A Latent Class Analysis of Manic and Psychotic Symptoms.
Bipolar spectrum disorders encompass heterogeneous clinical manifestations and comorbidities. A latent class analysis (LCA) was performed in 1846 subjects who experienced an episode of abnormally elevated or irritable mood to identify homogeneous groups of subjects, based on the distribution of 11 manic and 7 psychotic symptoms. LCA identified five classes: 1) two classes with irritability and with low and high level of psychosis (respectively "irritable," 29.1% of the sample, and "irritable-psychotic," 16.2%); 2) a class with expansive mood and hyperactivity ("expansive-hyperactive," 12.7%); and 3) two classes with manic symptoms and high and low level of psychosis ("manic-psychotic," 15.0%, and "manic," 27.2%). "Irritable" displayed lower rates of depressive episode, panic, and substance use disorders. Manic-psychotic displayed higher rates of depressive episode, panic, generalized anxiety, and substance use disorders. Use of mental health treatment more frequent in manic-psychotic and manic classes. Five classes of bipolar spectrum disorders were characterized by different sociodemographic and clinical patterns.


Regulation of dynein-dynactin-driven vesicular transport.
Most of the long-range intracellular movements of vesicles, organelles and other cargoes are driven by microtubule (MT)-based molecular motors. Cytoplasmic dynein, a multisubunit protein complex, with the aid of dynactin, drives transport of a wide variety of cargoes towards the minus end of MTs. In this article, I review our current understanding of the mechanisms underlying spatiotemporal regulation of dynein-dynactin-driven vesicular transport with a special emphasis on the many steps of directional movement along MT tracks. These include the recruitment of dynein to MT plus ends, the activation and processivity of dynein, and cargo recognition and release by the motor complex at the target membrane. Furthermore, I summarize the most recent findings about the fine control mechanisms for intracellular transport via the interaction between the dynein-dynactin motor complex and its vesicular cargoes.


Regional cerebral glucose metabolism in three sets of identical twins with psychotic symptoms.
Three sets of young identical twins where at least one had a psychotic episode were assessed in terms of psychiatric and psychological status and integrity of cerebral structure and metabolism. The psychiatric diagnoses for each set were normal/schizophrenia, prodromal/schizophrenia and schizoaffective/schizoaffective. The latter two sets were re-examined two years after the initial assessment. The data are considered from a case study perspective. Reduced cerebral metabolism was found for at least one region on eight of nine scans of patients with a psychotic history. On seven of the nine scans, glucose metabolism in the orbital frontal cortex was reduced. These findings are discussed with respect to previous studies of glucose metabolism in patients with schizophrenia, metabolic similarities found in normal identical twins and the known functional specialization of the orbital frontal cortex.


Role of community health service programs in navigating the medical ethical slippery slope-a 10-year retrospective study among medical students from southern China.
For promoting autonomous learning motivation, the learning effect of community-oriented service is beneficial, because through community participation and service, students can transfer their implicit cognition of ethics into explicit cognition, leading to the cultivation of a sympathetic partnership between the community and medical students. Despite the proven benefits of medical students' community health service (CHS) in Western countries, CHS programs designed for medical students are not well established in mainland China, and their effects on medical students' ethical cognition are largely unknown. This study evaluated the effects of CHS programs on the ethical cognition of medical students. A cross-sectional study was conducted on third- and fourth-year medical students and graduates working at Shantou University Medical College by using a self-administered anonymous questionnaire. Through interviews, we applied a thematic approach to analyze the responses of the participating students. The questionnaire adopted in this study was revised based on a review of the literature on medical ethics in medical students and on the CHS environment in China. The reviewed questionnaires included an evaluation questionnaire on cultivating medical ethics in a CHS context, and questionnaires used to explore the cultivation and transformation of medical ethics in medical students during the preclinical period. A total of 361 (54.4%) undergraduate medical students and 302 (45.6%) graduates participated in this survey. Significant differences were observed in self-evaluation of the cognitive development of ethics between those who had participated in CHS programs 1-5 times and those who had participated > 6 times. The successful identification of accepting money from the patients under the table as unethical behavior significantly differed (p = .031) among the graduates but not (p = .567) among the undergraduate students. The participants expressed the positive impact of CHS programs on their self-development. CHS programs can be widely applied in medical education in China. This educational strategy, which supports medical professionalism and incorporates humanitarian behavior as a complement to learning, should be encouraged and promoted nationally.


A quantitative evaluation of abdominal aorta aneurysm by CT images.
An abdominal aorta aneurysm (AAA) is a disease that aortic vessel inflates abnormally. The aorta blows up continuously, which may lead to the rupture of the aorta. The mortality of rupturing the aorta is between 75 and 90% to properly treat this disease, we need to accurate measure about variation of AAA size. our team performed that AAA is reconstructed as three dimensional (3D) images by computer tomography (CT), and analyzed the elements of inflation through a geometric parameter measurement . Subjects (seven males) who undergo an AAA are enrolled for the analysis. The authors used CT images as a primary source, and obtained secondary CT images 12 months later. By means of these data, the authors constructed 3D images of AAA and performed examinations using a geometric analysis that calculates geometric parameter such as the tortuosity, diameter, saccular and so on based on volume, area of the segmented region of the CT slices that is set up by the centroids and 8 points around it. The result of the severity biomechanical factor shows increased AAA tortuosity ratio (4.9%), AAA diameter expansion ratio [cm/year] (6.8%), AAA total diameter ratio (4.7%), AAA saccular ratio (2.4%) than 12-month before. Through these results, We can plan to endovascular repair surgery to undergoing AAA patients and possible diagnosis estimation of AAA.


Early, Persistent Lymphopenia Is Associated With Prolonged Multiple Organ Failure and Mortality in Septic Children.
Sepsis-associated immune suppression correlates with poor outcomes. Adult trials are evaluating immune support therapies. Limited data exist to support consideration of immunomodulation in pediatric sepsis. We tested the hypothesis that early, persistent lymphopenia predicts worse outcomes in pediatric severe sepsis. Observational cohort comparing children with severe sepsis and early, persistent lymphopenia (absolute lymphocyte count < 1,000 cells/µL on 2 d between study days 0-5) to children without. The composite outcome was prolonged multiple organ dysfunction syndrome (MODS, organ dysfunction beyond day 7) or PICU mortality. Nine PICUs in the National Institutes of Health Collaborative Pediatric Critical Care Research Network between 2015 and 2017. Children with severe sepsis and indwelling arterial and/or central venous catheters. Blood sampling and clinical data analysis. Among 401 pediatric patients with severe sepsis, 152 (38%) had persistent lymphopenia. These patients were older, had higher illness severity, and were more likely to have underlying comorbidities including solid organ transplant or malignancy. Persistent lymphopenia was associated with the composite outcome prolonged MODS or PICU mortality (66/152, 43% vs 45/249, 18%; p < 0.01) and its components prolonged MODS (59/152 [39%] vs 43/249 [17%]), and PICU mortality (32/152, 21% vs 12/249, 5%; p < 0.01) versus children without. After adjusting for baseline factors at enrollment, the presence of persistent lymphopenia was associated with an odds ratio of 2.98 (95% CI [1.85-4.02]; p < 0.01) for the composite outcome. Lymphocyte count trajectories showed that patients with persistent lymphopenia generally did not recover lymphocyte counts during the study, had lower nadir whole blood tumor necrosis factor-α response to lipopolysaccharide stimulation, and higher maximal inflammatory markers (C-reactive protein and ferritin) during days 0-3 ( p < 0.01). Children with severe sepsis and persistent lymphopenia are at risk of prolonged MODS or PICU mortality. This evidence supports testing therapies for pediatric severe sepsis patients risk-stratified by early, persistent lymphopenia.


Direct C-H Bond Arylation of Thienyl Thioamides Catalyzed by Pd-Phenanthroline Complexes.
A direct C-H bond arylation method for thienyl thioamides catalyzed by [Pd(phen)2](PF6)2 was developed. This reaction selectively afforded 2-monoarylated products, while the corresponding amide thiophene derivatives furnished 2,5-diarylated products. Mechanistic studies revealed that a Pd(II)-bisthioamide complex should be the active species for the reaction of thienyl thioamides in the presence of catalytic amounts of [Pd(phen)2](PF6)2. Similar to the reaction with amides, the reaction with thioamides selectively generated the 2,5-diarylated products when a preformed Pd(phen)PhI complex was used.


Healthy-eater self-schema and dietary intake.
The types and amounts of foods consumed have been shown to influence the health risks of individuals. Empirical evidence has documented a link between high dietary fat and low fiber intake and the risks for cardiovascular disease, some types of cancer, and obesity. Dietary surveys of Americans show higher fat and lower fiber intake than stipulated in the Dietary Guidelines for Americans, despite the noted increase in public awareness regarding the importance of adopting healthy eating habits. The lack of congruence between the availability of dietary knowledge and behavioral adherence to dietary recommendations suggests a need to further understand the predictors of dietary intake. In this study, the authors used the schema model of the self-concept to explore the role of self-beliefs in predicting dietary intake in community-dwelling, working-class, middle-aged adults.


Effect of the timing of discontinuation of last-line chemotherapy on patient prognosis in advanced and recurrent gastric cancer.
The present study aimed to determine the effect of the timing of treatment discontinuation on the prognosis of patients with advanced and recurrent gastric cancer chemotherapy. Between July 2014 and March 2017, 127 patients who underwent chemotherapy for advanced and recurrent gastric cancer at Ogaki Municipal Hospital (Ogaki, Japan) were examined. To determine factors associated with survival, multivariate analysis using the Cox proportional hazards model, and hazard ratios and their 95% confidence intervals (95% CI) were calculated. The reasons for discontinuation of last-line chemotherapy and the last hospitalization prior to mortality were surveyed. Age (≤51 years), number of treatment lines (≤1 line), and days between last dose of the final chemotherapy regimen and death (≤79 days) were independently and significantly associated with survival in the multivariate analysis. Compared with patients who did not receive chemotherapy in the last 79 days of life, those who received chemotherapy in the last 79 days of life days had a hazard ratio of 1.858 (95% CI, 1.059-3.261; P=0.031) for mortality. A decrease in the performance status was responsible for treatment discontinuation in 51 of 75 cases among patients who received chemotherapy in the last 79 days of life and 9 of 26 cases among patients who did not receive chemotherapy in this duration (P<0.001). Among patients who received chemotherapy in the last 79 days of life, 67 patients were hospitalized prior to mortality; among patients who did not receive chemotherapy in this duration, 15 patients were hospitalized prior to mortality (P<0.001). In conclusion, continuation of chemotherapy until just prior to mortality does not prolong the survival time in patients with advanced and recurrent gastric cancer.


The changing character of the medical profession: a theoretical overview.
Technological advances in medicine have greatly enhanced the ability of physicians to treat disease and disability, but, at the same time, changes in the organization and management of health care services in the United States have imposed constraints on their autonomy. How have these changes--medical advancement and professional decline--affected the theoretical concept of the medical profession? Challenging the prevailing model of professional dominance, the concepts of deprofessionalization, corporatization, and proletarianization emphasize the effects of recent social and economic developments on the changing status of the medical profession. There is evidence, however, that what the proponents of these concepts perceive as the profession's response to external forces are, in fact, the unanticipated consequences of the profession's campaign for autonomy.


[Effect of metalaxyl on the synthesis of RNA, DNA and protein in Phytophthora nicotianae].
Metalaxyl is used to control diseases caused by fungi of the order of the Perenosporales. We investigated the action of this fungicid eon nucleic acid and protein synthesis in liquid cultures of Phytophthora nicotianae. The uptake of 32P, 3H-uridine, 3H-thymidine and 14C-leucine as precursors of nuclei acid and protein synthesis by the mycelium was not inhibited by metalaxyl. RNA synthesis as indicated by 3H-uridine incorporation was strongly inhibited (about 80%) by 0.5 micrograms/ml of metalaxyl. The inhibition was visible already few minutes after addition of the toxicant. Since the inhibition of incorporation of 3H-thymidine into DNA and of 14C-leucine into protein became significant 2-3 hours later, we conclude that metalaxyl primarily interfers with RNA synthesis. Synthesis of ribosomal RNA is more affected (more than 90%) than that of tRNA (about 55%) and poly(A)-containing RNA. Since in the presence of actinomycin, in contrast to metalaxyl, protein synthesis is inhibited immediately as a consequence of complete inhibition of RNA synthesis and of the short life-time of mRNA, it is also evident that mRNA synthesis is less strongly inhibited, at least during the early period of metalaxyl action. The molecular mechanism of metalaxyl inhibition of the transcription process remains open. The fungicide did not inhibit the activity of a partially purified RNA polymerase isolated from the fungus. On the other hand, the RNA synthesis (14C-UTP-incorporation) by a cell homogenate and by isolated nuclear fractions was inhibited significantly. Possibilities of the molecular action of metalaxyl are discussed. The RNA synthesis of some plant systems (cell cultures of Lycopersicon peruvianum, isolated nuclei from the same cell cultures, purified RNA polymerase from Spinacia oleracea chloroplasts) was not inhibited by metalaxyl, not even at high concentrations.


Conjugation-length dependence of spin-dependent exciton formation rates in pi-conjugated oligomers and polymers.
We have measured the ratio, r = sigma(S)/sigma(T) of the formation cross section, sigma of singlet and triplet excitons from polarons in pi-conjugated oligomer and polymer films, using a spectroscopic technique we developed recently. We discovered a universal relation between r and the conjugation length (CL): r(-1) depends linearly on CL-1, irrespective of the chain structure. Since r is directly related to the maximum possible electroluminescence quantum efficiency in organic light emitting diodes (OLED), our results indicate that polymers have an advantage over small molecules in OLED applications.


[Progress in preparation and application of sodium alginate microspheres].
Sodium alginate (SA) is a kind of natural polymer material extracted from kelp, which has excellent biocompatibility, non-toxicity, biodegradability and abundant storage capacity. The formation condition of sodium alginate gel is mild, effectively avoiding the inactivation of active substances. After a variety of preparation methods, sodium alginate microspheres are widely used in the fields of biomaterials and tissue engineering. This paper reviewed the common methods of preparing alginate microspheres, including extrusion, emulsification, electrostatic spraying, spray drying and coaxial airflow, and discussed their applications in biomedical fields such as bone repair, hemostasis and drug delivery.


Strategies for changing the nursing preceptorship activity in Primary Health Care.
to present actions to qualify preceptorship and teaching-health service integration to strengthen nursing training in PHC internship. qualitative research, developed through the Appreciative Inquiry Research carried out with eight nurses, both from the fields of teaching and health service, within Primary Health Care. The production and documentation of information took place between April and June 2019, through five meetings that characterized the four phases that make up the "4D cycle": Discovery, Dream, Design, and Destiny. Ethical issues were respected. the participants dreamed of the best scenario for preceptorship and built a schedule of actions related to the qualification of preceptorship in Nursing and the strengthening of teaching-health service integration. it is possible, through effective participation of the actors involved in teaching and practice, the collective development of goals and actions, aiming at the qualification of nursing education.


Excessive vitamin A toxicity in mice genetically deficient in either alcohol dehydrogenase Adh1 or Adh3.
Alcohol dehydrogenase (ADH) deficiency results in decreased retinol utilization, but it is unclear what physiological roles the several known ADHs play in retinoid signaling. Here, Adh1, Adh3, and Adh4 null mutant mice have been examined following acute and chronic vitamin A excess. Following an acute dose of retinol (50 mg.kg(-1)), metabolism of retinol to retinoic acid in liver was reduced 10-fold in Adh1 mutants and 3.8-fold in Adh3 mutants, but was not significantly reduced in Adh4 mutants. Acute retinol toxicity, assessed by determination of the LD(50) value, was greatly increased in Adh1 mutants and moderately increased in Adh3 mutants, but only a minor effect was observed in Adh4 mutants. When mice were propagated for one generation on a retinol-supplemented diet containing 10-fold higher vitamin A than normal, Adh3 and Adh4 mutants had essentially the same postnatal survival to adulthood as wild-type (92-95%), but only 36% of Adh1 mutants survived to adulthood with the remainder dying by postnatal day 3. Adh1 mutants surviving to adulthood on the retinol- supplemented diet had elevated serum retinol signifying a clearance defect and elevated aspartate aminotransferase indicative of increased liver damage. These findings indicate that ADH1 functions as the primary enzyme responsible for efficient oxidative clearance of excess retinol, thus providing protection and increased survival during vitamin A toxicity. ADH3 plays a secondary role. Our results also show that retinoic acid is not the toxic moiety during vitamin A excess, as Adh1 mutants have less retinoic acid production while experiencing increased toxicity.


Emerging Roles for SIRT5 in Metabolism and Cancer.
Developing evidence in the literature suggests that sirtuin 5 (SIRT5) may be involved in metabolic reprogramming, an emerging hallmark of cancer by which neoplastic cells reconfigure their metabolism to support the anabolic demands of rapid cell division. SIRT5 is one of the seven members of the nicotinamide adenine dinucleotide-dependent sirtuin family of lysine deacetylases. It removes succinyl, malonyl, and glutaryl groups from protein targets within the mitochondrial matrix and other subcellular compartments. SIRT5 substrates include a number of proteins integral to metabolism. Recent Advances: New work has begun to elucidate the roles of SIRT5 in glycolysis, tricarboxylic acid cycle, fatty acid oxidation, nitrogen metabolism, pentose phosphate pathway, antioxidant defense, and apoptosis. In this study, we summarize biological functions of SIRT5 reported in normal tissues and in cancer and discuss potential mechanisms whereby SIRT5 may impact tumorigenesis, particularly focusing on its reported roles in metabolic reprogramming. Finally, we review current efforts to target SIRT5 pharmacologically. The biological significance of SIRT5 has been elucidated in the context of only an extremely small fraction of its targets and interactors. There is no doubt that further studies in this area will provide a wealth of insights into functions of SIRT5 and its targets in normal and neoplastic cells. Antioxid. Redox Signal. 28, 677-690.


In Vitro Study of Receptor-Mediated Silica Nanoparticles Delivery across Blood-Brain Barrier.
A brain drug delivery system has been demonstrated by attaching lactoferrin (Lf) on the silica nanoparticles (Si NPs). The nanoparticle surface was modified with polyethylene glycol to reduce protein adsorption. The transport efficiency of Lf attached Si NPs was studied using an in vitro blood-brain barrier (BBB) model consisting of three distinct types of cells: endocytes, pericytes, and astrocytes. Transfer of NPs from the apical side to the basolateral side is observed. The results indicated that Lf attached Si NPs demonstrated enhanced transport efficiency across the BBB with size-dependence compared to bare Si NPs. The maximum transport efficiency of lactoferrin conjugated silica nanoparticle was observed for 25 nm diameter particles. This receptor-mediated transcytosis of Si NPs across the cerebral endothelial cells can be employed to deliver drugs and imaging probes to the brain.


Transvenous onyx embolization for dural arteriovenous fistula with concomitant transvenous balloon protection of the venous sinus.
The purpose of this study was to evaluate the technical efficacy and safety of transvenous Onyx embolization for dural arteriovenous fistulas (DAVFs) with concomitant transvenous balloon protection of the venous sinus when transarterial route failed or was not feasible. Between September 2010 and December 2016, thirty-six patients presenting with intracranial DAVFs underwent transvenous balloon-assisted Onyx embolization. The technical efficacy, treatment-related complications, and angiographic and clinical outcomes were reviewed from our prospectively maintained DAVF database. According to the Cognard classification, 11 patients presented with clinically symptomatic Cognard type I; 11 cases with Cognard type IIa; 10 cases with Cognard type IIb and 4 cases with Cognard type IIa+b. Complete angiographic occlusion of the DAVFs at the latest follow-up (mean 18 months after transvenous embolization) was achieved in 28 patients (77.8%), near-complete angiographic occlusion with minimal residual fistula in 5 patients (13.9%) and significant flow reduction of the DAVF in 2 patients (5.6%) and residual fistula for further treatment in 1 (2.8%) patient. Total clinical cure or remission of the pre-treatment symptoms was achieved in 31 patients (31/36, 86.1%; 26 and 5 cases respectively). Affected venous sinus was preserved in 28 patients, intentionally occluded in 7 patients and gradually occluded in 1 patient. There were no immediate or long term persistent complications after treatment. Transvenous Onyx embolization of dural arteriovenous fistulas with combined transvenous balloon protection of the venous sinus is safe and effective in achieving high occlusion rate, low embolization-related complications and satisfactory clinical outcomes.


Norwalk-like gastroenteritis epidemic in a Toronto hospital.
An epidemic of gastroenteritis in a teaching hospital affected 57 patients and 69 staff over a 26-day period. The index case was a patient admitted with acute abdominal pain and diarrhea two days prior to the outbreak. The epidemic curve indicated person-to-person transmission. The incubation period, duration and types of symptoms were typical of Norwalk gastroenteritis, and Norwalk-like virus particles, serologically different from the prototype Norwalk virus strain, were observed in 17 of 20 fecal specimens examined by immune-electron microscopy.


Chronologically overlapping occurrences of nicotine-induced anxiety- and depression-related behavioral symptoms: effects of anxiolytic and cannabinoid drugs.
Anxiety and depression are among the most frequently-observed psychiatric symptoms associated with nicotine (NC). In addition to the similarity to other addictive drugs, these NC-induced symptoms are characteristic in that the opposite behavioral effects, i.e. anxiolytic and antidepressant effects, which may reinforce the habitual use of NC, have also been reported. In the present study, the time course of anxiety- and depression-related behavioral alterations was examined in mice. Furthermore, based on the reported similarity in the mechanisms responsible for NC-induced anxiety- and depression-related symptoms, as well as the contribution of brain cannabinoid (CB) receptors to these behavioral symptoms, the effects of anxiolytics and CB receptor ligands (CBs) against these behavioral symptoms were investigated. Repeated subcutaneous NC treatments (0.3 mg/kg, 4 days), compared with a single treatment (0.5 mg/kg), caused both prolonged anxiogenic effects in the elevated plus-maze test, and prolonged depressive effects in the forced swimming test, even at 120 min time point after the last NC treatment. A transient anxiolytic preference for open arms was also observed in the elevated plus-maze test. Among the anxiolytics and CBs, the serotonin 1A (5-HT1A) antagonist WAY 100135 and the endogenous mixed CB agonist/antagonist virodhamine (VD), when administered intraperitoneally before each NC treatment, provided the strongest antagonistic effects against the anxiety-related symptoms. However, against the depression-related symptoms, only VD provided significant antagonistic effects in both single and repeated treatment groups. The present results support the presence of a chronological overlap of NC-induced anxiety- and depression-related behavioral symptoms, and the contribution of brain CB receptors to these behavioral symptoms. The repeated NC-induced prolongation of these behavioral symptoms and the early transient anxiolytic behavioral alterations support an increased possibility of the habitual use of NC. Furthermore, based on the antagonistic effects of VD, one can predict that the characteristic effects on brain CB receptors as a mixed CB agonist/antagonist contributed to its therapeutic effects as both an anxiolytic and an antidepressant.


Impact of sea ice transport on Beaufort Gyre liquid freshwater content.
The Arctic Ocean's Beaufort Gyre (BG) is a wind-driven reservoir of relatively fresh seawater, situated beneath time-mean anticyclonic atmospheric circulation, and is covered by mobile pack ice for most of the year. Liquid freshwater accumulation in and expulsion from this gyre is of critical interest due to its potential to affect the Atlantic meridional overturning circulation and due to the importance of freshwater in modulating vertical fluxes of heat, nutrients and carbon in the ocean, and exchanges of heat and moisture with the atmosphere. Here, we investigate the hypothesis that wind-driven sea ice transport into/from the BG region influences the freshwater content of the gyre and its variability. To test this hypothesis, we use the results of a coordinated climate response function experiment with four ice-ocean models, in combination with targeted experiments using a regional setup of the MITgcm, in which we rotate the surface wind forcing vectors (thereby changing the ageostrophic component of these winds). Our results show that, via an effect on the net thermodynamic growth rate, anomalies in sea ice transport into the BG affect liquid freshwater adjustment. Specifically, increased ice import increases freshwater retention in the gyre, whereas ice export decreases freshwater in the gyre. Our results demonstrate that uncertainty in the ageostrophic component of surface winds, and in the dynamic sea ice response to these winds, has important implications for ice thermodynamics and freshwater. This sensitivity may explain some of the observed inter-model spread in simulations of Beaufort Gyre freshwater and its adjustment in response to wind forcing.


Porcine reproductive and respiratory syndrome virus (PRRSV) in pig meat.
Porcine reproductive and respiratory syndrome, caused by the porcine reproductive and respiratory syndrome virus (PRRSV), is an economically important disease in the swine industry. Previous studies demonstrated the presence of the virus in pig meat and its transmissibility by oral consumption. This study further analyzed the infectivity of PRRSV in commercial pig meat. Fresh bottom meat pieces (n = 1500) randomly selected over a period of 2 y from a pork ham boning plant located in Quebec, Canada, were tested by reverse transcriptase polymerase chain reaction (RT-PCR). Each trimmed meat was stored in the plant freezer, subsampled weekly for up to 15 wk, and tested with quantitative RT-PCR to determine the viral load. Meat infectivity was evaluated using specific pathogen-free piglets, each fed with approximately 500 g of meat at the end of the storage time. Genotype-specific RT-PCR confirmed the presence of PRRSV mainly during cold weather in 0.73% of the fresh meat pieces. Wild and vaccine strains of genotype 2 were detected. Porcine reproductive and respiratory syndrome virus nucleic acid was stable in meat stored at around -20°C during the 15 wk. Serological and molecular analysis showed the transmission of infection by a majority of PRRSV positive meat pieces (5/9) fed orally to naïve recipients. The results confirmed a low prevalence of PRRSV in market's pig meat, and virus transmissibility by oral consumption to naïve recipients even after several weeks of storage in a commercial freezer. It occurred mainly with meat harboring the highest PRRSV RNA copies, in the range of 109 copies per 500 g of meat, with both wild type and vaccine-related strains.


Biodegradable PELA block copolymers: in vitro degradation and tissue reaction.
Degradation of, and tissue reaction elicited by a series of polyethylene oxide (PEO)/polylactic acid (PLA) PELA block copolymers were studied in vitro and in vivo. In particular, the effect of pH, temperature and enzymatic activity was addressed. The mass loss was faster, the more basic the media, while, expectedly, PELA copolymers degraded faster with the higher temperature. The addition of an enzyme (carboxylic ester hydrolase) had no effect. The degradation process strongly affected the mechanical properties of the materials under investigation, the elongation at break dropping drastically after two days of degradation. After seven days, only gross observation of the extensively degraded samples was possible. The in vivo studies compared the tissue reaction elicited by various PELA copolymers to that evoked by PLA. Evaluation of tissue reaction observed with a PELA sample after sterilization with gamma radiation showed acute inflammation with considerable dispersion of the material, 12 days after implantation. The granulomatous reaction observed with PELA copolymers after ethylene oxide sterilization was identical to the reaction observed with PLA.


Tetra-gel enables superior accuracy in combined super-resolution imaging and expansion microscopy.
The accuracy of expansion microscopy (ExM) depends on the structural preservation of samples embedded in a hydrogel. However, it has been unknown to what extent gel embedding alters the molecular positions of individual labeled sites. Here, we quantified the accuracy of gel embedding by using stochastic optical reconstruction microscopy (STORM) to image DNA origami with well-defined structures. We found that embedding in hydrogels based on polyacrylamide, the most widely used chemistry in ExM, resulted in random displacements of labeled sites with a standard deviation of ~ 16 nm. In contrast, we found that embedding in tetra-gel, a hydrogel that does not depend on free-radical chain-growth polymerization, preserved labeled sites with a standard deviation of less than 5 nm. By combining tetra-gel ExM with STORM, we were able to resolve 11-nm structural features without the loss in accuracy seen with polyacrylamide gels. Our study thus provides direct measurements of the single-molecule distortions resulting from hydrogel embedding, and presents a way to improve super-resolution microscopy through combination with tetra-gel ExM.


Correlation between prostate needle biopsy and radical prostatectomy Gleason gradings of 111 cases with prostatic adenocarcinoma.
There are conflicting reports in the literature about correlation of biopsy and prostatectomy Gleason scores in prostate carcinoma. The goal of this study was to determine the correlation of grading in these two types of pathologic materials. The coupled Hematoxylin and Eosin slides of 111 patients with prostate carcinoma were collected. Gleason scores were determined. Patients who had undergone any therapy except surgery were excluded from the study. Correlation between grades was calculated by determination of correlation coefficient. Accuracy of biopsy grading in prediction of final grade was also determined by measuring the sensitivity, specificity, and positive and negative predictive values. In 50 cases (45%), grade was underestimated in the biopsy. After dividing the cases into Gleason scores of 2 to 4, 5 to 6, 7, and 8 to 10, the most of undergraded cases (84.2%) were in the first group (Gleason score 2 to 4) and this rate reached 5% in the fourth group (Gleason score 8 to 10). The correlation coefficient measured was 0.535 in grade to grade comparing and 0.514 in group to group comparison of the specimens. In low-grade tumors, grading in biopsy, in spite of high sensitivity (90.9%), had low positive predictive value (26.3%). There is a moderate direct linear relationship between scores in biopsy and prostatectomy specimens. But there is a high probability of underestimation of real Gleason score of the radical prostatectomy specimen in low-grade tumors. Pathologists and urologists must consider the phenomenon of undergrading in reporting prostate specimens and managing patients.


Characterization of small (≤3 cm) hepatic lesions with atypical enhancement feature and hypointensity in hepatobiliary phase of gadoxetic acid-enhanced MRI in cirrhosis: A STARD-compliant article.
It is difficult to characterize the nodular lesions in cirrhotic liver if typical enhancement pattern is not present on dynamic contrast-enhanced imagings. Although the signal intensity of the hepatobiliary phase in gadoxetic acid-enhanced magnetic resonance imaging (MRI) is helpful for characterization of the lesions, some dysplastic nodules may also exhibit low signal intensity in the hepatobiliary phase. We aimed to assess the usefulness of gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI including diffusion-weighted imaging (DWI) for differentiation between atypical small hepatocellular carcinomas (HCCs) and dysplastic nodules showing low signal intensity (SI) in the hepatobiliary phase, and to evaluate the MRI findings in determining the histological grade of atypical HCCs in patients with cirrhosis.A total of 43 cirrhotic patients with a small (≤3 cm) liver nodule (n = 25, HCC; n = 18, dysplastic nodule) who underwent Gd-EOB-DTPA-enhanced MRI and pathologic confirmation were retrospectively reviewed. Atypical HCC was defined as not showing arterial hyperenhancement and delayed washout on dynamic MRI.High SI on both T2WI and DWI (sensitivity 80.0%, specificity 100%, positive predictive value 100%, negative predictive value 78.3%) was the most specific feature to differentiate atypical HCCs from dysplastic nodules. High SI on both T2WI and DWI (100% vs 61.5%, P = .039) or low SI on pre-enhanced T1WI (83.3% vs 30.8%, P = .021) was more frequent observed in Edmonson grade II-III HCCs compared with those in grade I HCCs.The combination of DWI and T2WI is most useful for the differentiation of atypical small HCCs from dysplastic nodules showing low SI in the hepatobiliary phase. Combination of DWI and T2WI or pre-enhanced T1WI seems to be useful for predicting the histological grade of atypical HCCs.


THE DARWIN-FISHER THEORY OF SEXUAL SELECTION IN MONOGAMOUS BIRDS.
Males of monogamous birds often show secondary sexual traits that are conspicuous but considerably less extreme than those of polygynous species. We develop a quantitative-genetic model for the joint evolution of a male secondary sexual trait, a female mating preference, and female breeding date, following a theory proposed by Darwin and Fisher. Good nutritional condition is postulated to cause females to breed early and to have high fecundity. The most-preferred males are mated by early-breeding females and receive a sexual-selection advantage from those females' greater reproductive success. Results show that conspicuous male traits that decrease survival can evolve but suggest that the extent of maladaptive evolution is greatly limited relative to what is possible in a polygynous mating system for two reasons. First, in the absence of direct fitness effects of mate choice on the female, the equilibria for the male trait and female preference form a curve whose shape shows that the maximum possible strength of sexual selection on males (and hence the potential for maladaptive evolution) is constrained. Under certain conditions, a segment of the equilibrium curve may become unstable, leading to two alternative stable states for the male trait. Second, male parental care will often favor the evolution of mating preferences for less conspicuous males. We also find that sexual selection can appear in the absence of the nutritional effects emphasized by Darwin and Fisher. A review of the literature suggests that the assumptions of the Darwin-Fisher mechanism may often be met in monogamous birds and that other mechanisms may often reinforce it by producing additional components of sexual selection.


RETRACTED: Enhanced AC133-specific CAR T cell therapy induces durable remissions in mice with metastatic small cell lung cancer.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Following the publication of the above article, the Editor was notified that an error occurred in which all images were published with incorrect versions. The Editor has taken the decision that the manuscript is no longer acceptable in its current form, nor with a corrigendum, as the extensive changes to the figures and publication would lead to ambiguity for our readers. We have therefore made the decision to retract this manuscript from Cancer Letters with the possibility of resubmission and republication of the manuscript in its corrected form after peer review.


The wound repair response controls outcome to cutaneous leishmaniasis.
Chronic microbial infections are associated with fibrotic and inflammatory reactions known as granulomas showing similarities to wound-healing and tissue repair processes. We have previously mapped three leishmaniasis susceptibility loci, designated lmr1, -2, and -3, which exert their effect independently of T cell immune responses. Here, we show that the wound repair response is critically important for the rapid cure in murine cutaneous leishmaniasis caused by Leishmania major. Mice congenic for leishmaniasis resistance loci, which cured their lesions more rapidly than their susceptible parents, also expressed differentially genes involved in tissue repair, laid down more ordered collagen fibers, and healed punch biopsy wounds more rapidly. Fibroblast monolayers from these mice repaired in vitro wounds faster, and this process was accelerated by supernatants from infected macrophages. Because these effects are independent of T cell-mediated immunity, we conclude that the rate of wound healing is likely to be an important component of innate immunity involved in resistance to cutaneous leishmaniasis.


Prior knowledge in recalling arguments in bioethical dilemmas.
Prior knowledge is known to facilitate learning new information. Normally in studies confirming this outcome the relationship between prior knowledge and the topic to be learned is obvious: the information to be acquired is part of the domain or topic to which the prior knowledge belongs. This raises the question as to whether prior knowledge of various domains facilitates recalling information. In this study 79 eleventh-grade students completed a questionnaire on their prior knowledge of seven different domains related to the bioethical dilemma of prenatal diagnostics. The students read a text containing arguments for and arguments against prenatal diagnostics. After 1 week and again 12 weeks later they were asked to write down all the arguments they remembered. Prior knowledge helped them recall the arguments 1 week (r = 0.350) and 12 weeks (r = 0.316) later. Prior knowledge of three of the seven domains significantly helped them recall the arguments 1 week later (correlations between r = 0.194 and 0.394). Partial correlations with interest as a control item revealed that interest did not explain the relationship between prior knowledge and recall. Prior knowledge of different domains jointly supports the recall of arguments related to bioethical topics.


Development of a sensory afferent projection in the grasshopper embryo. II. Growth and branching of peripheral sensory axons within the central nervous system.
The morphogenesis of several types of sensory axon branching patterns has been described by cobalt filling the cercal nerve of the grasshopper embryo at a series of different stages in development, thus staining the earliest sensory axons as they grow through the CNS. This embryonic sensory projection contains all five types of cercal afferents seen in the adult, and no new sensory tracts are added during postembryonic life. When the embryonic sensory axons first follow their pioneer axons into the neuropil they choose pathways which are characteristic of the adult sensory tracts. Since the afferents follow these paths without sending collaterals into the other tracts, it appears that the growth axon chooses its specific pathway without extensive exploration of alternative routes. Likewise, nearly all of the branches which arise from the embryonic sensory axons remain within the eventual domain characteristic of each cell type. This precise, determinate pattern of initial growth implies that the sensory axons are guided through the neuropil and achieve their final branching patterns with a minimum of overgrowth and pruning. The fact that initial growth is so precise also suggests that the parameters which guide the growing axon may help to determine its eventual pattern of synaptic connectivity by limiting its physical access to large portions of the neuropil which contain potentially compatible synaptic partner cells. Two different types of neurons may be supplying the sensory afferents with guidance cues: (i) Although most of the cercal sensory axons diverge from the cercal pioneer axons within the CNS, some sensory afferents continue to follow the pioneers through several ganglia. (ii) In the adult, a large number of the cercal sensory axons form a hollow shell of arborization around the main dendrite of an identified synaptic target cell, the Medical Giant Interneuron (MGI). This structure, the interneuron dendrite and the shell of sensory arbor, is called the cercal glomerulus. Since the MGI's dendrite is already present at the stage when the first sensory axons enter the CNS, interactions between these cells could serve to guide the glomerular sensory axons away from the pioneers into their future tracts.


Advances in Natural Product Extraction Techniques, Electrospun Fiber Fabrication, and the Integration of Experimental Design: A Comprehensive Review.
The present review explores the growing interest in the techniques employed for extracting natural products. It emphasizes the limitations of conventional extraction methods and introduces superior non-conventional alternatives, particularly ultrasound-assisted extraction. Characterization and quantification of bioactive constituents through chromatography coupled with spectroscopy are recommended, while the importance of method development and validation for biomarker quantification is underscored. At present, electrospun fibers provide a versatile platform for incorporating bioactive extracts and have extensive potential in diverse fields due to their unique structural and functional characteristics. Thus, the review also highlights the fabrication of electrospun fibers containing bioactive extracts. The preparation of biologically active extracts under optimal conditions, including the selection of safe solvents and cost-effective equipment, holds promising potential in the pharmaceutical, food, and cosmetic industries. Integration of experimental design into extraction procedures and formulation development is essential for the efficient production of health products. The review explores potential applications of encapsulating natural product extracts in electrospun fibers, such as wound healing, antibacterial activity, and antioxidant properties, while acknowledging the need for further exploration and optimization in this field. The findings discussed in this review are anticipated to serve as a valuable resource for the processing industry, enabling the utilization of affordable and environmentally friendly, natural, and raw materials.


Physiologic levels of epidermal growth factor in saliva stimulate cell migration of an oral epithelial cell line, HO-1-N-1.
An oral epithelial cell line derived from buccal mucosa squamous cell carcinoma, HO-1-N-1, was used to elucidate the role of epidermal growth factor (EGF) in saliva on wound healing of the oral mucosa. The effects of EGF on DNA synthesis, and cell migration was studied and the related signal transduction pathways examined. DNA synthesis by HO-1-N-1 cells was stimulated dose-dependently by 1-10 ng ml(-1) EGF, but significantly inhibited by addition of a PI3-K inhibitor (wortmannin), a p38 MAPK inhibitor (SB203580) or an MEKs inhibitor (PD98059). Cell migration was also accelerated by addition of 1-10 ng ml(-1) EGF; however, the migration rate was decreased to 30% by adding PD98059, to 40% by adding a tyrosine kinase inhibitor (herbimycin A), and to 60% by adding wortmannin or dexamethasone. These results indicate that the physiologic concentration of EGF in saliva may stimulate proliferation and migration of oral epithelial cells for wound healing, when the oral mucosa has been injured. Furthermore, this study revealed that EGF-stimulated signal transduction pathways for epithelial cell proliferation and cell migration are different.


Unusual starch degradation pathway via cyclodextrins in the hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus strain 7324.
The hyperthermophilic archaeon Archaeoglobus fulgidus strain 7324 has been shown to grow on starch and sulfate and thus represents the first sulfate reducer able to degrade polymeric sugars. The enzymes involved in starch degradation to glucose 6-phosphate were studied. In extracts of starch-grown cells the activities of the classical starch degradation enzymes, alpha-amylase and amylopullulanase, could not be detected. Instead, evidence is presented here that A. fulgidus utilizes an unusual pathway of starch degradation involving cyclodextrins as intermediates. The pathway comprises the combined action of an extracellular cyclodextrin glucanotransferase (CGTase) converting starch to cyclodextrins and the intracellular conversion of cyclodextrins to glucose 6-phosphate via cyclodextrinase (CDase), maltodextrin phosphorylase (Mal-P), and phosphoglucomutase (PGM). These enzymes, which are all induced after growth on starch, were characterized. CGTase catalyzed the conversion of starch to mainly beta-cyclodextrin. The gene encoding CGTase was cloned and sequenced and showed highest similarity to a glucanotransferase from Thermococcus litoralis. After transport of the cyclodextrins into the cell by a transport system to be defined, these molecules are linearized via a CDase, catalyzing exclusively the ring opening of the cyclodextrins to the respective maltooligodextrins. These are degraded by a Mal-P to glucose 1-phosphate. Finally, PGM catalyzes the conversion of glucose 1-phosphate to glucose 6-phosphate, which is further degraded to pyruvate via the modified Embden-Meyerhof pathway.


Determination of time course of tablet disintegration I: numerical method.
A method is described for determining the time course of tabled disintegration. It involves a numerical analysis of the experimental dissolution profile of a tablet and the dissolution characteristics of the primary drug particles in the tablet. The disintegration profile is determined for an acetaminophen tablet to demonstrate the application of the method. Tablet dissolution is simulated with the disintegration-dissolution model, and the interrelationship between the two fundamental processes is studied theoretically by varying the parameters describing the two processes.


Causes of sudden death related to sexual activity: results of a medicolegal postmortem study from 2001 to 2005.
Sexual activity (SA), combined with organic heart disease, may cause sudden death (SD). However, the causes of SD related to SA are not known well. The aim of this study was to assess the causes of SD related to SA. From August 2001 to November 2005, all autopsies (n=1,379) performed at Kyungpook National University were prospectively searched for SD cases related to SA. Fourteen cases (46+/-11 yr old, 9 males) of SD related to SA were found. All were heterosexual. The toxicologic study was negative in all. Ten cases were witnessed; during SA in 4 cases, just after SA in another 4 cases, 2 and 5 hr after in 1 each case. In 4 unwitnessed cases the victims were found dead less than 12 hr from the end of their SA. The partners were steady extramarital partners (n=8), prostitutes (n=2), marital partner (n=1) and unknown (n=3). The causes of the SD were as follows; coronary artery disease in 6, subarachnoid hemorrhage with ruptured berry aneurysm in 4, fibromuscular dysplasia of the atrioventricular nodal artery in 2, and unknown in 2. Coronary artery disease and subarachnoid hemorrhage with ruptured berry aneurysm were important as causes of SD related to SA.


Berberine Protects Human Umbilical Vein Endothelial Cells against LPS-Induced Apoptosis by Blocking JNK-Mediated Signaling.
Endothelial dysfunction is a critical factor during the initiation of atherosclerosis. Berberine has a beneficial effect on endothelial function; however, the underlying mechanisms remain unclear. In this study, we investigated the effects of berberine on lipopolysaccharide- (LPS-) induced apoptosis in human umbilical vein endothelial cells (HUVECs) and the molecular mechanisms mediating the effect. The effects of berberine on LPS-induced cell apoptosis and viability were measured with 5-ethynyl-2'-deoxyuridine staining, flow cytometry, and Cell Counting Kit-8 assays. The expression and/or activation of proapoptotic and antiapoptotic proteins or signaling pathways, including caspase-3, poly(ADP-ribose) polymerase, myeloid cell leukemia-1 (MCL-1), p38 mitogen-activated protein kinase, C-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase, were determined with western blotting. The malondialdehyde levels, superoxide dismutase (SOD) activity, and production of proinflammatory cytokines were measured with enzyme-linked immunosorbent assays. The results demonstrated that berberine pretreatment protected HUVECs from LPS-induced apoptosis, attenuated LPS-induced injury, inhibited LPS-induced JNK phosphorylation, increased MCL-1 expression and SOD activity, and decreased proinflammatory cytokine production. The effects of berberine on LPS-treated HUVECs were prevented by SP600125, a JNK-specific inhibitor. Thus, berberine might be a potential candidate in the treatment of endothelial cell injury-related vascular diseases.


Cathodic electrodeposition of ceramic and organoceramic materials. Fundamental aspects.
Electrodeposition of ceramic materials can be performed by electrophoretic (EPD) or electrolytic (ELD) deposition. Electrophoretic deposition is achieved via motion of charged particles towards an electrode under an applied electric field. Electrolytic deposition produces colloidal particles in cathodic reactions for subsequent deposition. Various electrochemical strategies and deposition mechanisms have been developed for electrodeposition of ceramic and organoceramic films, and are discussed in the present article. Electrode-position of ceramic and organoceramic materials includes mass transport, accumulation of particles near the electrode and their coagulation to form a cathodic deposit. Various types of interparticle forces that govern colloidal stability in the absence and presence of processing additives are discussed. Novel theoretical contributions towards an interpretation of particle coagulation near the electrode surface are reviewed. Background information is given on the methods of particle charging, stabilization of colloids in aqueous and non-aqueous media, electrophoretic mobility of ceramic particles and polyelectrolytes, and electrode reactions. This review also covers recent developments in the electrodeposition of ceramic and organoceramic materials.


Health Care Costs attributable to Hospital-diagnosed Back Pain: A Longitudinal Register-based Study of the Danish Population.
Background: Back pain is one of most frequent musculoskeletal conditions with enormous impact to health care systems and society. Analytical studies that guide the management of this disease are strongly needed, but there is a lack of cost estimates for the attributable cost of severe or chronic back pain in particular. Objective: The objective of this study was to estimate the health care costs attributable to hospitaldiagnosed back pain across strata of age-, gender- and diagnostic entity. Methods: All adult Danes (N=4.3 million) were included in this longitudinal, controlled register-based study. One-year prevalence was defined according to a previously published and validated algorithm, which was applied to the Danish national patient registry. Data from other relevant health service use registries was appended along with data from the national cause of death registry in order to calculate cost rates per life year (2011 price year). The attributable health care cost was defined as the absolute difference in cost rates between individuals with versus individuals without hospital-diagnosed back pain, whereas the ratio between the two groups was used for the reporting of reference values. Results: The health care costs attributable to hospital-diagnosed back pain were estimated at Danish Crowns (DKK) 22,700 per year for the youngest age strata (16-24 years) and increased up to DKK 72,700 per year for the oldest age strata of males (>85 years). Hospital admissions and outpatient visits accounted for the majority of these costs. The ratio of health care costs for individuals with versus individuals without the condition ranged from less than 1 to almost 6, depending on the type of service use, age and gender. Conclusion: At the disease stage where back pain leads to contact with specialised health care, diseased individuals appear to use on average three times more health care than non-diseased individuals. This study provides detailed reference values, which can be used to inform health economic models.


Writing the prescription and informing the patient.
Having decided on the generic drug to prescribe the prescription needs to be written and the patient informed regarding the treatment. This article discusses some regulatory requirements for writing a legal prescription, but predominantly discusses important aspects of informing patients regarding drug therapy. The actual writing of a prescription is a small part of the prescribing process and needs to comply with local regulations. Including patients in the decision to embark on a treatment and informing them of drug treatment is a very important part of the prescribing process. There is no simple formula, but patients need to be informed on what they want to know, when they want to know it, and in the way that is most acceptable to them. It is important to use both verbal and written forms of communication and to allow patients to reflect over the information, ask questions, and be further informed over subsequent consultations. Consumer medicine information leaflets can be a useful aid, but require that the clinician understand and be prepared to answer questions raised by them.


Intravitreal Injection of a Rho-Kinase Inhibitor (Fasudil) for Recent-Onset Nonarteritic Anterior Ischemic Optic Neuropathy.
This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes received a 0.025 mg/0.05 mL IVF. Functional and structural outcomes were assessed 1 and 3 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measured, with mean deviation (MD) index of the VF test and peripapillary retinal nerve fiber layer thickness as secondary measures. There was a statistically significant improvement in the patients' BCVA 1 and 3 months following IVF; BCVA improved from 1.69 ± 0.55 logMAR at baseline to 0.98 ± 0.47 and 0.93 ± 0.51 logMAR at 1 and 3 months, respectively (P = .004). The change in BCVA was not significant between month 1 and month 3 (P = .22). Peripapillary retinal nerve fiber layer thickness decreased from 173.5 ± 29.28 µm in the baseline evaluation to 85.8 ± 8.8 µm at 1 month, and 62.9 ± 5.97 µm at 3 months (P = .003). MD values changed from 24.60 ± 3.80 to 21.0 ± 6.10 and 20.5 ± 6.50 at 1 and 3 months, respectively (P = .007 and .005, respectively). This pilot study suggests that IVF may be an effective treatment for patients with recent-onset NAION. Larger studies are required to establish the therapeutic role of fasudil for NAION.


Histamine and prostanoid receptors on glial cells.
Glial cells in vitro express at least two types (H1 and H2) of histamine receptors and three types (EP, FP, and TP) of prostanoid receptors. The receptors expressed by glial cells differ according to the cell type and source in the brain. Furthermore primary astrocytes of same type derived from the same brain region are composed of heterogeneous subpopulations expressing different subsets of receptors. Fura-2 based Ca2+ microscopy revealed that astrocyte processes are important sites for histamine-induced Ca2+ signalling. Histamine and prostanoid receptors on glial cells may play important roles in the actions of histamine and prostanoids in the central nervous system.


Nonlinear thermo-optical properties of two-layered spherical system of gold nanoparticle core and water vapor shell during initial stage of shell expansion.
Nonlinear thermo-optical properties of two-layered spherical system of gold nanoparticle core and water vapor shell, created under laser heating of nanoparticle in water, were theoretically investigated. Vapor shell expansion leads to decreasing up to one to two orders of magnitude in comparison with initial values of scattering and extinction of the radiation with wavelengths 532 and 633 nm by system while shell radius is increased up to value of about two radii of nanoparticle. Subsequent increasing of shell radius more than two radii of nanoparticle leads to rise of scattering and extinction properties of system over initial values. The significant decrease of radiation scattering and extinction by system of nanoparticle-vapor shell can be used for experimental detection of the energy threshold of vapor shell formation and investigation of the first stages of its expansion.PACS: 42.62.BE. 78.67. BF.


Effects of moderate variations in the macronutrient content of the diet on cardiovascular disease risk factors in obese patients with the metabolic syndrome.
The metabolic syndrome is a cluster of abnormalities that is accompanied by a 2-fold increase in the risk of cardiovascular disease. Even if there is full agreement that lifestyle changes to induce weight loss are the first-line approach, the ideal diet for the treatment of the metabolic syndrome remains uncertain. The objective was to compare the effects of 2 diets on cardiovascular disease risk factors in obese patients with the metabolic syndrome. The study was carried out in 100 patients randomly assigned to either a diet relatively rich in carbohydrate [65% of energy as carbohydrate, 13% as protein, and 22% as fat (17% as unsaturated fat)] or a diet that was low in carbohydrate and high in protein and in monounsaturated fat [48% of energy as carbohydrate, 19% as protein, and 33% as fat (24% as unsaturated fat)]. All 100 patients completed the 5-mo study. At the end of the study, all the components of the metabolic syndrome (except HDL, which did not change) decreased significantly in both groups. With the high-carbohydrate diet, a significant decrease in LDL-cholesterol concentrations was also observed. Although the extent of the resolution of the metabolic syndrome was not different between groups, the low-carbohydrate diet was associated with a greater decrease in the prevalence of hypertension (P < 0.05) and of hypertriacylglycerolemia (P < 0.001). Tailoring diet interventions to the specific presentation of the metabolic syndrome may be the best way of reducing the risk factors for cardiovascular disease.


Fatty acid binding proteins in bovine intestinal mucosa.
Cytosol obtained from bovine intestinal mucosa, contains two protein fractions that bind sulfobromophthalein and are able to remove [1-14C] palmitic acid from microsomal membranes. The high molecular weight protein fraction (F1) increases the binding of sulfobromophthalein 2 and 8 times respectively after heating at 60 degrees C during 5 min or delipidation. These changes do not correlate with the rate of palmitic acid removal from microsomes. F1 native or delipidated is more efficient than the low molecular weight protein (F2) on the removal of [1-14C]palmitic acid from microsomes. Two protein fractions DE-I and DE-II obtained from F1 by DEAE-cellulose chromatography have palmitic acid- and sulfobromophthalein-binding capacities respectively.


Effect of Ramadan on peptic ulcer complications.
Fasting during the month of Ramadan provides researchers with a good opportunity to study experimental hunger. The case histories of patients brought to Ankara Numune Hospital and hospitalized there because of peptic ulcer complaints during the period 1987-92 were retrospectively studied. The ratio of peptic ulcer complications was in all the years of the study higher during Ramadan than during the periods before Ramadan (0.05 > p > 0.01) and after Ramadan (0.1 > p > 0.05). Female patients tended to develop more haemorrhage and perforations during Ramadan. In the peptic ulcer perforation group the average age of women was significantly higher during Ramadan, whereas it was significantly lower in men. A type of partial hunger during Ramadan increased peptic ulcer complications.


Three-dimensional conformal radiation therapy and periodic irradiation with the deep insipration breath-hold technique for hepatocellular carcinoma.
Nine cases of primary hepatocellular carcinoma were treated with 3D-conformal radiation therapy using computerized planning system. This technique permits the precise delivery of a high dose of radiation to the target while sparing most of the normal liver tissue. In order to decrease the effect of organ movement related to respiration, periodical irradiation was combined with the deep inspiration breath-hold technique. The radiation dose was equivalent to conventional radiation with a total dose of 50-70 Gy with 2 Gy, 5 times a week. Irradiation was given in 1-10 fractions which encompassed the target with 90 per cent isodose line. The patients tolerated the treatment procedure well without any complications inherent to the technique. The tumors were decreased in size, the pain symptom and abdominal discomfort were relieved for 3-20 months. This technique is an effective and safe treatment for palliation in hepatocellular carcinoma especially in locally advanced stages with large or multiple lesions. However, long term follow-up should be done to evaluate the late radiation effect and clinical outcome.


Virtual screening of natural compounds as inhibitors of EGFR 696-1022 T790M associated with non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is the most dominating and lethal type of lung cancer triggering more than 1.3 million deaths per year. The most effective line of treatment against NSCLC is to target epidermal growth factor receptor (EGFR) activating mutation. The present study aims to identify the novel anti-lung cancer compounds form nature against EGFR 696-1022 T790M by using in silico approaches. A library of 419 compounds from several natural resources was subjected to pre-screen through machine learning model using Random Forest classifier resulting 63 screened molecules with active potential. These molecules were further screened by molecular docking against the active site of EGFR 696-1022 T790M protein using AutoDock Vina followed by rescoring using X-Score. As a result 4 compounds were finally screened namely Granulatimide, Danorubicin, Penicinoline and Austocystin D with lowest binding energy which were -6.5 kcal/mol, -6.1 kcal/mol, -6.3 kcal/mol and -7.1 kcal/mol respectively. The drug likeness of the screened compounds was evaluated using FaF-Drug3 server. Finally toxicity of the hit compounds was predicted in cell line using the CLC-Pred server where their cytotoxic ability against various lung cancer cell lines was confirmed. We have shown 4 potential compounds, which could be further exploited as efficient drug candidates against lung cancer.


Alterations in subcellular localization of p38 MAPK potentiates endothelin-stimulated COX-2 expression in glomerular mesangial cells.
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide with mitogenic actions linked to activation of tyrosine kinase signaling pathways. ET-1 induces cyclooxygenase-2 (COX-2), an enzyme that converts arachidonic acid to pro-inflammatory eicosanoids. Activation of each of the three major mitogen-activated protein kinase (MAPK) pathways, ERK1/2, JNK/SAPK, and p38 MAPK (p38), have been shown to enhance the expression of COX-2. Negative regulation of MAPK may occur via a family of dual specificity phosphatases referred to as mitogen-activated protein kinase phosphatases (MKP). The goal of this work was to test the hypothesis that wild type MKP-1 regulates the expression of ET-1-induced COX-2 expression by inhibiting the activation of p38 in cultured glomerular mesangial cells (GMC). An adenovirus expressing both wild type and a catalytically inactive mutant of MKP-1 (MKP-1/CS) were constructed to study ET-1-regulated MAPK signaling and COX-2 expression in cultured GMC. ET-1 stimulated the phosphorylation of ERK and p38 alpha MAPK and induced the expression of COX-2. Expression of COX-2 was partially blocked by U0126, a MEK inhibitor, and SB 203580, a p38 MAPK inhibitor. Adenoviral expression of MKP-1/CS augmented basal and ET-1-induced phosphorylation of p38 alpha MAPK with less pronounced effects on ERK1/2 phosphorylation. Ectopic expression of wild type MKP-1 blocked the phosphorylation of p38 alpha MAPK by ET-1 but increased the phosphorylation of p38 gamma MAPK. Co-precipitation studies demonstrated association of MKP-1 with p38 alpha MAPK and ERK1/2. Immunofluorescent image analysis demonstrated trapping of phospho-p38 MAPK in the cytoplasm by MKP-1/CS/green fluorescent protein. ET-1-stimulated expression of COX-2 was increased in MKP-1/CS versus LacZ or green fluorescent protein-infected control cells. These results indicate that MKP-1 demonstrates a relative selectivity for p38 alpha MAPK versus p38 gamma MAPK in GMC and is likely to indirectly regulate the expression of COX-2.


Engineering of a miniaturized, robotic clinical laboratory.
The ability to perform laboratory testing near the patient and with smaller blood volumes would benefit patients and physicians alike. We describe our design of a miniaturized clinical laboratory system with three components: a hardware platform (ie, the miniLab) that performs preanalytical and analytical processing steps using miniaturized sample manipulation and detection modules, an assay-configurable cartridge that provides consumable materials and assay reagents, and a server that communicates bidirectionally with the miniLab to manage assay-specific protocols and analyze, store, and report results (i.e., the virtual analyzer). The miniLab can detect analytes in blood using multiple methods, including molecular diagnostics, immunoassays, clinical chemistry, and hematology. Analytical performance results show that our qualitative Zika virus assay has a limit of detection of 55 genomic copies/ml. For our anti-herpes simplex virus type 2 immunoglobulin G, lipid panel, and lymphocyte subset panel assays, the miniLab has low imprecision, and method comparison results agree well with those from the United States Food and Drug Administration-cleared devices. With its small footprint and versatility, the miniLab has the potential to provide testing of a range of analytes in decentralized locations.


[Febrile state, bloody diarrhea and megacolon].
We report about a forty year old female patient with severe bloody diarrhoea and fever over a period of 14 days due to an infection with Salmonella enteritidis. X-ray of the abdomen showed a toxic megacolon. With the diagnosis of an infectious colitis we started therapy with ciprofloxacin i/v. The toxic megacolon progressed despite intensive care and parenteral nutrition. Additionally the patient received metronidazole i/v and in combination with a roll technique in bed in the knee-elbow-position the leucocytosis and the megacolon decreased. A toxic megacolon is in about 3% associated with an infection with Salmonella enteritidis. It is essentially diagnosed by X-ray. Patients should receive intensive care, and because of the high mortality rate an interdisciplinary management is required. The article discusses the major differential diagnosis of the toxic megacolon, as well as the pathogenesis and therapy of Salmonella ent, infection. In case of an infection with Salmonella ent. physicians should acknowledge the possibility of development of a toxic megacolon.


Causes of Death in Military Working Dogs During Operation Iraqi Freedom and Operation Enduring Freedom, 2001-2013.
Military working dogs (MWDs) are a major asset in the theater of operations. Their unique abilities make them ideal for tasks such as tracking, patrol, and scent detection. MWDs deployed to a war zone are exposed to harsh environments and battlefield dangers that increase their risk of disease, injuries, and death. Although canines have been used extensively in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF), no published studies have reported detailed causes of death among MWDs deployed to these conflicts. Potential cases were defined as U.S. military-owned MWDs that died while deployed in Iraq (OIF) or Afghanistan (OEF) from January 1, 2001 through December 31, 2013 and identified from both official sources and unofficial sources, that is, online searches. Cases included in this study were limited to MWDs with data on cause of death obtained by abstraction from official veterinary treatment records (VTRs) from the Department of Defense Military Working Dog Veterinary Service, Joint Base San Antonio-Lackland Air Force Base, San Antonio, Texas, and Special Operations Forces units. We identified 92 MWDs that died while deployed to OEF/OIF from 2001 through 2013 and had cause of death information from official VTRs. For both OEF and OIF, the most common training program was Multi-Purpose Canine (36.5% and 51.7%, respectively), followed by Improvised Explosive Detector Dog for OEF (34.9%) and Patrol Explosive Detector Dog for OIF (34.5%). Injuries were the primary cause of death for 77.2% of the MWDs for which we had cause of death data. The most frequent external injuries were gunshot wounds (GSW) (31.5%), explosion or blast (26.1%), and heat stress (9.8%). The proportion of deaths due to GSW was similar for OEF and OIF (30.2% vs. and 34.5%, respectively). However, a greater proportion of MWDs died from explosions during OEF than during OIF (30.2% vs. 17.2%, respectively). Diseases were the cause of death in 23.0% of the MWDs. The most common diseases were gastric dilation and volvulus (GDV, n = 3), pleuritis (n = 2), and sepsis (n = 3). Two deaths were associated with anesthesia-related medical procedures. A total of 8.7% of cases were missing cause of death, 8.7% were missing age, 32.6% of cases were missing data on necropsy, and 14.1% were missing data on final disposition of the body. Other variables of interest including number of deployments and duration of training had a very high proportion of missing values and thus could not be analyzed. Our study is the most comprehensive to date that reports causes of death of MWDs deployed to OIF and OEF. However, limitations in the available data lessen the potential of our results to inform improvements in training and point of injury medical care. Better documentation in VTRs and systematic data collection into an official MWD trauma registry could lead to improved training and facilitate further development and evaluation of guidelines to improve care of wounded MWDs in future conflicts.


Muscular activity and acceleration of box vibration in manual holding tasks: effects of load and height of the load's center of gravity.
This study recruited 14 participants to examine the effects of load and height of the load's center of gravity (COG) on muscular activities of the brachioradialis, biceps brachii and erector spinae, and on box vibration acceleration (g) in manual holding tasks. Each participant was asked to hold a box in 12 conditions (4 loads × 3 heights of the load's COG). The results showed that muscular activities of the brachioradialis, biceps brachii and erector spinae significantly increased with load; however, they were not affected by the height of the load's COG. In addition, box vibration acceleration increased with load, and decreased with the height of the load's COG. The interaction effect of load and height of the load's COG on box vibration acceleration was also significant. This study recommends that the load magnitude should be decreased for the holding task that requires low vibration.


Minimally Invasive Colorectal Cancer Surgery in Europe: Implementation and Outcomes.
Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse.In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared on the utilization of MIS versus open surgery. Cox regression models were applied to study associations between surgery type and survival of patients from the population-based registries. The study considered adjustment for potential confounders.The percentage of CRC patients undergoing MIS differed substantially between centers and generally increased over time. MIS was significantly less often used in stage II to IV colon cancer compared with stage I in most centers. MIS tended to be less often used in older (70+) than in younger colon cancer patients. MIS tended to be more often used in women than in men with rectal cancer. MIS was associated with significantly reduced mortality among colon cancer patients in the Netherlands (hazard ratio [HR] 0.66, 95% confidence interval [CI] (0.63-0.69), Sweden (HR 0.68, 95% CI 0.60-0.76), and Norway (HR 0.73, 95% CI 0.67-0.79). Likewise, MIS was associated with reduced mortality of rectal cancer patients in the Netherlands (HR 0.74, 95% CI 0.68-0.80) and Sweden (HR 0.77, 95% CI 0.66-0.90).Utilization of MIS in CRC resection is increasing, but large variation between European countries and clinical centers prevails. Our results support association of MIS with substantially enhanced survival among colon cancer patients. Further studies controlling for selection bias and residual confounding are needed to establish role of MIS in survival of patients.


Changes in intraocular pressure after exercise test.
The decrease in intraocular pressure (IOP) within exercise has been recently suggested; however, this change remained ambiguous following exercise test. The present study aimed to assess changes in IOP induced by exercise test in patients who suspected to coronary artery disease (CAD) and indicated for exercise test evaluation. In a cross-sectional study at the cardiovascular research center of Amin Heart Hospital in Isfahan, 101 eyes from 51 consecutive patients suspected to CAD aged 30-70 years referred for exercise testing were evaluated. IOP was measured at the three time points of before exercise test as well as 5 and 20 min after completing exercise test using Schiotz tonometer. All exercise tests were programmed by the treadmill. The mean IOP in all assessed eyes was 16.12 ± 2.61 mmHg initially that was gradually decreased to 13.79 ± 2.40 mmHg 5 min after the exercise test, but elevated to 15.67 ± 2.26 mmHg 20 min after the test. Assessing IOP following exercise testing showed a significant decrease in IOP in 75 eyes (74.3%), remained unchanged in 19.8% of eyes, and even elevated in 5.9% of eyes. There was a significant direct association between patients' age and IOP changes assessed by the Pearson's correlation test (r = 0.350,P = 0.009). No significant difference was revealed in the trend of the changes in IOP after exercise test between men and women, between left-sided and right-sided eyes as well as between different body mass index subgroups. IOP temporarily reduced after exercise test, but return to baseline value shortly after test. This lowering is more evident in advanced aging.


Ultrastructural localization of lectin receptors on the surface of the rat retinal pigment epithelium. Decreased sensitivity of the avidin-biotin method due to cell surface charge.
Monosaccharides on the apical processes of the retinal pigment epithelium were examined using lectin-affinity cytochemical methods. Lectin receptor sugars were localized with lectin-horseradish peroxidase (HRP) and lectin-ferritin conjugates as well as with biotinylated lectins, avidin, and biotinylated HRP. In contrast, only wheat germ agglutinin (WGA) receptors were identified with biotinylated WGA followed by avidin-ferritin or free avidin and biotinylated ferritin. Labeling with avidin-ferritin subsequent to biotinylated lectin treatment was dependent upon the source and lot of the reagent. These findings are similar to those reported for the endothelium of bone marrow sinusoids (Pino RM: Am J Anat, 169:259, 1984). Since both the retinal pigment epithelial and bone marrow sinusoidal surfaces are highly anionic (negative), we investigated the possibility that the charge of the lectin reagents and cell surfaces might affect the localization of monosaccharides on cell surfaces. Analytical isoelectric focusing revealed that biotinylated ferritin and some avidin-ferritins are highly anionic, while the other lectin reagents have more cationic (positive) components. Based on this information, a less charged biotinylated ferritin marker was made that made it possible to localize biotinylated lectins bound to the cell surface.


Persistent diarrhoea: socio-demographic and clinical profile of 264 children seen at a referral hospital in Addis Ababa.
Acute diarrhoea is a major public health problem in Ethiopian children under five years of age. Reports for other developing countries indicate that persistent diarrhoea is emerging as an important cause of mortality and morbidity in this age group. Little is, however, known about the extent of the condition in our setting. The socio-demographic and clinical characteristics of children with persistent diarrhoea seen at a teaching hospital in Addis Ababa over an 18-month period is presented. Of 5,762 children with all forms of diarrhoea seen during the study period 264 (5%) had persistent diarrhoea. Most of the children (83%) were below 18 months of age and the peak occurrence was between the ages of seven and 12 months. The majority (86%) of the patients had associated malnutrition and 83% of the infants under four months of age were either fully or partially weaned. Watery diarrhoea with no dehydration was the main clinical feature. Nearly 7% of the patients had dysentery. Average family income was low and parental literacy level seem to have had no effect. It is suggested that breastfeeding and appropriate weaning practices be strongly promoted. Further work is proposed in order to determine the magnitude of the problem and identify the risk factors associated with the disease, including the unfavourable child and family unit characteristics and care seeking behaviours.


Enzyme kinetic and spectroscopic studies of inhibitor and effector interactions with indoleamine 2,3-dioxygenase. 1. Norharman and 4-phenylimidazole binding to the enzyme as inhibitors and heme ligands.
The effects of norharman, one of the few known inhibitors of the heme protein indoleamine 2,3-dioxygenase, and of 4-phenylimidazole (4-PheImid), a heme ligand, on the catalytic (Vmax, Km) and spectroscopic properties (optical absorption, CD, and magnetic CD) of the rabbit small intestinal dioxygenase were investigated. Assays were performed with the substrate L- or D-tryptophan (Trp) and an ascorbic acid-methylene blue cofactor system at 25 degrees C. This study has revealed that both norharman and 4-PheImid exhibit noncompetitive inhibition with respect to L-Trp and D-Trp. The binding of norharman to the enzyme results in the formation of a low-spin complex in both the ferric and ferrous enzyme with comparable dissociation constants (Kd = approximately 10 microM at pH 7.0) that are about 10 times smaller than the observed Ki value. L-Trp exerts no effect for the ferric enzyme and slight negative cooperative effects for the ferrous enzyme on norharman binding. Close spectral similarities are observed between the adducts of the enzyme with norharman and 4-PheImid in the respective oxidation states. This, together with competition experiments using cyanide, demonstrates that norharman binds directly to the heme iron of the enzyme as a nitrogen donor ligand. Thus, norharman competes with O2 for the heme iron of the ferrous (active) enzyme, resulting in the observed inhibition. L-Trp and 4-PheImid appear to compete for the heme binding site in the ferric enzyme and display slight negative cooperativity on binding to the ferrous enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)


Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of Cytochrome c and Cardiolipin.
Cardiolipin oxidation and degradation by different factors under severe cell stress serve as a trigger for genetically encoded cell death programs. In this context, the interplay between cardiolipin and another mitochondrial factor-cytochrome c-is a key process in the early stages of apoptosis, and it is a matter of intense research. Cytochrome c interacts with lipid membranes by electrostatic interactions, hydrogen bonds, and hydrophobic effects. Experimental conditions (including pH, lipid composition, and post-translational modifications) determine which specific amino acid residues are involved in the interaction and influence the heme iron coordination state. In fact, up to four binding sites (A, C, N, and L), driven by different interactions, have been reported. Nevertheless, key aspects of the mechanism for cardiolipin oxidation by the hemeprotein are well established. First, cytochrome c acts as a pseudoperoxidase, a process orchestrated by tyrosine residues which are crucial for peroxygenase activity and sensitivity towards oxidation caused by protein self-degradation. Second, flexibility of two weakest folding units of the hemeprotein correlates with its peroxidase activity and the stability of the iron coordination sphere. Third, the diversity of the mode of interaction parallels a broad diversity in the specific reaction pathway. Thus, current knowledge has already enabled the design of novel drugs designed to successfully inhibit cardiolipin oxidation.


Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis.
Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.


[Construction of PTTGas antisense expression vector and its inhibitory effects on human ovarian carcinoma cell line SK-OV-3].
Pituitary tumor transforming gene (PTTG) is a new proto-oncogene and shows multiple actions of promoting tumorigenesis and metastasis. Most researches mainly focus on the problems of PTTG expression in different tumor tissues and its relative regulatory mechanisms, but no research of exploring the possibility of antisense blocking of PTTG gene has been reported by now. In present study, the authors constructed eukaryotic expression vector expressing full-length anti-sense PTTG mRNA and observed its blocking effect on the potential invasion of human ovarian carcinoma cell line SK-OV-3. PCR primers containing designed enzyme cut sites were used for cloning full-length PTTG gene fragment, and the resulting PCR product was inserted into the eukaryotic vector pcDNA3.1 in the antisense direction. The recombinant vector was then transfected into SK-OV-3 by lipofectamine. The positive cell clone was screened by G418,PTTG,and bFGF at protein level expression were detected by Western blot analysis. The changes of cell proliferation were analyzed by MTT method. The biological behavior change of transfection positive cells was observed by colony formation in soft agar assay. SK-OV-3 clones stably expressing full-length recombinant pcDNA3.1- PTTGas were obtained.The expression of PTTG and bFGF proteins in transfected cells were decreased by 61.5% and 52.3% respectively as compared with non-transfected ones. The cell proliferation was accelerated in transfected cells. The number of colony formation is reduced significantly in transfected cells (2.4+/-0.8) as compared with non-transfected and empty vector transfected cells (23.3+/-5.7 and 21.5+/-7.9, respectively, P< 0.01). The recombinant vector pcDNA3.1-PTTGas is a novel tool and brings us a new possibility of anti-sense gene therapy targeted at PTTG in human carcinoma.


In vitro antimalarial activity and cytotoxicity of some selected cuban medicinal plants.
Terrestrial plants have been demonstrated to be sources of antimalarial compounds. In Cuba, little is known about antimalarial potentials of plant species used as medicinals. For that reason, we evaluated the antimalarial activity of 14 plant species used in Cuba as antimalarial, antipyretic and/or antiparasitic. Hydroalcoholic extracts were prepared and tested in vitro for the antimalarial activity against Plasmodium falciparum Ghana strain and over human cell line MRC-5 to determine cytotoxicity. Parasite multiplication was determined microscopically by the direct count of Giemsa stained parasites. A colorimetric assay was used to quantify cytotoxicity. Nine extracts showed IC50 values lower than 100 µg/mL against P. falciparum, four extracts were classified as marginally active (SI < 4), one as partially active (Parthenium hysterophorus) exhibiting SI equal to 6.2 and two extracts as active (Bambusa vulgaris and Punica granatum), showing SI > 10. B. vulgaris showed the most potent and specific antiplasmodial action (IC50 = 4.7 µg/mL, SI = 28.9). Phytochemical characterization of active extracts confirmed the presence of triterpenoids in B. vulgaris and polar compounds with phenol free groups and fluorescent metabolites in both extracts as major phytocompounds, by thin layer chromatography. In conclusion, antimalarial use of B. vulgaris and P. hysterophorus was validated. B. vulgaris and P. granatum extracts were selected for follow-up because of their strong antimalarial activity.


Chemical peels: an overview.
Chemical peel treatments cause the regeneration of new cells to occur at a faster rate than they would do naturally. In this article, the author discusses the history of chemical peels, what the treatment entails for phenol peels, TCA peels and AHA peels. The patient history of skin pretreatment is important as it guides the probable depth achieved with the peel solution.


A new mouse tumor model system (RIF-1) for comparison of end-point studies.
A new tumor model system (RIF-1) was developed that is very suitable for studies in which clonogenic survival is compared with growth delay and control probability following various forms of treatment. The tumor was a radiation-induced sarcoma in the inbred female C3H/Km mouse. It had a low median tumor dose, had a satisfactory plating efficiency direct from in vivo to in vitro, was nonimmunogenic or minimally immunogenic, and metastasized only at a relatively advanced stage of growth. The cell line grew either as a monolayer on plastic dishes, as tumor spheroids in spinner culture, as lung nodules following injection of a single-cell suspension into the tail veins of syngeneic mice, or as a solid tumor. Both diploid and tetraploid clonogenic cells were found in monolayer cultures of the RIF-1 line.


Network analysis of wildlife translocations in New Zealand.
To identify network measures with relevance to disease spread in a network of movements derived from the Department of Conservation (DOC) translocation records from 1970 to mid-2014, and to identify conservation sites that should be prioritised for surveillance activities and improvements to data collection to make the best use of network analysis techniques in the future. Data included the source and destination of translocated specimens, the species and the dates the translocations were expected to occur. The data were used to construct a directed, non-weighted network in which a translocation event represented a tie in the network. Network density, in-degree (movements entering a node of interest) and out-degree (movements leaving a node of interest) and reciprocity were calculated. The data analysed consisted of 692 unique translocations between 307 sites, with the majority (518; 73%) being for birds. The constructed network for bird, reptile and frog translocations comprised 260 nodes, with 34/260 (13%) having two-way movements and 47/260 (18%) non-reciprocal movements. The median degree score (sum of in- and out-degree) was two (min 0, max 36) with a mean of 3.5 in a right skewed distribution. Most sites acted as receivers or senders of consignments with only a few having both high in- and high out-degree, and thus had characteristics that made them sites of interest for surveillance activities. These included the National Wildlife Centre at Mount Bruce, Tiritiri Matangi Island and Te Kakahu (Chalky Island). The presence of linking sites that join larger clusters within the network creates the potential for rapid disease spread if a pathogen were to be introduced. The important sites that supply or receive specimens for translocations are already well recognised by those performing translocations in New Zealand, and this paper provides further information by quantifying their role within the network.


Patterns of Drug-Resistant Bacteria in a General Hospital, China, 2011-2016.
Drug-resistant bacteria has been a threat to public life and property. We described the trends and changes in antibiotic resistance of important pathogens in a general hospital in Zhengzhou, China from 2011 to 2016, to control antimicrobial-resistant bacteria in hospital and provide support to clinicians and decision-making departments. Five dominant bacteria were enrolled based on the data from the general hospital during 6 years. The results of antimicrobial susceptibility testing were interpreted according to Clinical and Laboratory Standards Institute (CLSI). From 2011 to 2016, a total of 19,260 strains of bacteria were isolated, of which Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii accounted for 51.98%. The resistance rate of K. pneumoniae and E. coli to carbapenem was less than 15%, but resistance of K. pneumoniae to carbapenems increased with time and resistance of E. coli to meropenem increased. The rate of extended-spectrum beta-lactamase (ESBL) production among K. pneumoniae and E. coli was decreasing. For most antibiotics, the resistance rate of ESBL-positive isolates was higher than that of ESBL-negative isolates, excluding carbapenems and cefoxitin. For S. aureus, the rate of methicillin-resistant S. aureus (MRSA) was stable. Resistance of S. aureus to mostly antibiotics decreased with time. Besides polymyxin B, P. aeruginosa and A. baumannii showed high resistance to other antibiotics. For A. baumannii, the resistance rate to mostly antibiotics was increasing. The bacteria showed high levels of resistance and multiple drug resistance. Continuous surveillance and optimizing the use of antibiotics are essential. Drug-resistant bacteria has been a threat to public life and property. We described the trends and changes in antibiotic resistance of important pathogens in a general hospital in Zhengzhou, China from 2011 to 2016, to control antimicrobial-resistant bacteria in hospital and provide support to clinicians and decision-making departments. Five dominant bacteria were enrolled based on the data from the general hospital during 6 years. The results of antimicrobial susceptibility testing were interpreted according to Clinical and Laboratory Standards Institute (CLSI). From 2011 to 2016, a total of 19,260 strains of bacteria were isolated, of which Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii accounted for 51.98%. The resistance rate of K. pneumoniae and E. coli to carbapenem was less than 15%, but resistance of K. pneumoniae to carbapenems increased with time and resistance of E. coli to meropenem increased. The rate of extended-spectrum beta-lactamase (ESBL) production among K. pneumoniae and E. coli was decreasing. For most antibiotics, the resistance rate of ESBL-positive isolates was higher than that of ESBL-negative isolates, excluding carbapenems and cefoxitin. For S. aureus, the rate of methicillin-resistant S. aureus (MRSA) was stable. Resistance of S. aureus to mostly antibiotics decreased with time. Besides polymyxin B, P. aeruginosa and A. baumannii showed high resistance to other antibiotics. For A. baumannii, the resistance rate to mostly antibiotics was increasing. The bacteria showed high levels of resistance and multiple drug resistance. Continuous surveillance and optimizing the use of antibiotics are essential.


Enhancement of heterotransplanted human tumor graft survival in nude mice treated with antilymphocyte serum and in congenitally athymic-asplenic (Lasat) mice.
The latency period, success rate, and minimal cell inoculum size required for transplantation of continuously passaged human tumor lines into congenitally athymic (nude) mice, antilymphocyte serum (ALS)-treated congenitally athymic (nude) mice, and congenitally athymic-asplenic (lasat) mice were compared. The 11 tumor lines studied included examples of breast adenocarcinoma, transitional cell carcinoma, osteosarcoma, fibrosarcoma, Hodgkin's disease, malignant melanoma, and rhabdomyosarcoma. Of these 11 tumor lines, 3 were successfully transplanted into nude mice, compared to 5 of 10 tumor lines in ALS-treated nude mice and 9 of 11 lines in lasat mice. Moreover, the latency period was shorter and the minimal cell inoculum size was lower for lasat mice than for either nude or ALS-treated nude mice. Despite this enhancement of heterotransplantation into lasat mice and despite the growth of large local masses, no evidence of distant metastases was found.