into a constrained nonlinear optimization problem, and a metaheuristic algorithm, the flower pollination algorithm (FPA), is utilized to be the optimizer. The results of the contrast simulation with the LP elimination method show the efficiency of the proposed method. In addition, the superiority of the FPA-based structure is verified by comparing with other metaheuristic algorithms, the artificial bee colony technique, the bat algorithm, and the differential evolution algorithm, in terms of the compensation accuracy, algorithm stability, runtime consumption, and convergence performance. Ultimately, the image rejection ratio improvement on the actual platform after compensation is measured, which validates the proposed compensation structure and the corresponding optimization method practically, and the FPA is still the best choice among the competent optimizers.


Thrombopoietin stimulates endothelial cell motility and neoangiogenesis by a platelet-activating factor-dependent mechanism.
In this study, we demonstrate that human umbilical cord vein-derived endothelial cells (HUVECs) expressed c-Mpl, the thrombopoietin (TPO) receptor, and that TPO activates HUVECs in vitro, as indicated by directional migration, synthesis of 1-alkyl-/1-acyl-platelet-activating factor (PAF) and interleukin-8 (IL-8), and phosphorylation of the signal transducers and activators of transcription (STAT) STAT1 and STAT5B. The observation that WEB 2170 and CV3988, 2 structurally unrelated PAF receptor antagonists, prevented the motility of HUVECs induced by TPO suggests a role of PAF as secondary mediator. Moreover, kinetic analysis of TPO-induced tyrosine phosphorylation of STAT demonstrated that STAT5B activation temporally correlated with the synthesis of PAF. PAF, in turn, induced a rapid tyrosine phosphorylation of STAT5B and PAF receptor blockade, by WEB 2170, preventing both TPO- and PAF-mediated STAT5B activation. The in vivo angiogenic effect of TPO, studied in a mouse model of Matrigel implantation, demonstrated that TPO induced a dose-dependent angiogenic response that required the presence of heparin. Moreover, the in vivo angiogenic effect of TPO was inhibited by the PAF receptor antagonist WEB 2170 but not by the anti-basic fibroblast growth factor neutralizing antibody. These results indicate that the effects of TPO are not restricted to cells of hematopoietic lineages, because TPO is able to activate endothelial cells and to induce an angiogenic response in which the recruitment of endothelial cells is mediated by the synthesis of PAF. Moreover, biochemical analysis supports the hypothesis that STAT5B may be involved in the signaling pathway leading to PAF-dependent angiogenesis.


The effect of keishi-bushi-to on collagen-induced arthritis.
To evaluate the usefulness of a traditional Chinese medicine (Kampo prescription), Keishi-bushi-to (KBT), which is composed of five medicinal plants derived from Kampo prescriptions used to treat rheumatoid arthritis, we investigated the effect of KBT on the development of arthritis induced by type II collagen (CII). Oral administration of KBT at a dose of 500 mg/kg from 7 d before intradermal injection of CII significantly reduced the severity from 7 d after the onset of arthritis. The reduction in body weight resulting from the development of arthritis was not seen in rats treated with KBT. Plasma IgG and IgM anti-CII antibody levels were lower in KBT-treated rats than control rats. In addition, the clearance of IgG anti-CII antibody from circulating blood after intravenous injection was faster in KBT-treated rats than control rats. These results indicate that KBT is effective in suppressing collagen-induced arthritis and its effect is at least partly due to the suppression of humoral and cellular immunity.


[Analysis of the Cochrane Review: Angiotensin Converging Enzyme Inhibitors Versus Angiotensin Receptor Blockers for Primary Hypertension. Cochrane Database Syst Rev. 2014,8: CD009096].
Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are first line drugs in the treatment of hypertension. The aim of this review was to assess if there are differences between these drug classes regarding the prevention of total mortality, occurrence of cardiovascular events and of adverse effects. A systematic review and metanalysis was performed, searching for studies that compare angiotensin converting enzyme inhibitors and angiotensin receptor blockers face-to-face, in several databases until July 2014. The study selection and data extraction were performed by 2 independent researchers. Nine studies were included, with a total of 10 963 participants, 9 398 of which participated in the same study and had high cardiovascular risk. No differences were observed regarding total mortality, cardiovascular mortality or total cardiovascular events. A slightly smaller risk was observed with angiotensin receptor blockers regarding withdrawal due to adverse effects (55 people were needed to be treated with angiotensin receptor blockers for 4.1 years to avoid one withdrawal due to adverse effect), mainly due to the occurrence of dry cough with angiotensin converting enzyme inhibitors. Thus, no differences were observed between angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the prevention of total mortality and cardiovascular events, and angiotensin receptor blockers were better tolerated. Given the large proportion of participants with a high cardiovascular risk, the generalization of these results to other populations is limited.


Impact of antiretroviral treatment-related toxicities on hospital admissions in HIV-infected patients.
While classical opportunistic infections have decreased as the main cause of hospital admission of HIV-infected patients, other conditions including drug-related toxicities seem to have increased. We assessed the proportion of patients with hospital admission due to antiretroviral (ARV)-related toxicities over the last 7 years at a single HIV/AIDS reference institution located in Madrid. A total of 1981 consecutive hospital admissions in 1581 different HIV-infected patients were analyzed. Nearly half of them (45%) were on ARV therapy. Overall, ARV-related toxicities were the main or secondary reason for hospital admission in 141 patients (7%). Liver toxicity was the most frequent complication (n = 42; 30%), of which one-third were associated with NVP use and 80% occurred in subjects with underlying chronic hepatitis C virus (HCV) infection. Other main ARV-related toxicities were bone marrow toxicity due to zidovudine (17%), pancreatitis (13%), and indinavirassociated nephrolithiasis (6%). Eight patients presented with symptomatic hyperlactatemia, two of them with lactic acidosis. All subjects with ARV-related toxicities had a favorable outcome, except one with prior HCVrelated end-stage liver disease, who died after experiencing hepatic decompensation following initiation of a protease inhibitor-based regimen.


Continuous pO2 monitoring during dual perfusion of the term human placenta in vitro.
A computerized system has been developed to continuously monitor, collect and display pO2 in real time from the maternal and fetal arteries and veins in the dually perfused term placenta. Oxygen electrodes were installed in flow-through chambers in the tubing of the perfusion system. The signal from the O2 electrodes was digitized, acquired, analyzed and displayed in real time during the perfusions using a personal computer. Output from the O2 electrodes was linearly proportional to pO2 (33-502 mm Hg; r2 = 0.99). Running average pO2 values (mean +/- SD) were also calculated for every minute and stored. The captured data files can be recalled and analyzed after completion of the perfusion experiment and compared with other data collected during perfusion. One of the unique capabilities of the pO2 electrodes is their ability to respond rapidly to changing perfusion conditions. For example, as the fetal circulation begins to break down the change is noted before volume loss in the fetal circuit by decreasing fetal vein pO2.


Tissue-specific molecular and cellular toxicity of Pb in the oyster (Crassostrea gigas): mRNA expression and physiological studies.
Lead (Pb) is one of the ubiquitous and toxic elements in aquatic environment. In oysters, gills and digestive glands are the main target organs for Pb-induced toxicity, but there is limited information on the molecular mechanisms underlying its toxicity. The present study investigated the Pb-induced toxicity mechanisms in the Pacific oyster (Crassostrea gigas) based on transcriptome, phenotypic anchoring, and validation of targeted gene expression. Gene ontology and pathway enrichment analyses revealed the differential Pb toxicity mechanisms in the tissues. In the gills, Pb disturbed the protein metabolism, with the most significant enrichment of the "protein processing in endoplasmic reticulum" pathway. The main mechanism comprised of a Pb-stimulated calcium (Ca2+) increase by the up-regulation of transporter-Ca-ATPase expression. The disturbed Ca2+ homeostasis then further induced high expressions of endoplasmic reticulum (ER) chaperones, leading to ER stress in the oysters. Unfolded proteins induced ER associated degradation (ERAD), thereby preventing the accumulation of folding-incompetent glycoproteins. However, Pb mainly induced oxidative reduction reactions in the digestive gland with high accumulation of lipid peroxidation products and high expression of antioxidant enzymes. Further, Pb induced fatty acid β-oxidation and CYP450 catalyzed ω-oxidation due to increased metabolic expenditure for detoxification. The increased content of arachidonic acid indicated that Pb exposure might alter unsaturated fatty acid composition and disturb cellular membrane functions. Taken together, our results provided a new insight into the molecular mechanisms underlying Pb toxicity in oysters.


[Clinical findings and mutational spectrum in Venezuelan patients with delayed diagnosis of phenylketonuria].
Massive neonatal screening for phenylketonuria (PKU) began in developed countries in 1963, and eventually disappeared as a cause of mental retardation. Yet, this is not the case in most developing countries. To describe the phenotype and the genotype of PKU patients with a delayed diagnosis in order to draw attention to the importance of neonatal studies and molecular diagnosis. Clinical data were collected from five unrelated patients by means of a medical assessment. The molecular study was conducted using the DGGE, sequencing and/or restriction analysis techniques to search for mutations in the PAH gene. RESULTS. Owing to the delayed diagnosis all the patients presented severe clinical manifestations, such as psychomotor retardation, atypical behaviours and language disorders. Four of them presented epilepsy and there were two cases of microcephaly. The phenotype was as expected, given the genotype. Seven different mutations were detected in the 10 alleles that were studied. The IVS10nt +5 g>t mutation was the most frequent, followed by the Venezuelan mutation S349L. Furthermore, two patients presented mutated proteins with residual activity, and good results were obtained using BH4 therapy. In our country, as in most developing countries, PKU neonatal studies are performed but the programme does not cover the whole neonatal population. In this work, we want to stress the importance of neonatal studies in the welfare of children, as well as the use of molecular diagnosis to improve the therapeutic orientation and genetic counselling of the families involved.


Coaggregate of trypsin and chymotrypsin.
The method of chemical aggregation of enzymes has the advantage of yielding an immobilized enzyme preparation wherein reactor volume can be significantly reduced because of the absence of an inert carrier. A coaggregate of trypsin and chymotrypsin formed by extensive cross-linking with glutaraldehyde is described. A significant property of this aggregate is the reduced autolysis of the trypsin component of the coaggregate.


[Isolation and characterization of the matrix properties of electrophoretically homogeneous immunoglobulin L-chain mRNA from mouse myeloma MORC 21].
mRNA with m. w. 4.10(5) dalton was isolated by elution of one of the fractions of poly(A)-RNA from polyacrylamide gel. During reelectrophoresis this mRNA was electrophoretically homogeneous and had the same size. The isolated fraction represented the template activity in a wheat germ cell-free system of protein synthesis and stimulated the synthesis of polypeptides, electrophoretically correspondent to L-chain of authentic immunoglobulin. Comparative data of properties of electrophoretically homogenous mRNA and analogous fraction of mRNA, isolated from sucrose concentration gradient after fractionation of total poly(A)-containing RNA are given.


Reclassification of Agromonas oligotrophica into the genus Bradyrhizobium as Bradyrhizobium oligotrophicum comb. nov.
Agromonas oligotrophica JCM 1494(T) was isolated in Japan in 1983, and the name was validly published in 1985. Analysis of the 16S rRNA gene sequence showed that Agromonas oligotrophica LMG 10732(T) ( = JCM 1494(T)) is located within the genus Bradyrhizobium, with Bradyrhizobium denitrificans LMG 8443(T) as its closest relative, showing 99.6 % 16S rRNA gene sequence identity. However, Agromonas oligotrophica LMG 10732(T) and Bradyrhizobium denitrificans LMG 8443(T) can be distinguished by housekeeping gene sequence analysis, phenotypic characterization and DNA-DNA hybridization. Agromonas oligotrophica is also genotypically and phenotypically different from the remaining species of the genus Bradyrhizobium, and we therefore propose the reclassification of Agromonas oligotrophica into the genus Bradyrhizobium as Bradyrhizobium oligotrophicum comb. nov. (type strain LMG 10732(T) = JCM 1494(T) = ATCC 43045(T)).


Sex-determined susceptibility and differential IFN-gamma and TNF-alpha mRNA expression in DBA/2 mice infected with Leishmania mexicana.
Female DBA/2 mice have been shown to be relatively resistant to infection with Leishmania mexicana when compared with male mice. In order to determine the immunological basis behind this difference the draining lymph nodes from male and female DBA/2 mice were excised and the RNA extracted at different time-points following infection. Following reverse transcription, the polymerase chain reaction (PCR) was used to identify mRNA transcripts for interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), IL-10 and IL-12. The evolution of cytokine mRNA production was slow in both male and female mice as no newly synthesized transcripts were identified 5 weeks after infection. IL-10 was expressed constitutively in non-infected mice and was present throughout the experiment in all animals. By week 8, a clear dichotomy in cytokine mRNA expression was emerging between the resistant female and susceptible male mice. Whereas all females expressed IFN-gamma and one also expressed TNF-alpha only two out of five males expressed IFN-gamma and four out of five expressed TNF-alpha. The greatest lesion sizes at this time were recorded from those mice expressing TNF-alpha but not IFN-gamma. No differences in IL-4 or IL-12 were noted with transcripts for both cytokines present in both sexes at week 8. By week 12 males had developed large non-healing nodules and in females lesions had either disappeared or were slow growing. At this time only transcripts for TNF-alpha were present in males and only those for IFN-gamma were detected in females. Treatment of female mice following infection with IFN-gamma neutralizing antibody resulted in lesion growth equivalent to male mice. IFN-gamma production would, therefore, appear sufficient to limit the growth of L. mexicana in female DBA/2 mice while TNF-alpha production in the absence of IFN-gamma confers no protection to DBA/2 male mice.


[Reduction of gastric acid secretion: pathophysiologic and clinically relevant sequelae].
After proton pump inhibitors (omeprazole) became available, discussions about safety aspects of (particularly long-term) inhibition of gastric acid secretion have been renewed. In contrast to animals, hypergastrinaemia does not seem to be a relevant problem in man: marginal increases of serum gastrin during proton pump inhibition may induce proliferation of gastric endocrine ("enterochromaffin-like"; ECL-) cells in some cases which are without clinical importance, the risk for development of gastric carcinoids seems negligible if existent at all. Other aspects of acid inhibition (e.g. protein malabsorption, diminished iron and cobalamin absorption, bacterial overgrowth of the stomach, risk of gastric cancer) do also not appear to be of clinical relevance. However, data from larger numbers of patients on long-term therapy with proton pump inhibitors should be available until such treatment can be generally recommended.


Electrospray ion-trap multistage mass spectrometry for characterisation of co-monomer compositional distribution of bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) at the molecular level.
We report an electrospray ionisation multistage mass spectrometry (ESI-MSn) method that utilises molecular mass information for determination of sequence distribution and chemical structure of mass-selected macromolecules of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) biopolyester, PHBH. On the basis of ESI-MSn studies of PHBH oligomers obtained by partial alkaline depolymerisation of natural PHBH containing 13-14 mol% of hydroxyhexanoate (HH) units, the microstructure of this bacterial copolyester was assessed up to the level of 28 repeat units. The subtle structural details of the PHBH were evaluated based on sequencing of individual macromolecular ions thus showing the utility of this technique for the analysis of biological copolyester macromolecules. It was confirmed that both HH and hydroxybutyrate (HB) units of the PHBH copolymer are randomly distributed.


Idiopathic Angioedema: Current Challenges.
The etiological diagnosis of isolated recurrent angioedema poses problems because it must often be done urgently. Angioedema secondary to nonspecific mast cell activation (MC-AE) is the most frequent form and is usually mild. Bradykinin mediated angioedema (BK-AE) is rarer but potentially fatal in the absence of the correct treatment. Few biological markers exist. The C1-inhibitor (C1-inh) functional assay can exclude AE due to C1-inh deficiency. Genetic diagnoses of hereditary AE due to abnormal C1-inh AE have progressed with four currently known mutations. However, determining the physiopathological mechanism leading to some isolated AE cases is sometimes very difficult. In such cases, therapeutic tests are then the only solution: antihistamines at high doses and omalizumab for suspected MC-AE, icatibant for suspected AE-BK. Identifying new markers would be a great help.


Changes in Specific Biomarkers Indicate Cardiac Adaptive and Anti-inflammatory Response of Repeated Recreational SCUBA Diving.
Recreational SCUBA (rSCUBA) diving has become a highly popular and widespread sport. Yet, information on molecular events underlying (patho)physiological events that follow exposure to the specific environmental conditions (hyperbaric conditions, coldness, immersion, and elevated breathing pressure), in which rSCUBA diving is performed, remain largely unknown. Our previous study suggested that repeated rSCUBA diving triggers an adaptive response of cardiovascular and immune system. To elucidate further molecular events underlying cardiac and immune system adaptation and to exclude possible adverse effects we measured blood levels of specific cardiac and inflammation markers. This longitudinal intervention study included fourteen recreational divers who performed five dives, one per week, on the depth 20-30 m that lasted 30 min, after the non-dive period of 5 months. Blood samples were taken immediately before and after the first, third, and fifth dives. Copeptin, immunoglobulins A, G and M, complement components C3 and C4, and differential blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) were determined using standard laboratory methods. Cell-free DNA was measured by qPCR analysis and N-glycans released from IgG and total plasma proteins (TPP), were analyzed by hydrophilic interaction ultra-performance liquid chromatography. Copeptin level increased after the first dive but decreased after the third and fifth dive. Increases in immunoglobulins level after every dive and during whole studied period were observed, but no changes in C3, C4, and cfDNA level were detected. NLR increased only after the first dive. IgG and TPP N-glycosylation alterations toward anti-inflammatory status over whole studied period were manifested as an increase in monogalyctosylated and core-fucosylated IgG N-glycans and decrease in agalactosylated TPP N-glycans. rSCUBA diving practiced on a regular basis promotes anti-inflammatory status thus contributing cardioprotection and conferring multiple health benefits.


A 27-year-old man with recurrent sinopulmonary and cutaneous infections.
The increasing availability of genetic testing for modern immunologists in the evaluation of immune diseases could provide a definite diagnosis in elusive cases. A 27-year-old white male patient presented to the clinic with recurrent sinopulmonary and cutaneous infections since childhood. The patient's mother had seronegative polyarthritis, and one of two sisters of the patient had chronic sinopulmonary infections. Serum immunoglobulins, immunoglobulin G (IgG) subclasses, lymphocyte subset markers, mannose-binding lectin, mitogen and antigen stimulation, bacteriophage study, and Streptococcus pneumoniae titers to 23 serotypes were all normal. B-cell phenotyping revealed a decrease in both nonswitched memory B cells (CD19+CD27+IgD+) and switched memory B-cells (CD19+CD27+IgD-). Genetic testing and the improvement of clinical symptoms after IgG replacement led to the final diagnosis.


Dams, environment and regional development--harnessing the "elixir of life: water" for overall development.
Water--the Elixir of Life--has the potential to sustain human life and also to develop it further, and that is why various international instruments have aptly recognized its role in sustainable development. This paper reviews the global and Indian water scenario before presenting the case of Gujarat State, where perennial water scarcity has raised serious threats to the existence of millions of people and cattle and has led to environmental degradation and constrained economic development. More than 13,000 villages out of 18,028 villages of the State are facing scarcity in terms of crop failure this year. Drinking water supply is maintained by transporting water by road tankers, "water special" trains and even by ships via a sea route. Lack of access to safe and clean water for domestic use has a detrimental effect on the social fabric, and even incidences of migration and water riots are recorded. The paper discusses the efficacy of available options including rain water harvesting. The efforts of the State to harness the untapped waters of Narmada for the survival of millions and sustainable development of western India, are discussed adjudging socioeconomic and environmental impacts. The paper concludes that assured water supply is essentially critical for overall development.


Efficient Heterostructures of Ag@CuO/BaTiO3 for Low-Temperature CO2 Gas Detection: Assessing the Role of Nanointerfaces during Sensing by Operando DRIFTS Technique.
Tetragonal BaTiO3 spheroids synthesized by a facile hydrothermal route using Tween 80 were observed to be polydispersed with a diameter in the range of ∼15-75 nm. Thereon, BaTiO3 spheroids were decorated with different percentages of Ag@CuO by wet impregnation, and their affinity toward carbon dioxide (CO2) gas when employed as sensitive layers in a microsensor was investigated. The results revealed that the metal nanocomposite-based sensor had an exceptional stability and sensitivity toward CO2 gas (6-fold higher response), with appreciable response and recovery times (<10 s) and higher repeatability (98%) and accuracy (96%) at a low operating temperature of 120 °C, compared to those of pure BaTiO3 and CuO. Such improved gas-sensing performances even at a very low concentration (∼700 ppm) is attributable to both the chemical and electrical contributions of Ag@CuO forming intermittent nanointerfaces with BaTiO3 spheroids, exhibiting unique structural stability. The CO2-sensing mechanism of CuO/BaTiO3 nanocomposite was studied by the diffuse reflectance infrared Fourier transform spectroscopy technique that established the reaction of CO2 with BaO and CuO to form the respective carbonate species that is correlated with the change in material resistance consequently monitored as sensor response.


Multiple-Star System Adaptive Vortex Coronagraphy Using a Liquid Crystal Light Valve.
We propose the development of a high-contrast imaging technique enabling the simultaneous and selective nulling of several light sources. This is done by realizing a reconfigurable multiple-vortex phase mask made of a liquid crystal thin film on which local topological features can be addressed electro-optically. The method is illustrated by reporting on a triple-star optical vortex coronagraphy laboratory demonstration, which can be easily extended to higher multiplicity. These results allow considering the direct observation and analysis of worlds with multiple suns and more complex extrasolar planetary systems.


Adverse drug reactions in home care patients receiving nafcillin or oxacillin.
Documented adverse reactions to anti-infective agents in patients of a home infusion company were studied to determine whether the prevalence of reactions was greater in patients receiving nafcillin or oxacillin than in those receiving other i.v. antiinfectives. Data on adverse drug reactions (ADRs) were obtained by reviewing the discharge summaries of all patients who received anti-infective therapy in 1990-1994 and the company's quarterly and annual ADR reports for that period. The occurrence of ADRs per total courses of therapy was calculated for groups of antiinfectives, as were intensity and causality. For ADRs to nafcillin and oxacillin, patient demographics and treatment information and outcomes were reviewed. A total of 2488 courses of anti-infective therapy were documented, and ADRs occurred in 10.9%. Nafcillin and oxacillin accounted for 105 courses, with an ADR rate of 31.4%; 99 patients received one of these drugs and 24 had ADRs, with rash and phlebitis the most common ADRs. Thirty-nine patients receiving nafcillin or oxacillin had documented infection with methicillin-sensitive Staphylococcus aureus. Seventy-five patients receiving nafcillin or oxacillin did not have an ADR; therapy was successful in 62 of these patients. Of the 24 patients with ADRs to nafcillin or oxacillin, 13 were switched to other i.v. anti-infectives, which were successful in 10 of them. Five patients were hospitalized because of ADRs to nafcillin or oxacillin. Most nafcillin or oxacillin ADRs that resulted in a therapy change or hospitalization occurred in the second or third week of therapy. Home care patients who received nafcillin or oxacillin therapy had a disproportionately high number of ADRs, compared with patients who received other anti-infective agents.


Assay of the concentration and (13)C isotopic enrichment of propionyl-CoA, methylmalonyl-CoA, and succinyl-CoA by gas chromatography-mass spectrometry.
We developed gas chromatography-mass spectrometry assays for the concentration and mass isotopomer distribution of propionyl-CoA, methylmalonyl-CoA, and succinyl-CoA in tissues. The assays involves perchloric acid extraction of the tissue, spiking the extract with [(2)H(5)]propionyl-CoA and [(2)H(4)]succinyl-CoA internal standards, and isolation of short-chain acyl-CoA fraction on an oligonucleotide purification cartridge. Propionyl-CoA is reacted with sarcosine and the formed N-propionylsarcosine is assayed as its pentafluorobenzyl derivative. Methylmalonyl-CoA and succinyl-CoA are hydrolyzed and the corresponding acids assayed as tert-butyl dimethylsilyl derivatives. The assay was applied to a study of [U-(13)C(3)]propionate metabolism in perfused rat livers. While propionyl-CoA is only M3 labeled, succinyl-CoA is M3, M2, and M1 labeled because of isotopic exchanges in the citric acid cycle. Methylmalonyl-CoA is M3 and M2 labeled, reflecting reversal of S-methylmalonyl-CoA mutase. Thus, our assays allow measuring the turnover of the coenzyme A derivatives involved in anaplerosis of the citric acid cycle via precursors of propionyl-CoA, i.e., propionate, odd-chain fatty acids, isoleucine, threonine, and valine.


Placental transcriptome in development and pathology: expression, function, and methods of analysis.
The placenta is the essential organ of mammalian pregnancy and errors in its development and function are associated with a wide range of human pathologies of pregnancy. Genome sequencing has led to methods for investigation of the transcriptome (all expressed RNA species) using microarrays and next-generation sequencing, and implementation of these techniques has identified many novel species of RNA including: micro-RNA, long noncoding RNA, and circular RNA. These species can physically interact with both each other and regulatory proteins to modify gene expression and messenger RNA to protein translation. Transcriptome analysis is actively used to investigate placental development and dysfunction in pathologies ranging from preeclampsia and fetal growth restriction to preterm labor. Genome-wide gene expression analysis is also being applied to identify prognostic and diagnostic biomarkers of these disorders. In this comprehensive review we summarize transcriptome biology, methods of isolation and analysis, application to placental development and pathology, and use in diagnostic analysis in maternal blood. Key information for analysis methods is organized into quick reference tables where current analysis techniques and tools are cited and compared. We have created this review as a practical guide and starting reference for those interested in beginning an investigation into the transcriptome of the placenta.


Automated detection of the choroid boundary within OCT image data using quadratic measure filters.
A novel method for the automated detection of the outer choroid boundary within spectral-domain optical coherence tomography image data, based on an image model within the space of functions of bounded variation and the application of quadratic measure filters, is presented. The same method is used for the segmentation of retinal layer boundaries and proves to be suitable even for data generated without special imaging modes and moderate line averaging. Based on the segmentations, an automated determination of the central fovea region and choroidal thickness measurements for this and two adjacent 1-mm regions are provided. The quality of the method is assessed by comparison with manual delineations performed by five trained graders. The study is based on data from 50 children of the ages 8 to 13 that were obtained in the framework of the LIFE Child study at Leipzig University.


Anemia and left ventricular hypertrophy in chronic kidney disease populations: a review of the current state of knowledge.
The increasing awareness of the high prevalence of cardiovascular disease (CVD) in the dialysis population has led clinical nephrologists and researchers to focus their attention on processes and factors that are present in patients prior to dialysis. It is clear that many of the risk factors for kidney disease and cardiovascular disease are similar: This may account for the high prevalence of CVD within the dialysis population. However, it is evident that there are unique risk factors for CVD that are present in patients with chronic kidney disease (CKD). These unique uremia-related risk factors for CVD include anemia, hyperparathyroidism, abnormalities of mineral metabolism, and acidosis. Of note, the association of anemia, or lower levels of hemoglobin, have been consistently described in all populations with kidney disease. Left ventricular hypertrophy has long been known as an independent risk factor for death and CV events, in both the dialysis and general populations. There have been accumulating data that LVH and left ventricular (LV) growth occur prior to dialysis in patients with kidney disease, and that the prevalence of LVH in that group of patients is caused by, conventional risk factors for LVH (e.g., hypertension) as well as nonconventional risk factors such as anemia.


Results of treatment for pT1/pT2 carcinomas of the floor of mouth.
In pT2 floor of mouth cancer (FOMC), a standardized neck dissection (ND) should be carried out, due to the high risk of occult metastases. In cases of pT1 carcinomas with a clinically negative neck using high imaging standards and expertise a tight 'wait and watch' strategy can be used. To report on the oncologic results with primary surgical treatment of pT1/pT2 FOMC and to examine the benefit of elective ND in cN0. This was a retrospective study design including 216 patients who were treated between 1980 and 2010 for pT1/2 FOMC. The 5-year disease-specific survival (DSS), local and (loco)regional control based on the T and N classification and depth of infiltration were investigated. DSS was 79.5% and (loco)regional control was 89.8%. DSS in patients staged pN0 was significantly higher, at 84.6%, than in those staged pN+, at 60%. ND was performed in 165 patients, and adjuvant therapy was administered in 124 patients. Ninety patients (41.7%) were staged cN0, and 53.3% of them underwent elective ND. The risk of occult metastases was 4.8% in pT1 and 28.6% in pT2. A depth of infiltration of ≥ 5 mm showed a markedly higher relative frequency of occult neck metastases and pN+ status.


Purinergic and calcium signaling in macrophage function and plasticity.
In addition to a fundamental role in cellular bioenergetics, the purine nucleotide adenosine triphosphate (ATP) plays a crucial role in the extracellular space as a signaling molecule. ATP and its metabolites serve as ligands for a family of receptors that are collectively referred to as purinergic receptors. These receptors were first described and characterized in the nervous system but it soon became evident that they are expressed ubiquitously. In the immune system, purinergic signals regulate the migration and activation of immune cells and they may also orchestrate the resolution of inflammation (1, 2). The intracellular signal transduction initiated by purinergic receptors is strongly coupled to Ca(2+)-signaling, and co-ordination of these pathways plays a critical role in innate immunity. In this review, we provide an overview of purinergic and Ca(2+)-signaling in the context of macrophage phenotypic polarization and discuss the implications on macrophage function in physiological and pathological conditions.