Immunogenic and protective efficacy of recombinant protein GtxA-N against Gallibacterium anatis challenge in chickens.
Gallibacterium anatis is a major cause of reproductive tract infections in chickens. Here, we aimed to evaluate the efficacy of the recombinant protein GtxA-N at protecting hens, by addressing three objectives; (i) evaluating the antibody response following immunization (ii) scoring and comparing lesions, following challenge with G. anatis, in immunized and non-immunized hens and (iii) investigating if the anti-GtxA-N antibody titre in individual hens correlated with the observed lesions. Two consecutive experiments were performed in hens. In the first experiment hens were immunized with GtxA-N on day 0 and day 14, infected with G. anatis on day 28 and euthanized on day 56. The GtxA-N antibody response was assessed in pooled serum samples throughout the experiment, using an indirect enzyme-linked immunosorbent assay (ELISA). In the second experiment the GtxA-N antibody titres were assessed in individual hens before and after immunization. Subsequently, the hens were inoculated with G. anatis and finally all hens where euthanized and submitted for post mortem examination 48 h after inoculation. Immunization elicited strong antibody responses that lasted at least 8 weeks (P < .0001). The individual antibody titres observed in response to immunization varied considerably among hens (range: 174,100-281,500). Lesion scores following G. anatis infection were significantly lower in immunized hens compared to non-immunized hens (P = .004). Within the immunized group, no correlation was found between the individual antibody titres and the lesion scores. This study clearly demonstrated GtxA-N as a vaccine antigen able of inducing protective immunity against G. anatis.


AC conductivity of selectively located carbon nanotubes in poly(epsilon-caprolactone)/polylactide blend nanocomposites.
DC and AC electrical conductivity of bionanocomposites based on the immiscible polymer blend poly(epsilon-caprolactone)/polylactide (PCL/PLA, w/w 70/30), loaded with multiwall carbon nanotubes (CNT), were studied in a wide frequency range, 10(-3) < or = f < or = 10(7) Hz from 143 to 313 K. The nanofiller concentration ranged from 0 to 4 wt % and it was shown to be selectively located in the PCL phase. The PCL crystallinity degree was not affected by the presence of CNT. The variation of the DC conductivity allowed the determination of the percolation threshold, p(c) = 0.98 wt %, and the critical exponent t = 2.2 of the scaling law. The linear dependence of log (sigma(DC)) versus p(-1/3) showed the existence of tunneling conduction among CNT not yet in physical contact. The temperature independent results indicated a conventional tunnel effect. The AC conductivity of the nanocomposites followed the predictions of the universal dynamic response and the s exponents were determined at low concentrations. Master curves are presented showing the length and temperature-time superpositions.


[The pharmacokinetics of azlocillin after single and multiple intravenous injections during the third trimester].
Examining serum level values and urinary concentrations taken from non-pregnant control persons and pregnant women suffering from urinary tract infections (UTI) during the III. trimenon, the pharmacokinetic dates after single and repeated applications of 4 g azlocillin have been evaluated. We used a computer program based on the two-compartment model. It is shown that during pregnancy complicated by UTI the elimination half-life time will be prolonged and returns after therapy nearly to normal values. The results, discussed with the dates given by literature, allow us to state that it is not necessary to change dosage and application interval of azlocillin during pregnancy.


A hierarchic metric approach for integration of green issues in manufacturing: a paper recycling application.
This paper presents a hierarchic framework for environmentally conscious design. The framework integrates both product designers and stakeholders to evaluate not only the product features but also its environmental burden. In evaluating the product's burden, a life cycle assessment of the product is conducted through input-output analysis so that a comprehensive inventory of the product's actions and reactions to the environment could be documented. The analytic hierarchy procedure (AHP) is used to develop priority indices for customer requirements to highlight key features that must be present in the product. Subsequently, the quality function deployment is used to match design requirements to customer requirements. A cost-effective design plan is then finally developed. This framework adopts a systemic approach and ensures that environmentally conscious products are designed and manufactured.


Integrating palliative care information and hospice referral in medicaid primary care.
Hospice and palliative care (PC) remain underutilized by Medicaid patients. Our aim was to evaluate an intervention to improve communication about advance care planning (ACP) and symptom distress, and to facilitate referral to PC and hospice. We conducted a study in a statewide Medicaid primary care network with 510 Medicaid care managers (CMs). PC experts collaborated with leaders in the statewide primary care network on a quality improvement intervention. Training components included education and engagement with local hospice and PC providers. Quality improvement components included feedback of quality measures and a practice toolkit. Evaluation used participant surveys and tracking of key quality measures: 1) percent of at-risk subset of aged, blind, and disabled (ABD) Medicaid patients asked about ACP or symptom distress; 2) cumulative number of ABD Medicaid PC or hospice referrals; and 3) the percent of all nondual ABD Medicaid decedents enrolled in hospice. After training, CMs identified the following areas for expected practice change: ACP (29%), identifying/referring patients for hospice or PC (25%), supporting patients and families (21%), toolkit utilization (10%), and engaging medical providers (10%). Over one-year follow-up the percent of moderate and high-risk ABD Medicaid patients asked about ACP or symptoms increased from 7% to 31% and 8% to 41%, respectively (p<0.001). The cumulative number of PC or hospice referrals increased from 8 to 155. Hospice enrollment at death was unchanged (29% to 30%, p=NS [nonsignificant]). A statewide intervention targeting CMs in a Medicaid primary care practice network is effective to increase communication and hospice and PC referrals; longer follow-up may be required to determine effect on hospice use.


Src modulates serotonin-induced calcium signaling by regulating phosphatidylinositol 4,5-bisphosphate.
We tested the hypothesis that, in airway smooth muscle cells, stimulation of G-protein-coupled receptors by contractile agonists activates Src kinase and that this kinase modulates cell contractility and Ca(2+) signaling by affecting the levels of the phospholipase C substrate phosphatidylinositol 4,5-bisphosphate (PIP(2)). Stimulation of cultured rat tracheal smooth muscle cells with serotonin (5-HT) induced an increase in Src activity, Ca(2+) mobilization, and contraction (decrease in cell area). 5-HT-evoked cell contraction was reduced by a specific inhibitor of Src family kinases, 4-amino-5(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1). Peak Ca(2+) responses to 5-HT were attenuated by PP1 and an anti-Src-blocking antibody and augmented by expression of constitutively activated Y529F Src. Sustained phases of Ca(2+) responses to 5-HT and Ca(2+) influx resulting from emptying of Ca(2+) stores in the endoplasmic reticulum by thapsigargin were also decreased after PP1 treatment. PP1 significantly reduced the turnover of inositol phosphates produced on 5-HT stimulation and the amount of PIP(2) in the Triton X-100-insoluble lipid fraction. Overall, these data demonstrate that, in rat tracheal smooth muscle cells, Src kinase modulates 5-HT-evoked cell contractility and Ca(2+) signaling by regulating PIP(2) levels and Ca(2+) influx.


A case of chronic pancreatitis with pseudocysts complicated by infection and obstructive jaundice.
We report a case of chronic pancreatitis with pseudocysts complicated by infection and obstructive jaundice. A 49-yr-old male was admitted with the complaints of fever and jaundice. Laboratory findings included high biliary tract enzyme values and normal serum amylase value. Ultrasonography and computed tomographic scan demonstrated a cyst, 4 cm in diameter, in the pancreas head. Cholangiography revealed a long, tapered obstruction of the common bile duct which was apparently compressed by the cyst. Although the jaundice improved after percutaneous transhepatic biliary drainage, fever continued, and the cyst was aspirated. Bacteriological examination of the contents revealed infection. The symptoms disappeared rapidly and the cyst decreased in size soon after aspiration. The stenosis of the common bile duct showed improvement for several weeks but then regressed. In a patient with secondary pancreatic infection or obstructive jaundice following pancreatic disease, distinguishing the condition is an important aspect of accurate diagnosis and therapy.


Alcohol and violence in 2017 National Football League Super Bowl commercials.
Background: The National Football League (NFL) Super Bowl is a widely-viewed sports event and the commercials are especially popular among viewers. Previous research has demonstrated risky health behaviors in advertisements aired during sporting events. The purpose of this study was to analyze the content of the advertisements aired during the 2017 NFL Super Bowl. Methods: This cross-sectional study involved examining the content of all commercials, with an emphasis on health-compromising behaviors. The themes and highlights of the advertisements were analyzed based on whether there was a reference to alcohol or violence. Results: A total of 103 unique commercials were analyzed. The most common themes were humor (n=43), happiness (n=25), innovation (n=25), and enjoyment or relaxation (n=25).Alcohol was referenced in 13 (12.6%, 95% CI 7.5%, 20.4%) of the commercials. Advertisements with alcohol references were more likely to contain the themes of partying (odds ratio [OR]:16.2, 95% CI 1.4-193.4, P=0.041) and enjoyment or relaxation (OR: 4.7, 95% CI 1.4-15.6,P=0.014). There were 24 commercials with references to violence and these were more likely tobe promoting a movie (OR: 5.4, 95% CI 3.5-8.2, P<0.001) or television program (OR: 8.9,95% CI 2.6-30.26, P<0.001). Conclusion: Parents should consider whether it is appropriate for their children to watch a concentrated number of intense images containing references to alcohol and violence during this popular sporting event.


Hot-Injection Synthesis of Cu-Doped Cu₂ZnSnSe₄ Nanocrystals to Reach Thermoelectric zT of 0.70 at 450°C.
As a new class of potential midrange temperature thermoelectric materials, quaternary chalcogenides like Cu2ZnSnS4 (CZTS) and Cu2ZnSnSe4 (CZTSe) suffer from low electrical conductivity due to insufficient doping. In this work, Cu-doped CZTSe nanocrystals consisting of polygon-like nanoparticles are synthesized with sufficient Cu doping contents. The hot-injection synthetic method, rather than the traditional one-pot method, in combination with the hot-pressing method is employed to produce the CZTSe nanocrystals. In Cu-doped CZTSe nanocrystals, the electrical conductivity is enhanced by substitution of Zn(2+) with Cu(+), which introduces additional holes as charge carriers. Meanwhile, the existence of boundaries between nanoparticles in as-synthesized CZTSe nanocrystals collectively results in intensive phonon-boundary scatterings, which remarkably reduce the lattice thermal conductivity. As a result, an average thermoelectric figure of merit of 0.70 is obtained at 450 °C, which is significantly larger than that of the state-of-the-art quaternary chalcogenides thermoelectric materials. The theoretical calculations from the Boltzmann transport equations and the modified effective medium approximation are in good agreement with the experimental data.


Non-specific immunostaining by a rabbit antibody against gustducin α subunit in mouse brain.
Gustducin is a guanosine nucleotide-binding protein functionally coupled with taste receptors and thus originally identified in taste cells of the tongue. Recently, bitter taste receptors and gustducin have been detected in the airways, digestive tracts and brain. The existing studies showing taste receptors and gustducin in the brain were carried out exclusively on frozen sections. In order to avoid the technical shortcomings associated with frozen sectioning, we performed immunofluorescence staining using vibratome-cut sections from mouse brains. Using a rabbit gustducin antibody, we could not detect neurons or astrocytes as reported previously. Rather, we found dense fibers in the nucleus accumbens and periventricular areas. We assumed these staining patterns to be specific after confirmation with conventional negative control staining. For the verification of this finding, we stained gustducin knockout mouse brain and tongue sections with the same rabbit gustducin antibody. Whereas negative staining was confirmed in the tongue, intensive fibers were constantly stained in the brain. Moreover, immunostaining with a goat gustducin antibody could not demonstrate the fibers in the brain tissue. The present study implies a cross immunoreaction that occurs with the rabbit gustducin antibody in mouse brain samples, suggesting that the conventional negative controls may not be sufficient when an immunostaining pattern is to be verified.


SP174, NRAS Q61R Mutant-Specific Antibody, Cross-Reacts With KRAS Q61R Mutant Protein in Colorectal Carcinoma.
- NRAS is a member of the RAS family oncoproteins implicated in cancer. Gain-of-function NRAS mutations were reported in a subset of colorectal cancers. These mutations occur at codons 12, 13, and 61 and are detected by molecular genetic testing. Recently, an antibody (clone SP174) became available to immunohistochemically pinpoint NRAS Q61R mutant protein. In malignant melanoma, NRAS Q61R mutant-specific immunohistochemistry was shown to be a valuable supplement to traditional genetic testing. - To evaluate the significance of NRAS Q61R mutant-specific immunohistochemistry in a cohort of colorectal carcinomas. - A total of 1185 colorectal carcinomas were immunohistochemically evaluated with SP174 antibody. NRAS Q61R mutant-specific immunohistochemistry was validated by molecular genetic testing including Sanger sequencing, quantitative polymerase chain reaction (qPCR), and next-generation sequencing. - Twelve tumors showed strong SP174 immunoreactivity. Sanger sequencing detected an identical c.182A>G substitution, causing NRAS Q61R mutation at the protein level, only in 8 SP174-positive cases. These results were confirmed by qPCR study. Subsequently, NRAS wild-type tumors with strong SP174 staining were evaluated by next-generation sequencing and revealed KRAS c.182A>G substitutions predicted to cause KRAS Q61R mutation. Review of colorectal carcinomas with known KRAS and NRAS genotype revealed that none of 62 wild-type tumors or 47 mutants other than Q61R were SP174 positive. - SP174 immunohistochemistry allows sensitive detection of NRAS and KRAS Q61R mutants. However, molecular genetic testing is necessary to determine specifically which RAS gene is mutated.


Self similarity of liquid droplet coalescence in a quasi-2D free-standing liquid-crystal film.
Coalescence of droplets is an ubiquitous phenomenon in chemical, physical and biological systems. The process of merging of liquid objects has been studied during the past years experimentally and theoretically in different geometries. We introduce a unique system that allows a quasi two-dimensional description of the coalescence process: Micrometer-sized flat droplets in freely suspended smectic liquid-crystal films. We find that the bridge connecting the droplets grows linearly in time during the initial stage of coalescence, both with respect to its height and lateral width. We also verify self-similar dynamics of the bridge during the first stage of coalescence. We compare our results with a model based on the thin sheet equations. Our experiments confirm that the most important geometrical parameter influencing the coalescence rate is the contact angle of the droplets.


Installation of new damped cavities at the Photon Factory storage ring.
New damped cavities have been installed in the Photon Factory (PF) storage ring and successfully operated in the last scheduled user run of 1996. The new damped cavity is a simple single-cell cavity with somewhat large beam-duct holes. The part of the beam duct that is attached to the cavity is made of SiC, which works as a microwave absorber and damps the higher-order modes excited in the cavity. Because of its simple structure, the operation of the cavity is very stable and also a high power input of more than 150 kW is possible. No coupled-bunch instabilities due to the new cavity were observed during operation.


Evolutional aspects of Alzheimer's disease pathogenesis.
Tau lesions (pretangles, neuropil threads, neurofibrillary tangles) that develop in a few types of nerve cells in the brain are essential to the pathogenesis of Alzheimer's disease (AD). The formation of non-argyrophilic pretangles marks the beginning of the pathological process and is of increasing interest because it is temporally closer to the prevailing conditions that induce the pathological process underlying AD in contrast to late-stage disease. Not all of the pretangle material, however, converts into argyrophilic neurofibrillary lesions. The propensity to develop tau lesions may be related to the exceptionally protracted myelination of late developing portions in the human brain.


Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence.
An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications.


Improving coronary artery bypass grafting readmission outcomes from 2000 to 2012 in the Medicare population.
The study objective was to examine trends in 30-day readmission after coronary artery bypass grafting in the Medicare population over 13 years. The study included isolated coronary artery bypass grafting procedures in the Medicare population from January 2000 to November 2012. Comorbidities and causes of readmission were determined using Internal Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes. The cohort included 1,116,991 patients. Readmission rates decreased from 19.5% in 2000 to 16.6% in 2012 (P = .0001). There was significant improvement across all categories of admission status, age, race, gender, and hospital annual coronary artery bypass grafting volume that were analyzed. Adjusted odds of readmission in 2000 compared with 2012 was 1.28 (95% confidence interval, 1.24-1.32). Median length of stay for the readmission episode was 5 days, which improved to 4 days by 2012. Hospital mortality during the readmission episode was 2.8% overall and declined to 2.4% in 2012 (P = .0001). The most common primary readmission diagnoses were heart failure (12.6%), postoperative wound infection/nonhealing wound (8.9%), arrhythmias (6.4%), and pleural effusions (3.7%). Readmission for wound infections/nonhealing wounds decreased significantly over time, from 9.8% to 6.5% (P = .0001). In a large cohort of Medicare patients undergoing coronary artery bypass grafting over 13 years, there was a significant decrease in 30-day readmission rates, a reduction in readmission for wound infections, and reduced mortality during the readmission episode, despite an increase in patient comorbidities. The improvement in readmission rates was seen regardless of patient variables examined.


A morphologic analysis of the cells of ductal carcinoma of the breast and of adenocarcinoma of the ovary in pleural and abdominal effusions.
The cells in serous effusions from 14 cases of histologically proven ductal adenocarcinoma of the breast and from an equal number of proven adenocarcinomas of the ovary were morphologically analyzed, with quantitative values assigned to various cell parameters. The resulting data were then subjected to stepwise discriminant analysis. The presence of coarse chromatin proved to be the most significant discriminating factor, resulting in a correct classification of 100% of the mammary carcinomas (14 of 14) and 71.4% (10 of 14) of the ovarian carcinomas, for an overall rate of 85.7% correct classifications. When combined with other cell parameters, such as the presence of polygonal cells, multiple nucleoli and an isolated cell arrangement, the accuracy rate increased to 92.9% correct classifications. Ovarian carcinoma was more likely to have coarse chromatin and to occur in three-dimensional cell groups, in contrast to mammary carcinoma, which tended to have fine chromatin and more polygonal cell shapes and to occur more commonly in syncytial cell groups and as isolated cells.


[Serum anti-Müllerian hormone to predict ovarian response in assisted reproduction cycles].
To compare serum anti-Mullerian hormone (AMH) levels on the seventh day of ovarian stimulation between normal and poor responders. Nineteen women aged ≥35, presenting with regular menses, submitted to ovarian stimulation for assisted reproduction were included. Women with endometriosis, polycystic ovarian syndrome or those who were previously submitted to ovarian surgery were excluded. On the basal and seventh day of ovarian stimulation, a peripheral blood sample was drawn for the determination of AMH, FSH and estradiol levels. AMH levels were assessed by ELISA and FSH, and estradiol by immunochemiluminescence. At the end of the stimulation cycle patients were classified as normal responders (if four or more oocytes were obtained during oocyte retrieval) or poor responders (if less than four oocytes were obtained during oocyte retrieval or if the cycle was cancelled due to failure of ovulation induction) and comparatively analyzed by the t-test for hormonal levels, length of ovarian stimulation, number of follicles retrieved, and number of produced and transferred embryos. The association between AMH and these parameters was also analyzed by the Spearman correlation test. There was no significant difference between groups for basal or the seventh day as to AMH, FSH and estradiol levels. There was a significant correlation between seventh day AMH levels and the total amount of exogenous FSH used (p=0.02). AMH levels on the seventh day of the ovarian stimulation cycle do not seem to predict the pattern of ovarian response and their determination is not recommended for this purpose.


Rapid and efficient protocol for DNA extraction and molecular identification of the basidiomycete Crinipellis perniciosa.
DNA isolation from some fungal organisms is difficult because they have cell walls or capsules that are relatively unsusceptible to lysis. Beginning with a yeast Saccharomyces cerevisiae genomic DNA isolation method, we developed a 30-min DNA isolation protocol for filamentous fungi by combining cell wall digestion with cell disruption by glass beads. High-quality DNA was isolated with good yield from the hyphae of Crinipellis perniciosa, which causes witches' broom disease in cacao, from three other filamentous fungi, Lentinus edodes, Agaricus blazei, Trichoderma stromaticum, and from the yeast S. cerevisiae. Genomic DNA was suitable for PCR of specific actin primers of C. perniciosa, allowing it to be differentiated from fungal contaminants, including its natural competitor, T. stromaticum.


Chlamydia trachomatis induces an upregulation of molecular biomarkers podoplanin, Wilms' tumour gene 1, osteopontin and inflammatory cytokines in human mesothelial cells.
Chlamydia trachomatis is the most prevalent infection of the genital tract in women worldwide. C. trachomatis has a tendency to cause persistent infection and induce a state of chronic inflammation, which has been reported to play a role in carcinogenesis. We report that persistent C. trachomatis infection increases the expression of inflammatory tumour cytokines and upregulates molecular biomarkers such as podoplanin, Wilms' tumour gene 1 and osteopontin in primary cultures of mesothelial cells (Mes1) and human mesothelioma cells (NCI). Infection experiments showed that Mes1 and NCI supported the growth of C. trachomatisin vitro, and at an m.o.i. of 4, the inclusion-forming units/cell showed many intracellular inclusion bodies after 3 days of infection. However, after 7 days of incubation, increased proliferative and invasive activity was also observed in Mes1 cells, which was more evident after 14 days of incubation. ELISA analysis revealed an increase in vascular endothelial growth factor, IL-6, IL-8, and TNF-α release in Mes1 cells infected for a longer period (14 days). Finally, real-time PCR analysis revealed a strong induction of podoplanin, Wilms' tumour gene 1 and osteopontin gene expression in infected Mes1 cells. The aim of the present study was to investigate the inflammatory response elicited by C. trachomatis persistent infection and the role played by inflammation in cell proliferation, secretion of proinflammatory cytokines and molecular biomarkers of cancer. The results of this study suggest that increased molecular biomarkers of cancer by persistent inflammation from C. trachomatis infection might support cellular transformation, thus increasing the risk of cancer.


Pushing out the limits of electrical stimulation. A case study in the aggressive use of an alternative to voluntary exercise.
Recent advances in neuromuscular electrical stimulation (NMES) suggest that sophisticated techniques can exercise and train people aerobically. However, the limits of this exercise modality would be of interest to sportspeople, trainers and rehabilitation experts. Additionally, there are physical and other barriers which prevent many from undertaking aggressive voluntary exercise. Maximum voluntary and peak NMES efforts were assessed for 1) maximal heart rate and oxygen consumption, 2) excess postexercise oxygen consumption (EPOC), 3) lactate and 4) time-to-fatigue while exercising at 65% of predicted maximal heart rate (maximum voluntary versus peak NMES efforts). Heart rates: 195 bpm and 194 bpm; Oxygen consumption: 52 ml/kg/min and 39 ml/kg/min. EPOC: 110.5 kcal and 96.5 kcal; Lactate: 15.0 mmol/l and 15.3 mmol/l; Time-to-fatigue: 4 h and over 6 h. Sophisticated NMES compares well to voluntary exercise with potential applications for sportspeople and some who cannot exercise due to disease or injury.


Typhoid fever in San Antonio, Texas: an outbreak traced to a continuing source.
Eighty cases of typhoid fever occurred in San Antonio, Texas, with dates of onset from August 18, 1981, to October 26, 1981. Preliminary epidemiological investigations of the first 24 cases suggested a Mexican food takeout restaurant as the common source. A case-control study confirmed this association (P less than or equal to .001). Barbacoa , a mixture of muscle, lips, ears, tongue, and eyes from steamed bovine heads, was identified as the source of Salmonella typhi (P = .03). S typhi was cultured from the stool of one of 31 restaurant employees. Closure of the restaurant resulted in termination of the outbreak within a single incubation period. The restaurant was allowed to reopen after the remaining employees had demonstrated lack of excretion of S typhi in stools. This outbreak represents the largest restaurant-associated typhoid fever outbreak reported in the United States in greater than 50 years.


Small fibre neuropathies.
To summarize the recent advances in aetiology, diagnostic assessment, and treatment of small fibre neuropathies. New causes of small fibre neuropathy have been recognized and advances in neurophysiologic and neuropathologic techniques for investigating small fibres have been made, increasing the interest in this field. In particular, skin biopsy proved to be a sensitive method to diagnose small fibre neuropathy. It allows the detection of subclinical abnormalities of peripheral nerve function in patients with diabetes and tongue denervation in patients with burning mouth syndrome. This technique has also been used to demonstrate the neuroprotective effect of erythropoietin in experimental models of neuropathy. Among nonconventional neurophysiologic techniques for investigating small fibres, laser-evoked potential and contact heat-evoked potential stimulators have been developed and deserve particular interest. Several trials on neuropathic pain that is a typical feature of small fibre neuropathies have been performed and guidelines have recently been published. Detection of small fibre impairment allows earlier diagnosis of neuropathy and could be used as an outcome measure in future regenerative neuropathy trials. Standardization of skin biopsy can have an important impact on clinical practice and research. Further studies are needed to assess the reliability of current neurophysiologic techniques for testing small fibre function in peripheral neuropathies and the correlation with well established neuropathologic examination.


"Always on parade": Pregnancy experience of active-duty air force members.
Findings are reported from a qualitative study that sought to understand the maternity experience of active-duty women in the context of improved and expanded pregnancy accommodations. Semistructured interviews were conducted with 30 active-duty women serving in the United States Air Force (15 enlisted and 15 commissioned members). Women described experiencing negative pregnancy-related stereotypes and stigma in the workplace. Connotations unique to military culture were unavoidable changes to uniform and physical body shape, cultural expectations of fitness, and uniformity of dress/appearance. Use of necessary pregnancy accommodations led to increased exposure to stereotypes and stigma, such as being perceived as less disciplined, lazy, weak, or receiving unfair advantages/fewer duties at work. Women relied on "covering behaviors" to separate themselves from negative stereotypes. Extreme covering behaviors put pregnant women's health and well-being at risk. Finally, women navigated a shift in priorities from an indoctrinated "service before self" perspective to a prioritization of personal health and well-being during pregnancy. Leadership skills were strengthened through this change in perspective, which were perceived as positively influencing unit morale, cohesion, productivity, and retention. Study findings suggest the military will experience limited success in fully integrating and retaining active-duty women due to an organizational climate that lags behind the recent, progressive improvements in pregnancy policies and accommodations. Organizational culture related to pregnancy within the military must be targeted for change to reduce negative stigma and pregnancy-related bias. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Transferrin, haptoglobin and group-specific component types in tribal populations of Andhra Pradesh.
Five tribal populations, Koya Dora, Raj Gond, Naikpod, Pardhan, and Lambadi from Andhra Pradesh were examined for Tf, Hp, Gc, ceruloplasmin and albumin types. Koya Doras were sampled at five localities to study intra-tribal variation. Tf DChi, a mongoloid genetic marker, was found in high frequencies among Koya Doras (0.029) and Naikpods (0.033) whereas if was absent among Pardhans and showed a very low frequency in Lambadis. A new slow transferrin allele, Tf DGond, is reported from Raj Gonds and is found in polymorphic frequency (0.01). The Hp1 gene frequency ranged from 0.056 to 0.159, and Gc2 ranged from 0.165 to 0.397. No variation was observed with respect to ceruloplasmin. One new albumin variant was found in a single individual of the Koya Dora tribe. The intra-tribal variation in gene frequencies among Koya Doras equalled that found between different tribal populations.


Developing and Evaluating an Online Post-Traumatic Growth Program for Firefighters.
We evaluated how an online post-traumatic growth program affected rumination, social support, and post-traumatic growth. We recruited 33 firefighters from two Korean provinces and employed a nonequivalent control group pretest-post-test design. We administered the pretest for the intervention group (n = 16), consisting of eight sessions with an online workbook and messenger group counseling. We conducted post-tests immediately after the program and 4 weeks later. Post-traumatic growth and social support increased significantly. There were no statistically significant differences for intrusive or deliberate rumination. Psychological support programs should be developed to reflect firefighters' work characteristics and needs, including programs designed to induce rumination.


[Primary non-Hodgkin lymphoma of the stomach. A review with special reference to the MALT concept].
Primary extranodal malignant lymphomas are most often localized in the stomach. In contrast to gastric carcinomas, primary gastric non-Hodgkin's lymphomas show an increasing incidence. According to their grade of malignancy they are divided into low-grade and high-grade non-Hodgkin's lymphomas and according to their immunophenotype into B-cell and T-cell non-Hodgkin's lymphomas. In most cases they show a B-cell phenotype while high-grade tumors are more frequent than those of low-grade malignancy. However, primary gastric Hodgkin's disease is still a rarity. A new entity, the so-called low-grade B-cell non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT) type, is characterized by a diffuse infiltrate of centrocyte-like cells intermingled with immunoblasts of the same clone, plasma cell differentiation of the tumor cells, lymphoepithelial lesions, and reactive intratumoral lymphoid follicles. It may secondarily transform into a high-grade B-cell lymphoma but remains limited to the stomach for a considerable period of time with a favourable prognosis. The most important prognostic factors of primary gastric lymphomas are stage at initial diagnosis, classification and grading according to the histopathological concept of the MALT, and depth of infiltration. Although a considerable number of early stage gastric lymphomas achieve complete remission after surgical therapy only, primary treatment of gastric lymphoma is still controverted, thus underlining the urgency of a multicenter prospective study. Chronic Helicobacter pylori infection may play a major role in the pathogenesis of low-grade B-cell lymphoma of MALT type. Complete remission of some cases of low-grade B-cell lymphoma of MALT type with concomitant Helicobacter pylori gastritis after Helicobacter pylori eradication may lead to a new pathogenetic, therapeutic, and prognostic concept.


[A special form of pancytopenia].
Primary hyperoxaluria is a rare disease whose incidence is estimated at less than 1 cases/million inhabitants/year. This is a congenital abnormality of hepatic metabolism leading to an endogenous overproduction of oxalate with excess urinary excretion. We report the case of a 43-year-old patient, was followed to end-stage renal disease hemodialysis, consulting for anemic syndrome with mucocutaneous pallor. Laboratory tests found pancytopenia with aplastic anemia. Bone marrow was difficult to achieve, bringing medullary blood hyperdilué and uninterpretable . Radiographs showed a homogeneous splenomegaly and small dedifferentiated a kidney marrow biopsy was performed. Histological examination revealed a myelofibrosis and birefringent crystals in polarized light, diagnosis retained: spinal oxalosis.


Outcomes of immature oocytes collected from ovarian tissue for cryopreservation in adult and prepubertal patients.
The efficiency of oocyte in-vitro maturation (IVM) and vitrification procedures after ex-vivo collection from ovarian tissue were assessed according to patient age, number of retrieved oocytes and tissue transport conditions. The combined procedure was performed in 136 patients: 130 adults (mean 27.6 ± 5.6 years) and six prepubertal girls (mean 8.7 ± 2.3 years). A higher mean number of oocytes were collected in girls compared with adults (11.5 ± 8.0 versus 3.8 ± 4.2, respectively, P < 0.001) but the percentage of degenerated oocytes was significantly higher in girls (35.5% versus 17.1%, respectively, P < 0.001). IVM rates were significantly lower in prepubertal than postpubertal population (10.3% versus 28.1%, P = 0.002). In adults, a negative correlation was observed between number of retrieved oocytes and age (P = 0.002; r = -0.271); the correlation was positive between anti-Müllerian hormone (AMH) and number of collected oocytes (P = 0.002; r = 0.264). IVM rates were not correlated with AMH levels (r = 0.06) or age (r = -0.033). At present, nine oocytes and one embryo have been warmed in four patients and one biochemical pregnancy obtained. This suggests the combined procedure could be an additional option for fertility preservation.


Distribution of sodium-potassium ATPase in the rat testis and epididymis.
Sodium-potassium ATPase (Na+K(+)-ATPase) is a ubiquitous plasma membrane enzyme which uses the hydrolysis of ATP to regulate cellular Na+ and K+ levels and fluid volume. This ion pumping action is also thought to be involved in fluid movement across certain epithelia. There are several different genes for this enzyme, some of which are tissue specific. Using an antibody specific for the catalytic subunit of canine kidney Na+K(+)-ATPase, we have localized immunoreactivity in the seminiferous and epididymal epithelium of rats of various ages. There was no specific staining of 10-day-old rat testis. Faint staining was detected at 13 days and appeared to be associated with the borders of Sertoli cells. At 16 days prominent apical and lateral staining but no basal staining of Sertoli cell membranes was observed. This type of distribution continued until spermatids were present in the epithelium. In the adult rat testis, specific staining was detected in Sertoli cell crypts associated with elongating spermatids, and on the apical and lateral Sertoli cell membrane. In some instances immunoreactivity was concentrated at presumed sites of junctional specializations. In the excurrent ducts of immature and mature rats, Na+K(+)-ATPase staining was heavy in the efferent ducts and somewhat lighter in the epididymis. In all regions, the staining was basolateral although there were variations in intensity among the different parts of the epididymis. These results show 1) that rat testis and epididymal Na+K(+)-ATPase share some immunological determinants with the canine enzyme; 2) that the epididymal enzyme is located in the conventional basolateral position; and 3) that the distribution of Sertoli cell Na+K(+)-ATPase is probably apical and lateral rather than basal.


West Nile virus activity--United States, June 30-July 6, 2004.
During June 30-July 6, a total of 21 human cases of West Nile virus (WNV) illness were reported from two states (Arizona and California). During 2004, eight states have reported a total of 78 human cases of WNV illness to CDC through ArboNET. Of these, 57 (73%) were reported from Arizona. Forty-seven (61%) of the 78 cases occurred in males; the median age of patients was 53 years (range: 1-84 years); the dates of illness onset ranged from April 23 to June 28; and one case was fatal.


Analytical Method To Detect and Quantify Avocatin B in Hass Avocado Seed and Pulp Matter.
Avocatin B, an avocado-derived compound mixture, was demonstrated recently to possess potent anticancer activity by selectively targeting and eliminating leukemia stem cells. Avocatin B is a mixture of avocadene and avocadyne, two 17-carbon polyhydroxylated fatty alcohols (PFAs), first discovered in avocado seeds; their quantities in avocado pulp are unknown. Analytical methods to detect avocado seed PFAs have utilized NMR spectroscopy and GC-MS; both of these lack quantitative capacity and accuracy. Herein, we report a sensitive LC-MS method for the quantitation of avocadene and avocadyne in avocado seed and pulp. The method has a reliable and linear response range of 0.1-50 μM (0.03-17.2 ng/μL) for both avocadene and avocadyne ( r2 > 0.990) with a lower limit of quantitation (LLOQ) of 0.1 μM. The intra- and interassay accuracy and precision of the quality control (QC) samples at LLOQ showed ≤18.2% percentage error and ≤14.4% coefficient of variation (CV). The intra- and interassay accuracy and precision for QC samples at low and high concentrations were well below 10% error and CV. This method was successfully applied to quantify avocadene and avocadyne in total lipid extracts of Hass avocado pulp and seed matter.


A comparison of pine and spruce in recovery from winter stress; changes in recovery kinetics, and the abundance and phosphorylation status of photosynthetic proteins during winter.
During winter evergreens maintain a sustained form of thermal energy dissipation that results in reduced photochemical efficiency measured using the chlorophyll fluorescence parameter Fv/Fm. Eastern white pine (Pinus strobus L.) and white spruce [Picea glauca (Moench) Voss] have been shown to differ in their rate of recovery of Fv/Fm from winter stress. The goal of this study was to monitor changes in photosynthetic protein abundance and phosphorylation status during winter recovery that accompany these functional changes. An additional goal was to determine whether light-dependent changes in light harvesting complex II (LHCII) phosphorylation occur during winter conditions. We used a combination of field measurements and recovery experiments to monitor chlorophyll fluorescence and photosynthetic protein content and phosphorylation status. We found that pine recovered three times more slowly than spruce, and that the kinetics of recovery in spruce included a rapid and slow component, while in pine there was only a rapid component to recovery. Both species retained relatively high amounts of the light harvesting protein Lhcb5 (CP26) and the PsbS protein during winter, suggesting a role for these proteins in sustained thermal dissipation. Both species maintained high phosphorylation of LHCII and the D1 protein in darkness during winter. Pine and spruce differed in the kinetics of the dephosphorylation of LHCII and D1 upon warming, suggesting the rate of dephosphorylation of LHCII and D1 may be important in the rapid component of recovery from winter stress. Finally, we demonstrated that light-dependent changes in LHII phosphorylation do not continue to occur on subzero winter days and that needles are maintained in a phosphorylation pattern consistent with the high light conditions to which those needles are exposed. Our results suggest a role for retained phosphorylation of both LHCII and D1 in maintenance of the photosynthetic machinery in a winter conformation that maximizes thermal energy dissipation.


The toad fly Lucilia bufonivora: its evolutionary status and molecular identification.
The blow fly genus Lucilia is composed largely of saprophages and facultative myasis agents, including the economically important species Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) and Lucilia sericata (Meigen). Only one species is generally recognized as an obligate agent of myiasis, Lucilia bufonivora Moniez, and this is an obligate parasite of toads. Lucilia silvarum (Meigen), a sister species, behaves mainly as a carrion breeder; however, it has also been reported as a facultative parasite of amphibians. Morphologically, these species are almost identical, and historically this has led to misidentification, taxonomic ambiguity and a paucity of studies of L. bufonivora. In this study, dipterous larvae were analysed from toad myiasis cases from the U.K., The Netherlands and Switzerland, together with adult specimens of fly species implicated in amphibian parasitism: L. bufonivora, L. silvarum and Lucilia elongata Shannon (from North America). Partial sequences of two genes, cox1 and ef1α, were amplified. Seven additional blow fly species were analysed as outgroups. Bayesian inference trees of cox1, ef1α and a combined-gene dataset were constructed. All larvae isolated from toads were identified as L. bufonivora and no specimens of L. silvarum were implicated in amphibian myiasis. This study confirms L. silvarum and L. bufonivora as distinct sister species and provides unambiguous molecular identification of L. bufonivora.


Respiration and ecological niche influence bacterial membrane lipid compositions.
Bacterial membrane compositions vary widely between phyla and within related species. The types of lipids within membranes are as diverse as the selective pressures that influence bacterial lifestyles such as their mode of respiration and habitat. This study has examined the extent that respiration and habitat affect bacterial fatty acid (FA) and polar lipid (PL) compositions. To accomplish this, over 300 FA and PL profiles from 380 previously characterized species were assembled and subjected to multivariate statistical analyses in order to determine lipid to habitat/respiration associations. It was revealed that PL profiles showed a slight advantage over FA profiles for discriminating taxonomic relationships between species. FA profiles showed greater correlation with respiration and habitat than PL. This study identified that respiration did not consistently favour uniform FA or PL changes when lipid profiles were compared between examined phyla. This suggests that although phyla may adopt similar respiration methods, it does not result in consistent lipid attributes within one respiration state. Examination of FA and PL compositions were useful to identify taxonomic relationships between related species and provides insight into lipid variations influenced by the niche of its host.


When and why people are comparatively optimistic about future health risks: The role of direct and indirect comparison measures.
The goal of the current research was to test whether direct versus indirect measures of comparative optimism yield different results as a function of health risk severity and prevalence. A random-digit sample of community residents (N = 259) responded to interview questions about perceived vulnerability using both direct (i.e. self-to-peer risk) and indirect comparison measures (i.e. separate questions about self and peer risk). Responses to direct comparison measures were more affected by prevalence, whereas indirect comparison measures were more affected by severity. These results may offer guidance to researchers and practitioners about when it may be more appropriate to use direct versus indirect measures of comparative health risk.


Ultrasound Triggered Tumor Metabolism Suppressor Induces Tumor Starvation for Enhanced Sonodynamic Immunotherapy of Breast Cancer.
Sonodynamic therapy (SDT) as an emerging tumor treatment gained wide attention. However, tumor vascular destruction and oxygen depletion in SDT process may lead to further hypoxia. This may lead to enhanced glycolysis, lactate accumulation, and immunosuppression. A glycolysis inhibitor (3PO) loaded and PEG modified black phosphorus nanosheets (BO) is constructed for potent starvation therapy and efficient immune activation. Under ultrasound irradiation, the BO can produce ROS to destroy tumors and tumor blood vessels and lead to further hypoxia and nutrients block. Then, the released 3PO inhibits tumor glycolysis and prevents the hypoxia-induced glycolysis and lactate accumulation. Both SDT and 3PO can cut off the source of lactic acid, as well as achieve antitumor starvation therapy through the blockade of the adenosine triphosphate (ATP) supply. In addition, the combination of starvation treatment and SDT further facilitates dendritic cells (DC) maturation, promotes antigen presentation by DCs, and eventually propagates the antitumor immunity and inhibition of abscopal tumor growth. This is the first time that combines SDT with inhibition of glycolysis, achieving admirable tumor treatment and decreasing adverse events caused by SDT process and that has caused good immune activation. Our system provides a new idea for the future design of anti-tumor nanomedicines.


Fabrication of high-capacity polyelectrolyte brush-grafted porous AAO-silica composite membrane via RAFT polymerization.
Surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization has been utilized to fabricate high-capacity strong anion-exchange (AEX) membrane for the separation of protein. By means of RAFT polymerization, quaternized poly(3-(methacrylamidomethyl)-pyridine) brushes formed 3-dimensional nanolayers on the surface of porous anodic aluminum oxide (AAO)-silica composite membrane. The surface properties of the membranes were analyzed by SEM, water contact angle, ATR-FTIR, XPS and TGA. To investigate the adsorption performance, the new AEX membranes were applied to recover a model protein, ovalbumin (OVA). High adsorption capacities of 95.8mg/g membranes (static) and 65.3mg/g membranes (dynamic) were obtained at ambient temperature. In the further studies, up to 90% of the adsorbed OVA was efficiently eluted by using phosphate buffer-1M NaCl as elution medium. The successful separation of OVA with high purity from a mixture protein solution was also achieved by using the AEX membranes. The present study demonstrated that under mild reaction condition, RAFT polymerization can be used to fabricate ion-exchange membrane which has many remarkable features, such as high capacity and selectivity, easy elution and so on.


Risks associated with herbal medicinal products.
Health risks associated with the use of herbal medicinal products (HMPs) are often an emotionally discussed issue. The topic is, however, important not least because of the present popularity of HMPs. This article aims to provide a factual overview of this complex subject. The evidence relating to the toxicity, interactions and quality of a number of HMPs is reviewed. Toxicity data indicate that some HMPs have the potential to cause serious adverse events and fatalities. HMPs affect pharmacokinetic and pharmacodynamic factors and thus cause herb-drug interactions. Reports of HMPs affected by contamination, adulteration or substitution of botanical material have repeatedly caused concern. Asian HMPs are most often implicated. It is concluded that HMPs are not free of risk. More research and more information are required in order to maximize consumers' safety.


Bayes Node Energy Polynomial Distribution to Improve Routing in Wireless Sensor Network.
Wireless Sensor Network monitor and control the physical world via large number of small, low-priced sensor nodes. Existing method on Wireless Sensor Network (WSN) presented sensed data communication through continuous data collection resulting in higher delay and energy consumption. To conquer the routing issue and reduce energy drain rate, Bayes Node Energy and Polynomial Distribution (BNEPD) technique is introduced with energy aware routing in the wireless sensor network. The Bayes Node Energy Distribution initially distributes the sensor nodes that detect an object of similar event (i.e., temperature, pressure, flow) into specific regions with the application of Bayes rule. The object detection of similar events is accomplished based on the bayes probabilities and is sent to the sink node resulting in minimizing the energy consumption. Next, the Polynomial Regression Function is applied to the target object of similar events considered for different sensors are combined. They are based on the minimum and maximum value of object events and are transferred to the sink node. Finally, the Poly Distribute algorithm effectively distributes the sensor nodes. The energy efficient routing path for each sensor nodes are created by data aggregation at the sink based on polynomial regression function which reduces the energy drain rate with minimum communication overhead. Experimental performance is evaluated using Dodgers Loop Sensor Data Set from UCI repository. Simulation results show that the proposed distribution algorithm significantly reduce the node energy drain rate and ensure fairness among different users reducing the communication overhead.


MC4R-dependent suppression of appetite by bone-derived lipocalin 2.
Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity. In addition, osteoblast-derived LCN2 inhibits food intake. LCN2 crosses the blood-brain barrier, binds to the melanocortin 4 receptor (MC4R) in the paraventricular and ventromedial neurons of the hypothalamus and activates an MC4R-dependent anorexigenic (appetite-suppressing) pathway. These results identify LCN2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone.


Retrotransposon Ty1 RNA contains a 5'-terminal long-range pseudoknot required for efficient reverse transcription.
Ty1 retrotransposon RNA has the potential to fold into a variety of distinct structures, mutation of which affects retrotransposition frequencies. We show here that one potential functional structure is located at the 5' end of the genome and can assume a pseudoknot conformation. Chemoenzymatic probing of wild-type and mutant mini-Ty1 RNAs supports the existence of such a structure, while molecular genetic analyses show that mutations disrupting pseudoknot formation interfere with retrotransposition, indicating that it provides a critical biological function. These defects are enhanced at higher temperatures. When these mutants are combined with compensatory changes, retrotransposition is restored, consistent with pseudoknot architecture. Analyses of mutants suggest a defect in Ty1 reverse transcription. Collectively, our data allow modeling of a three-dimensional structure for this novel critical cis-acting signal of the Ty1 genome.


Bioactive Co-Cr alloy for biomedical applications prepared by surface modification using self-assembled monolayers and poly-γ-glutamic acid.
Cobalt-chromium (Co-Cr) alloys are used in clinical practice for the hard tissue reconstruction because of their favorable biocompatibility and mechanical properties. However, their applications have been limited because of their poor bioactivity, making them poor at bone-bonding. In this study, the bioactivity of a Co-Cr alloy was evaluated following the immobilization of cross-linked poly-γ-glutamic acid (γ-PGA) onto its surface via the formation of 11-aminoundecylphosphonic acid self-assembled monolayers (SAMs). Results of X-ray photoelectron spectroscopy revealed the presence of a new P2p peak, which confirms SAMs formation. Furthermore, the surface became highly hydrophobic following the immobilization with γ-PGA. Subsequent treatment with CaCl2 at 0.5 M or more and soaking in a simulated body fluid led to the formation of a low crystalline apatite. The present results show that chemical modification can be used to induce the formation of an apatite layer on the surface of a Co-Cr alloy in simulated body fluid.


Plasmonic Ti3C2Tx MXene Enables Highly Efficient Photothermal Conversion for Healable and Transparent Wearable Device.
Skin-mountable and transparent devices are highly desired for next-generation electronic applications but are susceptible to unexpected ruptures or undesired scratches, which can drastically reduce the device lifetime. Developing wearable and transparent materials with healable function that can recover their original functionality after mechanical damage under mild and noninvasive repairing operation is thus imperative. Herein, we demonstrate that the incorporation of ultrasmall quantities of plasmonic silver nanoparticle (AgNP)@MXene nanosheet hybrids to serve as photothermal fillers in waterborne elastic polyurethane enables high transparency as well as effective light-triggered healing capabilities for wearable composite coatings. The AgNP@MXene hybrid functions as a highly effective photon captor, energy transformer, and molecular heater due to the amalgamation of (1) ultrahigh photothermal conversion efficiency, high thermal conductivity, and structural properties of MXene, (2) the outstanding plasmonic effect of AgNPs, and (3) the synergistic effects from their hybrids. The resulting wearable composite coating with ultralow loading of plasmonic AgNP@MXene hybrids (0.08 wt % or 0.024 vol %) can produce a significant temperature increase of ∼111 ± 2.6 °C after the application of 600 mW cm-2 light irradiation for 5 min, while maintaining a high optical transmittance of ∼83% at a thickness of ∼60 μm. This local temperature increase can rapidly heal the mechanical damage to the composite coating, with a healing efficiency above 97%.


Cationic and Neutral Cp*M(NO)(κ2-Ph2PCH2CH2PPh2) Complexes of Molybdenum and Tungsten: Lewis-Acid-Induced Intramolecular C-H Activation.
Treatment of CH2Cl2 solutions of Cp*M(NO)Cl2 (Cp* = η5-C5(CH3)5; M = Mo, W) first with 2 equiv of AgSbF6 in the presence of PhCN and then with 1 equiv of Ph2PCH2CH2PPh2 affords the yellow-orange salts [Cp*M(NO)(PhCN)(κ2-Ph2PCH2CH2PPh2)](SbF6)2 in good yields (M = Mo, W). Reduction of [Cp*M(NO)(PhCN)(κ2-Ph2PCH2CH2PPh2)](SbF6)2 with 2 equiv of Cp2Co in C6H6 at 80 °C produces the corresponding 18e neutral compounds, Cp*M(NO)(κ2-Ph2PCH2CH2PPh2) which have been isolated as analytically pure orange-red solids. The addition of 1 equiv of the Lewis acid, Sc(OTf)3, to solutions of Cp*M(NO)(κ2-Ph2PCH2CH2PPh2) at room temperature results in the immediate formation of thermally stable Cp*M(NO→Sc(OTf)3)(H)(κ3-(C6H4)PhPCH2CH2PPh2) complexes in which one of the phenyl substituents of the Ph2PCH2CH2PPh2 ligands has undergone intramolecular orthometalation. In a similar manner, addition of BF3 produces the analogous Cp*M(NO→BF3)(H)(κ3-(C6H4)PhPCH2CH2PPh2) complexes. In contrast, B(C6F5)3 forms the 1:1 Lewis acid-base adducts, Cp*M(NO→B(C6F5)3)(κ2-Ph2PCH2CH2PPh2) in CH2Cl2 at room temperature. Upon warming to 80 °C, Cp*Mo(NO→B(C6F5)3)(κ2-Ph2PCH2CH2PPh2) converts cleanly to the orthometalated product Cp*Mo(NO→B(C6F5)3)(H)(κ3-(C6H4)PhPCH2CH2PPh2), but Cp*W(NO→B(C6F5)3)(κ2-Ph2PCH2CH2PPh2) generates a mixture of products whose identities remain to be ascertained. Attempts to extend this chemistry to include related Ph2PCH2PPh2 compounds have had only limited success. All new complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of most of them have been established by single-crystal X-ray crystallographic analyses.


NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy.
Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer, functioning as a metastasis suppressor by regulating epithelial-mesenchymal transition. Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation-specific polymerase chain reaction analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. Our data demonstrated that patients with NKX6.1 methylation presented poorer 5-year overall survival (P = 0.0167) and disease-free survival (P = 0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, these data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival (P = 0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel prognostic biomarker in CRC and that it may be used as a predictor of the response to chemotherapy.


Setting performance goals in geriatric nursing.
Behavioural techniques are increasingly being applied in the geriatric field as part of a broader emphasis on psychological and social treatments in the care of the elderly. The nurse is in the best position to analyse a patient's performance and manage an intervention programme; however, some nurses have had little experience of autonomously diagnosing problems and setting performance goals. The authors argue that it is important to set such goals and give examples of how performance may be objectively specified, prerequisites made explicit, criteria for success defined and the consequences of goal attainment or non-attainment discussed with those most concerned. A complex situation drawn from the geriatric setting which was used as part of a teaching workshop to help nurses define suitable targets for intervention is described in the Appendix.


SIMUNEO: Control and Monitoring System for Lung Ultrasound Examination and Treatment of Neonatal Pneumothorax and Thoracic Effusion.
Training with real patients is a critical aspect of the learning and growth of doctors in training. However, this essential step in the educational process for clinicians can potentially compromise patient safety, as they may not be adequately prepared to handle real-life situations independently. Clinical simulators help to solve this problem by providing real-world scenarios in which the physicians can train and gain confidence by safely and repeatedly practicing different techniques. In addition, obtaining objective feedback allows subsequent debriefing by analysing the situation experienced and learning from other people's mistakes. This article presents SIMUNEO, a neonatal simulator in which professionals are able to learn by practicing the management of lung ultrasound and the resolution of pneumothorax and thoracic effusions. The article also discusses in detail the hardware and software, the main components that compose the system, and the communication and implementation of these. The system was validated through both usability questionnaires filled out by neonatology residents as well as through follow-up sessions, improvement, and control of the system with specialists of the department. Results suggest that the environment is easy to use and could be used in clinical practice to improve the learning and training of students as well as the safety of patients.


Optimal digestion theory does not predict the effect of pathogens on intestinal plasticity.
One prediction of optimal digestion theory is that organisms will increase the relative length of their digestive tracts when food resources become limited. We used theory of optimal digestion to test whether tadpoles can adjust the relative length of their intestines when challenged with the fungal pathogen Batrachochytrium dendrobatidis (Bd). The degree of tadpole mouthpart damage, a symptom of Bd infections that reduces food consumption, was associated positively with the length of tadpole intestines relative to their body size, consistent with optimal digestion theory. After controlling for mouthpart damage, tadpoles exposed to Bd had shorter intestines relative to their body size, opposite to the predictions of optimal digestion theory. One explanation of why tadpoles with higher Bd loads have shorter relative intestinal lengths is that they divert energy from maintaining intestinal and overall growth towards anti-parasite defences.


Human herpesvirus type-8 (HHV-8) in haematopoietic neoplasia.
Human herpesvirus type-8 (HHV-8) is a lymphotropic herpesvirus originally identified in Kaposi's sarcoma. Among lymphoproliferative disorders, HHV-8 infection is restricted to body-cavity-based lymphoma (BCBL) and multicentric Castleman's disease (MCD). BCBL are B-cell lymphomas growing in liquid phase in the body cavities and most frequently associated with AIDS. BCBL express indeterminate phenotypes, in all cases are associated with HHV-8 infection, and frequently carry Epstein-Barr virus genomes in the absence of c-MYC rearrangements or other genetic lesions characteristic of B-cell lymphomas. The clinical outcome of BCBL is poor with a median survival of only few months. MCD is an atypical lymphoproliferative disorder which displays marked vascular hyperplasia and is commonly associated with Kaposi's sarcoma. HHV-8 infection occurs in 100% of AIDS-related MCD and in approximately 40% of AIDS-unrelated cases. Overall, the consistency of HHV-8 infection in BCBL and MCD, its selectivity throughout the spectrum of lymphoproliferative disorders and the high copy number of HHV-8 DNA sequences in infected cells suggest that the virus plays a pathogenetic role in these disorders.


[Analysis of recording of cardiac rhythm and myocardial function after exercise test].
A continuous telemetric registration of the cardiac contraction rate was made in 534 persons performing various physical exertions. The ensuing epxerimental graphs of changes in the rhythm obtained under the effect of physical loads are described by mathematical formulas. Three types of changes in the rhythm in effort have been established, viz. linear, exponential and logarithmic. To determine cardiac function quantitative coefficients, reflecting the rate of the cardiac rhythm coming up to the working level and relationship between the areas of the steady state cardiac contractions frequency phase and that of its rapid increment, are proposed.


Arthroscopic reconstruction of the posterior cruciate ligament using tibial-inlay and double-bundle technique.
Biomechanical research has suggested that the double-bundle and tibial inlay technique is superior to the single-bundle and the transtibial tunnel method for posterior cruciate ligament (PCL) reconstruction. A combination the posterior tibial inlay and femoral double-bundle technique is thought to be an ideal method for PCL reconstruction. Recently, we successfully performed arthroscopic PCL reconstruction using the tibial-inlay and double-bundle technique. Achilles tendon-bone allograft is used and the bone plug for the arthroscopic tibial inlay fixation is designed in a cylindrical shape and perpendicular to the fiber texture of the Achilles tendon. Achilles tendon is manually split into deep and superficial layers to reconstruct anterolateral and posteromedial bundles as the natural insertion of PCL. The intra-articular lengths of each bundle between tibial tunnel and 2 femoral tunnels are measured to achieve fixation of the graft to the original PCL attachment. After tibial bone plug fixation with an absorbable interference screw and additional suture anchoring, the anterolateral bundle is fixed in a reduction position with the knee in 90 degrees of flexion and the posteromedial bundle is fixed nearly in extension. This procedure makes it possible not only to reproduce the original concept of PCL tibial inlay graft arthroscopically without posterior arthrotomy, but also to achieve a more anatomic PCL reconstruction of the 2 bundles.


Cellular basis of host defence in pyelonephritis. III. Deletion of individual components.
Hosts were depleted of individual cellular components to determine the effects of these manipulations on cellular defence mechanisms in acute and chronic pyelonephritis. T-lymphocytes were found to have little or no involvement in host protection but cyclosporin A administration had a dramatic effect on the gross pathology and bacteriological status of experimentally induced pyelonephritis. This change represented a major depression of host defence status. Cyclosporin A also activated resolved lesions in chronic pyelonephritis, associated with an increase in bacterial numbers. Administration of antineutrophil serum also led to a 1000-fold increase in bacterial numbers in the acute phase but had little effect on the host-parasite balance in chronic pyelonephritis. Macrophage blockade, on the other hand, did not affect the course of either acute or chronic infection. These studies have provided additional information on the immunobiology of experimental pyelonephritis and have focussed attention on the role of neutrophils, and an unidentified mechanism, affected by cyclosporin A, in host defence to renal infection.


TGFbeta regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo.
Factors influencing the development of CD4+CD25+ T-cells in vivo are poorly understood. In order to investigate the contribution of TGFbeta1 to the development and function of CD4+CD25+ T-cells, we generated a gain of function mutation resulting in the overexpression of an active form of TGFbeta1 in T-cells under control of the human CD2 promoter. In peripheral lymphoid organs and in the thymus, the frequency of CD4+CD25+ T-cells was increased in transgenic mice. This appeared to be due to an autocrine effect of TGFbeta on T-cells, since concomitant impairment of TGFbeta-signaling in double transgenic mice resulted in a phenotype similar to wild type. In contrast, in single transgenic mice with impaired TGFbeta-signaling in T-cells, CD4+CD25+ T-cell numbers were reduced in peripheral lymphoid organs but not in the thymus. In addition, TGFbeta was found to regulate the expression of Foxp3 in vivo, a transcription factor essential for the generation and function of regulatory T-cells. In CD4+CD25+ T-cells, TGFbeta1 increased the expression of Foxp3, whereas a decreased expression was seen in CD4+CD25+ T-cells with impaired TGFbeta-signaling. TGFbeta1 induced the expression of IL-10 in transgenic T-cells, but the increased in vitro suppressive capacity observed in transgenic CD4+CD25+ T-cells was due to the secretion of TGFbeta and not IL-10. Therefore, our study provides in vivo evidence for a role of TGFbeta in the homeostasis of CD4+CD25+ T-cells.


A method for cross-species gene expression analysis with high-density oligonucleotide arrays.
DNA microarrays have been widely used in gene expression analysis of biological processes. Due to a lack of sequence information, the applications have been largely restricted to humans and a few model organisms. Presented within this study are results of the cross-species hybridization with Affymetrix human high-density oligonucleotide arrays or GeneChip using distantly related mammalian species; cattle, pig and dog. Based on the unique feature of the Affymetrix GeneChip where every gene is represented by multiple probes, we hypothesized that sequence conservation within mammals is high enough to generate sufficient signals from some of the probes for expression analysis. We demonstrated that while overall hybridization signals are low for cross-species hybridization, a few probes of most genes still generated signals equivalent to the same-species hybridization. By masking the poorly hybridized probes electronically, the remaining probes provided reliable data for gene expression analysis. We developed an algorithm to select the reliable probes for analysis utilizing the match/mismatch feature of GeneChip. When comparing gene expression between two tissues using the selected probes, we found a linear correlation between the cross-species and same-species hybridization. In addition, we validated cross-species hybridization results by quantitative PCR using randomly selected genes. The method shown herein could be applied to both plant and animal research.


Use of an UHPLC-MS/MS Method for Determination of Kuraridin and Characterization of Its Metabolites in Rat Plasma after Oral Administration.
Kuraridin is an active natural prenylated flavonoid ingredient originating from the well-known traditional Chinese medicine Sophora flavescens Ait., that possesses various bioactivities, such as antitumor activity, PLCγ1 inhibitory activity, glycosidase inhibitory activity, etc. However, there is no report on the plasma metabolic profile and pharmacokinetic study of kuraridin. The current study was designed to use an ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for the quantification and characterization metabolites in rat plasma after oral administration of kuraridin. A liquid-liquid extraction method with ethyl acetate-acetonitrile (1:3) was used to extract the kuraridin from rat plasma samples. The chromatographic separation was carried out on a Hypersil GOLD UHPLC C18 column equipped with a C18 guard cartridge using a gradient elution with organic solvent-water as mobile phase. Based on comparing the retention times with reference standards or on the basis of MS₂ fragmentation behaviors, a total of 19 metabolites were identified or tentatively characterized from rat plasma. Under the optimized conditions, the method showed good linearity (r² > 0.99) over the ranges of 1-500 ng/mL for kuraridin. The inter- and intra-day precisions were less than 8.95%, and the accuracy was in the range of -6.27-6.48%. The recovery of kuraridin ranged from 90.1% to 100.4%. The developed UHPLC-MS/MS method was thus successfully applied in the qualitative of metabolites and quantitative analysis of kuraridin in rat plasma.


A brief review of concurrent activation potentiation: theoretical and practical constructs.
Enhancing the acute quality of the resistance training stimulus is the goal of many research and applied professionals. To that end, many methods have been proposed and a variety of training strategies and ergogenic supplements have been investigated. Postactivation potentiation is one phenomenon that has been frequently examined, offering some promise in this regard. Though never previously applied in the strength and conditioning profession, dental research on jaw clenching, studies examining the Jendrassik maneuver and remote voluntary contractions and research on motor overflow together make a compelling case for the existence of a concurrent activation potentiation phenomenon and the acute ergogenic advantage associated with the simultaneous activation of muscles other than the prime mover or synergists. Evidence demonstrates that this advantage is accrued via activation of the H reflex and through cortical overflow. Ultimately, through research and practical application, athletes may be taught to optimize the type, timing, and magnitude of remote muscle actions in order to gain an ergogenic advantage and increase the acute response of the prime movers. This strategy may be especially useful during the most difficult portion of a resistance training repetition and during the most difficult repetitions of a resistance training set.


[Squamous cell carcinomas of the upper aerodigestive tract. Prognostic significance of the capsular rupture and extracapsular spread of lymph node metastases].
The capsular rupture and subsequent extranodal spread of lymph node metastases is of crucial and well established prognostic value in patients with squamous cell carcinomas of the upper aerodigestive tract. Besides the basic histologic definition of the extranodal spread (i.e. contact of the metastasis with perinodal fatty tissue), there is no agreement on the morphologic extent of transcapsular spread. As a measure of improvement, a histologic evaluation differentiating between seven gradual types of metastatic nodal affection was applied. The histologic scheme considers intranodal growth, infiltration of the capsule, the presence of desmoplasia and especially the rupture of the capsule and the subsequent extranodal spread of the metastasis. As extranodal spread is an easily reproducible and reliably significant prognostic criterion, it should be included in the current TNM classification, e.g., by an addition of the index R+ (lymph node metastasis with capsular rupture) or R- (lymph node metastasis without capsular rupture) to the N category.


The BRPF2/BRD1-MOZ complex is involved in retinoic acid-induced differentiation of embryonic stem cells.
The scaffold protein BRPF2 (also called BRD1), a key component of histone acetyltransferase complexes, plays an important role in embryonic development, but its function in the differentiation of embryonic stem cells (ESCs) remains unknown. In the present study, we investigated whether BRPF2 is involved in mouse ESC differentiation. BRPF2 depletion resulted in abnormal formation of embryoid bodies, downregulation of differentiation-associated genes, and persistent maintenance of alkaline phosphatase activity even after retinoic acid-induced differentiation, indicating impaired differentiation of BRPF2-depleted ESCs. We also found reduced global acetylation of histone H3 lysine 14 (H3K14) in BRPF2-depleted ESCs, irrespective of differentiation status. Further, co-immunoprecipitation analysis revealed a physical association between BRPF2 and the histone acetyltransferase MOZ in differentiated ESCs, suggesting the role of BRPF2-MOZ complexes in ESC differentiation. Together, these results suggest that BRPF2-MOZ complexes play an important role in the differentiation of ESCs via H3K14 acetylation.


Mini-laparotomy for repair of infrarenal abdominal aortic aneurysm.
In this study, we evaluated the surgical results of minimal incision aortic surgery (MIAS) compared with the transabdominal approach (TPA) and the retroperitoneal approach (RPA) to repair non-ruptured infrarenal abdominal aortic aneurysm (AAA). Three different surgical techniques were studied prospectively in 72 consecutive patients with non-ruptured infrarenal AAA. These patients were randomized into 3 groups of 24 patients each. Group I comprised of patients who underwent MIAS repair. They were compared with group II patients, who underwent the traditionally long midline TPA, and group III patients, who underwent the left RPA to repair non-ruptured infrarenal AAA. All surgery was performed between January 2000 and December 2004. Demographic characteristics, including age, sex, body weight, aneurysm size, previous abdominal operations and comorbid factors of the three groups studied, were compared using the Fischer's exact test. Parameters including operative time, intraoperative fluid administration, and transfusion requirements were compared using the 2-tailed Student t test. Length of stay in the Intensive Care Unit (ICU), time to resumption of regular dietary feeding, and hospital length of stay were recorded and compared using the Wilcox rank sum test. The incidence of 30 day postoperative complications and mortality were compared between the three groups. All 72 patients who entered this study had informed consent. There was no significant difference between group I (MIAS), group II (TPA), and group III (RPA) with regard to age, sex distribution, aneurysm size, or body weight. There was male sex prevalence in all three groups. Surgical exposure of the common femoral arteries was more commonly required in group III (RPA) than in the other groups. Although the length of incision tended to be longer in group III (RPA) than in group II (TPA) and I (MIAS), there was no significant difference in intraoperative time, or aortic cross-clamped time among the three groups. There was a significant difference in the need for intraoperative fluid, the most being in group II (TPA) and the least in group I (MIAS). There was significantly less blood loss in group I (MIAS), as compared with the other 2 groups, but intraoperative blood transfusion for all groups was not significantly different. ICU stay, return to general dietary feeding, and hospital length of stay for group I (MIAS) and III (RPA) were significantly lower than in group II (TPA), which had a higher incidence of postoperative ileus. MIAS is as safe as retroperitoneal repair and standard transabdominal repair in the treatment of non-ruptured infrarenal AAA, and also more costefficient than retroperitoneal and standard transabdominal repair.


Haemodynamic dose-response effects of intravenous oxprenolol in coronary heart disease.
The haemodynamic dose-response effects of intravenous oxprenolol over the range of 2--64 mg were measured in 28 patients with coronary heart disease. At rest there were statistically significant dose-response trends, linear or quadratic, between the cumulative doses of oxprenolol and reductions in systolic pressure, heart rate, and cardiac output and increases in stroke volume and pulmonary wedge pressure. The magnitude of the changes was uninfluenced by the degree of left ventricular functional disability as judged by the level of the pulmonary wedge pressure. During dynamic exercise the haemodynamic changes induced by oxprenolol were significantly greater in patients with more marked left ventricular disability than in those less severely affected. These observations define the immediate effects of intravenous oxprenolol over a relatively wide dose range and confirm its relative haemodynamic safety in patients with stable coronary heart disease.


An autonomic link between inhaled diesel exhaust and impaired cardiac performance: insight from treadmill and dobutamine challenges in heart failure-prone rats.
Cardiac disease exacerbation is associated with short-term exposure to vehicular emissions. Diesel exhaust (DE) might impair cardiac performance in part through perturbing efferent sympathetic and parasympathetic autonomic nervous system (ANS) input to the heart. We hypothesized that acute changes in ANS balance mediate decreased cardiac performance upon DE inhalation. Young adult heart failure-prone rats were implanted with radiotelemeters to measure heart rate (HR), HR variability (HRV), blood pressure (BP), core body temperature, and pre-ejection period (PEP, a contractility index). Animals pretreated with sympathetic antagonist (atenolol), parasympathetic antagonist (atropine), or saline were exposed to DE (500 µg/m(3) fine particulate matter, 4h) or filtered air and then treadmill exercise challenged. At 1 day postexposure, separate rats were catheterized for left ventricular pressure (LVP), contractility, and lusitropy and assessed for autonomic influence using the sympathoagonist dobutamine and surgical vagotomy. During DE exposure, atenolol inhibited increases in HR, BP, and contractility, but not body temperature, suggesting a role for sympathetic dominance. During treadmill recovery at 4h post-DE exposure, HR and HRV indicated parasympathetic dominance in saline- and atenolol-pretreated groups that atropine inhibited. Conversely, at treadmill recovery 21h post-DE exposure, HRV and PEP indicated sympathetic dominance and subsequently diminished contractility that only atenolol inhibited. LVP at 1 day postexposure indicated that DE impaired contractility and lusitropy while abolishing parasympathetic-regulated cardiac responses to dobutamine. This is the first evidence that air pollutant inhalation both causes time-dependent oscillations between sympathetic and parasympathetic dominance and decreases cardiac performance via aberrant sympathetic dominance.


Stress management through regulation of blood pressure among college students.
This paper introduces the concept of Deep Breathing and its applications as one of the means towards stress management through regulation of blood pressure among Indian College Engineering students. The underlying concept of deep breathing is that the relation between emotions and breathing is two way, i.e. not only do emotions affect the breathing, but controlled deep breathing also has an effect on emotions. The objective of the paper is to find out whether deep breathing technique is able to control blood pressure, and in turn, the level of stress. Sample students had a selection through initial screening and the students who reported high mental stress during interview were selected for the main drills. All the readings are taken using a sphygmomanometer (digital blood pressure meter). Students' t test are used for the purpose of hypothesis testing. The results indicated that the deep breathing technique provided significant results. It is recommended that this amazingly simple and yet highly effective ancient technique of deep breathing become part of students' routine curriculum. The paper aims at spreading the awareness of this yogic technique as one of the modes of Stress Management amongst Indian college students.


Circular RNA nuclear receptor interacting protein 1 promoted biliary tract cancer epithelial-mesenchymal transition and stemness by regulating the miR-515-5p/AKT2 axis and PI3K/AKT/mTOR signaling pathway.
Biliary tract cancer (BTC) is a devastating malignancy that is notoriously difficult to diagnose and is associated with high mortality. Circular RNA (circRNA) is a class of endogenous non-coding RNA which has been regarded as the key regulator of tumor initiation and progression, including BTC. Circular RNA nuclear receptor interacting protein 1 (circ_NRIP1), as a circular RNA, is abnormally expressed in many human tumors and exhibits diverse functions in cancer progression. However, its biological significance in BTC has not been thoroughly investigated. In this research, we elucidated that circ_NRIP1 was notably overexpressed in both BTC tissues and cells. We further established a correlation between circ_NRIP1 expression and clinicopathological features in BTC patients, highlighting its clinical relevance. Through functional assays, we observed that knockdown of circ_NRIP1 significantly inhibited tumor cell proliferation, invasion, stemness maintenance, and epithelial-mesenchymal transition, indicating its active involvement in promoting BTC progression. Additionally, it attenuated growth of xenograft and metastasis models. Mechanically, we revealed that circ_NRIP1 served as the competing endogenous RNA to sequester miR-515-5p through complementary base pairing mechanism, thereby upregulated AKT2 expression and indirectly activated PI3K/AKT/mTOR signaling pathway. Generally, targeting the circ_NRIP1/miR-515-5p/AKT2 axis and aberrant activation of the PI3K/AKT/mTOR pathway may hold promising therapeutic strategies for BTC. Our research contributes to a better understanding of the underlying biological basis of BTC and paves the way for the development of innovative treatment approaches.


Identification of the regulatory elements controlling the transmission stage-specific gene expression of PAD1 in Trypanosoma brucei.
Trypanosomatid parasites provide an extreme model for the posttranscriptional control of eukaryotic gene expression. However, most analysis of their differential gene regulation has focussed on comparisons between life-cycle stages that exist in the blood of mammalian hosts and tsetse flies, the parasite's vector. These environments differ acutely in their temperature, and nutritional, metabolic and molecular composition. In the bloodstream, however, a more exquisitely regulated developmental step occurs: the production of transmissible stumpy forms from proliferative slender forms. This transition occurs in the relatively homogenous bloodstream environment, with stumpy-specific gene expression being repressed until accumulation of a proposed parasite-derived signal, stumpy induction factor. Here, we have dissected the regulatory signals that repress the expression of the stumpy-specific surface transporter PAD1 in slender forms. Using transgenic parasites capable of stumpy formation we show that PAD1-repression is mediated by its 3'-untranslated region. Dissection of this region in monomorphic slender forms and pleomorphic slender and stumpy forms has revealed that two regulatory regions co-operate to repress PAD1 expression, this being alleviated on exposure to SIF in pleomorphs or cAMP analogues that act as stumpy induction factor mimics in monomorphs. These studies identify elements that regulate trypanosome gene expression during development in their mammalian host.


Thread embedding acupuncture for musculoskeletal pain: a systematic review and meta-analysis protocol.
Thread embedding acupuncture (TEA) is a special type of acupuncture that inserts certain medical threads (eg, catgut or polydioxanone) into subcutaneous tissue or muscles at specific points. Although TEA has been widely used for the treatment of musculoskeletal pain in Korea, China and Taiwan, evidence regarding its efficacy is lacking. The aim of this protocol is to evaluate the effectiveness and safety of TEA in the treatment of musculoskeletal pain, by conducting a systematic review and meta-analysis. The following 16 databases will be searched from their inception to 14 May 2017: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, three Chinese database (China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database and the Wanfang database) and eight Korean databases (Korean Medical Database, Korean Association of Medical Journal Editors, Korean Studies Information Service System, Korean National Assembly Digital Library, National Digital Science Library, Oriental Medicine Advanced Searching Integrated System, 'Database Periodical Information Academic and Korean Traditional Knowledge Portal'). The WHO International Clinical Trials Registry Platform will also be searched to retrieve the recently completed studies.All randomised controlled studies in which TEA was used on specific points for the treatment of musculoskeletal pain will be included and no restrictions on language will be applied. The risk of bias of each study will be evaluated by the Cochrane risk of bias tool.Mean difference or standardised mean difference for continuous data and risk ratio for dichotomous data will be calculated with 95% CIs using a random effects model or a fixed effects model. Additional subgroup and sensitivity analyses will be conducted according to a predefined protocol. No ethical issues are predicted. The systematic review will be published in a peer-reviewed journal or conference presentation. These findings will summarise the current evidence of TEA for the treatment of musculoskeletal pain and may provide guidance for clinicians and patients to select TEA for musculoskeletal pain. CRD42015019046.


Mixed hepatoblastoma in the adult: morphological and immunohistochemical findings.
A case of mixed hepatoblastoma in a 66-year-old man is discussed. Assessment of malignant mesenchymal and malignant epithelial elements yields the diagnosis. In the reported case, the epithelial area consisted of fetal hepatocytes. Distinct ductal differentiation, chondroid and even asteoid metaplasia were recorded. The morphological and immunohistochemical findings observed in the given patient are compared with data published in the world literature.


Aortic Arch. The Final Frontier in Cardiac Surgery.
Aortic arch pathologies such as acute aortic dissection and aneurysmal disease represent surgical challenges. Various emerging techniques and surgical prostheses have expanded the therapeutic armamentarium over the last years with one principal objective; to simplify the operation and reduce the surgical time. Besides the classic elephant trunk which has been regarded as an evolutionary leap in the treatment of extensive thoracic disease, other novel surgical approaches such as the frozen elephant trunk, the thoracic endovascular aortic repair (TEVAR) and the hybrid open branched stent grafts have been introduced. This brief review aims to evaluate the surgical alternatives used in the management of complex aortic arch and proximal descending aorta pathologies with particular consideration given to the contemporary approaches which endorse single stage operation.


Mammary hypoplasia: not every breast can produce sufficient milk.
Breast milk is considered the optimal form of nutrition for newborn infants. Current recommendations are to breastfeed for 6 months. Not all women are able to breastfeed. Mammary hypoplasia is a primary cause of failed lactogenesis II, whereby the mother is unable to produce an adequate milk volume. Women with mammary hypoplasia often have normal hormone levels and innervation but lack sufficient glandular tissue to produce an adequate milk supply to sustain their infant. The etiology of this rare condition is unclear, although there are theories that refer to genetic predisposition and estrogenic environmental exposures in select agricultural environments. Women with mammary hypoplasia may not exhibit the typical breast changes associated with pregnancy and may fail to lactate postpartum. Breasts of women with mammary hypoplasia may be widely spaced (1.5 inches or greater), asymmetric, or tuberous in nature. Awareness of the history and clinical signs of mammary hypoplasia during the prenatal period and immediate postpartum increases the likelihood that women will receive the needed education and physical and emotional support and encouragement. Several medications and herbs demonstrate some efficacy in increasing breast milk production in women with mammary hypoplasia.


Simulated effect of corneal asphericity increase (Q-factor) as a refractive therapy for presbyopia.
To determine the theoretical effect of an increase in the negative Q-factor (hyperprolateness) on the refractive state and its effect on presbyopia treatment. Ray tracing software was used to simulate the Navarro eye model. To simulate refractive therapy, corneal Q-factor ranged from 0 to -1.50. Refractive state of the model eye was defined as the target vergence required to maximize retinal image quality according to several image quality metrics. The change of refractive state produced by pupil constriction from 6 to 2 mm was estimated. For 0 ≥ Q ≥ -0.6, spherical aberration of the model eye is positive, therefore, pupil miosis causes a hypermetropic shift in refractive state. Over the range -0.6 ≥ Q ≥ -1.5, spherical aberration becomes negative and pupil constriction causes the eye's far point to approach the eye, inducing a myopic shift. A maximum 0.60-diopter myopic shift in refractive state due to pupil constriction occurred for Q=-1.25. Optical modeling predicts that surgically induced negative corneal Q-value will produce a change in the refractive state of the eye after pupillary miosis.


Influence of morphine on protein synthesis in discrete subcellular fractions of the rat brain.
Extensive time course (15 min to 24 hr) measurements were made of the effects of acute and chronic morphine treatment on the incorporation of 3H-lysine into rat brain proteins. Acute and chronic morphine treatment inhibited cortical protein synthesis in the microsomal (Mc), mitochondrial (Mw) and soluble fractions (Sol.). In the subcortex, acute morphine stimulated labelled protein accumulation in the Mc and Mw fractions, Chronic morphine treatment decreased 3H-lys-protein accumulation in these fractions.


Apathy and the processing of novelty in schizophrenia.
Apathy is a common negative symptom in schizophrenia that has been associated with poor medication compliance and treatment outcome. Recent studies in neurological patients have observed an association between apathy and reduced attention to novel stimuli. We evaluated whether patients with schizophrenia demonstrate a similar relationship. Participants included 20 patients with schizophrenia and 20 healthy comparison subjects matched for age, sex, handedness, and parental education. A self-paced visual novelty task was presented which assessed the duration that participants looked at frequent standard stimuli, infrequent target stimuli, and novel stimuli. Attention to novelty was defined as the duration of viewing novel relative to standard stimuli. Apathy was assessed with the Marin Apathy Evaluation Scale. Results revealed significantly greater self- and informant-reported apathy, slower reaction time to target stimuli, and longer viewing times to the stimuli, but not reduced attention to the novel stimuli, in the patient group. Although greater self-report of apathy was associated with longer viewing times for all stimuli in the patient group, this was accounted for by depressed mood. The present findings indicate that schizophrenia is associated with slowed information processing, but do not support the hypothesis that apathy in schizophrenia is associated with abnormal processing of novelty.