Chromatographic evidence of silyl ether formation (SEF) in supercritical fluid chromatography.
In this article, we propose that silyl ether formation (SEF) is a major contribution to retention and selectivity variation over time for supercritical fluid chromatography (SFC). In the past, the variations were attributed to instrumentation, but high performance SFC systems have shed new light on the source of variation. As silyl ethers form on the particle surface, the hydrophilicity is decreased, significantly altering the retention and selectivity observed. SEF is expected to occur with any chromatographic particle containing silanols but is slowed on hybrid inorganic/organic particles. The SEF reaction is between alcohols on the particle surface and in the mobile phase solvent. We have found that storage conditions of a column are paramount, which can either prevent or accelerate the process. Because SEF exists as an equilibrium between the liquid phase and the particle surface, the process is also reversible. The silanols can be hydroxylated (regenerated) to their original state upon exposure to water. The next generation of stationary phases will either advantageously utilize SEF or effectively mitigate its effects. Mitigation of SEF would be a significant improvement in SFC that has the potential to vault their performance to levels of similar reproducibility and reliability observed for high performance liquid chromatography (HPLC). Further research in SEF may lead to a better understanding of the mechanism of interaction between the solutes and chromatographic surface.


[Heatstroke: a rare cause of massive hepatic necrosis due to hypoxia].
The authors report the case of a 76 year-old woman affected by heatstroke complicated by massive liver cell necrosis and fulminant liver failure, with a favorable outcome. Liver cell necrosis was localized in centro- and medio-lobular areas and was not associated with hepatic vein congestion. These histological features suggest that the main causal factor of liver cell necrosis was relative liver cell hypoxia secondary to increased oxygen tissular requirements induced by hyperthermia.


4n-1 Is a "Sweet Spot" in DNA i-Motif Folding of 2'-Deoxycytidine Homopolymers.
Strands of DNA with four or more contiguous runs of 2'-deoxycytidine (dC) nucleotides have the potential to adopt i-motif folds, generally under mildly acidic conditions. Analysis of dC homo-oligonucleotide strands ranging in length from 10 to 30 nucleotides by five different pH-dependent methods identified a pattern in strand length vs stability. Beginning with dC11, which does not fold, the transition pH (pHT) increased with chain length with the addition of up to four nucleotides, after which the stability dramatically decreased, and the trend repeated this cycle up to dC27. The analysis found dCn strands of length 15, 19, 23, and 27 nucleotides (i.e., 4n-1) to have pHT values >7.2 and thermal stabilities >37 °C at pH 7.0. Model studies using thymidine nucleotides to lock in i-motif loop lengths support the conclusion that the most stable dCn i-motifs possess one nucleotide in each of the three loops and a core built of an even number of base pairs. The pattern identified from the model studies occurs with a frequency of four nucleotides at lengths of 15, 19, 23, and 27 in accordance with the results obtained for the dCn strands. This observation led us to interrogate the human genome for dCn runs. Inspection of the human genome indicates that dCn runs are enriched in critical regions of the genome (promoters, UTRs, and introns), while being depleted in coding and intergenic regions, and these findings may have biological implications. Lastly, the ability to tune i-motif stabilities by the length of the strand might be harnessed for stimulus-responsive applications in DNA scaffolds, sensors, nanotechnology, and other chemical applications.


Decreased Yes-Associated Protein-1 (YAP1) Expression in Pediatric Hearts with Ventricular Septal Defects.
Ventricular septal defects (VSDs) are the most common and simplest type of congenital heart diseases (CHDs). Animal studies have suggested that the downregulation of Yes-associated protein 1 (YAP1) during embryonic development causes VSD-associated CHDs. However, how YAP1 contributes to isolated VSD (iVSD) is unclear. Twenty right atrial specimens were obtained from iVSD patients during routine congenital cardiac surgery and we assessed YAP1 expression in these specimens. For controls, six right atrial specimens were obtained from normal hearts of children without heart disease, three of whom died from cerebral palsy, and three who underwent heart transplants. YAP1 mRNA and protein levels and nuclear localization were significantly reduced in iVSD specimens compared to normal heart specimens. Concomitantly, mRNA levels of YAP1 downstream targets CTGF and AXL were also significantly decreased in iVSD specimens. Although Ki67-positive cardiomyocytes in iVSD specimens were comparable to normal heart specimens, Ki67-positive non-cardiomyocytes were significantly decreased. YAP1 expression was markedly decreased in hearts of iVSD children. Given the important role of YAP1 during heart development, downregulation of YAP1 expression may contribute to iVSD and affect the proliferation of non-cardiomyocytes.


Prophylactic removal of impacted mandibular third molars: a systematic review and economic evaluation.
Impacted third molars are third molars that are blocked, by soft tissue or bone, from fully erupting through the gum. This can cause pain and disease. The treatment options for people with impacted third molars are removal or retention with standard care. If there are pathological changes, the current National Institute for Health and Care Excellence guidance states that the impacted third molar should be removed. The objective of this study was to appraise the clinical effectiveness and cost-effectiveness of the prophylactic removal of impacted mandibular third molars compared with retention of, and standard care for, impacted third molars. Five electronic databases were searched (1999 to 29 April 2016) to identify relevant evidence [The Cochrane Library (searched 4 April 2016 and 29 April 2016), MEDLINE (searched 4 April 2016 and 29 April 2016), EMBASE (searched 4 April 2016 and 29 April 2016), EconLit (searched 4 April 2016 and 29 April 2016) and NHS Economic Evaluation Database (searched 4 April 2016)]. Studies that compared the prophylactic removal of impacted mandibular third molars with retention and standard care or studies that assessed the outcomes from either approach were included. The clinical outcomes considered were pathology associated with retention, post-operative complications following extraction and adverse effects of treatment. Cost-effectiveness outcomes included UK costs and health-related quality-of-life measures. In addition, the assessment group constructed a de novo economic model to compare the cost-effectiveness of a prophylactic removal strategy with that of retention and standard care. The clinical review identified four cohort studies and nine systematic reviews. In the two studies that reported on surgical complications, no serious complications were reported. Pathological changes due to retention of asymptomatic impacted mandibular third molars were reported by three studies. In these studies, the extraction rate for retained impacted mandibular third molars varied from 5.5% to 31.4%; this variation can be explained by the differing follow-up periods (i.e. 1 and 5 years). The findings from this review are consistent with the findings from previous systematic reviews. Two published cost-effectiveness studies were identified. The authors of both studies concluded that, to their knowledge, there is currently no economic evidence to support the prophylactic removal of impacted mandibular third molars. The results generated by the assessment group's lifetime economic model indicated that the incremental cost-effectiveness ratio per quality-adjusted life-year gained for the comparison of a prophylactic removal strategy with a retention and standard care strategy is £11,741 for people aged 20 years with asymptomatic impacted mandibular third molars. The incremental cost per person associated with prophylactic extraction is £55.71, with an incremental quality-adjusted life-year gain of 0.005 per person. The base-case incremental cost-effectiveness ratio per quality-adjusted life-year gained was found to be robust when a range of sensitivity and scenario analyses were carried out. Limitations of the study included that no head-to-head trials comparing the effectiveness of prophylactic removal of impacted mandibular third molars with retention and standard care were identified with the assessment group model that was built on observational data. Utility data on impacted mandibular third molars and their symptoms are lacking. The evidence comparing the prophylactic removal of impacted mandibular third molars with retention and standard care is very limited. However, the results from an exploratory assessment group model, which uses available evidence on symptom development and extraction rates of retained impacted mandibular third molars, suggest that prophylactic removal may be the more cost-effective strategy. Effectiveness evidence is lacking. Head-to-head trials comparing the prophylactic removal of trouble-free impacted mandibular third molars with retention and watchful waiting are required. If this is not possible, routine clinical data, using common definitions and outcome reporting methods, should be collected. This study is registered as PROSPERO CRD42016037776. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 30. See the NIHR Journals Library website for further project information.


A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia.
This review identified 1275 studies examining cognitive deficits in people with schizophrenia, published between 1990 and 2003. Data from 113 studies (4365 patients and 3429 controls) were combined in a meta-analysis carried out on the five cognitive domains of IQ, memory, language, executive function, and attention. Studies were excluded where they lacked a suitable control group or failed to present complete information. In all five cognitive domains, analysis indicated a consistent trend for patients to perform more poorly than healthy controls, with significant heterogeneity across studies. Sources of heterogeneity were analyzed and a need to ensure more appropriate composition of patient and control groups and to adopt a more refined and methodologically correct, hypothesis-driven approach was identified.


Effects of appliance size, arch wire diameter, and alloy composition on the in vitro force delivery of the quad-helix appliance.
The quad-helix appliance is a fixed lingual arch wire appliance that produces slow maxillary expansion for the treatment of maxillary constriction or crossbite in the primary and mixed dentitions. Despite considerable success in the clinical treatment of patients, there is little quantitative information about the force delivery of this appliance. The purpose of this investigation was to characterize the in vitro force delivery of the quad-helix appliance. Appliances of four sizes were fabricated from Elgiloy blue and stainless steel wires with diameters of 0.032, 0.036, and 0.038 inch. The force delivery in grams for 8-mm activation was determined from the force-extension characteristics using an Instron mechanical testing machine. The results show that the force delivery of the quad-helix appliance is affected significantly by changes in the appliance size and arch wire diameter, but is independent of alloy type (stainless steel or Elgiloy blue). The quantitative results from this investigation should provide worthwhile information for clinical appliance selection and treatment of patients with varying arch dimensions.


[The treatment of multiple myeloma].
Median survival in patients with multiple myeloma, which amounted to 6-12 months during the pre-chemotherapy era, was improved to 28-43 months following the introduction of chemotherapy. Usually patients with stage II or III myeloma require treatment. Conventional chemotherapy with melphalan-prednisone is undertaken if their prognosis is good; in case of poor prognosis and good general condition, a more aggressive polychemotherapy is given. High-dose melphalan therapy alone induces high remission rates, but fails to prolong remission duration or survival. Resistance to cytostatic drugs due to the p-glycoprotein coded by the MDR-gene is treated by a combination of cyclosporin-A or verapamil and VAD. For the treatment of relapses or of primarily resistant patients several second-line regimens are available. As remission maintenance therapy, interferon has so far yielded the best results. Trials of other cytokines such as interleukin-2 and interleukin-4 are still inconclusive. For autologous bone marrow transplantation, primary reduction of the tumour mass by conventional polychemotherapy is recommended. Subsequently, high-dose melphalan or cyclophosphamide-busulfan--with or without total body irradiation--is used for conditioning and followed by the transplantation of either autologous bone marrow or peripheral blood stem cells. Significantly higher remission rates and longer survival of the patients may be expected. Allogenous bone marrow transplantation is burdened with a high early mortality rate, but it also promises longer disease-free survival times. Bone marrow transplantation should be performed as early as possible in the course of the disease. More controlled studies are required before a definite evaluation of its efficacy is possible.


Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can be expanded in vitro.
Follicular lymphomas (FLs) rarely induce clinically significant T-cell-mediated responses. We showed that freshly isolated tumor infiltrating T cells (T-TILs) lack tumor-specific cytotoxicity. Stimulation of these T cells with FL cells in the presence of interleukin-2 (IL-2) and/or costimulation via CD28 does not lead to T-cell activation and expansion. In contrast, when stimulated with FL cells preactivated via CD40, autologous T-TILs can be expanded by the addition of exogenous IL-2. These T cells can be further expanded in vitro by the addition of exogenous IL-4, IL-7, or interferon-gamma, but not IL-12. Once activated, these T cells showed FL-directed cytotoxicity in four of five patients tested. We concluded that autologous cytotoxic anti-FL-specific T cells exist, but can only be detected in vitro under optimized conditions for T-cell stimulation and expansion. This suggests that their frequency in vivo is either very low or that the microenvironment does not provide the necessary signals to activate these T cells. This model system allows dissection of the requisite conditions for activation and expansion of lymphoma-directed cytotoxicity and may permit expansion of previously activated cytotoxic T cells for adoptive transfer.


CA 50 compared with CA 19-9 as a serum tumour marker for pancreatic carcinoma.
This study compared the sensitivity and specificity of CA 50 and CA 19-9 as serum tumour markers for pancreatic cancer. One hundred and seventy one subjects were evaluated: 50 healthy controls, 50 patients with pancreatic carcinoma and 71 patients with chronic pancreatitis. Eighty per cent of the pancreatic cancer patients had raised CA 19-9 serum levels and 82% had raised CA 50 serum levels. In the group of patients ith chronic pancreatitis, false positive tests occurred in 8.4% for CA 19-9 and 11.3% for CA 50. For both markers the serum level showed a severe elevation in the advanced stage of cancer disease. Despite the good sensitivity and specificity of CA 50 as a serum tumour marker for pancreatic carcinoma, no major advantage was found compared to CA 19-9. Moreover, if the CA 50 cut-off, level is raised to 85 U/ml to exclude overlap with chronic pancreatitis, sensitivity falls sharply to 46% compared with 72% for CA 19-9 when a 100 U/ml cut-off level is used.


Rationale and feasibility of chemoprovention of hepatocellular carcinoma by cyclooxygenase-2 inhibitors.
Hepatocellular carcinoma (HCC) is a growing health problem worldwide. The limited treatment and poor prognosis of this disease emphasizes the importance of developing effective prevention, including chemoprevention. Improvement in early diagnosis of HCC and regular screen of individuals with increased risk for HCC provide the possibility of effective chemoprevention for HCC in the future. Hepatocarcinogenesis is best described as a continuity of regeneration, proliferation, unregulated hyperplasia, dysplasia, and malignant transformation. Uncontrolled proliferation of hepatocytes clearly plays a key role in hepatocarcinogenesis. Overexpression of cyclooxygenase-2 (COX-2) has been associated with tumorigenesis of colon cancer. Selective COX-2 inhibitors possess potent suppression on the growth of colon cancer. Overexpression of COX-2 has also recently been demonstrated in patients with HCC, especially in nontumorous tissue with cirrhosis and well-differentiated tumorous tissue. In vitro studies have revealed that both NS-398, a selective COX-2 inhibitor, and sulindac, an analog of nonsteroidal anti-inflammatory drugs, effectively inhibit growth of human hepatoma cell lines, which is mediated by a decreased rate of cell proliferation. Although further in vivo studies are required in animal models to confirm these findings and define optimal doses for future clinical trials in human subjects, these findings provide a rationale for the use of COX-2 inhibitors as HCC chemoprevention.


[Research progress on disease models and gene therapy of Duchenne muscular dystrophy].
Duchenne muscular dystrophy (DMD) is an X-linked, recessive and lethal genetic disease, which usually caused by gene mutations and the underlying mechanisms are complicated and diverse. The causal gene of DMD is the largest one in human that locates in the region of Xp21.2, encoding dystrophin. Currently there is no effective treatment for DMD patients. The treatment of DMD depends on gene mutation and molecular mechanism study of the disease, which requires reliable disease models such as mdx mouse model. Recently, researchers have increasingly discovered gene therapy strategies for DMD, and the efficacy has been demonstrated in DMD animal models. In addition, induced pluripotent stem cell technology can provide patient-specific cell source, offering a new platform for mechanism and therapy study of DMD.


Secretory hydrolases of Trichomonas vaginalis.
Supernatants of three Trichomonas vaginalis strains obtained from culture or after contact and cultivation with WISH cells were assayed to characterize the nature of the factor/s responsible for the cytotoxic activity on WISH cell monolayers. This factor, mainly secreted from the live, exponentially grown parasite, with a molecular weight higher than 10,000 daltons and heat-unstable, does not appear to be a protease. In its place, we demonstrated that the presence of some hydrolases (particularly acid phosphatase and beta-N-acetylglucosaminidase) was related to the cytotoxic activity of T. vaginalis strains. Hence, some hydrolytic enzymes may indicate the pathogenetic role of a T. vaginalis strain.


Lanthipeptides: chemical synthesis versus in vivo biosynthesis as tools for pharmaceutical production.
Lanthipeptides (also called lantibiotics for those with antibacterial activities) are ribosomally synthesized post-translationally modified peptides having thioether cross-linked amino acids, lanthionines, as a structural element. Lanthipeptides have conceivable potentials to be used as therapeutics, however, the lack of stable, high-yield, well-characterized processes for their sustainable production limit their availability for clinical studies and further pharmaceutical commercialization. Though many reviews have discussed the various techniques that are currently employed to produce lanthipeptides, a direct comparison between these methods to assess industrial applicability has not yet been described. In this review we provide a synoptic comparison of research efforts on total synthesis and in vivo biosynthesis aimed at fostering lanthipeptides production. We further examine current applications and propose measures to enhance product yields. Owing to their elaborate chemical structures, chemical synthesis of these biomolecules is economically less feasible for large-scale applications, and hence biological production seems to be the only realistic alternative.


Epithelial tumor, invasion and stroma.
Uncontrolled proliferation is a defining feature of the malignant phenotype. Nevertheless, the supportive network provided by the stroma is indispensable for further invasion, progression and metastasis of cancer cells. In addition, the role of inflammation in tumorigenesis is now generally accepted, and it has become evident that an inflammatory microenvironment is an essential component of tumor progression. Since skin tumors are common and easily assessable lesions with features at various stages of tumorigenesis, they provide a wide scope for research in this field to further our understanding of fundamental and clinical carcinogenesis. Some of the basic aspects of epithelial tumorigenesis, invasion and stromal reaction are reviewed in this paper.


Enhanced expression of vascular endothelial growth factor and increased microvascular density in women with endometrial hyperplasia: a possible relationship with uterine natural killer cells.
This case-control study aimed to investigate the expression of natural killer cells (NKCs) and the integrated optical density (IOD) of vascular endothelial growth factor (VEGF) and to quantify microvascular density (MVD) in endometrial biopsies from women with endometrial hyperplasia (EH) relative to normal subjects. Histological data from four groups were analyzed. The study population included 30 women with simple EH without atypia, 25 patients with complex EH without atypia, 25 with complex EH with atypia and 25 healthy women with non-hyperplastic endometrium (control group). Paraffin sections were immunostained with antibodies against CD56, VEGF-A and CD34 using an Avidin-Biotin-Peroxidase technique. The evaluation of NKC density and IOD of VEGF expression and measurement of MVD were performed using light microscopy examination and image analysis techniques. Increased numbers of NKCs were documented in cases of complex EH with atypia compared with the other groups (p<0.001). The number of NKCs was lower in cases of hyperplasia without atypia compared with the controls, but the difference was not significant. The IOD of VEGF-A and MVD increased significantly with progression from the non-hyperplastic endometrium through the three groups of EH (p<0.001). We observed a significant correlation between the MVD and the IOD of VEGF-A in the studied groups (r=0.434; p<0.001). Additionally, NKCs density was correlated significantly with IOD of VEGF-A (r=0.661; p<0.001) and with the MVD (r=0.473; p<0.001). These results suggest that NKC-count, IOD of VEGF and endometrial MVD are all related to the histological changes of the endometrium and that endometrial hyperplasia exhibits distinct immunological backgrounds in the context of NKC infiltration and VEGF production.


A semantic web approach applied to integrative bioinformatics experimentation: a biological use case with genomics data.
The numerous public data resources make integrative bioinformatics experimentation increasingly important in life sciences research. However, it is severely hampered by the way the data and information are made available. The semantic web approach enhances data exchange and integration by providing standardized formats such as RDF, RDF Schema (RDFS) and OWL, to achieve a formalized computational environment. Our semantic web-enabled data integration (SWEDI) approach aims to formalize biological domains by capturing the knowledge in semantic models using ontologies as controlled vocabularies. The strategy is to build a collection of relatively small but specific knowledge and data models, which together form a 'personal semantic framework'. This can be linked to external large, general knowledge and data models. In this way, the involved scientists are familiar with the concepts and associated relationships in their models and can create semantic queries using their own terms. We studied the applicability of our SWEDI approach in the context of a biological use case by integrating genomics data sets for histone modification and transcription factor binding sites. We constructed four OWL knowledge models, two RDFS data models, transformed and mapped relevant data to the data models, linked the data models to knowledge models using linkage statements, and ran semantic queries. Our biological use case demonstrates the relevance of these kinds of integrative bioinformatics experiments. Our findings show high startup costs for the SWEDI approach, but straightforward extension with similar data.


MicroRNA profiling and their pathways in South African individuals with prediabetes and newly diagnosed type 2 diabetes mellitus.
Early identification of individuals with elevated risk of developing diabetes mellitus, followed by the implementation of effective prevention interventions can delay the onset of the disease and related complications. In this regard, recent studies have shown that miRNAs are useful as early markers of certain disease types, including diabetes. We used high throughput sequencing to assess miRNA expression profiles from whole blood of 12 individuals with screen-detected diabetes, 12 with prediabetes and 12 with normal glucose tolerance, matched for age, blood pressure, smoking and body mass index. We identified a total of 261 (57 novel) differentially expressed miRNA profiles between the study groups. Comparison of the miRNA expression profiles between prediabetess and diabetes revealed 25 common miRNA, but highlighted some interesting differences. For instance, three miRNAs (miR-126-3p, miR-28-3p miR-486-5p) were dysregulated in prediabetes compared to screen-detected diabetes. Target gene analysis showed thousands of potential genes and KEGG pathway analysis revealed 107 significant pathways of which some are involved signal transduction, cell-cell communications, cell growth and death, immune response, endocrine system and metabolic diseases. This first detailed African study has shown both known and novel differentially expressed miRNAs in relation to glucose tolerance.


PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility.
The consequences of PARP-1 disruption or inhibition on DNA single-strand break repair (SSBR) and radio-induced lethality were determined in synchronized, isogenic HeLa cells stably silenced or not for poly(ADP-ribose) polymerase-1 (PARP-1) (PARP-1(KD)) or XRCC1 (XRCC1(KD)). PARP-1 inhibition prevented XRCC1-YFP recruitment at sites of 405 nm laser micro irradiation, slowed SSBR 10-fold and triggered the accumulation of large persistent foci of GFP-PARP-1 and GFP-PCNA at photo damaged sites. These aggregates are presumed to hinder the recruitment of other effectors of the base excision repair (BER) pathway. PARP-1 silencing also prevented XRCC1-YFP recruitment but did not lengthen the lifetime of GFP-PCNA foci. Moreover, PARP-1(KD) and XRCC1(KD) cells in S phase completed SSBR as rapidly as controls, while SSBR was delayed in G1. Taken together, the data demonstrate that a PARP-1- and XRCC1-independent SSBR pathway operates when the short patch repair branch of the BER is deficient. Long patch repair is the likely mechanism, as GFP-PCNA recruitment at photo-damaged sites was normal in PARP-1(KD) cells. PARP-1 silencing elicited hyper-radiosensitivity, while radiosensitization by a PARP inhibitor reportedly occurs only in those cells treated in S phase. PARP-1 inhibition and deletion thus have different outcomes in terms of SSBR and radiosensitivity.


Angelica sinensis polysaccharides promotes apoptosis in human breast cancer cells via CREB-regulated caspase-3 activation.
Angelica sinensis polysaccharide (ASP) is purified from the fresh roots of Angelica sinensis (AS). This traditional Chinese medicine has been used for thousands of years for treating gynecological diseases and used in functional foods for the prevention and treatment of various diseases, such as inflammation and cancer. The antitumor activity of ASP is related to its biological activities, because it suppresses a variety of pro-proliferative or anti-apoptotic factors that are dramatically expressed in cancer cells of given types. In this study, we show that angelica sinensis polysaccharide induced apoptosis in breast cancer cells of T47D over-expressing the Cyclic AMP response element binding protein (CREB), inducing apoptosis-related signaling pathway activity. The result also found that ASP caused cell death was linked to caspase activity, accompanied by the loss of mitochondrial membrane potential, cytochrome c release, and Bax translocation from the cytosol to the mitochondria. We found that ASP significantly affected the poly-ADP-ribose polymerase (PARP), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL and apoptotic protease activating facter-1 (Apaf1) protein expression in a dose- and time-dependent manner. DAPI staining and Flow cytometry were used to analyze apoptosis. The nude mice xenograft model was used to evaluate the antitumor effect of ASP in vivo. ASP has profound antitumor effect on T47D cells, probably by inducing apoptosis through CREB signaling pathway. Thus, these results suggest that ASP would be a promising therapeutic agent for breast cancer.


Superior Laryngeal Nerve Palsy in Revision Anterior Cervical Surgery.
Most spine surgeons routinely obtain preoperative ENT evaluation of recurrent laryngeal nerve function when contemplating revision anterior approaches to the cervical spine to avoid the potentially catastrophic consequences of bilateral vocal cord palsy. By contrast, there is less awareness of the potential for superior laryngeal nerve (SLN) injury-although a bilateral injury can, like bilateral injuries of the recurrent laryngeal nerve, have serious clinical consequences. This case report describes a 74-year-old man who, after a contralateral revision anterior approach to the upper cervical spine, developed bilateral SLN injury causing aspiration pneumonia and respiratory failure. We discuss risk factors associated with subclinical SLN injury and define at-risk patients who would benefit from preoperative SLN screening before revision anterior cervical surgery.


Providing Long-Acting Reversible Contraception in an Academic Family Medicine Center.
Providing long-acting reversible contraception (LARC), which includes the intrauterine device (IUD) and the implant, falls within the scope of family medicine. The study objective was to describe 12-month rates of LARC continuation, LARC elective removal, and IUD expulsion in an academic family medicine center in New Jersey. We conducted a retrospective electronic chart review of 219 LARC insertions that occurred from June 2009--May 2012. Life table analyses were used to determine 12-month rates of LARC continuation, elective removal, and IUD expulsion. To explore differences in outcomes based upon training level (faculty versus trainees), we conducted Cox proportional hazard models. Of 219 LARC insertions, faculty performed 100 (45.7%), and trainees (residents and students) performed 119 (54.3%). The 12-month continuation rate for all devices was 78%. The elective removal rate at 12 months was 17%; trainee-placed devices were more likely to be electively removed than faculty-placed devices (HR 2.43, 95% CI=1.05--5.62). The IUD expulsion rate at 12 months was 7.0%; expulsion rates did not differ by level of training. These data provide support for the fact that family physicians in an academic setting can provide LARC with continuation, elective removal, and IUD expulsion rates similar to those observed in outpatient specialist clinics without resident training. Potential causes for the higher removal rate associated with trainee-inserted devices should be further explored.


Pharmacology, tolerance, and antiviral activity of vidarabine monophosphate in humans.
Vidarabine (adenine arabinoside) is a purine nucleoside useful in humans for therapy of herpes simplex virus encephalitis and herpes zoster virus infections in immunocompromised patients. However, the potential usefulness of vidaribine is limited by its poor solubility, which requires continuous infusion in relatively large volumes of intravenous fluid. Vidarabine 5'-monophosphate is highly soluble and has the advantage that it can be administered intermittently intramuscularly or intravenously. In a clinical, pharmacokinetic study, plasma levels and urinary excretion of vidarabine 5'-monophosphate were determined after intravenous and intramuscular administration in 29 immunosuppressed patients with herpes simplex or zoster virus infections at dosages of 15 to 30 mg/kg per day administered for 5 days. As determined by high-pressure liquid chromatography, vidarabine 5'-monophosphate was metabolized in a fashion comparable to the metabolism of vidarabine and its major metabolite in plasma was arabinosyl hypoxanthine. After administration, 40 to 50% of the vidarabine 5'-monophosphate was recovered from the urine as arabinosyl hypoxanthine, and 3 to 4% was recovered as vidarabine. Determinations of areas under the curve for arabinosyl hypoxanthine were not statistically different by dosage for intramuscular or intravenous routes of administration. At all dosages studied, viral clearance appeared to occur with therapy. The advantage of increased solubility will lead to controlled clinical investigations in which vidarabine 5'-monophosphate is administered by intramuscular or intravenous routes against targeted human herpesvirus infections.


Research output in immunology journals from Chinese authors: 10-year survey of literature.
Over the past decade, immunological research in China has developed rapidly. Currently, little is known about China's contribution to the immunology field. The present study was designed to study research output in immunology journals during 1999-2008 in the three different regions of China-Mainland China (ML), Hong Kong (HK) and Taiwan (TW). We also examined the research output from other top-ranking countries-the United States (USA), Japan, Germany, United Kingdom (UK) and France during 1999-2008. Articles published in 114 journals related to immunology were retrieved from the PubMed database. The number and percentage of articles in the world's output showed significantly positive trends during 1999-2008 in ML and TW, but the trend for HK was not significant. China contributed 2.7% of the total 114 journals, 0.3% of the top 10% journals with the impact factor (IF) scores. The USA contributed 32.1% of the total world's output, 47.5% of the top 10% journals with the IF scores and ranked first. Our analysis describes the research output from the three regions of China and the positive trend in China during 1999-2008. Also, by contrast with other top-ranking countries, our results imply China falls behind the ranks in conducting immunology research.


Dose Coefficient Calculation for Use in Dosimetry Assessment of a Fission-Based Weapon.
In the event of a fission-based weapon or improvised nuclear device (IND) detonation, dose coefficients can be harnessed to provide dose assessments for defense, emergency preparedness, and consequence management, as well as to prospectively inform the assessment of radiation biomarkers and development of medical prophylaxis countermeasures for defense and homeland security stakeholders and decision-makers. Although dose coefficients have previously been calculated for this group, they would apply specifically to the studied population, the 1945 Japanese cohort, after which their anthropomorphic computational phantoms were modeled. For this reason, applications to other populations may be limited, and instead, an assessment of a more standardized population is desired. We employed a series of computational human phantoms representing international reference individuals: UF/NCI voxel phantom series containing newborn, 1-, 5-, 10-, 15-, and 35-year-old males and females. Irradiation of the phantoms was simulated using the Monte Carlo N-Particle transport code to determine organ dose coefficients under four idealized irradiation geometries at three distances from the detonation hypocenter at Hiroshima and Nagasaki using DS02 free-in-air prompt neutron and photon fluence spectra. Through these simulations, age-specific dose coefficients were determined for individual organs. Various articulated PIMAL stylized phantoms were simulated as well to estimate the effect of body posture on dose coefficients and determine the effect of posture on dosimetric estimation and reconstruction. Results additionally demonstrate that 137Cs and the Watt fission spectra are not ideal general surrogate sources for fission weapons, which may be considered for experimental testing of medical countermeasures. Supplementary data provided tabulates the compilation of organ dose-rate coefficients in this study.


Comparing Semiconductor Nanocrystal Toxicity in Pregnant Mice and Non-Human Primates.
Rationale: Despite growing use of engineered nanomaterials (ENM) in applications from electronics to medicine, the potential risk to human health remains a critical concern within clinical use. ENM exposure during pregnancy can potentially cause reproductive toxicity even at levels that produce no measurable harm to animals in normal conditions. Methods: Phospholipid micelle-encapsulated CdSe/CdS/ZnS semiconductor nanocrystals with an average hydrodynamic diameter of 60 nm were intravenously injected during pregnancy in both rodent and nonhuman primate animal models. Cadmium concentration levels and maternal haematological and biochemical markers were determined, along with histopathological examination of major organs. Results: Nanocrystals were found to have crossed the placenta from mother to fetus in both rodents and nonhuman primates. However, the animal models display different responses with respect to reproductive toxicity. In the rodent model, toxicity symptoms are absent in treated subjects, with no observed gestational or fetal abnormalities and complications. A significantly higher miscarriage rate of 60% is recorded for macaques after prenatal nanoparticle administration. There was a miscarriage rate of 15% in the general population despite only ~0.16% of the initial cadmium dose present in the fetus. Blood and biochemical markers of treated macaques indicate acute hepatocellular injury within a week after nanoparticle administration. Histology of major organs of the miscarried macaque fetuses show no abnormalities. Conclusion: The potential of nanomaterials to cross the placenta and impact fetal survival in primates suggest the necessity of precautionary measures to prevent gestational exposure of ENMs.


The Gene Structure and Expression Level Changes of the GH3 Gene Family in Brassica napus Relative to Its Diploid Ancestors.
The GH3 gene family plays a vital role in the phytohormone-related growth and developmental processes. The effects of allopolyploidization on GH3 gene structures and expression levels have not been reported. In this study, a total of 38, 25, and 66 GH3 genes were identified in Brassica rapa (ArAr), Brassica oleracea (CoCo), and Brassica napus (AnACnCn), respectively. BnaGH3 genes were unevenly distributed on chromosomes with 39 on An and 27 on Cn, in which six BnaGH3 genes may appear as new genes. The whole genome triplication allowed the GH3 gene family to expand in diploid ancestors, and allopolyploidization made the GH3 gene family re-expand in B. napus. For most BnaGH3 genes, the exon-intron compositions were similar to diploid ancestors, while the cis-element distributions were obviously different from its ancestors. After allopolyploidization, the expression patterns of GH3 genes from ancestor species changed greatly in B. napus, and the orthologous gene pairs between An/Ar and Cn/Co had diverged expression patterns across four tissues. Our study provides a comprehensive analysis of the GH3 gene family in B. napus, and these results could contribute to identifying genes with vital roles in phytohormone-related growth and developmental processes.


Investigation of erythrocyte shape, plasma membrane fluidity and conformation of haemoglobin haemoporphyrin under the influence of long-term space flight.
The investigation of long-term space flight (SF) effect on the blood cells function is of great importance for modern space biology and medicine. We established that the number of discocytes decreased in the period of early rehabilitation after long-term SF. After SF plasma membrane fluidity and phospholipid content decreased and cholesterol content increased. After SF the amount of haemoglobin decreased and the parameters characterizing haemoglobin haemoporyphyrin (HH) conformation changed. We suppose that erythrocyte shape, membrane fluidity and HH conformation are among factors affecting oxygen transfer during and after space flight.


Web-based learning in professional development: experiences of Finnish nurse managers.
The aim of this article is to describe the nurse managers' expectations, attitudes and experiences on web-based learning before and after participation in a web-based course. Information technology has rapidly become more common in health care settings. However, little is known about nurse managers' experiences on web-based learning, although they have a crucial role in promoting the professional development of their staff. Diagnostic assignments (n = 18) written before and interviews (n = 8) taken after the web-based education. The data were analysed by inductive content analysis. Nurse managers found web-based education to be a suitable and modern method of learning. On the basis of their experience they found multiple ways to utilize web-based learning environments in health care. Information technology skills, equipment, support and time were considered essential in web-based learning. Additionally, they found that their own experience might lead to more widespread implementation of web-based learning in health care settings. Information technology skills of nurse managers and staff need to be developed in order to use information technology effectively. In order to learn in a web-based environment, everyone needs the opportunity and access to required resources. Additionally, nurse managers' own experiences are important to promote wider utilization of web-based learning.


Squaramide-Catalyzed Asymmetric Reactions.
Bifunctional squaramides have emerged as powerful hydrogen-bonding catalysts for promoting a wide array of useful asymmetric reactions, which provides convenient methods for the construction of complex molecular structures and chiral biologically active compounds. This review highlights the recent advances of our research group in the chiral squaramide-catalyzed asymmetric reactions, including Michael addition, Mannich reaction, aza-Henry reaction, Strecker reaction as well as cascade or sequential reactions.


Short stature in genetic syndromes: Selected issues.
Short stature, which is defined as height below 2 standard deviations of the mean height for the age and sex, is one of the most frequent reasons for medical consultations in children. Short stature may occur due to a constitutional delay in growth, familial short stature or chronic diseases, including many genetic syndromes, metabolic and endocrine disorders. In this article the authors provide a mini-review of the most frequent genetic syndromes associated with short stature that should be taken into account in the differential diagnosis process. Syndromes caused by chromosomal aberrations and gene mutations were divided into 2 main groups: syndromes that are associated with intrauterine growth retardation (IUGR) and those in which IUGR does not occur in the natural history of the patient. The authors described the most important anomalies in each syndrome. Metabolic diseases and skeletal dysplasias were omitted, as they are major separate groups of diseases involving growth delay.


Probing single-molecule fluorescence spectral modulation within individual hotspots with subdiffraction-limit image resolution.
The enhancement of the electromagnetic field on the rough metallic nanostructure has been extensively applied to obtain chemical or biological information about molecules with high sensitivity and has received much attention due to its potential applications in new types of devices based on nanoelectronics and nanophotonics. The typical size of the field enhancement area, the so-called hotspot, is approximately 1 order of magnitude smaller than the optical diffraction limit. In the present study, an optical super-resolution microscopic and spectroscopic approach is introduced to explore single-molecule fluorescence within a hotspot where nonhomogeneous spectral modulation is resolved beyond the optical diffraction limit for the first time. Distinct Stokes shifts from individual dyes were directly observed within single hotspots, which were found to be independent of the local electromagnetic field strength. The method reported here provides a robust tool to probe the optical properties of nanoresonantors with high temporal and spatial resolution.


Echinococcus metacestode: in search of viability markers.
Epidemiological studies have demonstrated that most humans infected with Echinococcus spp. exhibit resistance to disease. When infection leads to disease, the parasite is partially controlled by host immunity: in case of immunocompetence, the normal alveolar echinococcosis (AE) or cystic echinococcosis (CE) situation, the metacestode grows slowly, and first clinical signs appear years after infection; in case of impaired immunity (AIDS; other immunodeficiencies), uncontrolled proliferation of the metacestode leads to rapidly progressing disease. Assessing Echinococcus multilocularis viability in vivo following therapeutic interventions in AE patients may be of tremendous benefit when compared with the invasive procedures used to perform biopsies. Current options are F18-fluorodeoxyglucose-positron emission tomography (FDG-PET), which visualizes periparasitic inflammation due to the metabolic activity of the metacestode, and measurement of antibodies against recEm18, a viability-associated protein, that rapidly regresses upon metacestode inactivation. For Echinococcus granulosus, similar prognosis-associated follow-up parameters are still lacking but a few candidates may be listed. Other possible markers include functional and diffusion-weighted Magnetic Resonance Imaging (MRI), and measurement of products from the parasite (circulating antigens or DNA), and from the host (inflammation markers, cytokines, or chemokines). Even though some of them have been promising in pilot studies, none has been properly validated in an appropriate number of patients until now to be recommended for further use in clinical settings. There is therefore still a need to develop reliable tools for improved viability assessment to provide the sufficient information needed to reliably withdraw anti-parasite benzimidazole chemotherapy, and a basis for the development of new alternative therapeutic tools.


[A study of the central nervous system complications after hematopoietic stem cell transplantation.].
To study the incidence, risk factors and prognosis of central nervous system (CNS) complications after hematopoietic stem cell transplantation (HSCT) in order to prevent or reduce its occurrence, provide better diagnosis and treatment and improve the survival of the patients. A total of 640 patients who consecutively underwent HSCT in our hospital between May 2001 and December 2007 were included. The clinical outcomes of the patients who developed CNS complications were analyzed. The patients received stem cells from haploidentical family members (Haplo, n = 289), identical siblings (IS, n = 237), unrelated donors (URD, n = 83), unrelated cord blood (n = 14), syngeneic siblings (n = 9) or autologous peripheral blood (n = 8). Fifty-seven of 640 patients (8.9%) developed CNS complications. The incidences were 12.0%, 13.5% and 3.4% in URD-HSCT, Haplo-HSCT and IS-HSCT respectively (P < 0.001). The incidences of CNS complications were 19.4% and 8.3% in cases who received or did not receive conditioning with TBI (P = 0.047). There was no significant difference in the incidences of CNS complications between children (15.3%) and adults (8.3%) (P = 0.072). Similar incidences of CNS complications were seen in patients with hematological malignancies (8.9%) and non-malignant hematological disorders (7.7%) (P = 1.000). Five of the 57 patients developed two kinds of CNS complications. The patterns of CNS complications included relapse (17 cases), infections (15 cases), cyclosporine or FK506 encephalopathy (9 cases), cerebral hemorrhage (8 cases), cerebral infarction (2 cases), Wernicke's encephalopathy (1 case), skull fracture (1 case), drug-related meningitis (1 case), hepatic encephalopathy (3 cases), post-transplant lymphoproliferative disorder (1 case) and undetermined causes (4 cases). The overall mortality in the patients who developed CNS complications was 57.9% and 66.7% of them died of CNS complications. CNS complications are not uncommon after HSCT and they have high mortality and poor prognosis. Our data suggest that haplo-HSCT, URD-HSCT and conditioning with TBI, but not the age and types of hematological diseases are the risk factors for development of CNS complications. Relapse and infections are the most common CNS complications in HSCT recipients. Early diagnosis and appropriate management are crucial to the improvement of clinical outcomes in these patients.


Hypotensive effect of captopril and decreased rat uterine bradykinin receptors.
To determine the role of local bradykinin at the level of the vascular smooth muscle receptors in the hypotensive effect of captopril, we assessed the effects of prolonged intravenous infusions for up to 7 days of bradykinin (0.1 microgram/min) and captopril (1.7 micrograms/min) on systolic blood pressure and uterine bradykinin receptors in normotensive rats. Bradykinin infusion was associated with a transient fall in systolic blood pressure at Day 1 (117.5 +/- 2.8 mmHg vs. 125.8 +/- 1.7, p less than 0.05) and returned to control levels by Day 3. Following captopril infusion there was a similar but more persistent fall in systolic blood pressure (115.3 +/- 2.4 mmHg vs. 125.8 +/- 1.7, p less than 0.01 at Day 1 and 111.0 +/- 2.4 mmHg vs. 125.0 +/- 1.9, p less than 0.001 at Day7). After 2 days of bradykinin infusion the number of bradykinin receptors was decreased (39.9 +/- 2.1 fmol/mg protein vs. 49. 9 +/- 2.4, p less than 0.01) and returned to controls at Day 7, while captopril infusion induced a prolonged decrease (42.3 +/- 1.8 fmol/mg protein vs. 49.9 +/- 2.4, p less than 0.05 at Day 2 and 38.8 +/- 2.4 fmol/mg protein vs. 44.5 +/- 1.3, p less than 0.05 at Day 7). Present results suggest that the increased vascular tissue level of bradykinin can contribute directly to the acute hypotensive effect of captopril. However, it may play only a minor role for the chronic hypotensive effect of captopril.


Cyclic six-membered palladium complexes derived from palladium mediated C-N coupling of organonitrile and formamidine.
Reactions of N,N'-bis(2,6-diisopropylphenyl)formamidinium chloride (1) with palladium acetate in acetonitrile or propanenitrile results in the formation of cyclic six-membered triazapentadiene-palladium dichloride complexes (4 and 5). The reaction of formamidinium salt containing non-coordinating anions, such as (BF4)(-) (2) and (PF6)(-) (3) with palladium acetate in acetonitrile or propanenitrile leads to the formation of cationic bis(1,3,5-triazapentadiene)palladium complexes 6, 7 or 8, 9 respectively. However, the reaction with acrylonitrile afforded an unprecedented cyclic and anionic six-membered palladacycle complex (10). In addition a reaction of 1 with Pd(OAc)2 in THF afforded an acyclic palladium complex (11), which is a possible intermediate formed before conversion to the cyclic six-membered palladium complexes (4, 5 and 10) in presence of organonitriles.


Motivational interviewing interactions and the primary health care challenges presented by smokers with low motivation to stop smoking: a conversation analysis.
Research indicates that one third of smokers have low motivation to stop smoking. The purpose of the study was to use Conversational Analysis to enhance understanding of the process in Motivational Interviewing sessions carried out by primary care doctors and nurses to motivate their patients to quit smoking. The present study is a substudy of the Systematic Intervention on Smoking Habits in Primary Health Care Project (Spanish acronym: ISTAPS). Motivational interviewing sessions with a subset of nine participants (two interview sessions were conducted with two of the nine) in the ISTAPS study who were current smokers and scored fewer than 5 points on the Richmond test that measures motivation to quit smoking were videotaped and transcribed. A total of 11 interviews conducted by five primary health care professionals in Barcelona, Spain, were analysed. Qualitative Content Analysis was used to develop an analytical guide for coding transcriptions. Conversation Analysis allowed detailed study of the exchange of words during the interaction. Motivational Interviewing sessions had three phases: assessment, reflection on readiness to change, and summary. The interaction was constructed during an office visit, where interactional dilemmas arise and can be resolved in various ways. Some actions by professionals (use of reiterations, declarations, open-ended questions) helped to construct a framework of shared relationship; others inhibited this relationship (focusing on risks of smoking, clinging to the protocol, and prematurely emphasizing change). Some professionals tended to resolve interactional dilemmas (e.g., resistance) through a confrontational or directive style. Interactions that did not follow Motivational Interviewing principles predominated in seven of the interviews analysed. Conversational analysis showed that the complexity of the intervention increases when a health professional encounters individuals with low motivation for change, and interactional dilemmas may occur that make it difficult to follow Motivational Interview principles. Incorporating different forms of expression during the Motivational Interviewing could help to build patient-centred health care relationships and, for patients with low motivation to stop smoking, offer an opportunity to reflect on tobacco use during the office visit. The study findings could be included in professional training to improve the quality of motivational interviewing.


Using machine learning to quantify structural MRI neurodegeneration patterns of Alzheimer's disease into dementia score: Independent validation on 8,834 images from ADNI, AIBL, OASIS, and MIRIAD databases.
Biomarkers for dementia of Alzheimer's type (DAT) are sought to facilitate accurate prediction of the disease onset, ideally predating the onset of cognitive deterioration. T1-weighted magnetic resonance imaging (MRI) is a commonly used neuroimaging modality for measuring brain structure in vivo, potentially providing information enabling the design of biomarkers for DAT. We propose a novel biomarker using structural MRI volume-based features to compute a similarity score for the individual's structural patterns relative to those observed in the DAT group. We employed ensemble-learning framework that combines structural features in most discriminative ROIs to create an aggregate measure of neurodegeneration in the brain. This classifier is trained on 423 stable normal control (NC) and 330 DAT subjects, where clinical diagnosis is likely to have the highest certainty. Independent validation on 8,834 unseen images from ADNI, AIBL, OASIS, and MIRIAD Alzheimer's disease (AD) databases showed promising potential to predict the development of DAT depending on the time-to-conversion (TTC). Classification performance on stable versus progressive mild cognitive impairment (MCI) groups achieved an AUC of 0.81 for TTC of 6 months and 0.73 for TTC of up to 7 years, achieving state-of-the-art results. The output score, indicating similarity to patterns seen in DAT, provides an intuitive measure of how closely the individual's brain features resemble the DAT group. This score can be used for assessing the presence of AD structural atrophy patterns in normal aging and MCI stages, as well as monitoring the progression of the individual's brain along with the disease course.


[Study on the genetic variations of the major neutralization antigen VP7 of group A rotavirus type G1 in China].
To study the genetic variations of the major neutralization antigen VP7 of group A rotavirus, type G1 in China. Twenty-three isolates derived from seven cities (Beijing, Shenyang, Xinxiang, Shanghai, Shenzhen, Guangzhou and Chongqing) during the period of 1988-1998 were analyzed for the VP7 cDNA sequences. An obvious homology was observed in amino acid sequences of VP7 in the 23 isolates. Compared with the standard strain Wa, the variations were found at the position of aa 41, 49, 57, 65, 68, 74, 94, 97, 147, 170, 217, 218, 268, 281 and 291, respectively, and all of these were located in the variable region(VR)3,4,5,7,8 as well as in the C-terminal of the peptide. There seemed to be no remarkable divergence among the samples collected from different cities and all of them shared the same genetic lineage with the strain Jpn-417, though there might be one or two amino acid substitutions as time passed. When detected simultaneously with ELISA using G1 serotype-specific monoclonal antibody, the location of amino acid 91 was found presumably related to the neutralization epitope in VP7 of the type G1. Variations at some position may be resulted in the change of electropherotype. The results indicated that the recent isolates with representative genetic and antigenic features should be used to develop effective vaccines, and the antigenic variations should be monitored periodically.


Relative estimation of ventilatory fow rate in the eel (Anguilla anguilla L.)
Freshwater eels (Anguilla anguilla L.) were experimented on in order to measure ventilatory flow rate (by means of a direct method of collecting expired water), and simultaneously, to record sub-opercular pressure changes and opercular displacements (operculogram). Significant correlations (p less than 0.01) were found between the ventilatory flow rate (V) and various characteristics of operculiogram records. The relationships which are significant in each fish experimented on are; V = a(f.lo) + b; V = a(f.Ao) % b and V = a(f.Ao2) + b(f: ventilatory frequency: Ao and lo: mean amplitude and result of integration of opercular tracings). Considering the technical difficulties in measuring the ventilation flow rate of the eel, the easier operculographic recording methods lead to a correct estimation of relative changes in ventilatory flow rate, by using the refined relationship: V = a(Ao1.63).


Physiological adaptations induced by swimming in mice fed a high fat diet.
This study examined physiological variables of animals fed with a high-fat diet (HFD) or with a normal diet (ND) subjected to swimming at low and moderate level. Over 16 weeks, a group of animals was fed with HFD or ND, and at the 8 weeks, they started swimming with 50% or 80% of the maximum load achieved in the progressive work test. Weekly, body weight and the amount of ingested food were registered. The glycemic level was measured at the beginning, middle and at the end of the experiment. Adipose tissue, gastrocnemius muscles and hearts were collected for morphometry. The results showed that the animals fed an HFD had a minor caloric intake; however, the HFD increased body weight and adiposity, likely causing cardiac hypertrophy and an increase in the glycemic level. In this context, swimming with an 80% load contributed positively to weight control, adiposity, glycemic level, to control cardiac hypertrophy and induce hypertrophy in the gastrocnemius muscle. All parameters assessed showed better results for the ND animals. Therefore, the importance of fat consumption was emphasized in relation to obesity onset. The practice of swimming with an 80% load produced greater benefits than swimming with a 50% load for overweight treatment.


Effects of dopamine agonists on dopamine secretion from PC12 cells: lack of functional autoreceptor activity.
In an effort to determine if PC12 cells have functional dopamine autoreceptors we found that carbachol-stimulated release of dopamine from undifferentiated PC12 cells was inhibited by the dopamine autoreceptor agonists apomorphine and U-68553B. Studies were conducted to determine the mechanism of this effect. The inhibition of dopamine release by apomorphine or U-68553B did not appear to result from effects on dopamine metabolism. When cells were exposed to the dopamine agonists for 2 minutes no changes in dopa, DOPAC or dopamine were observed. Over this same time interval, apomorphine and U68553B at 10 microM inhibited carbachol-stimulated dopamine release by 45.6% and 57.4% respectively. However, these drugs failed to inhibit the potassium dependent release of dopamine from cells suggesting no direct involvement with ion fluxes. Furthermore, haloperidol did not block the inhibitory effects of U-68553B on PC12 cells. This would appear to preclude activation of a dopamine autoreceptor as a possible mechanism. Kinetic analysis revealed that U-68553B is most likely a non-competitive inhibitor (Ki = 2 microM) of the nicotinic acetylcholine receptor. These data do not provide evidence for functional dopamine autoreceptors on undifferentiated PC12 cells but rather indicate that dopamine agonists may alter dopamine release by alternative mechanisms.


URG4 expression is a novel prognostic factor for the progression of nasopharyngeal carcinoma and overall survival of patient.
URG4, a novel oncogene, is involved in the development and progression of various tumors. This study investigated the clinicopathological significance of URG4 in nasopharyngeal carcinoma (NPC). We used five NPC tissues and adjacent normal nasopharyngeal tissues to determine URG4 expression and found that URG4 was upregulated in NPC tissues. Immunohistochemistry analysis found URG4 was expressed positively in 97.1% (99/102) of NPC samples and highly expressed in 41.2% (42/102) of NPC samples. Its level was positively correlated with advancing clinical stage. Kaplan-Meier analysis with the log-rank test found that patients with high URG4 expression had poor outcome and patients with low URG4 expression had better survival. Statistical analysis showed that there was a significant correlation between URG4 expression and clinical stage, larger tumor size, and lymph node involvement. Cox-regression analysis showed that URG4 expression could serve as a prognostic factor for NPC patients. In summary, this study showed that URG4 was upregulated in NPC tissues, patients with high URG4 expression had poor outcome, and URG4 was found to be a valuable biomarker for NPC progression.


The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells.
The amyloid precursor protein (APP), a large glycoprotein highly expressed in neurons, is cleaved in its intramembranous domain by gamma secretase to generate amyloid-beta and a free carboxyl-terminal intracellular fragment (APP-CT), which has previously been suggested to interact with the adapter protein Fe65 and the histone acetyltransferase Tip60. An identical gamma secretase activity mediates cleavage of Notch, releasing an intracellular signaling domain that translocates to the nucleus. We examined the effect of an ectopically expressed 58-amino acid APP-CT fragment (APP-C58) on human H4 neuroglioma cells. We demonstrate by confocal microscopy and fluorescence resonance energy transfer analysis that APP-C58 translocates to the nucleus and forms a complex in the nucleus with the Tip60, independent of interactions with Fe65. APP-C58 transfected H4 cells undergo apoptosis within 48-72 h, marked by nuclear blebbing, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, and blockade by a caspase inhibitor. When nuclear access of APP-C58 is prevented by fusing with a strong membrane-targeting farnesylation domain, apoptosis is blocked. APP-C58-induced apoptosis was markedly enhanced by co-transfection with wild type Tip60 and decreased by mutant Tip60 lacking histone acetyltransferase activity, suggesting that Tip60 mediates APP-CT-induced cell death. Thus, gamma secretase cleavage of APP may contribute to Alzheimer's disease-related neurodegeneration in two ways: release of amyloid-beta and liberation of a bioactive carboxyl-terminal domain from membrane-bound APP.


Personality differences between alcoholics anonymous members and nonmembers.
The purpose of this study was to determine whether there are personality differences between members of Alcoholics Anonymous and nonmembers . A total of 91 alcoholics who were active members of A.A. and who had completed at least six months of abstinence were matched by race and sex with 91 alcoholics who had recently completed alcoholism treatment and who were not A.A. members. Four scales of the Eysenck Personality Questionnaire ( EPQ ), measuring toughmindedness , emotionality, extroversion and " fakability ," were administered to both groups. A 2 X 2 X 2 multivariate analysis of variance was performed using sex (men, women), race (American Indian, Caucasian) and group (A.A., non-A.A.) as the independent variables and the four EPQ scales as the dependent variables. The main effects of race and group were significant, but none of the interaction effects was significant. American Indian alcoholics were significantly more toughminded than the Caucasians. A.A. members were significantly more extroverted and less toughminded and emotional than nonmembers .


Esophagitis and esophageal strictures.
Esophagitis and esophageal strictures are relatively uncommon but significant diseases in companion animals. Often, an esophageal disorder is suspected on the animal's medical history and clinical signs. Esophagitis and acquired esophageal strictures are caused by prolonged contact of caustic substances or foreign bodies with the esophageal lining, leading to mucosal injury. In cases of stricture, damage extends into the submucosal and muscular layers. Timely detection and appropriate management of esophagitis and esophageal strictures significantly improve nutritional status, dysphagia, and pain and often return the animal to a normal quality of life. This article reviews the current literature and focuses on the diagnosis and treatment of esophagitis and esophageal strictures caused by fibrosis secondary to esophageal inflammation.


Platelets in liver transplantation: friend or foe?
Apart from the well-known role of blood platelets in hemostasis, there is emerging evidence that platelets have various nonhemostatic properties that play a critical role in inflammation, angiogenesis, tissue repair and regeneration, and ischemia/reperfusion (I/R) injury. All these processes may be involved in the (patho)physiological alterations occurring in patients undergoing liver transplantation. Experimental and clinical research points toward a dualistic role of platelets in patients undergoing liver transplantation, resulting in both beneficial and detrimental effects. Although a low platelet count is generally considered a risk factor for perioperative bleeding, recent studies have indicated that platelet function in patients with cirrhosis may not be as abnormal as previously assumed. Platelet transfusions are frequently considered in liver transplant recipients to correct low platelet counts and to prevent bleeding; however, evidence-based transfusion thresholds are lacking, and the other detrimental and nonhemostatic properties of platelets are generally not weighed in this respect. First, platelets have been shown to contribute to I/R injury of the liver graft via induction of sinusoidal endothelial cell apoptosis. Second, platelet transfusion has been identified as an independent risk factor for reduced survival via mechanisms that are not completely understood yet. On the other hand, recent studies indicate that platelets are critically involved in restoration after liver injury and in liver regeneration via serotonin-mediated mechanisms. These findings make platelets both friend and foe in liver transplantation. The scientific challenge will be to further dissect the mechanisms and clinical relevance of these contrasting roles of platelets in liver transplantation.


Characterization of peripheral blood T lymphocyte subsets in pulmonary sarcoidosis.
The peripheral blood of sarcoidosis patients has been shown to have abnormalities in the T Lymphocyte subsets. There is a consistent reduction in the helper/suppressor T Lymphocyte ratio caused by an increase in suppressor cell percentage as determined by monoclonal antibodies. These findings suggest that the peripheral blood T Lymphocyte subsets may be a useful adjunct for determining the underlying immunological cellular dysfunction in sarcoidosis patients.


A kinetic study on the binding of monomeric and polymeric derivatives of NAD+ to yeast alcohol dehydrogenase.
The binding to yeast alcohol dehydrogenase of NAD+ and its five derivatives (N6-[2-[N-[2-[N-(2-methacrylamidoethyl)carbamoyl]ethyl] carbamoyl]ethyl]-NAD (I), N6-[N-[2-[N-(2-methacrylamidoethyl) carbamoyl]ethyl]carbamoylmethyl]-NAD (II), copolymer of I with acrylamide (PA-I), copolymer of II with acrylamide (PA-II), and copolymer of I with N,N-dimethylacrylamide (PDMA-I] were studied statically and kinetically by the stopped-flow method by using the quenching of the enzyme fluorescence in the presence of pyrazole. Apparent dissociation constants and apparent rate constants were determined therefrom. It was concluded that (1) the N6-CH2CH2CO group (of I) is effective in making the derivative bind more strongly as well as faster than NAD+, while the N6-CH2CO group (of II) is not; and (2) the binding of the polymer derivatives of NAD+ to the enzyme is not essentially weaker and slower than that of native NAD+, but is even faster in some cases. The coenzymic activities of the above compounds were also determined with yeast alcohol dehydrogenase, pig heart malate dehydrogenase, and rabbit muscle lactate dehydrogenase.


Simvastatin and GGTI-2133, a geranylgeranyl transferase inhibitor, increase erythrocyte deformability but reduce low O(2) tension-induced ATP release.
Statin drugs inhibit 3-hydroxy-3-methylglutaryl CoA reductase, which reduces the synthesis of both cholesterol and isoprenoids (geranylgeranyl pyrophosphate and farnesyl pyrophosphate), with the latter being lipid molecules responsible for the posttranslational modification of small GTP-binding proteins such as Rho. Effects of statins, independent of lowering blood cholesterol levels, are thought to occur by inhibition of Rho/Rho kinase. The Rho kinase inhibitor Y-27632 has been reported to increase both erythrocyte deformability and low O2 tension-induced ATP release. Here, we tested the hypothesis that by inhibiting Rho/Rho kinase, simvastatin would increase both erythrocyte deformability and low O2 tension-induced ATP release. Male Sprague-Dawley rats were divided into two groups, control or simvastatin treated [simvastatin-supplemented chow (0.02%)], for 4 wk. Simvastatin treatment increased rat erythrocyte deformability compared with controls (n = 6, P < 0.05). However, erythrocytes of simvastatin-treated rats (n = 9, P < 0.05) exhibited impaired low O2 tension-induced ATP release. Similarly, the geranylgeranyl transferase inhibitor GGTI-2133 (10 μM) also increased deformability and impaired low O2 tension-induced ATP release in healthy human erythrocytes (P < 0.05). Interestingly, ATP release in response to mastoparan 7 (n = 7, P < 0.05), which directly activates Gi, and isoproterenol (n = 5, P < 0.05), which signals through Gs, was not altered by incubation with GGTI-2133. These results suggest that although statins increase erythrocyte deformability, likely by inhibiting geranylgeranylation, the finding that both statins and a geranylgeranyl transferase inhibitor attenuated low O2 tension-induced ATP release demonstrates that factors in addition to erythrocyte deformability are critical for ATP release in response to this physiological stimulus.


Identification of differentially expressed genes and small molecule drugs for the treatment of tendinopathy using microarray analysis.
Tendinopathy is a critical clinical problem as it is often asymptomatic at onset and during development, and is only recognized upon rupture of the tendon. It is common among recreational and competitive athletes. The present study sought to examine the molecular mechanism of the progression of tendinopathy by screening out differentially expressed genes (DEGs) and investigating their functions. In addition, the present study aimed to identify the small molecules, which exhibit potential effects, which could be utilized for the treatment of tendinopathy. The gene expression profile of tendinopathy, GSE26051 was downloaded from the Gene Expression Omnibus database, which included 23 control samples and 18 samples of tendinopathy. The DEGs were identified using the Limma package in the R programming language, and gene ontology and pathway enrichment analysis were performed. In addition, the potential regulatory microRNAs and the target sites of the transcription factors were screened out based on the molecular signature database. In addition, the DEGs were mapped to the connectivity map database to identify the potential small molecule drugs. A total of 318 genes were filtered as DEGs between diseased samples and normal control tendons. Additionally, genes, including laminin, α4, platelet‑derived growth factor α, laminin γ1 and Src homology 2 transforming protein 1 may induce tendinopathy through the focal adhesion pathway. Furthermore, the transcription factor, lymphoid enhancer‑binding factor 1 and its target genes, pantothenate kinase 2 and G protein‑coupled receptor kinase 5 were identified. The most significant microRNA, miR‑499, was screened and was found to regulate specific genes, including CUGBP2 and MYB. Additionally, the small molecules, Prestwick‑1082 and viomycin were identified to have the potential to repair disordered metabolic pathways and furthermore to remedy tendinopathy. The results of the present study assessed the mechanism of tendinopathy and screened small molecule drugs as potential treatments for this condition. In addition, the present findings have the potential for use in a clinical setting for the treatment of tendinopathy in the future.


Continuous tube feeding versus intermittent oral feeding for intermediate position enterostomy in infants.
The stoma of intermediate position enterostomy (IPE) often leads to high output, which is related to electrolyte abnormalities, and prolongs patient recovery post-operatively. The continuous nasogastric tube feeding method has the advantage of reducing the risk of feeding intolerance, and improves nutrient absorption. In the current study, we review our experience with continuous tube feeding and compare the clinical outcomes with intermittent oral feeding in patients with an IPE post-operatively. This was a retrospective review of 118 infants with IPEs in our hospital. The infants were categorized into two groups (intermittent oral feeding [OF] group [n=68 infants, 1-14 days of age] and continuous tube feeding [TF] group [n=50 infants, 1-14 days of age]). Differences in stool volume, daily intravenous fluid infusion, weight gain, nutrition indices, and post-operative complications were reviewed. The stool volume and intravenous fluid infusion in the TF group were less than the OF group from week 2. The weight gain was higher in the TF group than the OF group from week 3. The pre-albumin and retinol binding protein levels were significantly higher in the TF group than the OF group in weeks 3-4 post-operatively. The incidence of cholestasis and waterelectrolyte disturbances in the TF group was significantly lower than the OF group, and the incidence of intestinal obstruction was lower than the control group, but the differences were not significant. Continuous tube feeding had better clinical outcomes than intermittent oral feeding in IPE patients.


Nutrition in hepatic failure and liver transplantation.
Chronic liver disorders predispose to complex metabolic disturbances that lead to malnutrition, which is universally present in patients with hepatic failure undergoing liver transplantation and is associated with increased morbidity and mortality. The nutritional status is an important factor for survival after liver transplantation. Aggressive nutritional support is essential during all phases of liver transplantation. This review article focuses on nutritional problems seen in patients with hepatic failure, with emphasis on the nutritional assessment and support of patients before and after liver transplantation.


Revisiting bacterial cyclic nucleotide phosphodiesterases: cyclic AMP hydrolysis and beyond.
Cyclic-3',5'-adenosine monophosphate (cAMP) is a universal second messenger that regulates vital activities in bacteria and eukaryotes. Enzymes that hydrolyze cAMP, called phosphodiesterases (PDEs), negatively regulate the levels of this messenger molecule and are therefore crucial for signal 'termination'. In this minireview, I shall summarize the available literature on bacterial cAMP-PDEs, with particular emphasis on enzymes belonging to the ubiquitously encoded Class III PDE family exemplified by CpdA from Escherichia coli and Rv0805 from Mycobacterium tuberculosis. Using available biochemical, structural and biological information, I shall make a case for re-examining the functions of these enzymes as merely regulators of intrabacterial cAMP levels and suggest that some members of this class may have evolved cAMP-independent functions as well. Finally, I shall highlight the major lacunae in our understanding of these enzymes and present unanswered questions in the area.


Transcriptional activation in vitro by the human immunodeficiency virus type 1 Tat protein: evidence for specific interaction with a coactivator(s).
The Tat protein encoded by human immunodeficiency virus type 1 is a strong transcriptional activator of gene expression from the viral long terminal repeat and is essential for virus replication. We have investigated the molecular mechanism of Tat trans-activation by using a cell-free transcription system. We find that the trans-activation domain of Tat, amino acid residues 1-48 [Tat-(1-48)], can inhibit specifically--i.e., "squelch," transcriptional activation by full-length Tat [Tat-(1-86)]. Squelching depends upon the functional integrity of the Tat trans-activation domain because the mutant [Ala41]Tat-(1-48), which is defective in Tat trans-activation in vivo and in vitro, does not squelch in vitro Tat trans-activation. Inhibition is selective because Tat-activated transcription, but not Tat-independent transcription, is squelched. Preincubation experiments with Tat or Tat-(1-48) and nuclear extracts show that the trans-activation region of Tat can interact with cellular coactivator(s) required for Tat trans-activation and that this interaction can occur in the absence of the human immunodeficiency virus long terminal repeat promoter. Furthermore, the putative coactivator(s) mediating trans-activation by Tat differ from those mediating trans-activation by the acidic activator VP16, as shown by reciprocal squelching experiments in vitro. Our results suggest that specific cellular coactivator(s) are required for mediating activated transcription by human immunodeficiency virus type 1 Tat.


Critical structure factors of bilinear fields in O(N) vector models.
We compute the two-point correlation functions of general quadratic operators in the high-temperature phase of the three-dimensional O(N) vector model by using field-theoretical methods. In particular, we study the small- and large-momentum behavior of the corresponding scaling functions, and give general interpolation formulas based on a dispersive approach. Moreover, we determine the crossover exponent phi(T) associated with the traceless tensorial quadratic field, by computing and analyzing its six-loop perturbative expansion in fixed dimension. We find phi(T)=1.184(12), phi(T)=1.271(21), and phi(T)=1.40(4) for N=2,3,5, respectively.


[Endoscopic third ventriculostomy: risk factors for failure and evolution of ventricular size].
Endoscopic third ventriculostomy is the treatment of choice for non communicating hydrocephalus at our institution. Several factors have been associated with failure of endoscopic third ventriculostomy. The goals of the study have been to evaluate the outcome, the influence of factors theoretically prone to failure of ventriculostomy and the evolution of ventricular size. Fifty-six patients (mean age 48.5 yrs) treated with an endoscopic third ventriculostomy during the period 1997-2002 were analysed retrospectively. Hydrocephalus was classified as acute (68%) and chronic forms. Etiology was classified in space-occupying lesions (59%), primary aqueductal stenosis (34%) and Chiari malformation (7%). The presence of the following factors theoretically prone to failure was considered: age below one year, history of mielomeningocele, cerebrospinal fluid (CSF) infection, intracranial haemorrhage, radiotherapy, craniotomy and previous treatment of hydrocephalus with a shunt. Ventricular size was measured linearly with four ventricular index pre- and postoperatively. The global success rate was 71.4% (mean follow-up 26 months). Endoscopic third ventriculostomy for hydrocephalus secondary to cerebral metastases obstructing CSF pathways was associated with a higher risk of failure (p=0.006). None of the risk factors considered was associated with a higher risk of failure. The evolution of the ventricular size measured with linear methods is associated with outcome. Evans ratio, third ventricle index, cella media index and ventricular score decreased in patients whose outcome is satisfactory and increased in those cases deemed clinical failures (p< 0.05). The risk of failure increases in patients with cerebral metastases close to CSF pathways, likely due to the concurrence of mechanisms other than obstruction. Changes in ventricular size are associated with outcome.


[Observation on therapeutic effect of round-sharp needle of new nine-needle and elongated needle for piriformis syndrome with triple puncture method].
To compare the efficacy differences between round-sharp needle of new nine-needle and elongated needle for piriformis syndrome, and explore its action mechanism. Eighty cases were randomly divided into a round-sharp needle of new nine-needle group (round-sharp needle group) and an elongated needle treatment group (elongated needle group), 40 cases in each group. The round-sharp needle group was treated with round-sharp needle (0.60 mm x 125 mm) at three points in piriformis with triple puncture method, while the elongated needle group was treated with elongated needle of ordinary specifications (0.32 mm x 125 mm) at three points in piriformis with triple puncture method. Besides, the two groups were also treated with routine acupuncture at Weizhong (BL 40) and Yanglingquan (GB 34), 3 times every week, 2 weeks as one course of treatment. After one course of treatment, the clinical effect was evaluated and the pain threshold values were measured before and after treatment in the two groups. The total effective rate in the round-sharp needle group was 92.5% (37/40), which was superior to 77.5% (31/40) in the elongated needle group (P < 0.05). Compared before treatment, the pain threshold values after treatment in two groups were improved significantly (both P < 0.01). The increment of pain threshold value in the round-sharp needle group was higher than that in the elongated needle group (P < 0.01). Round-sharp needle of new nine-needle is effective in treatment of piriformis syndrome and is better than ordinary elongated needle, which is related to that it can effectively increase pain threshold value of the local tissue.


Calcium ionophore, A23187 and its amino acid complexes: spectroscopic and molecular modeling studies.
The circular dichroism, fluorescence, Nuclear Magnetic Resonance and BLM conductance studies indicate that A23187 forms a stable complex with amino acids at low ionophore concentrations (< 10(-4)M). However, A23187 prefers to be in a dimeric structure with no significant binding to amino acids, at concentrations higher than 10(-4)M. It was also observed that at lower concentrations, at which the amino acids bind to the ionophore, the affinity for calcium ions was several orders of magnitude lower than that at higher ionophore concentrations. We have also conducted molecular modeling studies to examine the structure of the A23187 dimer and its amino acid complexes. The results of these modeling studies strongly support our experimental results and validate the formation of a hydrogen bonded and energetically stable A23187 dimer and its amino acid complexes.


Palladium or platinum exacerbates hydroxyl radical mediated DNA damage.
Strand breakage of supercoiled pBR322 DNA by a Fenton system is increased in the presence of palladium or platinum (Pt) ions. Neither Pd nor Pt ions can substitute for iron in the Fenton system. We have obtained several lines of evidence that Pd and Pt ions in the presence of a Fenton system can augment the production of OH., as monitored by a spectrophotometric method quantifying hydroxylated salicylate or by a fluorometric method quantifying catechol production. Furthermore, the promoting effect of both metal ions on OH. production was substantiated by the identification of multiple hydroxylated products of salicylate [2,3-dihydroxybenzoate (A), 2,5-dihydroxybenzoate (B), and catechol (C)] using HPLC. The concentrations of A, B, and C produced in the control were 4.5, 8.0, and 2.0 microM, respectively; whereas, their respective concentrations increased to 23.6, 42.0 and 10.0 microM with the addition of Pd ions. The observed phenomenon was further confirmed by the identification of HO-DMPO spin adducts using ESR spectroscopy. Taken together, our data suggest that the mechanism of Pd or Pt ion-mediated exacerbation of DNA damage by a Fenton system is due to the promotion of OH. production by these metal ions.


[Monitoring of extravascular lung water in patients with severe sepsis].
The key objective of the case study was the possibility to monitor the extravascular lung water (EVLW) in severe cases. Twelve mechanically ventilated patients with severe sepsis complicated by septic shock and by an acute lung injury (ALI) were involved in the prospective study. The measurements, performed on days 1 and 3 after the onset of sepsis, comprised hemodynamics, EVLW as assessed by Pulsion PiCCO method, blood gases and severity scores. The EVLW correlated significantly with lung injury score (r = 0.46), oxygenation (r = -0.46) and with pulmonary compliance (r = -0.58) versus the central venous pressure. The EVLW and lung injury scores were found to be essentially higher in non-survivors on day 3. The clinical situations, described in the present article, are indicative of a potential EVLW value applicable to sepsis treatment. Finally, the monitoring of EVLW is a useful tool in the purpose-oriented therapy of sepsis-induced ALI; moreover, the method has an important prognostic value.


Chloroquine Improves Deoxynivalenol-Induced Inflammatory Response and Intestinal Mucosal Damage in Piglets.
We investigated the effects of rapamycin (RAPA) and chloroquine (CQ) in supporting growth performance and the intestinal mucosal barrier in response to deoxynivalenol (DON) in piglets. A total of 32 healthy weaned piglets (bodyweight 7.10 ± 0.58 kg) were divided into four groups and treated daily with RAPA (1 mg/kg BW), CQ (10 mg/kg BW), or a control volume of normal saline (two groups) until the end of the experiment. After feeding a basal diet for seven days, three groups were then switched to mildewed feed containing 1 mg kg/DON for a further seven days. In contrast to the control group, DON-treated piglets showed decreased average daily gain (ADG) and daily feed intake (ADFI), as well as negatively affected intestinal morphology as indicated by villus height, crypt depth, and tight junction protein expression. A group treated with RAPA and DON showed increased intestinal autophagy, aggravated inflammatory responses, and damage to the intestinal mucosa and permeability, leading to reduced growth performance. Meanwhile, a group treated with CQ and DON showed indices comparable to the non-DON control group, with alleviated inflammatory cytokines and healthy intestinal morphology and structure. They also showed better growth performance compared to DON treatment alone. These findings have important implications for mediating autophagy against DON in vivo, as well as the potential for CQ in improving growth performance and maintaining intestinal barrier integrity in weanling piglets.


A single session of education for a patient with negative beliefs about low back pain: A case report of 16-month follow-up.
The effectiveness of education in patients with low back pain (LBP) remains controversial and inconclusive. This case report describes the long-term effects of a single educational session on the rehabilitation of a patient with chronic LBP (CLBP). A 57-year-old woman presented with the main complaint of LBP and inability to prostrate for several years. The intervention consisted of a single session of patient-specific education that targeted negative cognitive beliefs. This education included instructions about the obtained findings, spinal anatomy, patient reassurance, the relationship between imaging findings and patient symptoms, proposed treatment, and a home exercise program. The patient was able to independently complete the prostration task immediately after the session without pain. This improvement was maintained for at least 16 months, as demonstrated by the Numeric Pain Rate Scale, Patient-Specific Functional Scale, Fear Avoidance Belief Questionnaire, and the Keele STarT Back Screening Tool. In conclusion, a single session of patient-specific education was effective, both immediately and over the long term, in addressing pain and function in patients with CLBP.


Antifungal Susceptibility and Clinical Outcome in Neonatal Candidiasis.
Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI. This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18-22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III). Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed. Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.


Organic Cation Transporters are Involved in Fluoxetine Transport Across the Blood-Brain Barrier In Vivo and In Vitro.
The research and development of drugs for the treatment of central nervous system diseases faces many challenges at present. One of the most important questions to be answered is, how does the drug cross the blood-brain barrier to get to the target site for pharmacological action. Fluoxetine is widely used in clinical antidepressant therapy. However, the mechanism by which fluoxetine passes through the BBB also remains unclear. Under physiological pH conditions, fluoxetine is an organic cation with a relatively small molecular weight (<500), which is in line with the substrate characteristics of organic cation transporters (OCTs). Therefore, this study aimed to investigate the interaction of fluoxetine with OCTs at the BBB and BBB-associated efflux transporters. This is of great significance for fluoxetine to better treat depression. Moreover, it can provide a theoretical basis for clinical drug combination. In vitro BBB model was developed using human brain microvascular endothelial cells (hCMEC/D3), and the cellular accumulation was tested in the presence or absence of transporter inhibitors. In addition, an in vivo trial was performed in rats to investigate the effect of OCTs on the distribution of fluoxetine in the brain tissue. Fluoxetine concentration was determined by a validated UPLC-MS/MS method. The results showed that amantadine (an OCT1/2 inhibitor) and prazosin (an OCT1/3 inhibitor) significantly decreased the cellular accumulation of fluoxetine (P <.001). Moreover, we found that N-methylnicotinamide (an OCT2 inhibitor) significantly inhibited the cellular uptake of 100 and 500 ng/mL fluoxetine (P <.01 and P <.05 respectively). In contrast, corticosterone (an OCT3 inhibitor) only significantly inhibited the cellular uptake of 1000 ng/mL fluoxetine (P <.05). The P-glycoprotein (P-gp) inhibitor, verapamil, and the multidrug resistance associated proteins (MRPs) inhibitor, MK571, significantly decreased the cellular uptake of fluoxetine. However, intracellular accumulation of fluoxetine was not significantly changed when fluoxetine was incubated with the breast cancer resistance protein (BCRP) inhibitor Ko143. Furthermore, in vivo experiments proved that corticosterone and prazosin significantly inhibited the brain-plasma ratio of fluoxetine at 5.5 h and 12 h, respectively. OCTs might play a significant role in the transport of fluoxetine across the BBB. In addition, P-gp, BCRP, and MRPs seemed not to mediate the efflux transport of fluoxetine.


Proteomic Analysis of the Molecular Mechanism of Lovastatin Inhibiting the Growth of Nasopharyngeal Carcinoma Cells.
Metabolic abnormalities are one of the essential features of tumors. Increasingly more studies have shown that lovastatin, a lipid-reducing drug, has visible inhibitory effects on tumors, but it has not been reported in nasopharyngeal carcinoma. In this paper, we explored the effects of lovastatin on the growth of nasopharyngeal carcinoma cells and its possible molecular mechanisms. After treating nasopharyngeal carcinoma cells with different concentrations of lovastatin, we found that lovastatin can inhibit the growth of nasopharyngeal carcinoma in a time- and dose-dependent manner. To explore the molecular mechanism of how lovastatin inhibits the growth of nasopharyngeal carcinoma, we examined the proteome of nasopharyngeal carcinoma cells treated at different time points using an LC/MS whole-proteomic strategy. The molecular network of differentially expressed proteins was constructed using IPA software. It was found that lovastatin inhibited the growth of nasopharyngeal carcinoma cells mainly by affecting the EIF2 and the mTOR pathways, which regulate cell metabolism and apoptosis. The results of this study provide a robust basis for further research on the molecular mechanism of lovastatin's inhibition of nasopharyngeal carcinoma cells and provide a reference for the clinical use of lovastatin in the treatment of nasopharyngeal carcinoma.


DDX53 Regulates Cancer Stem Cell-Like Properties by Binding to SOX-2.
This study investigated the role of cancer/testis antigen DDX53 in regulating cancer stem cell-like properties. DDX53 shows co-expression with CD133, a marker for cancer stem cells. DDX53 directly regulates the SOX-2 expression in anticancer drug-resistant Malme3MR cells. DDX53 and miR-200b were found to be involved in the regulation of tumor spheroid forming potential of Malme3M and Malme3MR cells. Furthermore, the self-renewal activity and the tumorigenic potential of Malme3MR-CD133 (+) cells were also regulated by DDX53. A miR-200b inhibitor induced the direct regulation of SOX-2 by DDX53 We therefore, conclude that DDX53 may serve as an immunotherapeutic target for regulating cancer stem-like properties of melanomas.