Association between cardiologist evaluation and mortality in myocardial injury after non-cardiac surgery.
Myocardial injury after non-cardiac surgery (MINS) is strongly associated with mortality, but few studies assessed treatment strategies. This study aimed to identify whether evaluation by cardiologists could reduce mortality in MINS patients. From a single-centre retrospective cohort, we enrolled a total of 5633 adult patients diagnosed with MINS between January 2010 and June 2019. The patients were divided into two groups based on evaluation by cardiologist, which was defined as a cardiology consultation or transfer to the cardiology department. For the outcome, 30-day mortality was compared in crude and propensity-score matched populations. Of a total of 5633 patients, 2120 (37.6%) were evaluated by cardiologists and 3513 (62.4%) were not. Mortality during the first 30 days after surgery was significantly lower in MINS patients who were evaluated by cardiologists compared with those who were not (5.8% vs 8.3%; HR, 0.64; 95% CI 0.51 to 0.80; p<0.001 for all-cause mortality and 1.6% vs 2.0; HR 0.62; 95% CI 0.40 to 0.96; p=0.03 for cardiovascular mortality). The propensity score matched analysis showed similar results (5.6% vs 8.6%; HR 0.64; 95% CI 0.50 to 0.81; p<0.001 for all-cause mortality and 1.3% vs 2.2%; HR 0.58; 95% CI 0.35 to 0.95; p=0.03 for cardiovascular mortality). Cardiologist evaluation was associated with lower mortality in patients diagnosed with MINS. Further studies are needed to identify effective treatment strategies for MINS. KCT0004244.


A glucose-powered antimicrobial system using organic-inorganic assembled network materials.
A new glucose-driven photodynamic antimicrobial system was developed to efficiently kill bacteria and fungi, taking advantage of organic-inorganic network materials encapsulating glucose oxidase and horseradish peroxidase and bioluminescence resonance energy transfer (BRET).


Nutritional status of pre-school children in an integrated child development service (ICDS) block of Chandigarh.
Nutritional status of 1286 pre-school children selected by a stratified random sampling and residing in urban, rural and slum areas of Chandigarh was assessed by weight for age criteria by making domicilliary visits. The overall prevalence of protein energy mulnutrition (PEM) was found to be 51.6% while 65.4%, 26.3%, 5.3% and 3% of children had grades I, II, II and IV PEM, respectively. The prevalence of malnutrition significantly increased with increase in age till 3rd year, then started declining (P<0.001). The prevalence of PEMwas significantly higher among Integrated Child Development Service (ICDS) beneficiaries (53.8%) than non-ICDS beneficiaries (46.9%); P<0.05. More attention and better impetus are required to be given to improve the nutritional status of pre-school children in Chandigarh.


Glycemic control after metabolic surgery: a Granger causality and graph analysis.
The purpose of this study was to examine the contribution of nonesterified fatty acids (NEFA) and incretin to insulin resistance and diabetes amelioration after malabsorptive metabolic surgery that induces steatorrhea. In fact, NEFA infusion reduces glucose-stimulated insulin secretion, and high-fat diets predict diabetes development. Six healthy controls, 11 obese subjects, and 10 type 2 diabetic (T2D) subjects were studied before and 1 mo after biliopancreatic diversion (BPD). Twenty-four-hour plasma glucose, NEFA, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) time courses were obtained and analyzed by Granger causality and graph analyses. Insulin sensitivity and secretion were computed by the oral glucose minimal model. Before metabolic surgery, NEFA levels had the strongest influence on the other variables in both obese and T2D subjects. After surgery, GLP-1 and C-peptide levels controlled the system in obese and T2D subjects. Twenty-four-hour GIP levels were markedly reduced after BPD. Finally, not only did GLP-1 levels play a central role, but also insulin and C-peptide levels had a comparable relevance in the network of healthy controls. After BPD, insulin sensitivity was completely normalized in both obese and T2D individuals. Increased 24-h GLP-1 circulating levels positively influenced glucose homeostasis in both obese and T2D subjects who underwent a malabsorptive bariatric operation. In the latter, the reduction of plasma GIP levels also contributed to the improvement of glucose metabolism. It is possible that the combination of a pharmaceutical treatment reducing GIP and increasing GLP-1 plasma levels will contribute to better glycemic control in T2D. The application of Granger causality and graph analyses sheds new light on the pathophysiology of metabolic surgery.


Imaging of immunolabeled membrane receptors in uncoated SEM specimens.
Epidermal growth factor receptors (EGFR) were labeled with 10 nm immunogold and examined on uncoated specimens of A431 human epidermoid carcinoma cells. A field emission gun and a high-sensitivity YAG ring detector were used to demonstrate the affinity labeling simultaneously in the secondary-electron (SE) and backscattered-electron (BSE) modes with a low accelerating voltage (Vo). At Vo = 2 kV, the SE and BSE signals were too weak to identify all markers, while at Vo = 3-7 kV labeling was observed unambiguously in both the SE and BSE modes with smaller and higher working distances. Increasing the Vo to above 7 kV sometimes provokes instability of the specimens. A Vo of > or = 10 kV produces charging artifacts in the SE image, but permits a BSE image of the gold markers providing additional topographic information. In conclusion, immunogold labeling can be used with good results for uncoated specimens.


Control of chemotaxis in Physarum polycephalum.
Plasmodia migrate towards those situations which increase the frequency of their alternations in streaming, and away from those which decrease the frequency. Therefore peristalsis-like waves in Physarum move in the direction opposite from the net movement of the organism. The mechanism is fundamentally related to other known types of chemotaxis.


Increased ratio of mitochondrial rDNA to cytoplasmic rDNA during zoosporic and germinating cyst stages of the life cycle of Phytophthora infestans (Mont.) de Bary.
A differential RNA display approach was used to study the gene expression in zoospores (Z) and germinating cysts (GC) of the late blight pathogen Phytophthora infestans. Four differentially amplified cDNAs were selected and cloned. The clone pGPiZ0.5 showed a 2.7-kb transcript highly expressed in Z. A BLAST search revealed an almost full sequence homology (98%) to the P. infestans mitochondrial large subunit rRNA. Northern blot analysis showed a twofold accumulation of the mitochondrial rRNA (mit rRNA) in Z compared with that of GC and mycelia of P. infestans. The high level of mit rRNA in Z might reflect an increased number of gene copies, an increased rDNA transcription rate, or both. Dot blot experiments indicated that the amount of mitochondrial rDNA (mit rDNA) relative to cytoplasmic rDNA is twofold higher in Z and GC than in mycelia. This relatively elevated mit rDNA could explain the high level of mit rRNA in the zoosporic phase. On the contrary, GC conserves the mit rDNA content, but the level of mit rRNA drops to 50% that of Z. The data are consistent with a very active mitochondrial protein synthesis during zoosporic phase, followed by a rapid down-regulation of mitochondrial activity during cyst formation.


[Prenatal diagnosis. A 35 amniocentesis study (author's transl)].
The results of 35 amniocentesis, between 13 and 17 weeks of pregnancy are presented. Cytogenetic study was performed in 28 of them. Chromosomic anomalies were detected in 3 cases: A 21-trisomy, a 14/21 translocation with 21-trisomy and a partial trisomy of chromosome 2. The values of alpha-feto protein were measured in 10 cases, and were in normal range. Amniocentesis indications in the early detection of chromosomic anomalis in high risk couples and the interest of alpha-feto protein detection in the prediction of neural-tube defects, are commented.


Injuries among solid waste collectors in the private versus public sectors.
Solid waste collection is among the occupations with the highest risk for injuries and illnesses. Solid waste collector injuries were characterized in terms of injury risk and employment industry sector (public versus private) using Kentucky workers' compensation first reports of injury and claims data. When compared to 35-44-year-old workers, solid waste collectors who were under 35 years of age were less likely to have a workers' compensation first report of injury or claim that resulted in awarded benefits. The probability that a workers' compensation first report of injury or claim would result in an awarded benefit was higher if the worker was employed as a solid waste collector in the private sector compared to the public sector, or was injured due to a motor vehicle-related injury or a push-or-pull type of injury. A better understanding of the differences in the contributing factors for an injury that results in a first report of injury or claim with awarded benefits (e.g., job activities, new and refresher worker safety training, type of equipment used, differences in collection vehicle automation, and differential reporting of injuries on the job) between the public and private sectors is necessary to target injury prevention strategies in this high-risk occupation.


Detection and quantitation of copy number variation in the voltage-gated sodium channel gene of the mosquito Culex quinquefasciatus.
Insecticide resistance is typically associated with alterations to the insecticidal target-site or with gene expression variation at loci involved in insecticide detoxification. In some species copy number variation (CNV) of target site loci (e.g. the Ace-1 target site of carbamate insecticides) or detoxification genes has been implicated in the resistance phenotype. We show that field-collected Ugandan Culex quinquefasciatus display CNV for the voltage-gated sodium channel gene (Vgsc), target-site of pyrethroid and organochlorine insecticides. In order to develop field-applicable diagnostics for Vgsc CN, and as a prelude to investigating the possible association of CN with insecticide resistance, three assays were compared for their accuracy in CN estimation in this species. The gold standard method is droplet digital PCR (ddPCR), however, the hardware is prohibitively expensive for widespread utility. Here, ddPCR was compared to quantitative PCR (qPCR) and pyrosequencing. Across all platforms, CNV was detected in ≈10% of mosquitoes, corresponding to three or four copies (per diploid genome). ddPCR and qPCR-Std-curve yielded similar predictions for Vgsc CN, indicating that the qPCR protocol developed here can be applied as a diagnostic assay, facilitating monitoring of Vgsc CN in wild populations and the elucidation of association between the Vgsc CN and insecticide resistance.


Identifying dimensions of performance in local public health systems: results from the National Public Health Performance Standards Program.
This article uses data from the National Public Health Performance Standards Program to explore how the performance of essential public health services varies across communities and to identify underlying domains of activity that appear to drive variation in performance. Cross-sectional data were used from 315 local public health jurisdictions located within seven states that participated in the Performance Standards Program pilot tests between 1999 and 2001. Results demonstrate that local public health systems vary considerably in the extent to which they perform essential services and meet established performance standards. Factor analysis results indicate that four underlying domains of activity explain much of the variation observed in the individual performance measures, and that achieving performance standards for a single essential public health service often involves more than one underlying domain of activity. The findings suggest that composite measures constructed from the Performance Standards Program can assist public health decision makers in monitoring the performance of public health systems and identifying promising pathways for improving performance.


The Role of the Buccal Fat Pad in Facial Aesthetic Surgery.
Social media have triggered a buccal fat pad excision frenzy. Not surprisingly, there is tremendous appeal of having a slimmer lower face and more defined jawline after undergoing a small intraoral procedure under local anesthesia. Although this procedure is great for social media and seemingly beneficial for jawline aesthetics, the evidence remains limited as to whether or not this is an effective long-term solution. How much the buccal fat pad persists or diminishes as we age is an area of debate. However, the possibility of causing premature aging and midface distortion in the long run is disconcerting.


Children's Preference for Causal Information in Storybooks.
Fostering early literacy depends in part on engaging and inspiring children's early interest in reading. Enriching the causal content of children's books may be one way to do so, as causal information has been empirically shown to capture children's attention. To more directly test whether children's book preferences might be driven by causal content, we created pairs of expository books closely matched for content and complexity, but with differing amounts of causal information embedded therein. Three and 4 years old participants (n = 48) were read both books and their interests and preferences were evaluated. When asked to choose, children preferred the highly causal over the minimally causal books. Results are discussed in terms of broader implications for creating books that optimally engage young children, as well as guiding book selections parents and educators make in their endeavors to promote interest in reading and early literacy.


[Non-invasive measurement of stroke volume in steady-state and unsteady-state workload with CO2 rebreathing].
During steady-state exercise the noninvasive measurement of cardiac output using CO2-rebreathing has been found to be reliable and reproducible. In contrast, reliability of cardiac output measurement during unsteady state exercise is unclear. The ability to determine cardiac output (CO) noninvasively during steady state and unsteady state exercise was assessed in nine healthy students aged 25.7 +/- 7.4 years. Two cycle ergometer exercise tests were performed, one maximal unsteady state test with 25 watts increment of workload per minute, and also one steady state test at 25, 50, and 75 percent of max. VO2. CO was measured using the equilibrium CO2-rebreathing technique during unloaded cycling in both tests, at 75 and 150 watts in the unsteady state test and at all workloads during steady state exercise. Mean max. VO2 was 31.4 +/- 5.9 ml/kg/min and mean VO2 at the anaerobic threshold 24.5 +/- 7.2 ml/kg/min, respectively. During unsteady state exercise the CO2/workload slope was linear (r = 0.973), as with steady state exercise (r = 0.976). There was no difference concerning the slopes of both curves, but the elevation of VO2 with unsteady state exercise was lower, compared to steady state (p < 0.005). The relationships of CO/VO2 during unsteady and steady state exercise were best expressed by linear equations: CO = 7.49 x VO2 + 2.35 (r = 0.866) and CO = 8.24 x VO2 + 1.4 (r = 0.852), respectively. Similar to VO2/workload, both regressions did not have different slopes, but did have different elevations (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


Studies on the high molecular weight form of polypeptide chain elongation factor-1 from pig liver. II. Interaction with guanine nucleotides and aminoacyl-tRNA.
The high molecular weight form of polypeptide chain elongation factor-1, or EF-1H, has been purified from pig liver to apparent homogeneity and shown to be a 1:1:1 complex of EF-1 alpha, EF-1 beta, and EF-1 gamma, namely, EF-1 alpha beta gamma (Hattori, S. and Iwasaki, K. (1980) J. Biochem. 88, 725-736). Therefore, its enzymatic properties were investigated in detail. The effects of various components such as NH4Cl, Mg(CH3COO)2, guanine nucleotides and Phe-tRNA on its heat stability were investigated and it was found that its properties were very close to those of the aminoacyl-tRNA binding enzyme from rabbit reticulocytes (McKeehan, W.L. and Hardesty, B. (1969) J. Biol. Chem. 244, 4330-4339). Furthermore, it was reported that EF-1 alpha beta gamma seemed to dissociate into EF-1 alpha and EF-1 beta gamma when guanine nucleotides were present, and also to form a complex of EF-1 alpha . GTP . [14C]Phe-tRNA when both GTP and [14C]Phe-tRNA were present. On the contrary, however, when the interaction between EF-1 alpha beta gamma and guanine nucleotides was analyzed by gel filtration at 4 degrees C, the dissociation of EF-1 alpha beta gamma could not be detected, instead the formation of binary complexes containing EF-1 alpha beta gamma and guanine nucleotides was observed. The dissociation constants of the EF-1 alpha beta gamma . GDP and EF-1 alpha beta gamma . GTP complexes were estimated to be 6.8 x 10(-6) M and 7.3 x 10(-6) M, respectively, and the number of binding sites per molecule of EF-1 alpha beta gamma for these nucleotides was estimated to be one. Little, if any, interaction was detected between EF-1 alpha beta gamma and aminoacyl-tRNA even in the presence of GTP. The controversial results obtained by different methods as described above seemed to be compatible with each other, if one assumes that the dissociation constant for the conversion of EF-1 alpha beta gamma into EF-1 alpha and EF-1 beta gamma increased with the increase in temperature. When gel filtration of EF-1 alpha beta gamma was carried out with a solution containing both GTP and [14C]Phe-tRNA, the formation of a ternary complex containing EF-1 alpha, GTP and [14C]Phe-tRNA was detected at 4 degrees C, although the amount was very small. From these results, we assumed that EF-1 alpha beta gamma interacts with GTP and aminoacyl-tRNA (aa-tRNA) according to the following sequences; EF-1 alpha beta gamma + GTP in equilibrium with EF-1 alpha beta gamma . GTP EF-1 alpha beta gamma . GTP in equilibrium with EF-1 alpha . GTP + EF-1 beta gamma EF-1 alpha . GTP + aa-tRNA in equilibrium with EF-1 alpha . GTP . aa-tRNA.


Regardless of psychiatric severity the addition of contingency management to standard treatment improves retention and drug use outcomes.
The relationship between psychiatric severity and substance use disorders treatment outcome was assessed in 393 individuals who received either standard treatment or standard treatment plus contingency management. The sample was divided into groups of low, moderate, and high psychiatric severity based upon baseline Addiction Severity Index psychiatric composite scores. Participants in the high psychiatric severity group reported a greater prevalence of psychiatric hospitalization, psychiatric medications, and suicide attempts, as well as poorer baseline psychosocial functioning. In terms of treatment outcome, a significant interaction between psychiatric severity and treatment modality was found in relation to treatment retention. Participants in the standard treatment condition were more likely to dropout of treatment earlier as psychiatric severity increased, while retention was similar across the psychiatric severity groups in the contingency management condition. Psychiatric severity was not linked to longest duration of abstinence achieved during treatment or adherence with contingency management procedures. Overall, these findings suggest contingency management is an efficacious and appropriate intervention for substance use disordered individuals across a range of psychiatric problems.


Intravenous Immunoglobulin as Potential Adjunct Therapy for Interstitial Lung Disease.
Intravenous Ig (IVIg) is a pooled plasma product consisting primarily of monomeric IgG. For the past several decades, the use of IVIg has expanded to include the treatment of various autoimmune and inflammatory disorders, including Kawasaki's disease, antineutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosis, and the inflammatory myopathies. IVIg is thought to exert its immunomodulatory effects through a variety of mechanisms: neutralization of pathogenic autoantibodies; alteration of immune cell effector function; suppression of cytokine and chemokine activity; and interference with complement activation. Interstitial lung disease (ILD) is a frequent complication of autoimmune disorders and connective tissue diseases, and the presence of ILD is associated with significant morbidity and mortality. Although there are currently no large studies to support the use of IVIg in the treatment of ILD, it is being used off-label with increasing frequency for refractory cases that have failed to respond to standard immunosuppression. Although associated with less systemic toxicity and global immunosuppression than traditional agents, IVIg is much more costly. Therefore, although the routine use of IVIg to treat ILD is not currently recommended, future studies to determine its role in pulmonary disease are warranted.


Pronounced skin capillary ischemia in the feet of diabetic patients with bad metabolic control.
Skin capillary circulation is impaired during postocclusive reactive hyperaemia (PRH) in toes of diabetic patients independent of diabetes duration and macrocirculation. The aim of this study was to examine its relation to metabolic control. The skin microcirculation was investigated in 20 patients with insulin-dependent diabetes mellitus: 10 patients with bad [HbA1c > 7.5 (8.7 +/- 0.8) %], and 10 patients with good metabolic control [HbA1c < 7.5 (6.3 +/- 1.0) %]. The diabetes duration was similar in both groups (16 +/- 9 and 16 +/- 6 years, respectively). None had macroangiopathy. Thirteen healthy subjects served as controls. The capillary blood cell velocity (CBV) in the nailfold of the great toe was investigated by videophotometric capillaroscopy, and the total skin microcirculation by laser Doppler fluxmetry (LDF). CBV and LDF were studied during rest and after 1-min arterial occlusion. The vibration perception thresholds (VPT) of the feet were higher (p < 0.05) in the patients with bad (34 +/- 12 V), as compared to patients with good metabolic control (18 +/- 10 V) and to healthy subjects (13 +/- 3 V). Peak CBV during PRH was reduced in both patient groups (p < 0.01), and lowest in the patients with bad metabolic control (p < 0.05). Time to peak CBV was prolonged (p < 0.01) in the patients with bad, while normal in the patients with good metabolic control. LDF was similar in all groups. An inverse correlation was found between HbA1c and peak CBV during PRH (r = 0.60; p = 0.008), while positive correlations were found to time to peak CBV (r = 0.62; p = 0.004) and VPT (r = 0.60; p = 0.01). No associations were seen between VPT and the microcirculatory variables. The results indicate that the metabolic control is of importance for the nutritive capillary circulation and the peripheral nerve function in the diabetic foot.


Fine-needle and screw-needle samples in CT-assisted biopsies of chest lesions.
We compared samples obtained using a fine-needle with those made using a screw-needle (Rotex) of equal diameter in 28 patients. The biopsies were performed with the aid of computed tomography. All patients had lesions suggesting primary lung neoplasia or metastatic disease located in the lung parenchyma, pleura and in the ribs (17, 9 and 2 patients, respectively). Diagnostic material was obtained from 25 patients. There was no statistically significant difference in the yield of diagnostic material produced by the two procedures. Malignancy was found in 12 patients. Pneumothorax was the most common complication, occurring in 7 patients. CT-guided diagnostic needle biopsies have high diagnostic accuracy and a low complication rate. The diagnostic yield of the fine-needle and the screw-needle is equal.


Physicians' use of clinical information systems in the discharge process: an observational study.
This study has been performed in order to categorize and measure usage of different information sources and types in a well defined stage of clinical work. The underlying motivation is to improve computer-supported presentation and retrieval of relevant information and to be able to evaluate the functionality of a future improved interface to the electronic patient record (EPR). By observing and analyzing 52 discharge processes, we have seen that the EPR is primarily used for background information and verification. There is a large potential for improved EPR systems that support the clinicians in the plan/future part of the discharge.


Residual root preparation for socket-shield procedures: a facial window approach.
Two common complications that occur following immediate implant placement and provisionalization procedures in the anterior maxilla are changes to the facial periimplant soft tissue levels and the facial contours. To counteract these changes, different techniques and treatments have been recommended. The recently introduced socket-shield technique (SST) appears to be a viable treatment option for stabilizing the facial osseous and gingival architecture; however, preparation of the root fragment can present challenges. This article describes a surgical approach designed to facilitate preparation of the facial root fragment.


[Endoscopic negative pressure therapy of the upper gastrointestinal tract. German version].
Endoscopic negative pressure therapy (ENPT) has been adapted for upper gastrointestinal tract applications. More than 400 patients have already been treated with ENPT due to transmural defects in the upper gastrointestinal tract, with a success rate of 87%. The greatest experience exists for the treatment of anastomotic leakages and perforations of the esophagus. The ENPT is also used in the duodenum, pancreas and for complications after bariatric surgery. There are new indications that go beyond treatment in complication management. Innovative drainage types and endoscopic techniques have been developed that broaden the spectrum of applications. The aim of this article is to give an overview of the current status of ENPT in the upper gastrointestinal tract.


Resection arthroplasty: when enough is enough.
Resection arthroplasty following THA is rarely performed but occasionally indicated. It is a relatively low risk procedure and generally is a much shorter operative procedure associated with fewer perioperative complications compared to major revision procedures. Results are extremely variable. With all of the arthroplasty and bone graft options available for hip joint reconstruction, resection arthroplasty rarely is performed as a definitive procedure. It is, however, the best option for selected patients.


Kinks, rings, and rackets in filamentous structures.
Carbon nanotubes and biological filaments each spontaneously assemble into kinked helices, rings, and "tennis racket" shapes due to competition between elastic and interfacial effects. We show that the slender geometry is a more important determinant of the morphology than any molecular details. Our mesoscopic continuum theory is capable of quantifying observations of these structures and is suggestive of their occurrence in other filamentous assemblies as well.


Induction of ceramide-mediated apoptosis by the anticancer phospholipid analog, hexadecylphosphocholine.
The prototype of a new class of antiproliferative phospholipid analogs, hexadecylphosphocholine (HePC), has been shown to inhibit tumor growth and is currently used for the treatment of cutaneous metastases of mammary carcinomas. Although several cellular targets of HePC, e.g. protein kinase C and CTP:phosphocholine cytidylyltransferase, have been proposed, the mechanisms of HePC-induced anticancer activity are still unclear. Considering that the antiproliferative effect of HePC correlates with inhibition of phosphatidylcholine biosynthesis, which is tightly coupled to sphingomyelin biosynthesis, we tested the hypothesis that treatment of cells with the anticancer drug leads to increased cellular ceramide and subsequently to apoptotic cell death. In the present study, we showed that 25 micromol/liter HePC induced apoptosis. In further experiments, we demonstrated that HePC inhibited the incorporation of radiolabeled choline into phosphatidylcholine and at a later time point into sphingomyelin. This was confirmed by metabolic labeling of the lipid backbone using radiolabeled serine, and it was shown that HePC decreased the incorporation of serine into sphingomyelin by 35% and simultaneously increased the incorporation of serine into ceramide by 70%. Determination of the amount of ceramide revealed an increase of 53% in HePC-treated cells compared with controls. In accordance with the hypothesis that elevated ceramide levels may be the missing link between the metabolic effects of HePC and its proapoptotic properties, HePC-induced apoptosis was blocked by fumonisin B1, an inhibitor of ceramide synthesis. Furthermore, we found that membrane-permeable ceramides additively increased the apoptotic effect of HePC.


Effects of megestrol acetate on weight gain, body composition, and pulmonary function in patients with cystic fibrosis.
Malnutrition is a negative prognostic indicator in patients with cystic fibrosis (CF) and may accentuate pulmonary decline. We tested whether megestrol acetate would have beneficial effects on growth in patients with CF and pancreatic insufficiency. We performed a randomized, double-blind, placebo controlled study. All patients were taking replacement enzymes to compensate for pancreatic insufficiency. Patients (n = 17) were randomly assigned to receive either megestrol acetate or placebo. The treatment group had a significant increase in weight-for-age z scores compared with placebo and reached 100% of their ideal body weight within 3 months of initiating therapy. Weight gain included both fat and fat-free mass. Improved pulmonary function (forced vital capacity and forced expiratory volume in 1 second) was noted in the treatment group compared with placebo (P <.04). Reversible adrenal suppression was observed in the majority of patients who received megestrol acetate. Short-term use of megestrol acetate results in significant weight gain and improved pulmonary function in malnourished subjects with CF. Our study provides a controlled basis for this intervention, identifies important side effects, and provides the foundation for multiyear, longitudinal trials in a larger number of patients with CF.


Magnesium-enriched hydroxyapatite at immediate implants: a histomorphometric study in dogs.
To evaluate the influence of magnesium-enriched hydroxyapatite (MHA) (SintLife(®)) on bone contour preservation and osseointegration at implants placed immediately into extraction sockets. In the mandibular pre-molar region, implants were installed immediately into extraction sockets of six Labrador dogs. MHA was placed at test sites, while the control sites did not receive augmentation materials. Implants were intended to heal in a submerged mode. After 4 months of healing, the animals were sacrificed, and ground sections were obtained for histomorphometric evaluation. After 4 months of healing, one control implant was not integrated leaving n=5 test and control implants for evaluation. Both at the test and the control sites, bone resorption occurred. While the most coronal bone-to-implant contact was similar between test and control sites, the alveolar bony crest outline was maintained to a higher degree at the buccal aspect of the test sites (loss: 0.7 mm) compared with the control sites (loss: 1.2 mm), even though this difference did not reach statistical significance. The use of MHA to fill the defect around implants placed into the alveolus immediately after tooth extraction did not contribute significantly to the maintenance of the contours of the buccal alveolar bone crest.


Limb movements during embryonic development in the chick: evidence for a continuum in limb motor control antecedent to locomotion.
New imaging technologies are revealing ever-greater details of motor behavior in fetuses for clinical diagnosis and treatment. Understanding the form, mechanisms, and significance of fetal behavior will maximize imaging applications. The chick is readily available for experimentation throughout embryogenesis, making it an excellent model for this purpose. Yet in 40 yr since Hamburger and colleagues described chick embryonic behavior, we have not determined if motility belongs to a developmental continuum fundamental to posthatching behavior. This study examined kinematics and synchronized electromyography (EMG) during spontaneous limb movements in chicks at four time points between embryonic days (E) 9-18. We report that coordinated kinematic and/or EMG patterns were expressed at each time point. Variability observed in knee and ankle excursions at E15-E18 sorted into distinct in-phase and out-of-phase patterns. EMG patterns did not directly account for out-of-phase patterns, indicating study of movement biomechanics will be critical to fully understand motor control in the embryo. We also provide the first descriptions of 2- to 10-Hz limb movements emerging E15-E18 and a shift from in-phase to out-of-phase interlimb coordination E9-E18. Our findings revealed that coordinated limb movements persist across development and suggest they belong to a developmental continuum for locomotion. Limb patterns were consistent with the half center model for a locomotor pattern generator. Achievement of these patterns by E9 may thus indicate the embryo has completed a critical phase beyond which developmental progression may be less vulnerable to experimental perturbations or prenatal events.


Tesio catheter access for long-term maintenance hemodialysis.
To retrospectively determine the long-term outcome (>6 months) of placement of tunneled hemodialysis catheters. The HIPAA-compliant study protocol was approved by the Committee on Human Research, which waived the requirement for informed consent. The records of patients who underwent hemodialysis with the Tesio system (Medcomp, Harleysville, Pa) at a single outpatient dialysis unit between March 1994 and March 2004 were reviewed. The length of catheter access and the requirements for percutaneous revision were recorded, and unassisted- and assisted-access survival times were computed by using the Kaplan-Meier method. Three hundred three primary Tesio accesses were created in 200 patients (mean age, 62.3 years +/- 16.3 [standard deviation]; 102 women [51.0%]). Fifty-nine of 303 accesses (19.5%) were percutaneously revised with catheter exchange. During follow-up, 200 of 303 accesses (66.0%) were terminated (117 because they were no longer needed and 83 because of catheter malfunction), and 103 (34.0%) accesses were functioning at the time of last follow-up. The mean duration of catheter access was 247 days (range, 3-2016 days). One hundred twenty-six (41.6%) accesses remained in use for more than 6 months; 50 (16.5%), for more than 1 year; 20 (6.6%), for more than 2 years; 14 (4.6%), for more than 3 years; and five (1.7%), for more than 4 years. Assisted-access survival was 78.1%, 60.0%, 51.5%, 51.5%, and 46.8% at 6 months and 1, 2, 3, and 4 years, respectively. Tesio catheters frequently function for periods longer than 6 months and, when necessary, they can function for many years.


[Study on the immune functions of dendritic cells regulated by histone deacetylase inhibitor Belinostat].
Objective: To explore effects of histone deacetylase inhibitor Belinostat on the immunologic function of dendritic cells (DC) and its possible mechanism. Methods: Cultured mouse bone marrow-derived DC from C57BL/6 mouse in vitro. The experiments were divided into 0, 50, 100 nmol/L Belinostat + immature DC (imDC) group, and 0, 50, 100 nmol/L Belinostat mature DC (mDC). The changes of the ultrastructure of DC were observed by transmission electron microscope (TEM). Immunophenotype and CCR7 expression rate were detected by FCM, and the migration rate was observed by chemotaxis assay. The proliferation of lymphocytes stimulated by different DC was detected by mixed lymphocyte culture reaction. The cytokines in the culture supernatant, including TNF-α, IL-12 and IL-10, were examined by ELISA. RQ-PCR was used to examine the relative expression of mRNA in RelB. Results: Successful cultured and identified the qualified imDC and mDC. Belinostat decreased the expression of CCR7 on imDC [(25.82±7.25)% vs (50.44±5.61)% and (18.71±2.00)% vs (50.44±5.61)%], meanwhile increased the rate on mDC [(71.14±1.96)% vs (64.90±1.47)%]. Chemotaxis assay showed that the migration rate of Belinostat+imDC and Belinostat+mDC group were both decreased, but the difference in imDC was not significant. T lymphocyte proliferation rate stimulated by 100 nmol/L Belinostat+imDC group was lower than imDC group in condition irritation cell∶reaction cell=1∶2 [(227.09±13.49)% vs (309.49±53.69)%]. Belinostat significantly suppressed the secretion of cytokines TNF-α, IL-12 and IL-10 (all P<0.01). The relative expression of mRNA in RelB was slightly decreased in Belinostat+imDC and Belinostat+mDC group (all P<0.05). Conclusion: Belinostat could effectly suppress DC maturation and regulate immune tolerance of DC, which may be due to the down-regulation of mRNA level of RelB in DC.


Synthetic study of (-)-norzoanthamine: construction of the ABC ring moiety.
Throw your hat in the ring: A highly diastereoselective synthesis of the ABC rings of (-)-norzoanthamine has been achieved starting from the (-)-Hajos-Parrish ketone (see scheme). Three asymmetric quaternary carbon centers on the C ring were constructed by a 1,4-addition, and an intramolecular Diels-Alder reaction provided a trans-decalin scaffold on the AB rings.


Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products.
Toll/interleukin-1 receptor (TIR) domain proteins function in cell death and immunity. In plants and bacteria, TIR domains are often enzymes that produce isomers of cyclic adenosine 5'-diphosphate-ribose (cADPR) as putative immune signaling molecules. The identity and functional conservation of cADPR isomer signals is unclear. A previous report found that a plant TIR could cross-activate the prokaryotic Thoeris TIR-immune system, suggesting the conservation of plant and prokaryotic TIR-immune signals. Here, we generate autoactive Thoeris TIRs and test the converse hypothesis: Do prokaryotic Thoeris TIRs also cross-activate plant TIR immunity? Using in planta and in vitro assays, we find that Thoeris and plant TIRs generate overlapping sets of cADPR isomers and further clarify how plant and Thoeris TIRs activate the Thoeris system via producing 3'cADPR. This study demonstrates that the TIR signaling requirements for plant and prokaryotic immune systems are distinct and that TIRs across kingdoms generate a diversity of small-molecule products.


The psychoanalytic theory of fertility.
The motives of reproduction in women--the reasons why they want to have children--are experienced on three different levels: (1) as an elementary and universal human event which, however, event on casual observation betrays its recondite and complex motivation. For the psychotherapist and social scientist it becomes soon (2) a complex question in which covert psychological and sociogenic motives interact. In our time, moreover, reproduction has become (3) an enormous, and ominous social problem. Freud's theory of the motives of reproduction can be viewed as a basic sequence and can be conceived as a linear process. The changes this theory has undergone are defined by the separation of reproductive and sexual motives, and are discussed in some detail.


Self-Report Measures in the Assessment of Antiretroviral Medication Adherence: Comparison with Medication Possession Ratio and HIV Viral Load.
Adherence is a major determinant of the effectiveness of antiretroviral therapy (ART). We determined the association between self-reported adherence (SRA) and medication possession ratio (MPR), a pharmacy-based adherence measure, and their respective associations with viral load. Adherence to ART was assessed by MPR over 6 months and by self-report which included a question with a Likert-type scale response, a visual analogue scale (VAS), and an inquiry about the last time the patients skipped any prescribed medications. Taking MPR as the "gold standard," all 3 SRA measures displayed high specificity but low sensitivity. The prevalence ratio (95% confidence interval) for viral load ≥50 copies/mL was 2.19 (1.07-4.50) for MPR <90%, 1.98 (1.04-3.78) for poor/fair/good versus excellent/very good ability to take antiretroviral drugs, 1.47 (0.79-2.75) for skipping medications within the past 2 weeks, and 2.51 (1.39-4.53) for VAS <95%. These data suggest various SRA measures hold clinical value in screening for poor ART adherence.


5-Azacytidine inhibits the lpr gene-induced lymphadenopathy and acceleration of lupus-like syndrome in MRL/MpJ-lpr/lpr mice.
MRL/MpJ-lpr/lpr mice spontaneously develop a lupus-like autoimmune disorder characterized by massive proliferation of T cells and rapidly fatal immune complex glomerulonephritis. We evaluated the therapeutic effect of 5-azacytidine (5AC), a cytidine analogue known as an inhibitor of DNA methylation, in MRL/MpJ-lpr/lpr mice. Intraperitoneal injection of 5AC (50 micrograms, twice a week) starting from 6 weeks of age retarded the development of lymphadenopathy and autoimmune syndrome. Its beneficial effects included: (a) increased life-span, (b) diminution of lymphadenopathy and splenomegaly, (c) reduction in circulating levels of autoantibodies such as anti-DNA and rheumatoid factors, and (d) suppression of lupus glomerulonephritis. However, similar treatment in BALB/c mice did not affect the development of IgG anti-human IgG antibody responses. These results suggest that the protective effect of 5AC is related to the inhibition of the lpr gene-induced T cell proliferation, thereby suppressing the autoimmunity-accelerating effect mediated by the lpr gene.


Generation and live imaging of an endogenous Cdx2 reporter mouse line.
To understand cell fate specification and maintenance during development, it is essential to visualize both lineage markers and cell behaviors in real time using endogenous markers to report cell fate. We have generated a reporter line in which eGFP is fused to the endogenous locus of Cdx2, a transcription factor essential for trophectoderm specification, allowing us to visualize cell fate decisions in the preimplantation mouse embryo. We used two-photon laser scanning microscopy to visualize expression of the endogenous Cdx2 fusion protein and show that Cdx2 undergoes phases of upregulation. Additionally, we show that as late as the 32-cell stage, outer trophectoderm cells may change their fates by migrating inward and losing Cdx2 expression. Furthermore, the tools and techniques we report allow for dual-colored imaging, which will greatly facilitate the study of not only preimplantation development, but later stages of development and tissues where Cdx2 plays an important role.


Nationwide survey of nutritional management in an Asian upper-middle income developing country government hospitals: Combination of quantitative survey and focus group discussion.
The objective of this study was to identify the differences in pattern, process, and management of nutrition care in government hospitals in Thailand (an Asian upper-middle income developing country). This is a combination of a quantitative nationwide questionnaire survey and focus group discussions. A total of 2300 questionnaires were sent to government hospitals across Thailand. The responders were divided by routine-nutrition screening/assessment unit vs. non-routine-nutrition screening/assessment unit (RSA vs. NRSA). The comparison between the groups was reported as percentage and cross-sectional odds ratio (CS-OR) with 95% confidence interval (CI). The significant difference was defined as p < 0.05. A total of 814 questionnaires (35.4%) were returned. The three most common tools of RSA were 42% Bhumibol Nutrition Triage (BNT), 21.2% Subjective Global Assessment (SGA) and 20.2% Nutrition Alert Form (NAF). The RSA was significantly higher in proportion for the role of the nurses (RSA vs. NRSA; CS-OR [95% CI]: 68.3% vs. 11.9%; 15.8 [11.1 to 22.7]; p < 0.01), the multidisciplinary team (90.1% vs. 0.4%; 2266 [558 to 1909]; p < 0.01), the nutrition management guidelines (60.6% vs. 2.8%; 53.6 [29.6 to 102.8]; p < 0.01), the nurse-driven enteral feeding protocols (31.7% vs. 17.5%; 2.2 [1.5 to 3.1]; p < 0.01) and preference for hospital formula enteral nutrition (91.4% vs.69.7%; 4.6 [2.9 to 7.4]; p < 0.01). For focus group discussions, the main barrier of RSA implementation was that there was no national recommendation of a screening/assessment tool, inconsistency of policy and reimbursement, and professional and acceptable workload. Nutrition screening/assessment tools were found to be varied in Thailand. RSA affected the nutrition management working process and the types of nutrition support. The main barriers of RSA implementation were inconsistency of policy and reimbursement, acceptable workload, and national guidance as regards - screening/assessment tools.


Lung function in Malay children.
We conducted a study to measure the peak expiratory flow rate (PEFR), forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) in a group of normal Malay primary school children aged 7 to 12 years. PEFR was measured in 920 children (482 boys and 438 girls) while FVC and FEV1 were measured in 292 of them (168 boys and 124 girls). In agreement with previous studies, we found that PEFR was correlated with age and height of the subjects but FVC and FEV1 were correlated with height only. Prediction equations for all 3 lung function indices for Malay boys and girls were formulated. In comparison with the lung function values from Western and Chinese subjects, the lung function values in our subjects are lower.


Friend or Enemy: A Dual Role of Autophagy in Plant Virus Infection.
Autophagy is a primary protective process that involves removing damaged organelles or dysfunctional proteins in eukaryotes. The autophagy pathway not only maintains cellular homeostasis, but also modulates the host's cellular response to pathogen infection. Several studies proved that autophagy plays a dominant role in plant fitness and immunity. As intracellular parasites, the replication and spread of viruses entirely rely upon the molecular machinery of the host cell, including the autophagy process. Plant viruses severely affect crop yields and quality. During infection, complex interactions occur between viral proteins and host factors in relation to plant defense and virus counter-defense. An increasing number of studies demonstrated that plants use autophagy to eliminate and inhibit viruses; some viruses were shown to manipulate the process of autophagy to promote their own replication and survival in plant cells. In this review, we summarize recent advances in plant autophagy, with an emphasis on the role of autophagy in plant virus infection.


[Prevention of extravasation necroses as a complication following intravenous cytostatic drug therapy. Results of an open pilot study].
Extravasation of some cytostatics applied i.v. can often cause local edema with skin redness, thrombophlebitis and not infrequently skin necrosis with chronic ulcera. Local treatment is usually ineffective, and so far surgical excision of ulcera is the only curative approach. Tetrachlorodecaoxygen anion complex (TCDO) has shown high activity in healing chronic leg ulcera, by increasing pO2 in hypoxic wound tissue and stimulating phagocytosis as one of anti-inflammatory processes To study the local activity of TCDO in tissue necrosis and chronic ulcera caused by cytostatic extravasation, 23 patients with local skin complications underwent local treatment with TCDO, made as isotonic water solution. Seventeen patients experienced only local edema with redness, while 6 patients showed deep chronic ulcera. All the skin changes were complications after i.v. doxorubicin, cisplatinum, dactinomycin or vinblastine application. The treatments with TCDO followed 1-3 months after ulcera appeared, while skin inflammations were treated 1-8 days after they occurred. TCDO was applied locally twice a day by impregnated cotton tissue for 4-6 weeks. Evaluable were only measurable lesions. From 17 patients with only skin inflammation 3 patients obtained complete resolution, 8 partial resolution and 6 had stable lesions. Thus, overall response was recorded in 65% of patients (11/17). In 6 patients with deep chronic ulcera a longer treatment (6 weeks) was needed, and in 5 of them the complete epithelization and resolution occurred. One patient had a partial wound healing. No side effects of treatment were observed. The effect of locally applied TCDO in chronic ulcera seems to be preferable to surgical treatment. A controlled study will show the exact therapeutic value of this new anti-inflammatory compound.


[Determination of arsenic speciation in 17 commonly used traditional Chinese herbal medicines by HPLC-ICP-MS].
The element speciation analysis for heavy metals in herbal medicines is still in the beginning stage. In this study,the total amount of arsenic( As) in 103 batches of 17 commonly used Chinese medicines( including 16 plant medicines and 1 medicinal fungus) was detected by inductively coupled plasma mass spectrometry( ICP-MS). Furthermore,based on HPLC-ICP-MS,the simultaneous detection methods of six As speciation kinds in traditional Chinese medicines were established. An AS7 anion exchange column was selected and the As forms in 17 traditional Chinese medicines was systematically analyzed. The results showed that the method of pretreatment of medicinal materials by microwave digestion and the detection of total amount of As by ICP-MS was stable and reliable. As for the speciation analysis of As,the high-speed ultrasonic extraction method was adopted,and it showed that the linear relationship of the six As speciation was satisfied with the correlation coefficient R2>0. 999 9. The LOQ of six kinds of As speciation were 0. 20,0. 10,0. 15,0. 10,0. 25,0. 10 μg·L~(-1) for arsenic betaine( As B),arsenious acid [As( Ⅲ) ],dimethyl arsenic( DMA),arsenic choline( As C),monomethyl arsenic( MMA),arsenic acid[As( Ⅴ) ],respectively. The recoveries were between 84. 24% and 121. 5%,and the relative standard deviations were 2. 7% to 11%. Among the 103 batches of medicinal materials,only one batch of sample As exceeded the Chinese Pharmacopoeia limit standard; As( Ⅲ) and As( Ⅴ) had high detection rate in 103 batches of Chinese herbal medicines,within which As( Ⅴ) was the main detected form,and inorganic As accounted for the ratio reached 80. 90%-98. 73%; some samples detected DMA,MMA and As B,As C was not detected in any batch. This study established an analytical method suitable for the speciation of As in Chinese herbal medicines,and provided basic data for As residual residue in Chinese herbal medicines,which can provide important reference for the risk assessment and quality standards.


[Pharmacokinetics of sulfalene and sulfamethoxine after combined administration with benzylpenicillin and ampicillin].
The binding of sulfadimethoxine by serum proteins of rabbits did not change in the presence of benzylpenicillin and ampicillin, while the binding of sulfalen increased. The 1.2-2-fold decrease in the proportion of sulfalen not bound by blood proteins was accompanied by its acetylation in rabbits. This in its turn resulted in a decreased rate of the drug elimination. The penicillins did not change the kinetics of sulfadimethoxine in rabbits. When the dose of sulfadimethoxine was increased 2 times, the rate of its elimination in rabbits increased, which is likely to be due to increased acetylation of the drug. This may be associated with the increased level of the free sulfadimethoxine fraction in the blood because of the drug lower binding by serum proteins. When the dose of sulfalen was increased 2 times, its kinetics in rabbits did not change.


Malignant granular cell tumor of the skull base.
Malignant granular cell tumors (MGCTs) are extremely rare, high-grade sarcomas of Schwann cell origin. They often metastasize and are associated with short survival. We describe a patient with a large MGCT arising from the suboccipital nerve that eroded the posterior skull base, invaded the perifocal neck muscles, demonstrated perineural extension, and metastasized to regional lymph nodes. A 60-year-old woman with several years' history of neck pain noticed a right-sided suboccipital swelling 4 months prior to seeking medical attention. Magnetic resonance imaging (MRI) showed a 5-cm bone-eroding suboccipital tumor and a second tumor, anterocaudal to this, 4 cm in diameter. The patient underwent surgery. A 4-cm multinodular tumor was removed, freeing it from the internal jugular vein. A 5-cm suboccipital tumor infiltrated the trapezius, semispinalis capitis, and longissimus capitis muscles. The major and minor rectus capitis muscles were completely engulfed by tumor and their attachments to the occipital bone completely eroded. The oblique capitis muscle was infiltrated at its attachment to the C1 transverse process. These muscles were resected with a free margin to remove all tumor tissue. We then removed tumor encasing the right vertebral artery, the medial mastoid process up to the transverse sinus and anteriorly to the stylomastoid foramen, and lastly, the posterior third of the occipital condyle, achieving a gross total removal and no visible residual on postoperative contrast-enhanced MRI. This case represents the first report of resected primary MGCT involving the posterior fossa and arising from the suboccipital nerve.


Effects of haloperidol and clozapine on preprotachykinin-A messenger RNA, tachykinin tissue levels, release and neurokinin-1 receptors in the striato-nigral system.
The effects of haloperidol and clozapine on tachykinin tissue levels, preprotachykinin-A messenger RNA, spontaneous and potassium-evoked tachykinin release, dopamine D2 receptors, and [125I]Bolton-Hunter-substance P binding sites in the striato-nigral system were examined. Chronic administration (10 days) of the dopamine receptor antagonist haloperidol (2 mg/kg i.p.) significantly decreased tissue levels of substance P like-immunoreactivity and neurokinin A like-immunoreactivity in the striatum and the substantia nigra. The corresponding preprotachykinin-A mRNA was decreased in the striatum. Haloperidol did not affect the potassium-evoked tachykinin release in the substantia nigra but significantly increased the spontaneous release. Haloperidol increased the number of D2-receptors but left [125I]Bolton-Hunter-substance P binding sites, representing neurokinin 1 (NK-1) receptors, as determined by competition experiments with selective ligands, unchanged. Clozapine (30 mg/kg, i.m.) did not influence nigral and striatal tachykinin tissue levels, preprotachykinin-A mRNA and potassium-evoked release or spontaneous efflux in the substantia nigra, or D2-receptors and [125I]Bolton-Hunter-substance P binding sites. The present data indicate that neuroleptics influence the striato-nigral tachykinin system in different ways. Tachykinins may, therefore, contribute to the therapeutic and/or untoward effects of certain neuroleptic drugs.


Protection of the Geum japonicum Thunb. var. chinense extracts against oxygen-glucose deprivation and re-oxygenation induced astrocytes injury via BDNF/PI3K/Akt/CREB pathway.
Geum japonicum Tunb. var. chinense (GJ) is a traditional Chinese medicine usually used for the alleviation of dizziness and headache. Previous studies have reported that the GJ extracts could alleviate cerebral I/R injury by reducing apoptosis in vivo. To further elucidate the positive role and underlying mechanism of the GJ extracts in cerebral I/R injury, the current study investigated the effects of the GJ extracts on oxygen-glucose deprivation and re-oxygenation (OGD/R)-induced astrocytes injury in light of BDNF/PI3K/Akt/CREB signaling pathway with seropharmacological method. In the present study, the LC-MS profiling of the GJ extracts, obtain by reflux extraction, led to the identification of three possible active components were 5-desgalloylstachyurin, tellimagrandin II (TG II) and 3,4,5-Trihydroxybenzaldehyde (THBA). Drug-containing serum was collected from rats given different doses of the GJ extracts (0, 1.75 g/kg, 7 g/kg). Data indicated that the GJ extracts could increase the cell viability and decrease apoptosis and the expression of glial fibrillary acidic protein (GFAP) in OGD/R-induced astrocytes. In addition, the detection of apoptosis-related factors showed that the GJ extracts could obviously increase the expression of Bcl-2 and reduce the expression of Bax, Caspase-3 and cleaved-Caspase-3. Furthermore, the GJ extracts markedly increased the expression of BDNF, TrkB, PI3K, p-Akt and p-CREB. All these effects of the GJ extracts could be significantly reversed by LY294002, an inhibitor of PI3K. These data indicated that the GJ extracts could protect astrocytes against OGD/R-induced injury by inhibiting astrocytes reactivity and apoptosis, owing to the activation of the BDNF/PI3K/Akt/CREB pathway. The results support the application of the GJ extracts in the treatment of ischemic stroke and other ischemic encephalopathy.


Comparison of Central Corneal Thickness Measurements Obtained by RTVue OCT, Lenstar, Sirius Topography, and Ultrasound Pachymetry in Healthy Subjects.
To compare central corneal thickness (CCT) measurement results obtained by RTVue OCT, Lenstar, Sirius topography, and ultrasound pachymetry (UP) (OcuScan RxP Ophthalmic Ultrasound System, Alcon Laboratories) in healthy subjects. 256 eyes of 128 healthy subjects were included in the study. CCT measurements were obtained from the eyes for each subject using the UP, Lenstar, Sirius topography, and RTVue OCT instruments. Ultrasound pachymetry measurements were performed after the eyes were anesthetized with one drop of 0.5% proparacaine hydrochloride and were performed at the same day after 15 minutes after previous measurements. Of 128 participants, 84 were male and 44 were female with a mean age of 33.15 ± 12.95 years (ranging from 18 to 75 years). The mean CCTs for UP, Lenstar, Sirius topography, and RTVue OCT were 535.60 ± 35.15 (440,00-668,00); 532.63 ± 34.44 (449,00-650,00); 526.05 ± 36.45 (314,00-640,00); 525.89 ± 33.21 (437,00-646,00) µm, respectively. The mean CCT measurements were statistically different among the three groups (p = 0.002). CCT measurements obtained using RTVue-OCT were significantly thinner than those obtained using UP (p = 0.009). Sirius CCT measurements were also thinner than UP (p = 0.011). Mean CCT measurements between UP and Lenstar were similar (p = 0.769). Measurements with Lenstar (r = 0.849), Sirius topography (r = 0.883), and RTVue OCT (0.949) were highly correlated with UP measurements. RTVue OCT and Sirius topography significantly underestimated the CCT compared with UP. Although highly correlated, the measurement values with these devices are not directly interchangeable in clinical practice.


The benefits of virtual learning webinars to both low- and high-income countries.
The coronavirus disease 2019 (COVID-19) pandemic has brought about many changes in the relationships between high-income countries and partner organisations in low- or low-middle-income countries, such as predominate in sub-Saharan Africa. Medicine, surgery and in particular urology is no exception to the changes that COVID-19 has demanded. Urolink represents the British Association of Urological Surgeons (BAUS) on the global urology stage and has been deleteriously impacted by the pandemic. Education, one of the pillars of Urolink's founding philosophies, has conventionally been delivered by face-to face teaching, training, or mentoring by UK urologists at their host's site outside of the UK. As a consequence of the inability to travel due to the pandemic, BAUS Urolink has evolved a virtual on-line webinar package evolved by, and delivered between, urologists in Lusaka, Zambia, and various centres in the UK. The aim was to deliver curricular-based educational topics to trainees in both countries. This programme has generated a number of live webinars and archived recordings during the pandemic that has proven accessible and educationally acceptable to trainees in the UK and Zambia. This webinar series has also generated relationships between young urologists on different continents, given each a different view of healthcare delivery outside of their country of origin at no appreciable cost, and would appear to be an educational mechanism that is durable for, and applicable to, a wider participation in the post-pandemic world.


Fine needle aspiration cytodiagnosis of primary and metastatic squamous cell carcinoma of the breast.
To assess the diagnosis of squamous cell carcinoma involving the breast by fine needle aspiration cytology in four cases (two primary and two metastatic). All patients were women between the ages of 42 and 74 years. The aspiration findings were confirmed by cell blocks of the aspirates, biopsy and/or comparison of the tissue from the previous primary. The aspirate was obtained using multiple passes in the breast masses while maintaining negative pressure. The cytohistologic features in all cases were characterized by numerous malignant squamous cells with hyperchromatic, enlarged, dense nuclei; thickened nuclear membranes; coarse chromatin; abundant eosinophilic, keratinizing glassy cytoplasm; and a necrotizing background with keratin debris. The diagnostic value of immunocytochemical study was considered questionable despite immunopositivity for cytokeratin and epithelial membrane antigen and negative staining for carcinoembryonic antigen and B72.3 in all cases. The identification of malignant squamous cells in breast aspirates is an important observation. Such cells, when seen as the predominant ones in an aspirate, should prompt a search for other sources of a primary tumor before a diagnosis of squamous cell carcinoma of the breast is accepted.


Effect of Bleaching Agents on Discoloured Resin-Based Composites for Direct Restorations: A Systematic Review.
The purpose of the review was to assess the influence of office and home bleaching on the color durability after staining of resin-based composites (RCs) for direct restorations. A web-based search for possibly relevant scientific papers in the English language between January 2013 and August 2022 was conducted in the databases such as PubMed, Scopus, Cochrane Library, and EMBASE. In-vitro studies that explored the influence of in-office and other bleaching treatments on the discolored RC for direct restorations in extracted human teeth were included. Case studies, case series, animal studies, systematic reviews, and letters to the editor were not considered. A total of 212 articles from a web-based search and 32 studies from a manual search were retrieved. After removal of duplicate records, 181 titles and abstracts were reviewed for eligibility; 92 were chosen for full-text analysis, and nine in-vitro studies matched the inclusion criteria. The two examiners examined the methodological quality of the selected studies independently based on the study design, methodological soundness, and data analysis. Distinct values were assigned to studies evaluating color variations of stained RC subjected to bleaching agents. The methodological quality scores were expressed as a percentage of the highest possible score based on the established scoring system and categorized as indicating a low, moderate, and high level of evidence. The reversal of color alterations following home and office bleaching was found to be dependent on the RC used. Within the limitations of the in-vitro investigations, it was deduced that the bleaching agents were successful in eliminating stains and improving the durability of the color to near baseline values.


Brainstem projections to the phrenic nucleus: an anterograde and retrograde HRP study in the rabbit.
Brainstem projections to the phrenic nucleus were studied in rabbits using horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) as a retrograde and anterograde neuronal tracer. Injections of 1% WGA-HRP were centered in the phrenic nucleus in the C4-C5 ventral horn in 4 rabbits to identify pontomedullary nuclear groups that contain neurons projecting to the midcervical spinal cord. Regions of the rabbit brainstem that are homologous to the ventral respiratory group (VRG), dorsal respiratory group (DRG), Bötzinger Complex (BötC) and Kölliker-Fuse nucleus in the cat and rat were shown to provide the major pontomedullary projections to the phrenic nucleus. Injections of WGA-HRP into physiologically identified locations within DRG, VRG and BötC anterogradely labelled bulbospinal axons of these groups. These injections produced presumptive terminal labelling in the C4-C5 ventral horn in the region containing the phrenic cell column and the transverse phrenic motoneuron dendrite bundles as defined by WGA-HRP labelling of phrenic motoneurons. These results indicate: 1) The presumptive excitatory (DRG, VRG) and inhibitory (BötC) bulbospinal control of phrenic motoneurons arise from the same medullary respiratory groups in the rabbit as in the cat and rat. 2) The bulbospinal control of phrenic motoneurons is primarily via direct projections to the phrenic motor nucleus, and not through segmental propriospinal interneurons. 3) As in the rat, the bulbospinal contribution of the DRG is less pronounced in the rabbit than in the cat. 4) The rabbit and rat have a slight ipsilateral predominance in their bulbospinal projections to phrenic nucleus; whereas these projections have a contralateral predominance in the cat.


Treatment with MOPP or ChlVPP chemotherapy only for all stages of childhood Hodgkin's disease.
Fifty-three children with Hodgkin's disease were clinically staged and treated with chemotherapy alone. Forty-six received mechlorethamine (Mustargen; Merk Sharpe & Dohme, West Point, PA), vincristine (Oncovin; Eli Lilly and Company, Indianapolis), procarbazine, and prednisolone (MOPP) and 7 chlorambucil, vinblastine, prednisolone, and procarbazine (ChlVPP). There were four events in the 38 children with stage I and II disease. One patient with massive mediastinal disease failed to remit and subsequently failed mantle irradiation and changes of chemotherapy. Another relapsed at the site of local disease and was salvaged with involved field irradiation and further courses of MOPP. Two other children died as a result of acute graft-v-host disease (GVHD) following transfusion. At autopsy there was no evidence of Hodgkin's disease. Fifteen children had stage III and IV disease and 14 achieved complete remission (CR) and none have relapsed. The child who failed to achieve remission died of virus infections. A mediastinal mass greater than 1/3 the thoracic width was present in 19 children of whom 18 achieved remission and none relapsed. An infradiaphragmatic presentation occurred in eight, all achieved remission and none relapsed. Overall at a median follow-up time of 45 months survival was 94%; the percent of patients without treatment failure was 92; and the percent without relapse was 98.


[Differentiating into islet-like cell clusters from human first trimester umbilical cord perivascular cells in vitro].
To study the characteristics of the human umbilical cord perivascular cells (HUCPVC) isolated from human first trimester umbilical cord perivascular layer tissues and the differentiation into islet-like cell clusters in vitro. The HUCPVC derived from human first trimester umbilical cord which was donated by the volunteers were isolated and subcultured. The surface markers such as stage-specific embryonic antigen 1 (SSEA-1), SSEA-3, SSEA-4, OCT-4, TRA-1-60, and TRA-1-81 were detected by immunohistochemical method. The first trimester HUCPVC were induced to embryoid bodies (EB)-like cell aggregations and islet-like cell clusters in vitro through a simple stepwise culture protocol (5 steps). The expressions of specific markers [α-fetoprotein (AFP), Nestin, and smooth muscle actin (SMA)] were measured by immunohistochemical method; and the ability of glucose-stimulated insulin secretion was analyzed. The first trimester HUCPVC were successfully isolated and could be passaged steadily more than 10 generations, which expressed SSEA-3, SSEA-4, OCT-4, TRA-1-61, and TRA-1-81. The first trimester HUCPVC were successfully induced into EB-like cell aggregations and islet-like cell clusters. The EB-like cell aggregations could express markers of three germ lineages: AFP, Nestin, and SMA. The islet-like cell clusters could release insulin significantly in response to elevated concentrations of glucose in vitro (t = 7.444, P = 0.002). The insulin contents were (23.2 ± 5.3) mU/L and (7.0 ± 0.5) mU/L in high and low glucose media, respectively. The first trimester HUCPVC has the ability to differentiate into islet-like cell clusters which can secret insulin in vitro.


Change in Driving Performance following Arthroscopic Shoulder Surgery.
The current study aimed to measure perioperative changes in driving performance following arthroscopic shoulder surgery using a validated driving simulator.21 patients who underwent arthroscopic surgery for rotator cuff or labral pathology were tested on a driving simulator preoperatively, and 6 and 12 weeks postoperatively. An additional 21 subjects were tested to establish driving data in a control cohort. The number of collisions, centerline crossings, and off-road excursions were recorded for each trial. VAS and SPADI scores were obtained at each visit.The mean number of collisions in the study group significantly increased from 2.05 preoperatively to 3.75 at 6 weeks (p<0.001), and significantly decreased to 1.95 at 12 weeks (p<0.001). Centerline crossings and off-road excursions did not significantly change from preoperative through 12 weeks, although centerline crossings were statistically different from the controls at each time point (p<0.001). Surgery on the dominant driving arm resulted in greater collisions at 6 weeks than surgery on the non-dominant driving arm (p<0.001).Preliminary data shows that driving performance is impaired for at least 6 weeks postoperatively, with a return to normal driving by 12 weeks. Driving is more profoundly affected in conditions that require avoiding a collision and when the dominant driving arm is involved.


Significance of symmetry in the nuclear spin Hamiltonian for efficient heteronuclear dipolar decoupling in solid-state NMR: A Floquet description of supercycled rCW schemes.
Symmetry plays an important role in the retention or annihilation of a desired interaction Hamiltonian in NMR experiments. Here, we explore the role of symmetry in the radio-frequency interaction frame Hamiltonian of the refocused-continuous-wave (rCW) pulse scheme that leads to efficient 1H heteronuclear decoupling in solid-state NMR. It is demonstrated that anti-periodic symmetry of single-spin operators (Ix, Iy, Iz) in the interaction frame can lead to complete annihilation of the 1H-1H homonuclear dipolar coupling effects that induce line broadening in solid-state NMR experiments. This symmetry also plays a critical role in cancelling or minimizing the effect of 1H chemical-shift anisotropy in the effective Hamiltonian. An analytical description based on Floquet theory is presented here along with experimental evidences to understand the decoupling efficiency of supercycled (concatenated) rCW scheme.


Fortified foods contribute one half of recommended vitamin A intake in poor urban Guatemalan toddlers.
Vitamin A intake from food sources, not including breast milk, was determined from seven consecutive 24-h recalls for 55 children (mean age 20.8 mo, SD 8.9) from two poor communities of Guatemala City. Not including vitamin A derived from fortified sugar or breast milk, the median daily vitamin A intake was 194 retinol equivalents (RE). Including vitamin A derived from fortified sugar but not including that derived from breast milk, the median total vitamin A intake (25th and 75th percentiles) was 338 RE (146 and 617 RE) of which 78% was preformed retinol and 22% provitamin A. More than 90% of total vitamin A intake from non-breast milk food sources was derived from only 10 items; over half came from three fortified foods: fortified sugar, Incaparina and margarine. Sugar samples from 91 households in 1991 had a median of 3.3 RE/g (range, 0.0-29.9 RE/g), <25% of the target level (13-17 RE/g); nevertheless, fortified sugar provided 25% of these children's total vitamin A intake (81 RE/d) from non-breast milk food sources and their intake approached the level recommended by the FAO/WHO (400 RE/d). These results show that fortified foods make an important contribution towards vitamin A intake in this sample of poor urban Guatemalan toddlers.


Clinical trials in metastatic prostate cancer--has there been real progress in the past decade?
Hormone refractory prostate cancer remains a challenge. While only palliative treatment strategies were available for the past several decades, many promising agents have been investigated over the past decade. Of those the taxanes appeared with significant anti-tumor activity and recently, two large randomized controlled trials demonstrated for the first time, a survival and palliative benefit with docetaxel based chemotherapy. In the current era, recurrent disease after local treatment for localized disease is diagnosed long before evidence of systemic disease. With earlier institution of hormonal treatments, patients are becoming "hormone refractory" earlier in the course of their disease with considerable long life expectancy. Hence, there is a greater need than ever for more treatment options for this expanding group of patients. A number of new systemic therapies have recently emerged, based on a deeper understanding of prostate cancer biology. Novel chemotherapeutics such as the epothilones, molecularly targeted therapies against angiogenesis, the proteosome and endothelin receptor antagonists, as well as biological agents such as anti-sense oligonucleotides are being tested as part of the armamentarium. Key to progress in the therapy of this fatal disease is the commitment and timely enrolment of prostate cancer patients in clinical trials.


Clinical Presentation and Microbial Analyses of Contact Lens Keratitis; an Epidemiologic Study.
Microbial keratitis is an infective process of the cornea with a potentially and serious visual impairments. Contact lenses are a major cause of microbial keratitis in the developed countries especially among young people. Therefore, the purpose of the present study was to evaluate the frequency and microbiological characteristic of CLK in patients referred to the emergency department (ED) of teaching hospitals, Babol, Iran. This is a cross-sectional study of all patients with contact lens induced corneal ulcers admitted to the teaching hospitals of Babol, Iran, from 2011- 2013. An ophthalmologist examined patients with the slit-lamp and clinical features of them were noted (including pain, redness, foreign body sensation, chemosis, epiphora, blurred vision, discomfort, photophobia, discharge, ocular redness and swelling). All suspected infectious corneal ulcers were scraped for microbial culture and two slides were prepared. Data were analyzed using SPSS software, version 18.0. A total of 14 patients (17 eyes) were recruited into the study (100% female). The patients' age ranged from 16-37 years old (mean age 21.58±7.23 years). The most prevalent observed clinical signs were pain and redness. Three samples reported as sterile. The most common isolated causative organism was pseudomonas aeroginosa (78.6%), Staphylococcus aureus 14.3%, and enterobacter 7.1%, respectively. Treatment outcome was excellent in 23.5%, good in 47.1%, and poor in 29.4% of cases. Improper lens wear and care as well as the lack of awareness about the importance of aftercare visits have been identified as potential risk factors for the corneal ulcer among contact lens wearers. Training and increasing the awareness of adequate lens care and disinfection practices, consulting with an ophthalmologist, and frequent replacement of contact lens storage cases would greatly help reducing the risk of microbial keratitis.


Microbial electrolysis cell accelerates phosphate remobilisation from iron phosphate contained in sewage sludge.
Phosphate was remobilised from iron phosphate contained in digested sewage sludge using a bio-electric cell. A significant acceleration above former results was caused by strongly basic catholytes. For these experiments a dual chambered microbial electrolysis cell with a small cathode (40 mL) and an 80 times larger anode (2.5 L) was equipped with a platinum sputtered reticulated vitreous carbon cathode. Various applied voltages (0.2-6.0 V) generated moderate to strongly basic catholytes using artificial waste water with pH close to neutral. Phosphate from iron phosphate contained in digested sewage sludge was remobilised most effectively at pH ∼13 with up to 95% yield. Beside minor electrochemical reduction, hydroxyl substitution was the dominating remobilisation mechanism. Particle-fluid kinetics using the "shrinking core" model allowed us to determine the reaction controlling step. Reaction rates changed with temperature (15-40 °C) and an activation energy of Ea = 55 kJ mol(-1) was found. These analyses indicated chemical and physical reaction control, which is of interest for future scale-up work. Phosphate remobilisation rates increased significantly, yields doubled and recovered PO4(3-) concentrations increased four times using a task specific bio-electric system. The result is a sustainable process for decentralized phosphate mining and a green chemical base generator useful also for many other sustainable processing needs.


Nonodontogenic Sources of Dental Pain.
Nonodontogenic sources of dental pain can be extremely challenging to diagnose. It is critical to establish a proper diagnosis to ensure that treatment is directed toward the source of the pain rather than the site of the pain.


Vesicle-Cloaked Virus Clusters Are Optimal Units for Inter-organismal Viral Transmission.
In enteric viral infections, such as those with rotavirus and norovirus, individual viral particles shed in stool are considered the optimal units of fecal-oral transmission. We reveal that rotaviruses and noroviruses are also shed in stool as viral clusters enclosed within vesicles that deliver a high inoculum to the receiving host. Cultured cells non-lytically release rotaviruses and noroviruses inside extracellular vesicles. In addition, stools of infected hosts contain norovirus and rotavirus within vesicles of exosomal or plasma membrane origin. These vesicles remain intact during fecal-oral transmission and thereby transport multiple viral particles collectively to the next host, enhancing both the MOI and disease severity. Vesicle-cloaked viruses are non-negligible populations in stool and have a disproportionately larger contribution to infectivity than free viruses. Our findings indicate that vesicle-cloaked viruses are highly virulent units of fecal-oral transmission and highlight a need for antivirals targeting vesicles and virus clustering.


Temporary occlusion of the hepatic artery plus infusion and systemic chemotherapy for inoperable cancer of the liver.
Fourteen patients with diffuse tumors of the liver were treated with temporary occlusion of the hepatic artery (HA) by an external tourniquet followed by infusion and systemic chemotherapy. Three patients had primary neoplasms (one hepatocarcinoma and two cholangiocarcinomas) and eleven had metastatic disease (nine from carcinoma of the colon and rectum, one from retroperitoneal liposarcoma, and one from pulmonary small cell cancer). Infusion chemotherapy in all patients was based on 5-FU, Mitomycin and Vincristine. Systemic chemotherapy was FIVB in metastatic carcinoma and Adriamycin in primary liver tumors. All patients showed improvement of the performance status according to the Karnofsky Index. Objective response (OR) was present in 54% of cases. At present, median survival time in 12.5 months. Aggressive treatment combining hepatic ischemia with infusion and systemic polychemotherapy seems to provide an effective method of palliation in diffuse tumors of the liver. Delayed occlusion by an external tourniquet appears safer than intraoperative ligation of the HA.


Assessment of myocardial perfusion by intermittent harmonic power Doppler using SonoVue, a new ultrasound contrast agent.
The authors evaluated the potential of SonoVue, a new echo contrast agent, for the detection of myocardial perfusion abnormalities using intermittent harmonic power Doppler (IHPD) imaging and different pulse repetition frequencies (PRFs). Experiments were performed in vitro (in a tissue-mimicking phantom) and in vivo (in minipigs) in harmonic power Doppler using an ATL HDI 3000 with second harmonic software. SonoVue was injected intravenously in an auricular vein in bolus (dose range 0.01-0.05 mL/kg) in closed-chest animals or as an infusion (rate = 0.1 mL/kg/minute) in open-chest minipigs with reversible left anterior descending coronary artery (LAD) occlusion. The animals were imaged using IHPD gated on the electrocardiogram at end-systole (pulsing interval at each cardiac cycle). The efficacy of SonoVue was evaluated at six PRFs from 500 to 6000 Hz either qualitatively using a subjective scoring system or quantitatively using a digital image analyzer. SonoVue at a dose of 0.01 mL/kg produced a strong and homogeneous myocardial opacification in IHPD. Higher doses prolonged the duration of the contrast effect. Varying the PRF allowed the discrimination of flow velocities in vitro and the detection of perfusion differences within the myocardium during transient LAD occlusion and during immediate reperfusion in vivo. Low PRFs were particularly useful to differentiate the ischemic bed from the healthy one during LAD occlusion. The high flows caused by coronary hyperemia during immediate reperfusion were detected clearly in the reperfused area at high PRFs. SonoVue is a promising agent for myocardial opacification studies using IHPD. The latter imaging modality is particularly well suited for blood flow detection in tissues. Varying the PRF provides additional information on flow velocity and improves the detection of perfusion differences in the myocardium.


Effect of Chitosan- and Alginate-Based Coatings Enriched with Cinnamon Essential Oil Microcapsules to Improve the Postharvest Quality of Mangoes.
During this study, fresh mangoes were packed into multilayer coatings made from chitosan containing cinnamon essential oil microcapsules and alginate solutions that were alternately deposited on the mango surfaces by electrostatic interaction. We then compared the physical and chemical indexes to examine the changes in the mangoes during 14 d of storage. The results showed that the microcapsules prepared in the experiment were of uniform size, with the sustained release of essential oil exceeding 168 h. Compared with uncoated mangoes, the mangoes coated with the coatings could effectively inhibit the decrease of the titratable acid, soluble solids, and vitamin C contents; slow down the increase of the weight loss and pH; delay the appearance of mango respiration peaks; and preserve the firmness at storage conditions of 25 °C and 50% RH. Our findings revealed that mangoes without treatment showed losses in their edible and commercial value after 14 days in storage, and the mangoes coated with five layers still retained food and commercial value. Cross-sectional scanning electron microscopy images of the coatings showed that they had distinct layers and were of good uniformity and tight binding, and they also had good adhesion to the mango surface. These findings provide important insights into the use of coatings for the packaging of fruits during storage, which is essential for promoting the application of coatings for packaging preservation without big cost and expensive equipment.


Assessment of a cardiac output device using arterial pulse waveform analysis, Vigileo, in cardiac surgery compared to pulmonary arterial thermodilution.
Many devices are available to assess cardiac output (CO) in critically ill patients and in the operating room. Classical CO monitoring via a pulmonary artery catheter involves continuous cardiac output (CCO) measurement. The second generation of Flotrac/Vigileo monitors propose an analysis of peripheral arterial pulse waves to calculate CO (APCO) without calibration. The aim of our study was to compare the CO between the Swan Ganz catheter and the VigileoT. In this observational study, nine patients undergoing coronary artery bypass grafting were prospectively included. APCO, mean (CCO) and instantaneous CO (ICO) were measured. Perioperative and postoperative assessments were performed up to 24 hours post-surgery. Measurements were recorded every minute, resulting in the collection of 6492 data pairs. Comparison of APCO and ICO showed a limited bias of -0.1 l/min but an important percentage error of 48%. Corresponding values were -0.1 l/min and 46% for the APCO versus CCO comparison, and 0 and 17% for ICO versus CCO comparison. Large inter-individual variability does exist. During cardiac surgery and after leaving the operating room, Vigileo is not clinically equivalent to continuous thermodilution by pulmonary artery catheter Nevertheless, the connection between CCO and ICO relates the difference between APCO and CCO more to the different algorithms used. Further efforts should be concentrated on assessing the ability of this device to track changes in cardiac output.


Diarylureas and diarylamides with pyrrolo[2,3-d]pyrimidine scaffold as broad-spectrum anticancer agents.
A series of diarylureas and diarylamides possessing pyrrolo[2,3-d]pyrimidine scaffold was designed and synthesized. The in vitro antiproliferative activities of a selected group of the target compounds against NCI-60 cell line panel were tested and compared with Sorafenib and Imatinib as reference compounds. Most of the compounds showed strong and broad-spectrum antiproliferative activities. Compounds IVa, IVb, and IVd with benzamido moiety at position 4 of the pyrrolo[2,3-d]pyrimidine nucleus, para-disubstituted phenyl ring at N1-position of pyrrolo[2,3-d]pyrimidine scaffold, and urea linker showed strong and broad-spectrum anticancer results with high potencies and efficacies. In addition, the amide derivatives Vb and Vc demonstrated one-digit nanomolar IC50 values over two and one cell line(s), respectively. Amid all the target compounds, compound IVa demonstrated the best results in both one-dose and five-dose testing modes. It showed 109.18% mean % inhibition over the NCI-60 cancer cell line panel at 10 µM concentration, submicromolar 50% inhibitory concentration (IC50) values over eight cell lines of eight different cancer types, and high efficacy with total growth inhibition (TGI) and 50% lethal concentration (LC50) values less than 4.22 µM over three colon, ovarian, and prostate cancer cell lines. It showed superior potency and efficacy to Sorafenib and Imatinib over most of the tested cell lines.


An estimate of the cost of administering intravenous biological agents in Spanish day hospitals.
To estimate the unit costs of administering intravenous (IV) biological agents in day hospitals (DHs) in the Spanish National Health System. Data were obtained from 188 patients with rheumatoid arthritis, collected from nine DHs, receiving one of the following IV therapies: infliximab (n=48), rituximab (n=38), abatacept (n=41), or tocilizumab (n=61). The fieldwork was carried out between March 2013 and March 2014. The following three groups of costs were considered: 1) structural costs, 2) material costs, and 3) staff costs. Staff costs were considered a fixed cost and were estimated according to the DH theoretical level of activity, which includes, as well as personal care of each patient, the DH general activities (complete imputation method, CIM). In addition, an alternative calculation was performed, in which the staff costs were considered a variable cost imputed according to the time spent on direct care (partial imputation method, PIM). All costs were expressed in euros for the reference year 2014. The average total cost was €146.12 per infusion (standard deviation [SD] ±87.11; CIM) and €29.70 per infusion (SD ±11.42; PIM). The structure-related costs per infusion varied between €2.23 and €62.35 per patient and DH; the cost of consumables oscillated between €3.48 and €20.34 per patient and DH. In terms of the care process, the average difference between the shortest and the longest time taken by different hospitals to administer an IV biological therapy was 113 minutes. The average total cost of infusion was less than that normally used in models of economic evaluation coming from secondary sources. This cost is even less when the staff costs are imputed according to the PIM. A high degree of variability was observed between different DHs in the cost of the consumables, in the structure-related costs, and in those of the care process.


The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction.
In the last 2 years, major advances have been made in the understanding of inhibin physiology. Discovery of an inhibin receptor and binding protein has expanded our knowledge of the mechanism whereby inhibin antagonizes activin action. Controlled experimental studies have clarified the regulation and physiology of inhibin A and inhibin B, providing evidence for their use as markers of ovarian function. Clinical studies continue to uphold the use of inhibin as a marker for ovarian cancer, but have not generally supported its use over standard prognostic markers in assisted reproductive technologies. Finally, ongoing work suggests alterations in inhibin and follistatin that may be linked to the pathophysiology of polycystic ovary syndrome. Thus, the mechanism of inhibin action and its role in normal and abnormal ovarian function continues to emerge.


Investigating the Levels of Soluble Extracellular Domain of HER2 Protein in the Sera of Meningioma Patients.
Bearing in mind the association of breast cancer and meningioma, the present study aimed to investigate the levels of the soluble extracellular domain of HER2 protein in meningioma cases and control group. Besides, in the present research, its associations with pathological features and prognostic indicators of meningioma were examined. A total of 68 meningioma patients along with 20 healthy age-sex matched individuals, as controls, were selected. Levels of HER2 in the sera were measured by a quantitative enzyme-linked immunosorbent assay (ELISA). The observations showed that Serum HER2 levels in meningioma patients were significantly lower than normal controls. However, outlier quantities were mostly observed in the cases. Furthermore, in meningiomas with higher histological grade (grade II, III), statistically significant elevated serum levels of HER2 were observed compared to patients with low-grade meningiomas (grade I). Serum HER2 levels were a poor biomarker for determination of pathological and prognostic characteristics of meningiomas and coupling serum HER2 levels with immunohistochemistry examination of HER2 in meningioma tissue samples would be helpful in future studies.


Responsive, di-metallic lanthanide complexes of a piperazine-bridged bis-macrocyclic ligand: modulation of visible luminescence and proton relaxivity.
The synthesis of a new functionalised bis-macrocyclic ligand (L1) is described together with the corresponding Ln(III) complexes, Ln(2)- (Ln = Gd(III), Eu(III)). Phosphorescence measurements on Gd(2)- at 77 K allowed the ligand-centred triplet state ((3)pi-pi*) to be estimated at ca. 28500 cm(-1). Steady state and time-resolved measurements confirmed emission from the f-centred excited state ((5)D(0)) for Eu(2)-. (1)H NMRD profiles revealed the longitudinal proton relaxivity (r(1)) of Gd(2)- to be 8.3 mM(-1)s(-1)(30 MHz, 25 degrees C). The interaction of Cu(II) and Hg(II) with the lanthanide complexes was probed using luminescence and relaxivity measurements. Addition of Cu(II) (10 eq.) resulted in quenching of the Eu(III) emission, but no increase in r(1) of the Gd(III) dimer. Addition of Hg(II) (10 eq.) caused changes to the hypersensitive emission bands of Eu(III) together with an increase in r(1) of Gd(2)- to be 10.3 mM(-1)s(-1)(30 MHz, 25 degrees C) suggesting a net increase in hydration at the Gd(III) centres.


In vivo effect of melatonin and gonadotropin-releasing hormone on testicular function in Rana temporaria.
Studies concerning pineal-gonadal interactions and investigations about the effect of the putative pineal hormone melatonin in male amphibians are very scarce. In this work we investigate the effects of melatonin, synthetic gonadotropin-releasing hormone (GnRH), or both when injected in Rana temporaria males. We conclude that melatonin inhibits spermiation and spermatogonial multiplication when injected alone or with GnRH. We have been unable to find any significant differences in plasma testosterone levels when melatonin or GnRH are injected alone, but when melatonin is injected with GnRH the levels of testosterone are significantly increased. These results seem to demonstrate that melatonin could play a role in the regulation of the gonadal function in the male Rana temporaria.


Interaction of glutamate- and adenosine-induced decrease of acetylcholine quantal release at frog neuromuscular junction.
In a frog neuromuscular preparation of m. sartorius, glutamate had a reversible dose-dependent inhibitory effect on both spontaneous miniature endplate potentials (MEPP) and nerve stimulation-evoked endplate potentials (EPP). The effect of glutamate on MEPP and EPP is caused by the activation of metabotropic glutamate receptors, as it was eliminated by MCPG, an inhibitor of group I metabotropic glutamate receptors. The depression of evoked EPP, but not MEPP frequency was removed by inhibiting the NO production in the muscle by L-NAME and by ODQ that inhibits the soluble NO-sensitive guanylyl cyclase. The glutamate-induced depression of the frequency of spontaneous MEPP is apparently not caused by the stimulation of the NO cascade. The particular glutamate-stimulated NO cascade affecting the evoked EPP can be down-regulated also by adenosine receptors, as the glutamate and adenosine actions are not additive and application of adenosine partially prevents the further decrease of quantal content by glutamate. On the other hand, there is no obvious interaction between the glutamate-mediated inhibition of EPP and inhibitory pathways triggered by carbacholine and ATP. The effect of glutamate on the evoked EPP release might be due to NO-mediated modulation (phosphorylation) of the voltage-dependent Ca2+ channels at the presynaptic release zone that are necessary for evoked quantal release and open during EPP production.


Cannabis masks diabetic ketoacidosis.
This is the first series to identify that diabetic ketosis presenting in cannabis users has a different and conflicting acid base profile compared to non-cannabis users and can confuse the need for intensive or critical care in these at-risk patients. This association of drugtaking history and clinical presentation has implications for how the authors treat the drug using sector of the population with diabetes.


Tuning Coordination Geometry of Nickel Ketoiminates and Its Influence on Thermal Characteristics for Chemical Vapor Deposition of Nanostructured NiO Electrocatalysts.
Nickel-based nanostructured materials have gained widespread attention, particularly for energy-related applications. Employing chemical vapor deposition (CVD) for NiO necessitates suitable nickel precursors that are volatile and stable. Herein, we report the synthesis and characterization of a series of new nickel β-ketoiminato complexes with different aliphatic and etheric side chain substitutions, namely, bis(4-(isopropylamino)-pent-3-en-2-onato)nickel(II) ([Ni(ipki)2], 1), bis(4-(2-methoxyethylamino)pent-3-en-2-onato)nickel(II) ([Ni(meki)2], 2), bis(4-(2-ethoxyethylamino)pent-3-en-2-onato)nickel(II) ([Ni(eeki)2], 3), bis(4-(3-methoxy-propylamino)-pent-3-en-2-onato)nickel(II) ([Ni(mpki)2], 4), and bis(4-(3-ethoxypropylamino)pent-3-en-2-onato)nickel(II) ([Ni(epki)2], 5). These compounds have been thoroughly characterized with regard to their purity and identity by means of nuclear magnetic resonance spectroscopy (NMR) and electron impact mass spectrometry (EI-MS). Contrary to other transition metal β-ketoiminates, the imino side chain strongly influences the structural geometry of the complexes, which was ascertained via single-crystal X-ray diffraction (XRD). As a result, the magnetic momenta of the molecules also differ significantly as evidenced by the magnetic susceptibility measurements employing Evan's NMR method in solution. Thermal analysis revealed the suitability of these compounds as new class of precursors for CVD of Ni containing materials. As a representative precursor, compound 2 was evaluated for the CVD of NiO thin films on Si(100) and conductive glass substrates. The as-deposited nanostructured layers were stoichiometric and phase pure NiO as confirmed by XRD, Rutherford backscattering spectrometry (RBS), and nuclear reaction analysis (NRA). X-ray photoelectron spectroscopy (XPS) indicated the formation of slightly oxygen-rich surfaces. The assessment of NiO films in electrocatalysis revealed promising activity for the oxygen evolution reactions (OER). The current densities of 10 mA cm-2 achieved at overpotentials ranging between 0.48 and 0.52 V highlight the suitability of the new Ni complexes in CVD processes for the fabrication of thin film electrocatalysts.