Proteolyzed matrix as a template for the regulation of tumor progression.
Pericellular proteolysis plays a pivotal function in cell invasion, a hallmark of tumor growth and metastasis. The minidegradome constituted of two matrix metalloproteinases (MMP), i.e. MMP-2 and MT1-MMP, associated with tissue inhibitor of metalloprotease-2 (TIMP-2) and integrin (alpha(v)beta(3)) or CD(44), is mainly involved in such invasive program. It catalyzes matrix degradation but, alternatively, proteolytic exposure of matricryptic sites or matrikines liberation by those enzymes regulates either positively or negatively tumor cell migration. That applies to types I and IV collagens, elastin, laminin 5, as described here, but such phenomenon might be extended to other matrix macromolecules. The development of tumors from epithelium origin is related to aging. Senescent fibroblasts are characterized by increased expression of MMPs, (particularly collagenase-1 (MMP-1) and stromelysin-1 (MMP-3)) and deposited matrix by those aged cells was shown to favor cancer cell growth. Thus, compositional variation of matrix-surrounding tumor cells, with formation of matricryptic sites and matrikines, can be considered as one main epigenetic factor contributing to tumor progression. A matrix-directed pharmacological approach in cancer is now emerging.


[Polarization of intrinsic fluorescence of proteins. II. Application for the study of equilibrium dynamics of tryptophan residues].
Additional support of some statements essential for interpretation of the data obtained by the rotational depolarization technique is given. They are: (i) after excitation at the red edge of absorption band of tryptophan there occurs no intertryptophan excitation energy transfer, (ii) at the red edge excitation 1La is the only excited state involved in absorption and emission processes, and (iii) the polarization value (PoCa, 0,256) experimentally measured for some model compounds retains to be consistent also for tryptophan residues in proteins and is independent of the polarity of their microenvironment. An attempt is made to prove possibility of intermolecular rotational mobility of the tryptophanyl indole rings inside the protein globule during the excited state lifetime.


Chain Coupling and Luminescence in High-Mobility, Low-Disorder Conjugated Polymers.
Optoelectronic devices based on conjugated polymers often rely on multilayer device architectures, as it is difficult to design all the different functional requirements, in particular the need for efficient luminescence and fast carrier transport, into a single polymer. Here we study the photophysics of a recently discovered class of conjugated polymers with high charge carrier mobility and low degree of energetic disorder and investigate whether it is possible in this system to achieve by molecular design a high photoluminescence quantum yield without sacrificing carrier mobility. Tracing exciton dynamics over femtosecond to microsecond time scales, we show that nearly all nonradiative exciton recombination arises from interactions between chromophores on different chains. We evaluate the temperature dependence and role of electron-phonon coupling leading to fast internal conversion in systems with strong interchain coupling and the extent to which this can be turned off by varying side chain substitution. By sterically decreasing interchain interaction, we present an effective approach to increase the fluorescence quantum yield of low-energy gap polymers. We present a red-NIR-emitting amorphous polymer with the highest reported film luminescence quantum efficiency of 18% whose mobility concurrently exceeds that of amorphous-Si. This is a key result toward the development of single-layer optoelectronic devices that require both properties.


Organotins in fish, shrimp, and cephalopods from the Pearl River Estuary, China: Dietary exposure risk to Indo-Pacific humpback dolphin and human.
Food has regularly been proven to be a key source of exposure to environmental pollutants, drawing attention to the dietary exposure risks of contaminants to mammals with significant daily food intake. Here, the levels of six organotin compounds (OTs) in 18 fish (n = 310), three cephalopods (n = 50), and one shrimp (n = 34) from the Lingdingyang (LDY) and west four region (WFR) of the Pearl River Estuary (PRE) and their dietary exposure risks to Indo-Pacific humpback dolphins and humans were first investigated. Total OT levels ranged from 3.84 to 901. 48 ng/g wet weight (ww) in 22 prey species from the LDY, and from 14.37 to 1364.64 ng/g ww in 19 species from the WFR. The LDY marine species generally accumulated higher butyltin levels but lower phentyltin levels than those in the WFR. All species have a phenyltin degradation index <1 and over 60 % of the sampled species have a butyltin degradation index <1, suggesting the PRE marine species might be exposed to the fresh discharge of OTs. A total of nine marine species exceeded the threshold levels of OT intake for adverse health effects on human juveniles by consumption, all 22 marine species posed high dietary risks to the PRE humpback dolphins. Moreover, probabilistic risk assessment using Monte Carlo simulation revealed that the probabilities of RQ values associated with WFR OT exposure higher than 1 were 18.87 % for human adults, 40.55 % for human juveniles, 100 % for both humpback dolphin adults and humpback dolphin juveniles. Our results highlighted the potentially high dietary exposure risks of OTs to marine mammals and residents in the PRE.


Antigenic sites of human growth hormone and related molecules detected by monoclonal antibodies to human growth hormone.
Four major antigenic sites for human growth hormone (hGH) were identified by 27 mouse monoclonal antibodies to hGH. Sites 1 and 2 are spatially close whereas sites 3 and 4 are located in other parts of the molecule. There also appears to be a subdivision of antigenic sites. A panel of 10 monoclonal antibodies, which included representatives from each antigenic site group, were used to determine cross-reactivities between hGH and human placental lactogen (hPL), human prolactin (hPRL), the 20,000 mol. wt variant of hGH (hGH20K) and a disulfide-linked dimer of hGH (diS-dimer). The data suggest a high conformational dependence of antigenic sites in hGH. DiS-dimer retains all four antigenic sites of hGH, although all have been altered. hGH20K retains sites 2-4 but site 1 has been dramatically altered. hPL retains site 3, whereas sites 1 and 4 have been dramatically altered and site 2 may be lacking. The extremely low cross-reactivity observed for hPRL is consistent with the dissimilarity between hGH and hPRL. Antigenic site 3 is the most conserved of all sites. The lack of structural similarity compared with hGH of site 1 in hGH20K and of a portion of site 3 in diS-dimer suggests that it may be possible to develop specific radioimmunoassays for these structural variants of hGH.


Psychosocial distress in cancer patients undergoing radiotherapy: a prospective national cohort of 1042 patients in Germany.
Psychosocial distress is common among cancer patients in general, but those undergoing radiotherapy may face specific challenges. Therefore, we investigated the prevalence and risk factors for distress in a large national cohort. We performed a secondary analysis of a multicenter prospective cross-sectional study which surveyed cancer patients at the end of a course of radiotherapy using a patient-reported questionnaire. Distress was measured with the distress thermometer (DT), using a cut-off of ≥ 5 points for clinically significant distress. Univariate analyses and multivariate multiple regression were used to assess associations of distress with patient characteristics. A two-sided p-value < 0.05 was considered statistically significant. Out of 2341 potentially eligible patients, 1075 participated in the study, of which 1042 completed the DT. The median age was 65 years and 49% (511/1042) of patients were female. The mean DT score was 5.2 (SD = 2.6). Clinically significant distress was reported by 63% (766/1042) of patients. Of the patient characteristics that were significantly associated with distress in the univariate analysis, a lower level of education, a higher degree of income loss, lower global quality of life, and a longer duration of radiotherapy in days remained significantly associated with higher distress in the multivariate analysis. Yet effect sizes of these associations were small. Nearly two in three cancer patients undergoing radiotherapy reported clinically significant distress in a large multicenter cohort. While screening and interventions to reduce distress should be maintained and promoted, the identified risk factors may help to raise awareness in clinical practice. DRKS: German Clinical Trial Registry identifier: DRKS00028784.


A quantitative assay method of Toxoplasma gondii HSP70 mRNA by quantitative competitive-reverse transcriptase-PCR.
Toxoplasma gondii (T. gondii)-derived heat shock protein 70 (T.g.HSP70) has been identified as a virulent molecule expressing only in T. gondii tachyzoites during lethal acute infection. Therefore, it is of importance to determine the expression of T.g.HSP70 mRNA in a quantitative manner for analysis of virulence of T. gondii in tissues. We have constructed a competitor T.g.HSP70 and have successfully established a quantitative competitive-reverse transcriptase-polymerase chain reaction (QC-RT-PCR) targeting T.g.HSP70 gene. By using the established QC-RT-PCR method, we have demonstrated that the copy number of T.g.HSP70 mRNA per T. gondii tachyzoite was highest in the lung among the organs examined in interferon-gamma knockout (GKO) mice.


Central and peripheral hypotensive effects of the optical isomers of nicardipine, a dihydropyridine calcium channel antagonist, in rats.
Central and peripheral hypotensive effects of (+)- and (-)-nicardipine (1-10 micrograms/kg i.v. or i.c.v.) were investigated in normotensive and SH rats. The results suggest that a stereoselectivity exists for the peripheral and central hypotensive effects of the nicardipine isomers. (+)-Nicardipine was shown to be 3-8 times as potent as the (-) isomer in reducing blood pressure in all the experiments.


Visualizing and trapping transient oligomers in amyloid assembly pathways.
Oligomers which form during amyloid fibril assembly are considered to be key contributors towards amyloid disease. However, understanding how such intermediates form, their structure, and mechanisms of toxicity presents significant challenges due to their transient and heterogeneous nature. Here, we discuss two different strategies for addressing these challenges: use of (1) methods capable of detecting lowly-populated species within complex mixtures, such as NMR, single particle methods (including fluorescence and force spectroscopy), and mass spectrometry; and (2) chemical and biological tools to bias the amyloid energy landscape towards specific oligomeric states. While the former methods are well suited to following the kinetics of amyloid assembly and obtaining low-resolution structural information, the latter are capable of producing oligomer samples for high-resolution structural studies and inferring structure-toxicity relationships. Together, these different approaches should enable a clearer picture to be gained of the nature and role of oligomeric intermediates in amyloid formation and disease.


Validation of diagnostic and predictive biomarkers for hereditary angioedema via plasma N-glycomics.
Hereditary angioedema (HAE) is a rare disease with heterogeneous clinical symptoms. It is vitally important to predict whether an HAE patient will develop severe symptoms in clinical practice, but there are currently no predictive biomarkers for HAE stratification. Plasma N-glycomes are disease-specific and have great potential for the discovery of non-invasive biomarkers. In this study, we profiled the plasma N-glycome of HAE patients from two independent cohorts to identify candidate biomarkers. Linkage-specific sialylation derivatization combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry detection and automated data processing was employed to analyze the plasma N-glycome of two independent type-1 HAE cohorts. HAE patients had abnormal glycan complexity, galactosylation, and α2,3- and α2,6-linked sialylation compared to healthy controls (HC). The classification models based on dysregulated glycan traits could successfully discriminate between HAE and HC with area under the curves (AUCs) being greater than 0.9. Some of the aberrant glycans showed response to therapy. Moreover, we identified a series of glycan traits with strong associations with the occurrence of laryngeal or gastrointestinal angioedema or disease severity score. Predictive models based on these traits could be used to predict disease severity (AUC > 0.9). These results were replicated in an independent cohort. We reported the full plasma N-glycomic signature of HAE for the first time, and identified potential biomarkers. These findings may play a critical role in predicting disease severity and guide the treatment of HAE in clinical practice. Further protein-specific and prospective studies are needed to validate our findings.


Biliary extracorporeal shockwave lithotripsy.
Biliary extracorporeal lithotripsy has been considered one of the alternatives to surgery for the treatment of gallstones in the bile ducts and in the gallbladder. Although this technique can fragment almost all gallstones, the clinical effectiveness of this new treatment modality must be measured by successful elimination of all fragments. Some physical principles, stone targeting, patient protocol, complications, and clinical results are presented.


Pepducins: an effective means to inhibit GPCR signaling by neutrophils.
G-protein-coupled receptors (GPCRs) have a central role not only in the competent development of an innate myeloid response to foreign pathogens but, if dysregulated, might contribute to phagocyte-mediated organ injury. Here, recent findings from a study in which neutrophil trafficking is inhibited by using a novel family of GPCR signaling inhibitors, known as pepducins, are discussed.


Pressure ulcer scanners rolled out to more trusts after successful trial.
A hand-held scanner that has helped to eliminate pressure ulcers is to be rolled out across NHS community hospitals where Virgin Care operates.


Inhibitory effect of a selective cyclooxygenase inhibitor on the invasion-stimulating activity of orthotopic fibroblasts for scirrhous gastric cancer cells.
The cyclooxygenase (COX)-2 inhibitor has been reported to impede the progression of gastric cancer, but underlying mechanisms remain unclear. We therefore investigated the effect of a COX-2 inhibitor, JTE-522, on the ability of orthotopic fibroblasts to stimulate invasion of scirrhous gastric carcinoma cells. The human scirrhous gastric cancer cell lines OCUM-2D or OCUM-2M, and human gastric fibroblasts (NF-21) were cultured in the absence or presence of JTE-522 at various concentrations. Cancer cells were then assayed for invasiveness in vitro by invasion assay. The effect of prostaglandins (PG) on growth factor production in NF-21 cells was examined by ELISA. Finally, the effects of orally administrated JTE-522 on orthotopically transplanted tumors were examined in nude mice. NF-21 cells stimulated invasion by OCUM-2D cells, an effect suppressed by JTE-522 at 5 x 10(-6) M. Hepatocyte growth factor (HGF) and PGE2 production by NF-21 cells were suppressed by JTE-522 (P < 0.01). PGE2 stimulated HGF production by NF-21 cells in a dose-dependent manner. JTE-522 significantly suppressed orthotopic tumor growth and lymph node metastasis, and also decreased HGF expression by fibroblasts within the gastric tumor. In conclusion, we found that gastric fibroblasts stimulated invasiveness in scirrhous gastric cancer cells, whereas a selective COX-2 inhibitor inhibited this paracrine effect by decreasing fibroblast PGE2 production, resulting in downregulation of HGF production.


Mechanisms involved in reduction of ochratoxin A produced by Aspergillus westerdijkiae using Debaryomyces hansenii CYC 1244.
Aspergillus westerdijkiae is one of the most relevant ochratoxin A (OTA) producing species within the Section Circumdati contaminating a number of agroproducts. The yeast Debaryomyces hansenii CYC 1244 was previously reported to be able to reduce growth and extracellular OTA produced by A. westerdijkiae. In this work, we examined several mechanisms possibly involved in this OTA reduction in in vitro experiments. OTA biosynthesis was evaluated by quantitation of expression levels of pks (polyketide synthase) and p450-B03 (cytochrome p450 monooxygenase) genes using newly developed and specific real time RT-PCR protocols. Both genes showed significant lower levels in presence of D. hansenii CYC 1244 suggesting an effect on regulation of OTA biosynthesis at transcriptional level. High levels of removal of extracellular OTA were observed by adsorption to yeast cell walls, particularly at low pH (98% at pH 3). On the contrary, no evidences were obtained of absorption of OTA into yeast cells or the production of constitutively expressed enzymes that degrade OTA by D. hansenii CYC 1244. These results described the potential of this yeast strain as a safe and efficient biocontrol agent to decrease OTA in A. westerdijkiae and two important mechanisms involved which may permit its application at different points of the food chain.


Palisaded myofibroblastoma--an uncommon tumour of lymph nodes.
We report a case of palisaded myofibroblastoma of the groin in a woman aged 20 years who presented with a large groin swelling. It is an uncommon benign tumour mainly arising in a lymph node.


[Comparative mapping of mink (Mustela vison) chromosome 8p: localization of three human BAC clones].
Using fluorescent in situ hybridization (FISH), three human BAC clones, localized in the terminal region of human chromosome 17p (HSA17p13; 1.44--3.68 Mp), were mapped to chromosome 8p of American mink (MVI8p). It was demonstrated that in MVI8p the region, homeologous to HSA17p13, was split into three fragments, which were detected within terminal, pericentric, and probably nucleolus-organizing regions. Using human BAC clones as heterologous markers for mapping of the gene sequences to the chromosomes of American mink, regional localization of eight sequences (PRPF8, SLC43A2, and RILP in MVI8p25; C17orf31 in MVI8p21-22; and CTNS, TAX1BP3, and P2RX5 in MVI8p11) was deduced.


A new peptide vaccine OCV-501: in vitro pharmacology and phase 1 study in patients with acute myeloid leukemia.
Wilms' tumor 1 (WT1) is a promising target of new immunotherapies for acute myeloid leukemia (AML) as well as for other cancers. OCV-501 is a helper peptide derived from the WT1 protein. OCV-501 induced OCV-501-specific Type 1 T-helper (Th1) responses dose-dependently and stimulated helper activity of the specific Th1 cells in peripheral blood mononuclear cells from healthy donors. OCV-501 also enhanced the increase in WT1-killer peptide-specific cytotoxic T lymphocytes. OCV-501 stimulated the OCV-501-specific Th1 clones in an HLA class-II restricted manner and formed a complex with HLA class-II protein. OCV-501-specific Th1 clones demonstrated significant OCV-501-specific cytolytic activity against OCV-501-pulsed B-lymphoblastoid cell line cells. Based on the pre-clinical results, phase 1 clinical trial was conducted. The result of this trial suggested that the subcutaneous administration of OCV-501 once weekly for 4 weeks at doses of 0.3, 1, and 3 mg in older patients with AML during complete remission was safe and well tolerated. The maximum tolerated dose was considered to be ≥3 mg. Of the nine subjects enrolled, neither relapse nor blast cells were observed during the study. Immunological responses were observed in OCV-501-specific delayed-type hypersensitivity test. This trial was registered at http://www.clinicaltrials.gov as NCT 01440920.


The anatomy of the caudal vas deferens in patients with a genital anomaly.
To present a hypothesis to explain the various anatomical variants of children with both a vas deferens and retained vagina. A child with both vasa entering into a blind-ending vaginal sinus opening into the prostatic urethra is presented, followed by a review of studies published in English describing children with a vas deferens and a retained vagina, and normal and abnormal vaginal development. The caudal end of the vas deferens and its relationship to a retained vagina are not well described in the literature. Adequate exocrine levels of androgen inside the Wolffian duct may allow its preservation in conjunction with a related vagina (secondary to inadequate endocrine levels of androgen), with incorporation of the vas into the vaginal wall. We propose that testosterone and Müllerian-inhibiting substance/anti-Müllerian hormone reach the Wolffian and Müllerian ducts by exocrine passage through the Wolffian duct. Thus, where the gonad is a dysgenetic testis the ipsilateral Wolffian duct will be preserved in proportion to the amount of testosterone available. Where a fetus has adequate exocrine secretion of androgen down the Wolffian duct, but inadequate endocrine blood levels of androgen, the vas deferens and vagina can coexist, with incorporation of the vas into the wall of the vagina.


Minimally invasive unicompartmental knee replacement with a nonimage-based navigation system.
In a prospective study, two groups of 20 unicompartmental knee replacements (UKR) each were operated either using a CT-free navigation system or the conventional minimal invasive technique. Radiographic assessment of postoperative alignment was performed by long-leg coronal and lateral radiographs. The results revealed a significant difference between the two groups in favor of navigation. In the computer-assisted group, 95% of UKRs were in a range of 4-0 degrees varus (mechanical axis) compared with 70% in the conventional group. The only inconvenience was a prolonged operation time (+19 min). Due to the limited exposure, the navigation system is helpful in achieving a more precise component orientation. The danger of overcorrection is diminished by real-time information about the leg axis at each step during the operation.


The Role of MAPT in Neurodegenerative Diseases: Genetics, Mechanisms and Therapy.
Microtubule-associated protein tau (MAPT) is a gene responsible for encoding tau protein, which is tightly implicated in keeping the function of microtubules and axonal transport. Hyperphosphorylated tau protein participates in the formation of neurofibrillary tangles (NFTs), which characterize many neurodegenerative disorders termed tauopathies. Genome-wide association studies (GWAS) have demonstrated numerous single nucleotide polymorphisms (SNPs) located in MAPT associated with various neurodegenerative diseases. Thus, it has been presumed that MAPT plays a crucial role in pathogenesis of neurodegeneration via affecting the structure and function of tau. Here, we review the advanced studies to summarize the biochemical properties of MAPT and its encoded protein, as well as the genetics and epigenetics of MAPT in neurodegeneration. Finally, given the potential mechanisms of MAPT to neurodegeneration pathogenesis, targeting MAPT and tau might present significant treatments of MAPT mutation-related neurodegeneration. Affirmatively, the identification of MAPT is extremely beneficial for improving our understanding of the pathogenesis of various neurodegenerative diseases and developing the mechanism-based therapies.


Genetic association of the functional CDHR3 genotype with early-onset adult asthma in Japanese populations.
Recent studies have demonstrated that a coding SNP (rs6967330, Cys529→Tyr) in cadherin-related family member 3 (CDHR3), which was previously associated with wheezing illness and hospitalizations in infancy, could support efficient human rhinovirus C (RV-C) entry and replication. Here, we sought to examine the genetic contribution of this variant to the development of adult asthma. We performed a candidate gene case-control association study of 2 independent Japanese populations (a total of 3366 adults). The odds ratios (ORs) for association of the A allele at rs6967330 with adult asthma were calculated according to age at onset of asthma. In addition, the effect of the CDHR3 genotype on the development of specific asthma phenotypes was examined. The A allele was associated with asthma (OR = 1.56; Mantel-Haenszel p = 0.0040) when the analysis was limited to patients with early-onset adult asthma. In addition, when the analysis was limited to atopic individuals, a stronger association of the CDHR3 variant with early-onset asthma was found, and interaction of the CDHR3 genotype with atopy was demonstrated. Finally, a significant association of this variant was specifically found with a phenotype of asthma characterized by atopy, early-onset, and lower lung function. Our study supports the concept that the CDHR3 variant is an important susceptibility factor for severe adult asthma in individuals who develop the disease in early life. The interaction between the CDHR3 variant and atopy indicates that genetic predisposition to early respiratory viral infection is combined with atopy in promoting asthma.


Transthyretin cardiac amyloidosis in aortic stenosis: Prevalence, diagnostic challenges, and clinical implications.
Transthyretin cardiac amyloidosis (ATTR-CA) is a challenging and underdiagnosed cause of heart failure. Advances in cardiac imaging have enabled noninvasive diagnosis of ATTR-CA, causing the recent upsurge in disease awareness and detection. ATTR-CA has been increasingly recognized in patients with degenerative aortic stenosis (AS). With the growing number of elderly patients undergoing aortic valve intervention, the identification of ATTR-CA in this group of patients is of high clinical importance. Timely and correct diagnosis is essential for amyloid-directed therapies, as well as deciding on the AS treatment strategy. This review provides a comprehensive overview of the recent studies investigating coexistence of these two entities. We present the data on the prevalence of ATTR-CA in AS and their prognostic associations. As the diagnosis of ATTR-CA may be challenging, special attention is paid to the diagnostic utility of different imaging modalities, namely, echocardiography, cardiovascular magnetic resonance, nuclear imaging, and distinctive imaging features, in patients with dual pathology. We also present a flowchart summarizing integrated imaging in patients with suspected ATTR-CA.


Deep learning for predicting major pathological response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer: A multicentre study.
This study, based on multicentre cohorts, aims to utilize computed tomography (CT) images to construct a deep learning model for predicting major pathological response (MPR) to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC) and further explore the biological basis under its prediction. 274 patients undergoing curative surgery after neoadjuvant chemoimmunotherapy for NSCLC at 4 centres from January 2019 to December 2021 were included and divided into a training cohort, an internal validation cohort, and an external validation cohort. ShuffleNetV2x05-based features of the primary tumour on the CT scans within the 2 weeks preceding neoadjuvant administration were employed to develop a deep learning score for distinguishing MPR and non-MPR. To reveal the underlying biological basis of the deep learning score, a genetic analysis was conducted based on 25 patients with RNA-sequencing data. MPR was achieved in 54.0% (n = 148) patients. The area under the curve (AUC) of the deep learning score to predict MPR was 0.73 (95% confidence interval [CI]: 0.58-0.86) and 0.72 (95% CI: 0.58-0.85) in the internal validation and external validation cohorts, respectively. After integrating the clinical characteristic into the deep learning score, the combined model achieved satisfactory performance in the internal validation (AUC: 0.77, 95% CI: 0.64-0.89) and external validation cohorts (AUC: 0.75, 95% CI: 0.62-0.87). In the biological basis exploration for the deep learning score, a high deep learning score was associated with the downregulation of pathways mediating tumour proliferation and the promotion of antitumour immune cell infiltration in the microenvironment. The proposed deep learning model could effectively predict MPR in NSCLC patients treated with neoadjuvant chemoimmunotherapy. This study was supported by National Key Research and Development Program of China, China (2017YFA0205200); National Natural Science Foundation of China, China (91959126, 82022036, 91959130, 81971776, 81771924, 6202790004, 81930053, 9195910169, 62176013, 8210071009); Beijing Natural Science Foundation, China (L182061); Strategic Priority Research Program of Chinese Academy of Sciences, China (XDB38040200); Chinese Academy of Sciences, China (GJJSTD20170004, QYZDJ-SSW-JSC005); Shanghai Hospital Development Center, China (SHDC2020CR3047B); and Science and Technology Commission of Shanghai Municipality, China (21YF1438200).


"Refusing appearance anxiety": A content analysis of body positive posts on Chinese social media.
"Body positivity" is a global movement trending on social media. It aims to challenge predominant appearance ideals in media and encourage women to accept and appreciate all bodies regardless of appearance. In Western contexts, an increasing number of research has explored the potential of body positive social media to benefit young women's body image. However, similar research in China is lacking. This study aimed to explore the content of body positivity posts on Chinese social media. Eight hundred eighty-eight posts from Xiaohongshu (one of China's most popular social media platforms) were coded for positive body image themes, physical appearance-related attributes, and self-compassion themes. The results showed that these posts depicted diverse body sizes and appearances. Additionally, while over 40% of the posts conveyed appearance-focused messages, most contained positive body image themes, and nearly half contained self-compassion themes. The study clarified the content of body positivity posts on Chinese social media and provides theoretical support for future research on body positivity in social media content in China.


Spin-Coated vs. Electrodeposited Mn Oxide Films as Water Oxidation Catalysts.
Manganese oxides (MnOx), being active, inexpensive and low-toxicity materials, are considered promising water oxidation catalysts (WOCs). This work reports the preparation and the physico-chemical and electrochemical characterization of spin-coated (SC) films of commercial Mn₂O₃, Mn₃O₄ and MnO₂ powders. Spin coating consists of few preparation steps and employs green chemicals (i.e., ethanol, acetic acid, polyethylene oxide and water). To the best of our knowledge, this is the first time SC has been used for the preparation of stable powder-based WOCs electrodes. For comparison, MnOx films were also prepared by means of electrodeposition (ED) and tested under the same conditions, at neutral pH. Particular interest was given to α-Mn₂O₃-based films, since Mn (III) species play a crucial role in the electrocatalytic oxidation of water. To this end, MnO₂-based SC and ED films were calcined at 500 °C, in order to obtain the desired α-Mn₂O₃ crystalline phase. Electrochemical impedance spectroscopy (EIS) measurements were performed to study both electrode charge transport properties and electrode-electrolyte charge transfer kinetics. Long-term stability tests and oxygen/hydrogen evolution measurements were also made on the highest-performing samples and their faradaic efficiencies were quantified, with results higher than 95% for the Mn₂O₃ SC film, finally showing that the SC technique proposed here is a simple and reliable method to study the electrocatalytic behavior of pre-synthesized WOCs powders.


The occlusal plane in the facial context: inter-operator repeatability of a new three-dimensional method.
The repeatability of a non-invasive digital protocol proposed to evaluate the three-dimensional (3D) position of the occlusal plane in the face is assessed. Dental virtual models and soft tissue facial morphology of 20 adult subjects were digitally integrated using a 3D stereophotogrammetric imaging system. The digital 3D coordinates of facial and dental landmarks were obtained by two different operators. Camper's (facial) and occlusal (dental) planes were individuated, and their 3D relationships were measured. The repeatability of the protocol was investigated and showed no significant differences in repeated digitizations. The angle between occlusal and Camper's planes was smaller than 2° in the frontal and horizontal projections. In the sagittal projection, the angle was observed to be, on average, 4.9°. The determined occlusal plane pitch, roll and yaw values show good agreement with previously published data obtained by different protocols. The current non-invasive method was repeatable, without inter-operator differences and can facilitate assessment of healthy subjects.


Retentive pin systems: a laboratory comparison of effectiveness of seating and other characteristics.
An evaluation in vitro of a number of currently available pin systems used for retaining direct restorative materials was made in this study. The criteria used for evaluation of the systems were completeness of pin seating in the prepared channels and overall effectiveness of the design of the shoulder-stop-style pins. There was a wide range of difference in the ability to seat pins completely, and the seating of the shoulder-stops on the dentin floor was quite inconsistent.


Hydrodynamic controls on connectivity of the high commercial value shrimp Parapenaeus longirostris (Lucas, 1846) in the Mediterranean Sea.
In the Strait of Sicily (SoS), a wide passage of the Mediterranean Sea, Parapenaeus longirostris, (Lucas, 1846; DPS hereafter) is the main target species of trawl fisheries, with an estimated annual market value of about 80 million euro. The exploitation of this resource is shared between Italian, Tunisian and Maltese bottom trawlers and its management raises social, economic and environmental interests. Recent stock assessment revealed high fishing mortalities and low size at first capture, thus promoting the adoption of a strategic plan for a sustainable management. However, the current knowledge of the geographical boundaries of the stock, supporting the implementation of such management plan is still poor. In this respect, under different hydrodynamic regimes, particle-tracking modelling was used to explore connectivity between both, known and unexplored, spawning and nursery areas of DPS in the SoS. Ensembles scenarios derived by model outcomes displayed decadal changes in connectivity between spawning and nursery areas in the north side of the SoS, hence confirming the presence of a single stock in this area. Expanding the area of investigation, the model results showed weak connectivity between spawning ground in the north side of SoS and nurseries on the African shelf-break. This method could support the spatial management of the stock, such as the protection of the nursery and spawning areas, by providing estimates of how connectivity is influenced by hydrodynamic regimes at different temporal and spatial scales.


Analysis and Causation of All Inaccurate Outcomes After WaveLight Contoura LASIK with LYRA Protocol.
This study analyzes every eye that had an outcome greater than 0.25D of sphere or astigmatism from planned goal after treatment with WaveLight Contoura with LYRA Protocol. The study included 266 consecutive eyes treated with LASIK Contoura using the LYRA Protocol. All LASIK procedures were performed on the WaveLight EX500 excimer laser. Flaps were created with either the Alcon WaveLight FS200 femtosecond laser or the Moria M2 microkeratome. Eyes that were off by >0.25 diopters (D) sphere or cylinder from the targeted goal within 3 months after surgery were identified and analyzed for cause. Topographical, higher-order aberration, and epithelial maps were created. Causes for inaccurate outcomes were biomechanical corneal change from LASK flap creation (9.78% of total eyes), pre-operative epithelial compensation of corneal higher-order aberration (4.1% of total eyes), changes to lamellar corneal tension from laser ablation causing a hyperopic shift (1.9% of total eyes), epithelial thickening over the ablation area post-operatively causing a refractive change (1.5% of total eyes), and posterior astigmatism (0.75%). The causes of the majority of inaccurate outcomes have not been properly defined and must be incorporated into further improving outcomes. Current and planned advances in technology do not address the majority of these causes.


Hippocampal volume is preserved and fails to predict recognition memory impairment in aged rhesus monkeys (Macaca mulatta).
Aged monkeys exhibit deficits in memory mediated by the medial temporal lobe system, similar to the effects of normal aging in humans. The contribution of structural deterioration to age-associated memory loss was explored using magnetic resonance imaging techniques. We quantified hippocampal, cerebral and ventricular volumes in young (n = 6, 9-12 years) and aged (n = 6, 24-29 years) rhesus monkeys. Eleven subjects were tested on a recognition memory task, delayed non-matching-to-sample (DNMS). Compared to young animals, aged monkeys exhibited robust learning deficits and significant memory impairments when challenged with longer retention intervals. Hippocampal volume was statistically equivalent across age groups, differing by less than 6%, and there was no correlation between this measure and DNMS performance. Variability in cerebral volume was greater in the aged compared to young monkeys and this parameter was marginally correlated with DNMS performance with a 10-min delay. These findings confirm and extend the conclusion of recent post-mortem histological analyses demonstrating that normal cognitive aging occurs independently of gross structural deterioration in the primate hippocampus.


A VxD-based automatic blending system using multithreaded programming.
This paper discusses the object-oriented software design for an automatic blending system. By combining the advantages of a programmable logic controller (PLC) and an industrial control PC (ICPC), an automatic blending control system is developed for a chemical plant. The system structure and multithread-based communication approach are first presented in this paper. The overall software design issues, such as system requirements and functionalities, are then discussed in detail. Furthermore, by replacing the conventional dynamic link library (DLL) with virtual X device drivers (VxD's), a practical and cost-effective solution is provided to improve the robustness of the Windows platform-based automatic blending system in small- and medium-sized plants.


Early treatment with talk therapy or antidepressants in severely bereaved people and risk of suicidal behavior and psychiatric illness: an instrumental variable analysis.
Losing a loved one to death is a common and natural life-course experience. Still, bereavement has been associated with an increased risk of suicidal behavior and psychiatric hospitalization and little is known of how to counter these adverse events. We aimed to study the effect of early treatment in primary care with talk therapy (TT) or antidepressants (AD) in severely bereaved people. We conducted a population-based cohort study including 207,435 adult Danes who experienced a severe loss in 1996-2013. We compared treatment and no treatment with either of the two treatment regimens within 6 months after the loss. The main outcome was a serious mental health condition (defined as suicide, deliberate self-harm, or psychiatric hospitalization) occurring >6 months after bereavement. Adjusted risk differences (RDs) 2 years after bereavement were calculated using both standard regression analysis and instrumental variable analysis (IVA) in which estimated physician preferences for treatment served as instruments. The standard adjusted regression analysis showed a higher risk of developing a serious mental health condition associated with both TT (RD, 7.1; 95% CI, 5.0 to 9.1 per 1000 people) and AD (RD, 30.1; 95% CI, 25.7 to 34.6 per 1000 people). The IVA, which was used to control for unmeasured confounding, showed that TT was associated with a lower risk of a serious mental health condition (RD, -17.1; 95% CI, -30.7 to -3.5 per 1000 people), whereas the results were inconclusive for AD (RD, -8.6; 95% CI, -62.6 to 45.4 per 1000 people). This study suggests that early treatment with TT is associated with reduced long-term risk of serious mental health conditions in severely bereaved people. No clear benefit or harm of treatment with AD after bereavement was ascertained since the statistical precision was low.


American College of Cardiology--48th annual scientific session. 7-10 March 1999, New Orleans, LA, USA.
This scientific session was designed to provide participants with the most up-to-date information on cardiovascular (CV) research. The emphasis of this year's conference included: clinical trials involving growing blood vessels; vitamin E and fish oil; invasive versus non-invasive treatments; angioplasty versus stents; and, new oral antiplatelet drugs. Invited speakers, via podium and poster presentations, provided comprehensive overviews on these topics. The targeted audience for this symposium was scientists and physicians involved in CV research. Over 2300 abstracts were presented during this three-day conference.


Effects of various media on micellization, adsorption and thermodynamic behaviour of imipramine hydrochloride and antimicrobial surfactant mixtures.
The effect of various media (aqueous, NaCl, urea (U) and thiourea (TU)) on the micellization and adsorption activity of varied mixtures of imipramine hydrochloride (IMP) and benzethonium chloride (BZCl) is investigated via tensiometry. In an aqueous medium, the interactions between IMP and BZCl are also evaluated using UV-visible and FTIR spectroscopy. The interaction between components increases with increased mole fraction (α 1) of BZCl in the mixed system (IMP + BZCl). Different parameters, such as micellar and the mixed monolayer component composition, the interaction parameters of the solution and the interface, the activity coefficients of the components in solution and at the interface, and thermodynamic parameters, are computed using different proposed theoretical models (i.e. Clint, Motomura, Rubingh and Rosen). The cmc values obtained for the pure components and mixtures (IMP + BZCl) of all the compositions are found to be less in NaCl than in the aqueous solution while found more in the presence of U or TU. TU is more effective in increasing the cmc of the pure and mixed systems than U. The Gibbs free energy ( Δ G mic ∘ ) values of the studied pure and mixed systems are negative, showing the spontaneous nature of the reaction.


Beneficial effects of magnetite nanoparticles on soybean-Bradyrhizobium japonicum and alfalfa-Sinorhizobium meliloti associations.
Nanoparticles (NPs)-based growth stimulators have promising usage in agriculture. This research analyzed the impact of citric acid-coated magnetite nanoparticles (Fe3O4-NPs; 50 mg Fe L-1) added once at pre-sowing on soybean and alfalfa seedlings growing in association with their corresponding microsymbiont partners, Bradyrhizobium japonicum and Sinorhizobium meliloti; also on the in vitro growth rate of these microorganisms. Fe-EDTA (50 mg Fe L-1) was used as a comparator. Fe3O4-NPs significantly augmented the growth rate constant (7-17%) and extracellular polysaccharides production of both microsymbionts (B. japonicum: 2-fold; S. meliloti: 43%), which probably favored bacterial adhesion to the root hairs. In both legumes, Fe3O4-NPs increased chlorophyll content (up to 56% in soybean) and improved plant growth, evidenced by a greater root biomass system (80-90% higher than the control), and increased shoot biomass (30-40%). Besides, Fe3O4-NPs addition resulted in earlier nodule formation and enhanced nodule biomass (about 2.5-fold in both species). Nodules were mainly located in the crown of the root in the NP50 treatment, while they were evenly distributed along lateral roots in the control and the comparator. Fe3O4-NPs also augmented significantly nodule leghemoglobin content (∼50-70%) and total N in legumes' shoots (ca. 20%). CAT activity increased only under NP50 treatment and no symptoms of oxidative damage were evidenced. In this work, we found that besides not being toxic neither to soybean and alfalfa plants nor to their microsymbiont partners, Fe3O4-NPs do not exert adverse effects on the symbioses establishment; oppositely, a more efficient nodulation pattern was verified in both plant species.


Cortical depth-dependent modeling of visual hemodynamic responses.
A physiologically based three-dimensional (3D) hemodynamic model is developed to predict the experimentally observed blood oxygen level dependent (BOLD) responses versus the cortical depth induced by visual stimuli. Prior 2D approximations are relaxed in order to analyze 3D blood flow dynamics as a function of cortical depth. Comparison of the predictions with experimental data for evoked stimuli demonstrates that the full 3D model performs at least as well as previous approaches while remaining parsimonious. In particular, the 3D model requires significantly fewer assumptions and model parameters than previous models such that there is no longer need to define depth-specific parameter values for spatial spreading, peak amplitude, and hemodynamic velocity.


Newly developed method for mouse olfactory behavior tests using an automatic video tracking system.
The mouse is the most popular animal model in olfactory research. Behavior tests with odorants are essential for determining olfactory phenotype. To the best of our knowledge, the mouse olfactory behavior test has not been standardized, making the results vulnerable to inter-observer variation. We sought to develop a new mouse olfactory behavior test assessed by an automatic video tracking system with minimal inter-observer variation. A video-tracking system was used to automatically track mouse behavior in standard breeding cages with C57BL/6N mice. We tested two odorants (peanut butter for the preference test, 2MB acid for the avoidance test) and distilled water (for a control). Mouse behavior was recorded for 3min and analyzed. For the preference test, investigation time was measured. For the avoidance test, time spent in sectors away from the odorant zone was measured. To confirm our experimental settings, we also evaluated an anosmia mouse model prepared with intranasal administration of ZnSO4. All strains of mice showed reproducible behavior patterns of preference or avoidance for the odorants. The anosmia mouse model, as expected, failed to show an olfactory ability for preference or avoidance, and this was well-matched by histologic changes caused by the ZnSO4 treatment. The automatic video tracking system successfully tracked and automatically calculated mouse behavior with good reproducibility. Our olfactory behavior test offers a simple and accurate method to evaluate olfactory function in mice. This test can be utilized as a possible standard method to search for features of olfactory phenotypes in mice.


Maternal-Newborn Health System Changes and Outcomes in Ontario, Canada, During Wave 1 of the COVID-19 Pandemic-A Retrospective Study.
To determine the population-level impact of COVID-19 pandemic-related obstetric practice changes on maternal and newborn outcomes. Segmented regression analysis examined changes that occurred 240 weeks pre-pandemic through the first 32 weeks of the pandemic using data from Ontario's Better Outcomes Registry & Network. Outcomes included birth location, length of stay, labour analgesia, mode of delivery, preterm birth, and stillbirth. Immediate and gradual effects were modelled with terms representing changes in intercepts and slopes, corresponding to the start of the pandemic. There were 799 893 eligible pregnant individuals included in the analysis; 705 767 delivered in the pre-pandemic period and 94 126 during the pandemic wave 1 period. Significant immediate decreases were observed for hospital births (relative risk [RR] 0.99; 95% CI 0.98-0.99), length of stay (median change -3.29 h; 95% CI -3.81 to -2.77), use of nitrous oxide (RR 0.11; 95% CI 0.09-0.13) and general anesthesia (RR 0.69; 95% CI 0.58- 0.81), and trial of labour after cesarean (RR 0.89; 95% CI 0.83-0.96). Conversely, there were significant immediate increases in home births (RR 1.35; 95% CI 1.21-1.51), and use of epidural (RR 1.02; 95% CI 1.01-1.04) and regional anesthesia (RR 1.01; 95% CI 1.01-1.02). There were no significant immediate changes for any other outcomes, including preterm birth (RR 0.99; 95% CI 0.93-1.05) and stillbirth (RR 1.11; 95% CI 0.87-1.42). Provincial health system changes implemented at the start of the pandemic resulted in immediate clinical practice changes but not insignificant increases in adverse outcomes.


Further experimental evidence for the involvement of ecdysone in the control of meiotic reinitiation in oocytes of Locusta migratoria (Insecta, Orthoptera).
Ecdysone has recently been shown to be able to trigger meiotic reinitiation in vitro in submature oocytes of Locusta. In the present study we have experimentally depressed (by 60-70%) ecdysone biosynthesis in the ovaries of adult females by rearing them on a diet with a modified sterol profile. Mature oocytes from such females fail to undergo normal reinitiation, but when incubated in vitro, can be induced to break their meiotic arrest by the addition of exogenous ecdysone. These results lend further support to the hypothesis that in Locusta, ovarian ecdysone is involved in the control of meiotic reinitiation.


Stability of HE4 and CA125 in blood samples from patients diagnosed with ovarian cancer.
To investigate the influence of handling and storage on HE4 and CA125 serum and EDTA plasma levels to clarify any important consequences for a clinical setting. Blood samples from 13 ovarian cancer (OC) patients were collected and allowed to clot or sediment for up to 72 hours at 4 °C or 20 °C, then processed into serum and EDTA plasma. Furthermore, the effects of up to eight repetitive cycles of freeze/thaw were investigated. HE4 and CA125 were analyzed using a Chemiluminescent Microparticle Immunoassay on the Architect i2000sr System. No significant effect of processing time for HE4 could be shown. HE4 EDTA plasma levels were insignificantly lower (3%) than serum levels (p = 0.41). Similarly, no significant effect of processing time for CA125 could be demonstrated. CA125 levels at 4 °C were significantly reduced compared to levels at 20 °C (p = 0.024). No significant difference between CA125 serum and plasma levels were found (p = 0.46). Serum and EDTA plasma samples were stable during the eight cycles of freezing and thawing (CA125: all p > 0.2; HE4: all p > 0.5). No systematic difference could be demonstrated for HE4. CA125 is not dependent on processing time, EDTA plasma or serum. Levels of CA125 are significantly reduced at 4 °C compared to levels at 20°C, but this difference was less than 6% and is not considered clinically relevant.


Evaluation of Diagnostic Accuracy of Eight Commercial Assays for the Detection of Rubella Virus-Specific IgM Antibodies.
Rubella and congenital rubella syndrome are caused by the rubella virus and are preventable through vaccination, making disease eradication possible. Monitoring of progress toward global eradication and local elimination requires high-quality, sensitive disease surveillance that includes laboratory confirmation of cases. Previous evaluations of anti-rubella IgM detection methods resulted in the broad adoption of the Enzygnost (most recently manufactured by Siemens) enzyme-linked immunosorbent assay (ELISA) kits within WHO's global measles and rubella laboratory network, but they have been discontinued. This study evaluated seven comparable ELISAs from six manufacturers (Trinity Biotech, Euroimmun, Clin-Tech, NovaTec and Virion\Serion) as well as one automated chemiluminescent assay (CLIA) from DiaSorin. These assays include three IgM capture assays and five indirect ELISAs. A panel of 238 sera was used for the evaluation that included 38 archival rubella IgM-positive sera and 200 sera collected from patients with symptomatically similar diseases, such as measles, dengue, parvovirus B19 infection, and roseola. With this panel of sera, the sensitivity of the methods ranged from 63.2% to 100% and the specificity from 80.0% to 99.5%. No single method had both sensitivity and specificity of >90%, unless sera with equivocal results were considered presumptively positive. Some assays, particularly the Serion ELISA, had a large number of false positives with parvovirus B19 IgM-positive sera as well as sera from confirmed measles cases. The performance characteristics identified in this evaluation serve as a reminder to not rely solely on rubella IgM results for case confirmation in elimination settings.


Hepatocyte nuclear factor 4 gamma (HNF4G) is correlated with poor prognosis and promotes tumor cell growth by inhibiting caspase-dependent intrinsic apoptosis in colorectal cancer.
The hepatocyte nuclear factor 4 gamma (HNF4G), a member of orphan nuclear receptors, is up-regulated and functions as an oncoprotein in a variety of tumors. Recent advances in understanding the biologic function and action mechanism of HNF4G in colorectal cancer (CRC) have not been fully elucidated. In the present study, we observed that HNF4G expression levels were significantly increased in CRC tissues compared with adjacent normal tissues, and HNF4G overexpression correlated with worse prognosis in colorectal cancer. Transfection with a small interference RNA (siRNA) targeting HNF4G in HCT116 and SW480 CRC cell lines significantly inhibited cell proliferation and promoted apoptosis in vitro. In contrast, overexpression of HNF4G increased cell proliferation and decreased the percentage of apoptotic cells. Moreover, we discovered that HNF4G was involved in CRC cell apoptosis via the caspase-dependent intrinsic pathway. Finally, knockdown of HNF4G expression led to attenuated colorectal cancer growth and promoted apoptosis in a xenograft mouse model. Collectively, these results indicate that HNF4G exerts as an oncogenic role in colorectal cancer and provides a potential therapeutic target.


Hepcidin: iron-hormone and anti-microbial peptide.
Hepcidin is a beta-defensin-like peptide and a principle regulator of systemic iron homeostasis. In concordance with this dual function its expression is modulated by systemic iron requirements and in response to infectious and inflammatory stimuli. Studies of hepcidin provide novel insight into the molecular mechanisms involved in maintaining iron homeostasis in the healthy state and iron redistribution in response to chronic infections and inflammation. Furthermore, a deregulation of hepcidin may cause elevated intestinal iron absorption that hallmarks a group of frequent iron overload disorders, the Hereditary Hemochromatosis. The aim of this review is to discuss hepcidin function in iron-homeostasis under normal physiological and pathophysiological conditions.


Factors that impact the patellofemoral contact stress in the TKA: a review.
Abnormal retro patellar stress is believed to contribute to patellofemoral complications after total knee arthroplasty (TKA), but the causal link between TKA and patellofemoral contact stress remains unclear. By reviewing the relevant studies, we found that both TKA implantation and additional patellar resurfacing increase retro patellar pressure. The rotation and size of the femoral component, thickness and position of the patellar component, installation of the tibial component, prosthesis design and soft tissue balance further influence patellofemoral stress. Specific measures can be applied to reduce stress, including the installation of the femoral prosthesis with an appropriate external rotation angle, placing the tibial component at a more posterior position and the patellar button at a more medial position, avoiding over-sized femoral and patellar components, selecting posterior-stabilized design rather than cruciate-retaining design, using gender-specific prosthesis or mobile-bearing TKA system, and releasing the lateral retinaculum or performing partial lateral facetectomy. Despite these measures, the principle of individualization should be followed to optimize the patellofemoral biomechanics.


Fine sediment and nutrient dynamics related to particle size and floc formation in a Burdekin River flood plume, Australia.
The extreme 2010-2011 wet season resulted in highly elevated Burdekin River discharge into the Great Barrier Reef lagoon for a period of 200 days, resulting in a large flood plume extending >50km offshore and >100km north during peak conditions. Export of suspended sediment was dominated by clay and fine silt fractions and most sediment initially settled within ∼10km of the river mouth. Biologically-mediated flocculation of these particles enhanced deposition in the initial low salinity zone. Fine silt and clay particles and nutrients remaining in suspension, were carried as far as 100km northward from the mouth, binding with planktonic and transparent exopolymer particulate matter to form large floc aggregates (muddy marine snow). These aggregates, due to their sticky nature, likely pose a risk to benthic organisms e.g. coral and seagrass through smothering, and also by contributing to increased turbidity during wind-induced resuspension events.


Intelligence and development in Aarskog syndrome.
To test the hypothesis that overall intelligence quotient (IQ) is decreased in patients with Aarskog syndrome. 21 boys under 17 years of age with a confirmed clinical diagnosis of Aarskog syndrome were assessed using the Griffiths mental development scales and the British ability scales. IQ ranged from 68 to 128 and followed a normal distribution. This study does not support the hypothesis that Aarskog syndrome is associated with a lowering of mean IQ.


Influence of the histaminergic system on opiate-induced neurosecretion and behaviour.
The influence of the histaminergic system on fentanyl (Fe)-induced growth hormone (GH) and prolactin (PRL) release as well as on Fe-induced increase of noradrenaline (NA) plasma levels has been studied in male volunteers. These volunteers received, according to a randomized block design, different pretreatments: the H1-antagonist dimethindene (Di) (0.1 mg/kg i.v.), or the H2-antagonist cimetidine (Ci)(5 mg/kg i.v.), or a combination of dimethindene and cimetidine (Di + Ci), or saline. The PRL increase caused by Fe (0.2 mg/70 kg) was not altered by pretreatment with the H1-antagonist Di, the H2-antagonist Ci, or the combination of both. The increase of NA plasma levels after Fe also was not modified by the histamine antagonists. In contrast, the maximum GH increase after Fe was blunted by the combination of Ci and Di, but not by either Ci or Di alone. These results suggest an involvement of the histaminergic system in opiate-induced GH-release.


Anatomy of the kisspeptin neural network in mammals.
Kisspeptin has been recognized as a key regulator of GnRH secretion during puberty and adulthood, conveying the feedback influence of endogenous gonadal steroids onto the GnRH system. Understanding the functional roles of this peptide depends on knowledge of the anatomical framework in which it acts, including the location of kisspeptin-expressing cells in the brain and their connections. In this paper, we review current data on the anatomy of the kisspeptin neuronal network, including its colocalization with gonadal steroid hormone receptors, anatomical sites of interaction with the GnRH system, and recent evidence of neurochemical heterogeneity among different kisspeptin neuronal populations. Evidence to date suggests that kisspeptin cells in mammals comprise an interconnected network, with reciprocal connections both within and between separate cell populations, and with GnRH neurons. At the same time, there is more functional and anatomical heterogeneity in this system than originally thought, and many unanswered questions remain concerning anatomical relationships of kisspeptin neurons with other neuroendocrine and neural systems in the brain.


Performance of remote target pointing hand movements in a 3D environment.
In this study, we investigated and modeled the performance of target pointing hand movements in a hand free, touchless 3D environment. The targets had different positions, sizes and distances. Performance measurements included total movement time and movement trajectories. The total movement time consisted of a "primary submovement time" and a "secondary submovement time". Results indicated that the total movement time for targets with depth in the upper part of the spherical framework (3.10s) was shorter than for targets without depth (3.79s). The time for targets without depth in the lower part of the spherical framework (2.94s) was shorter than for targets with depth (3.57s). Within a 3D perspective display, the perception of distance and size depends on its depth position. Our results confirmed the adequacy of the 3D information in the display by showing the longest total movement time was observed for the reach of the "forward" target (3.94s). Fitts' model explained the total movement time (for targets without depth r(2)=.72; for targets with depth r(2)=.72). This study showed that participants navigated the 3D space naturally and could move the cursor using both sequential a axis moving strategy and a straight line moving strategy. Real-life applications of the proposed method include interface design for 3D perspective displays and hand movements in 3D environments.


Repair of degenerative nucleus pulposus by polyphenol nanosphere-encapsulated hydrogel gene delivery system.
Intervertebral disc degeneration (IDD) progresses due to local inflammatory response, gradually unbalanced anabolic/catabolic activity, and progressive functional impairment within the nucleus pulposus. Antagomir-21, a cholesterol-modified miRNA-21 inhibitor, has potential extracellular matrix (ECM) regenerative ability, but its application for IDD is limited by inadequate local delivery systems. An injectable hydrogel gene delivery system encapsulating a modified tannic acid nanoparticles (TA NPs) vector was engineered for on-demand and sustained delivery of antagomir-21 into the nucleus pulposus. After nucleus pulposus cell uptake, antagomir-21 was released from TA NPs and regulated the ECM metabolic balance by inhibiting the MAPK/ERK signaling pathway. TA NPs scavenged intracellular ROS and reduced inflammation by downregulating TNF-α expression. In vivo, synergistic anti-inflammatory effects and ECM regeneration effectively promoted therapeutic efficacy against IDD. This hydrogel gene delivery system represents a creative, promising strategy for IDD repair.


Report of a rare case of congenital mitral valve prolapse with chronic kidney disease--reconsidered genotype-phenotypic correlations.
Mitral valve prolapse (MVP) is a common cardiovascular disease defined as a late systolic click or mitral valve lobes that move up into the left atrium during ventricular systole, with or without mitral insufficiency. Dachsous catherin-related 1 (DCHS1) is one of the two known pathogenic genes associated with MVP. However, there is little information about the renal dysfunction caused by MVP and DCHS1 mutations. We analyzed the genetic etiology in a rare case of 9-year-old boy affected by chronic renal failure with MVP. Subsequently, we constructed stable cell lines overexpressing wild-type DCHS1 or mutant DCHS1 (c.8309G>A, p.R2770Q) to evaluate the influence of the DCHS1 mutation on the proliferation, apoptosis, and autophagy. Complete exome sequencing and pedigree verification revealed a mutation p.R2770Q (c.8309G>A) in exon 21 of the DCHS1 gene carried by the patient, which may affect the DNA binding. No such mutation was detected in his parents, indicating that this was a new mutation. Potential functional impact of sequence variants was predicted using in silico prediction programs including SIFT, Polyphen2, and Condel. This variant was determined to be a pathogenic mutation that has not been reported elsewhere. Subsequently, we used a stable DCHS1 gene-mutated HK-2 cell line to analyse proliferation, apoptosis, and autophagy, showed that kidney volume decreased with increasing cell death associated with a reduced proliferation. Our analysis revealed a heterozygous variation of DCHS1 in a child with MVP. Our observations highlight previously unrecognized phenotypes of the currently recognized MVP genotype, including distinct chronic renal failure.


Enhanced hepatic insulin sensitivity, but peripheral insulin resistance in patients with type 1 (insulin-dependent) diabetes.
Sensitivity to insulin in vivo was studied in 8 normal weight C-peptide negative Type 1 (insulin-dependent) diabetic patients (age 23 +/- 1 years, diabetes duration 6 +/- 2 years), and in 8 age, weight and sex matched healthy subjects, using the euglycaemic clamp and 3-3H-glucose tracer technique. Prior to the study diabetic patients were maintained normoglycaemic overnight by a glucose controlled insulin infusion. Sequential infusions of insulin in 3 periods of 2 h resulted in mean steady state insulin levels of 12 +/- 2 versus 11 +/- 1, 18 +/- 2 versus 18 +/- 2 and 28 +/- 3 versus 24 +/- 2 microU/ml in diabetic patients and control subjects. Corresponding glucose utilization rates were 2.4 +/- 0.2 versus 2.4 +/- 0.1, 2.4 +/- 0.2 versus 3.0 +/- 0.3 and 2.9 +/- 0.3 versus 4.6 +/- 0.6 mg.kg-1.min-1, p less than 0.02. Portal insulin values in the three periods were calculated to 12 +/- 2 versus 25 +/- 3, 18 +/- 2 versus 32 +/- 3 and 28 +/- 3 versus 37 +/- 3 microU/ml in the diabetic patients and control subjects using peripheral insulin and C-peptide concentrations and assuming a portal to peripheral insulin concentration gradient of 1 in diabetic patients and of 2.4 in control subjects. Corresponding glucose production rates were 2.5 +/- 0.2 versus 2.4 +/- 0.1, 1.6 +/- 0.1 versus 0.9 +/- 0.2 and 0.7 +/- 0.1 versus 0.4 +/- 0.2 mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Lack of effect of baclofen on substance P and somatostatin release from the spinal cord in vitro.
High concentrations of K+ increase the release of substance P (SP) and somatostatin (SRIF) from superfused slices of rat spinal cord. This increase is Ca-dependent. Baclofen (100-500 microM) does not significantly alter the K+-evoked release of SP or SRIF. Stereoisomers of baclofen and GABA, similarly, are without effect. The spinal analgesic action of baclofen does not appear to be due to alterations in the release of SP or SRIF.


Multisystemic Therapy for social, emotional, and behavioral problems in youth aged 10-17.
Multisystemic Therapy (MST) is an intensive, home-based intervention for families of youth with social, emotional, and behavioral problems. Masters-level therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behavior. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. Most MST trials were conducted by program developers in the USA; results of one independent trial are available and others are in progress. To provide unbiased estimates of the impacts of MST on restrictive out-of-home living placements, crime and delinquency, and other behavioral and psychosocial outcomes for youth and families. Electronic searches were made of bibliographic databases including the Cochrane Library, C2-SPECTR, PsycINFO, Science Direct and Sociological Abstracts) as well as government and professional websites, from 1985 to January 2003. Reference lists of articles were examined, and experts were contacted. Studies where youth (age 10-17) with social, emotional, and/or behavioral problems were randomised to licensed MST programs or other conditions (usual services or alternative treatments). Two reviewers independently reviewed 266 titles and abstracts; 95 full-text reports were retrieved, and 35 unique studies were identified. Two reviewers independently read all study reports for inclusion. Eight studies were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from these studies.Significant heterogeneity among studies was identified (assessed using Chi-square and I(2)), hence random effects models were used to pool data across studies. Odds ratios were used in analyses of dichotomous outcomes; standardised mean differences were used with continuous outcomes. Adjustments were made for small sample sizes (using Hedges g). Pooled estimates were weighted with inverse variance methods, and 95% confidence intervals were used. Pooled results show no significant effects of MST on the likelihood or duration of restrictive out-of-home placements, proportion of youth who were arrested or convicted, or numbers of arrests/convictions within one-year post-intervention. There were no significant differences on drug tests or self-reported drug use at a 6-month follow-up. In analyses of post-treatment data for program completers, there were no significant between-group differences on self-reported delinquency, peer relations, youth behavior problems, youth psychiatric symptoms, parent psychiatric symptoms, or family functioning. There is little evidence of the superiority of MST over other interventions with youth. There is also no evidence that MST has harmful effects.


The Bunocephalus coracoideus Species Complex (Siluriformes, Aspredinidae). Signs of a Speciation Process through Chromosomal, Genetic and Ecological Diversity.
Bunocephalus is the most species-rich Aspredinidae genus, corresponding to a monophyletic clade with 13 valid species. However, many species have their classification put in question. Here, we analyzed individuals from four Amazonian populations of Bunocephalus coracoideus by cytogenetic and molecular procedures. The geographic distribution, genetic distances and karyotype data indicate that each population represents an Evolutionary Significant Unit (ESU). Cytogenetic markers showed distinct 2n and karyotype formulas, as well as different numbers and locations of the rDNA sites among ESUs. One of such populations (ESU-D) highlighted an extensive polymorphic condition, with several cytotypes probably due to chromosomal rearrangements and meiotic non-disjunctions. This resulted in several aneuploid karyotypes, which was also supported by the mapping of telomeric sequences. Phylograms based on Maximum Likelihood (ML) and Neighbor Joining (NJ) analyses grouped each ESU on particular highly supported clades, with the estimation of evolutionary divergence indicating values being higher than 3.8-12.3% among them. Our study reveals a huge degree of chromosomal and genetic diversity in B. coracoideus and highly points to the existence of four ESUs in allopatric and sympatric speciation processes. In fact, the high divergences found among the ESUs allowed us to delimitate lineages with taxonomic uncertainties in this nominal species.


Transformation-defective mutants of Rous sarcoma virus with longer sizes of genome RNA and their highly frequent occurrences.
Transformation-defective (td) mutants with different sizes of genomic RNA were isolated from the Prague strain of Rous sarcoma virus, subgroup C(PR-C). All six td viruses (tdTYPR-C) isolated from a single UV-irradiated stock of PR-C (clone 2 of TYPR-C) had slightly longer RNA than did the ordinary class b RNA of tdB77 and Rous-associated virus-7. td viruses spontaneously segregated in uncloned TYPR-C also contained genomic RNA of a size similar to tdTYPR-C RNA. On the other hand, two td mutants isolated from another stock of PR-C (LAPR-C) had the class b RNA. Fingerprint analysis confirmed that tdTYPR-C and tdLAPR-C were derived by deletion from clone 2 of TYPR-C and LAPR-C, respectively, and also showed that clone 2 of TYPR-C had sequences in its genome RNA different from those of LAPR-C, although it gave a fingerprinting pattern similar to the latter. These results strongly suggest that differences between the nucleotide sequences in TYPR-C and LAPR-C RNA may result in different extents of deletion.


Increased Prevalence of Diastolic Heart Failure in Patients with Rheumatoid Arthritis Correlates with Active Disease, but Not with Treatment Type.
Although heart failure (HF) is a major cause of premature mortality, there is little information regarding its prevalence and associated risk factors in patients with rheumatoid arthritis (RA). In this study, we evaluated the prevalence of HF in a community-based RA cohort. Further, we investigated the effect of RA activity and present treatment on HF rate and cardiac structure. A diagnostic workup for HF according to the European Society of Cardiology recommendations was performed in 157 patients with RA fulfilling the American College of Rheumatology/European League Against Rheumatism criteria (68% women, age 61 ± 13 yrs) from our outpatient clinic and in 77 age- and sex-matched controls. The prevalence of HF in patients with RA (24%) was unexpectedly high and differed significantly from the control sample (6%, p = 0.001). Diastolic HF was the dominant type (23% vs 6%), and clinical symptoms alone were of low diagnostic value. Active RA (28-joint Disease Activity Score ≥ 2.6: OR 3.4, 95% CI 1.3-9.8) was an independent risk factor of HF, as well as systemic inflammation (erythrocyte sedimentation rate > 16 mm/h: OR 5.4, 95% CI 2.1-16; C-reactive protein > 10 mg/l: OR 2.6, 95% CI 0.8-8.0) and RA duration > 10 years (OR 2.6, 95% CI 1.2-5.8). HF in RA was associated with concentric hypertrophy (48% vs 17%, p < 0.001) and reduced longitudinal strain (-17.2% vs -19.7%, p < 0.001). However, the prevalence of HF was equivalent between the treatment groups [conventional synthetic disease-modifying antirheumatic drugs (DMARD) 25%, tumor necrosis factor inhibitors 22%, other biological DMARD 27%]. Recognition of all diastolic HF in RA requires a complex diagnostic approach. Active rather than inactive RA places patients at a higher risk for HF, whereas influence of RA treatment on HF risk needs to be elucidated in further studies.


Evaluation of commonly used adjuvants in the prevention of postoperative adhesions.
The uterine horns of 30 rats were subjected to both division and microsurgical anastomosis of the proximal segment and division only of the distal segment. They were equally assigned to three groups, of which group 2 received dexamethasone and group 3 received ibuprofen preoperatively and postoperatively for a total of eight doses. During operation, five rats of each group were irrigated with normal saline and the other five, with 32% dextran 70 (Hyskon). The left uterine horn was anastomosed with 7-0 coated Vicryl, and the right horn, with 7-0 Dexon-S sutures. At repeat laparotomy 2 weeks later, the intraperitoneal adhesions were graded blindly according to their severity. Tissue blocks were obtained from the areas of anastomosis and division only for histologic assessment. Total adhesion scores were 104 for group 1, 53 for group 2 (p less than 0.05), and 90 for group 3 (p = 0.7). The histologic evaluation showed no difference between the three groups. The inflammatory tissue reaction was least around the areas of division only and greatest at the anastomotic sites, where it was most pronounced around the surgical knots. No difference in gross adhesions or histologic assessment was observed between the left horn and the right horn. Adhesions were significantly less in the Hyskon-treated animals (p less than 0.05) but the histologic evaluation showed similar inflammatory reactions. These results suggest that in this species there is no difference between Dexon-S and coated Vicryl sutures, that dexamethasone and Hyskon are effective in preventing postoperative adhesions, and that the inflammatory tissue reaction is not altered by these adjuvants but is significantly augmented by the presence and quantity of suture material.


Soft robotic exosuit augmented high intensity gait training on stroke survivors: a pilot study.
Stroke is a leading cause of serious gait impairments and restoring walking ability is a major goal of physical therapy interventions. Soft robotic exosuits are portable, lightweight, and unobtrusive assistive devices designed to improve the mobility of post-stroke individuals through facilitation of more natural paretic limb function during walking training. However, it is unknown whether long-term gait training using soft robotic exosuits will clinically impact gait function and quality of movement post-stroke. The objective of this pilot study was to examine the therapeutic effects of soft robotic exosuit-augmented gait training on clinical and biomechanical gait outcomes in chronic post-stroke individuals. Five post-stroke individuals received high intensity gait training augmented with a soft robotic exosuit, delivered in 18 sessions over 6-8 weeks. Performance based clinical outcomes and biomechanical gait quality parameters were measured at baseline, midpoint, and completion. Clinically meaningful improvements were observed in walking speed ([Formula: see text] < 0.05) and endurance ([Formula: see text] < 0.01) together with other traditional gait related outcomes. The gait quality measures including hip ([Formula: see text] < 0.01) and knee ([Formula: see text] < 0.05) flexion/extension exhibited an increase in range of motion in a symmetric manner ([Formula: see text] < 0.05). We also observed an increase in bilateral ankle angular velocities ([Formula: see text] < 0.05), suggesting biomechanical improvements in walking function. The results in this study offer preliminary evidence that a soft robotic exosuit can be a useful tool to augment high intensity gait training in a clinical setting. This study justifies more expanded research on soft exosuit technology with a larger post-stroke population for more reliable generalization. Trial registration This study is registered with ClinicalTrials.gov (ID: NCT04251091).


Rectal prolapse.
Rectal prolapse is a common occurrence in cattle and small ruminants. This article discusses the causes, correction, and postoperative treatment of rectal prolapse in cattle and sheep.


Sinomenine potentiates degranulation of RBL-2H3 basophils via up-regulation of phospholipase A2 phosphorylation by Annexin A1 cleavage and ERK phosphorylation without influencing on calcium mobilization.
Sinomenine (SIN), an alkaloid derived from the Chinese medicinal plant Sinomenium acutum, is the major component of Zhengqing Fongtong Ning (ZQFTN), a pharmaceutical drug produced by Hunan Zhengqing Pharmaceutical Co. Ltd. in China for the treatment of rheumatoid arthritis and other autoimmune diseases. Some clinic reports indicate that ZQFTN may induce an anaphylactic reaction via potentiating the degranulation of immune cells. In the current study, we aimed to examine whether SIN is capable of inducing the degranulation of basophilic leukemia 2H3 (RBL-2H3) cells to elucidate how the anaphylactic reaction occurs. The results revealed that SIN could up-regulate β-hexosaminidase levels in RBL-2H3 cells without significant cytotoxicity, suggesting that SIN could induce the degranulation of RBL-2H3 cells. Furthermore, SIN increased the release of prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) in RBL-2H3 cells via promoting the expression of phosphorylated-extracellular signal-regulated kinase (P-ERK), the cleavage of Annexin A1 (ANXA1), and phosphorylated-cytosolic phospholipase A2 (P-cPLA2), as well as cyclooxygenase-2 (COX-2). The ERK inhibitor, PD98059, significantly attenuated the up-regulatory effect of SIN on cPLA2 phosphorylation. Interestingly, SIN did not significantly increase Ca(2+) influx in the cells. These findings not only explored the anaphylactic reaction and underlying mechanism of ZQFTN in RBL-2H3 cells, but may promote the development of relevant strategies for overcoming the adverse effects of the drug.


Selective impairment of attentional networks of orienting and executive control in schizophrenia.
Difficulty attending is a common deficit of schizophrenic patients. However, it is not known whether this is a global attentional deficit or relates to a specific attentional network. This study used the attention network test to compare schizophrenic patients (N=77) with controls (N=53) on the efficiency of three anatomically defined attentional networks: alerting, orienting, and executive control. Schizophrenic patients showed a large and highly significant deficit in the executive network and a smaller but significant deficit in the orienting network as well as in overall RT and accuracy. There was no deficit in the alerting network. These results suggest some specificity in the attentional networks influenced by the disorder. The executive attention network has been shown in normal subjects to activate the anterior cingulate and lateral prefrontal areas. Previous data using neuroimaging with schizophrenic patients has shown abnormal control by the anterior cingulate. Our findings support this previous research by indicating that the major attentional deficit in schizophrenic patients is in a network that includes the anterior cingulate.


Trainee radiologist reports as a source of confirmation bias in radiology.
To assess and quantify the relationship between trainee reporting and radiology errors. A retrospective analysis of the 100 most recent cases reviewed by a discrepancy forum in a tertiary neuroradiology service was performed. Data on the time of the scan and the presence of a trainee report were collected, with comparison being made between the cohort of erroneous reports and the overall service. Although out-of-hours imaging only constituted 18% of the overall service, 36% of erroneous reports originated from scans performed out-of-hours. Eighteen percent of scans were first reported by a trainee and then checked by a consultant, with the remaining 82% being solely reported by the consultant. Despite this, 52% of errors were from consultant-checked trainee reports. Although out-of-hours imaging has long been associated with error, this study identifies consultant checking of trainee reports as another error-associated reporting context. This is likely to relate to confirmation bias, in which the pre-existing trainee report may result in inattentional blindness on the part of the checking consultant. Awareness of this phenomenon is important for the reduction of error in this specific and widely underestimated reporting context.


Assessment of bacteriophage-encoded endolysin as a potent antimicrobial agent against antibiotic-resistant Salmonella Typhimurium.
This study was designed to evaluate the potential of using newly purified Salmonella phage-encoded endolysin LysPB32 as novel antibiotic alternative. The endolysin LysPB32 was characterized by analyzing pH and thermal stability, lytic spectrum, antimicrobial activity, and mutant frequency against Salmonella Typhimurium KCCM 40253 (STKCCM), S. Typhimurium ATCC 19585 (STATCC), S. Typhimurium CCARM 8009 (STCCARM), Klebsiella pneumoniae ATCC 23357 (KPATCC), K. pneumoniae CCARM 10237 (KPCCARM), Pseudomonas aeruginosa ATCC 27853 (PAATCC), Listeria monocytogenes ATCC 1911 (LMATCC), Staphylococcus aureus ATCC 25923 (SAATCC), and S. aureus CCARM 3080 (SACCARM). The molecular weight of LysPB32 is 17 kDa that was classified as N-acetyl-β-d-muramidase. The optimum activity of LysPB32 against the outer membrane (OM) permeabilized STKCCM, STATCC, and STCCARM was observed at 37 °C and pH 6.5. LysPB32 had a broad spectrum of muralytic activity against antibiotic-sensitive STKCCM (41 mOD/min), STATCC (32 mOD/min), and SBKACC (25 mOD/min) and antibiotic-resistant STCCARM (35 mOD/min) and KPCCARM (31 mOD/min). The minimum inhibitory concentrations (MICs) of polymyxin B against STKCCM, STCCARM, and STATCC were decreased by 4-, 4-, and 8-folds, respectively, when treated with LysPB32. The combination of LysPB32 and polymyxin B effectively inhibited the growth of STKCCM, STCCARM, and STATCC after 24 h of incubation at 37 °C, showing 4.9-, 4.4-, and 3.3-log reductions, respectively. The mutant frequency was low in STKCCM, STCCARM, and STATCC treated with combination of LysPB32-polymyxin B system. The results suggest the LysPB32-polymyxin system can be a potential candidate for alternative therapeutic agent to control antibiotic-resistant pathogens.


Association of bisphenol A with 25(OH)D, 1,25(OH)2D levels and 1,25(OH)2D/25(OH)D ratio in cord blood.
The aim was to investigate the association between bisphenol A (BPA), 25-hydroxy vitamin D [25(OH)D], and 1α,25 dihydroxy vitamin D [1,25(OH)2D] levels in the cord blood of newborn babies. BPA was measured by high pressure liquid chromatography (HPLC) and vitamin D levels by commercial ELISA or ECLIA kits. BPA and Vitamin D levels were grouped according to tertile values. In the cord blood, the median 25(OH)D level was 14.9 ng/mL (IQR: 8.5-20.8) and median 1,25(OH)2D level was 53.3 pg/dL (IQR: 42.3-98.4). 25(OH)D levels were < 20 ng/mL in 76.5% of the babies. BPA was detectable in 72.4% of the cord blood samples; median BPA level was 1.57 ng/mL (IQR: < DL-4.05 ng/mL). Frequencies of vitamin D deficiency and frequencies of cases having the highest tertile active vitamin D levels were similar in groups of BPA tertiles in both univariate and multivariate analysis. In conclusion, both BPA exposure and insufficient vitamin D transfer via cord blood are common in newborns. Bisphenol A levels were not correlated with vitamin D levels in cord blood of healthy mother-fetus pairs.


The effect of aqueous progesterone on operative adhesion formation.
Progesterone (P) has been shown to have antiinflammatory and immunosuppressive properties. This study was designed to evaluate these effects on operative adhesion formation. Forty guinea pigs received standardized injuries to their uterine horns. Four groups were examined. Normal saline was used as an irrigant in the first, or control, group. Aqueous P (50 mg or 1 ml) was dripped over the injured site and instilled intraperitoneally in the second group. The third group received intramuscular aqueous P (3.3 mg/kg body weight) 1 day postoperatively, the day of surgery, and either 6 or 13 days postoperatively until reexploration. In the fourth group 1 ml of 32% dextran 70 (Hyskon) was administered in the same manner as aqueous P in the second group. The animals in all groups were reexplored 1 or 2 weeks after the initial surgical procedure, and the adhesions were scored. Adhesion formation was significantly reduced (P less than 0.001) in all treatment groups when compared with the control group. Aqueous P may have a role in the prevention of adhesion formation associated with pelvic surgery and, in particular, microscopic tubal and ovarian surgery.


A rise in intracellular Ca2+ underlies light adaptation in dogfish retinal 'on' bipolar cells.
1. This investigation was to determine the extent to which retinal 'on' bipolar cells contribute to the adaptive changes that occur with light, which enable the rod visual system to operate over a wide range of ambient light intensities, and to elucidate the underlying adaptive mechanism. 2. Whole-cell voltage clamp recordings were obtained from bipolar cells in dark-adapted dogfish retinal slices. Current responses to brief flashes and steps of light were analysed. 'On' bipolar cell inward current light responses are mediated by a metabotropic glutamate receptor linked to the control of a cGMP cascade, with cGMP opening cation channels. Outward current responses to light of 'off' bipolar cells are mediated by the closure of ionotropic glutamate receptor channels. 3. When Ca2+ buffer was omitted from the patch pipette solution, 'on' bipolar cells rapidly desensitized to steps of light as dim as one rhodopsin molecule bleached per rod per second (1 Rh* s-1), whereas 'off' bipolar cells did not desensitize. Responses of 'on' bipolar cells to flashes in the presence of dim backgrounds recovered after a delay, but with diminished sensitivity, i.e. the cells adapted. 4. With the Ca2+ chelator BAPTA in the patch pipette solution, step responses of 'on' bipolar cells were sustained and flash responses following steps showed rapid recovery. Buffering Ca2+ in the patch pipette solution to 1 microM prevented desensitization, whereas 50 microM free Ca2+ reduced the 'on' bipolar cell flash responses, suppressed inward dark current and decreased input conductance. 5. We conclude that a major component of adaptation of the visual system is due to a reduction in gain at the rod-'on' bipolar cell synapse as a result of Ca2+ loading of the dendrites when their cGMP-gated cation channels open with light.


Preoperative evaluation of the thoracic aorta using MRI and angiography.
The ability of ECG-gated magnetic resonance imaging (MRI) to evaluate disease of the thoracic aorta compared with angiography was prospectively assessed in 28 patients. MRI identified abnormalities in all patients, with confirmation at operation in 22 (79%) and by angiography alone in all 28. In 20 of the patients, MRI correctly diagnosed 20 of 21 aneurysms of the thoracic aorta (6 dissecting, 4 saccular, 10 fusiform), but 1 surgically proven fusiform aneurysm was categorized as an enlarged aortic dissection based on both MRI and angiographic findings. One dissection and 1 fusiform aneurysm were shown by MRI only. Coarctation of the aorta was identified in 4 patients. Ascending aortic enlargement and left ventricular hypertrophy were identified by MRI in 4 patients with aortic stenosis. In 7 patients (25%), MRI provided additional important information not shown by angiography and in 1 patient, the MRI findings resulted in a change in the surgical approach. In 14 of 28 patients (50%), angiography was necessary for definitive preoperative evaluation of the aortic valve, the coronary arteries, or the brachiocephalic vessels. MRI was a useful noninvasive supplement to angiography for the preoperative assessment of thoracic aortic disease.


Transcriptional down-regulation of human alpha(2A)-adrenoceptors by IFNgamma and TNFalpha in intestinal cells.
alpha(2A)-adrenoceptors are expressed on intestinal cells and they participate in the control of epithelial functions such as solute and water transport or cell proliferation. In pathological conditions, pro-inflammatory cytokines secreted by lymphocytes are responsible for modification of intestinal cell characteristics including phenotype switch and changes in the expression of pumps and ion channels. Using the HT29 cell line as a model, the present work examined the effect of two inflammatory cytokines, interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha), on the expression of the human alpha(2A)-adrenoceptor. Exposure of cells to either IFNgamma or TNFalpha resulted in a concentration- and time-dependent diminution of [(3)H]RX821002 binding sites, which is preceded by a large decrease in the amount of alpha(2A)-adrenoceptor mRNA. The cytokines did not affect the receptor mRNA half-life, but inhibited the activity of a luciferase construct containing the promoter region of alpha(2A)-adrenoceptor gene, indicating that a decrease in the transcription rate is primarily responsible for the diminution of receptor expression. Exposure of cells to either IFNgamma or TNFalpha caused increased production of reactive oxygen species and transient phosphorylation of extracellular signal-regulated kinase (Erk1/2). The effect of cytokines was mimicked by H(2)O(2) but was unaffected by the addition of anti-oxidants. The blockade of Erk1/2 activation by PD98059 blunted the effect of TNFalpha but not of IFNgamma. In conclusion, the present findings demonstrate that IFNgamma and TNFalpha diminish the alpha(2A)-adrenoceptor expression in HT29 cells by decreasing the transcription rate without modifying the stability of mRNA. The transcription inhibition is however triggered via different signalling pathways. The results suggest that cytokine-mediated down-regulation of alpha(2A)-adrenoceptor could contribute to the pathogenesis of inflammatory bowel disease.


Improving the process of ordering outside genomic testing for lung cancer FNA and small biopsy specimens - A multidisciplinary quality improvement project.
Lung cancer is an important cause of mortality in the United States. Targeted mutation analysis has the potential to alter mortality in those with non-small-cell lung cancer. As such, the importance of timely tissue turnaround time (TAT) is substantial. We evaluated TAT at Mayo Clinic Arizona and found it to be delayed relative to national standards. We conducted a series of plan, do, study, and act (PDSA) cycles at a single institution to identify areas for improvement with our lung cancer genomic testing. We assembled a multidisciplinary team and held serial meetings to discuss data from each PDSA cycle. Using PDSA cycles and multidisciplinary discussions, we were able to identify a number of process limitations slowing TAT. We were then able to generate enhanced and timely communication between providers and pathology, educate and enforce the order/requisition workflow, and establish pathology accessioning with lung cancer specimens top priority. We were able to generate and implement a standard operating procedure for genomic testing of lung cancer specimens at our institution, thereby reducing tissue TAT.


Mobile submuscular mass resembling a hard-boiled egg: case report.
A 68-year-old woman had a rare mobile mass on her back. The mass was similar to encapsulated fat necrosis except for its unusual stalked appearance, large size, and high degree of mobility underneath the anterior serratus muscle on the back. Based on previous descriptions of encapsulated fat necrosis, the clinical presentation of the mass might be regarded as an extreme example of this rare condition.


[Modified Ishiguro extension block technique for fracture-dislocation of the distal interphalangeal joint].
Reconstruction of the anatomic configuration of the articular surface and restoration of complete movement of the finger joint. Fracture of the distal interphalangeal (DIP) joint involving > or = 30% of the articular surface. Luxation or subluxation of the distal phalanx. Fracture-dislocation > or = 2 mm. Old fractures. Closed reduction impossible. Closed reduction and pin fixation modified from Ishiguro technique without penetrating the fracture fragment. Cast fixation for 4 weeks with the finger in functional position or with the proximal interphalangeal joint flexed to relax the pulley. After 4 weeks, removal of the cast and the pin and start of active motion exercises. Twelve patients with fracture-dislocation of the DIP joint involving more than one third of the articular surface were treated with the modified extension block technique according to Ishiguro. Time from injury to surgery was 5 days (range, 0-8 days). At a mean follow-up of 15 months (range, 9-31 months), pain on the visual analog scale (VAS, 0 = no pain, 10 = maximum pain), the active range of motion, and criteria according to Warren et al. were evaluated. Eleven patients were pain-free and one patient suffered from mild pain during strenuous work. The mean active range of motion was from -3 degrees extension (range, 0-10 degrees ) and flexion to 79 degrees (range, 45-100 degrees ). The results according to Warren et al. were very good in ten and good in two cases.


Embryology: does prepatterning occur in the mouse egg?
A recurring question in developmental biology has been whether localized determinants play any role in mammalian preimplantation development. This is a controversial issue that brings back the idea of prepatterning and is explored further by Plusa et al., who claim it is the first cleavage of the mouse zygote that predicts the blastocyst axis, rather than the animal pole or sperm entry point, as previously suggested. However, other evidence indicates that the blasotcyst axis is not predetermined and there is no prepatterning in the mouse egg. Here we investigate the origin of these different views and conclude that they arise from differences in the data themselves and in their interpretation.


A systematic review of online learning programs for nurse preceptors.
Nurse preceptors guide students to integrate theory into practice, teach clinical skills, assess clinical competency, and enhance problem solving skills. Managing the dual roles of a registered nurse and preceptor poses tremendous challenges to many preceptors. Online learning is recognized as an effective learning approach for enhancing nursing knowledge and skills. The systematic review aims to review and synthesise the online learning programs for preceptors. A systematic review was designed based on the Cochrane Handbook for Systematic Reviews of Programs. Articles published between January 2000 and June 2016 were sought from six electronic databases: CINAHL, Medline OVID, PubMed, Science Direct, Scopus, and Web of Science. All papers were reviewed and quality assessment was performed. Nine studies were finally selected. Data were extracted, organized and analysed using a narrative synthesis. The review identified five overarching themes: development of the online learning programs for nurse preceptors, major contents of the programs, uniqueness of each program, modes of delivery, and outcomes of the programs. The systematic review provides insightful information on educational programs for preceptors. At this information age, online learning offers accessibility, convenience, flexibility, which could of great advantage for the working adults. In addition, the online platform provides an alternative for preceptors who face challenges of workload, time, and support system. Therefore, it is paramount that continuing education courses need to be integrated with technology, increase the flexibility and responsiveness of the nursing workforce, and offer alternative means to take up courses.