A clonal analysis of human peripheral blood lymphocytes displaying natural killer-like activity.
Human Fc gamma receptor-bearing lymphocytes and T cells, prepared by sorting peripheral blood lymphocytes using the B73.1 monoclonal antibody, have been cloned by limiting dilution. Although quiescent lymphocytes of either cell type were unresponsive to interleukin 2 (IL 2), following induction with phytohemagglutinin and/or the BSM B lymphoblastoid cell line they could be expanded in IL 2 utilizing a mixed irradiated feeder system. Clones originating from B73.1+ lymphocytes displayed a characteristic large granular lymphocyte (LGL) morphology but were otherwise functionally and phenotypically heterogeneous. Of 36 clones analyzed 19 displayed significant natural killer (NK)-like activity, each clone having a target cell repertoire identical to uncloned NK effectors. Furthermore, only a minority of clones (i.e. 5) displayed significant antibody-dependent cellular cytotoxicity, while levels of lectin-induced cellular cytotoxicity were normally commensurate with a clones level of NK-like activity. No correlation was evident between the phenotype of a clone and its cytotoxic activity since of 12 cytotoxic clones phenotyped, 8 expressed the OKT3 antigen but lacked the B73.1 antigen; 2 lacked the OKT3 antigen but expressed the B73.1 antigen and one lacked both OKT3 and B73.1 antigens. In addition the expression of OKT8 and OKT4 antigens was not in any way predictive of the cytotoxic capacity of a given clone. Several clones expressing T cell associated antigens bore a phenotype that distinguished them from T cell clones insofar as T cell subset antigens were expressed in the absence of the OKT3 antigen and vice versa.(ABSTRACT TRUNCATED AT 250 WORDS)


Biological therapies in otology.
Hearing loss is present in millions of people worldwide. Current treatment for patients with severe to profound hearing loss consists of cochlear implantation. Providing the cochlear nerve is intact, patients generally benefit greatly from this intervention, frequently achieving significant improvements in speech comprehension. There are, however, some cases where current technology does not provide patients with adequate benefit. Ongoing research in cell transplantation and gene therapy promises to lead to new developments that will improve the function of cochlear implants. Translation of these experimental approaches is presently at an early stage. This review focuses on the application of biological therapies in severe hearing loss and discusses some of the barriers to translating basic scientific research into clinical reality. We emphasize the application of these novel therapies to cochlear implantation.


Metadherin confers chemoresistance of cervical cancer cells by inducing autophagy and activating ERK/NF-κB pathway.
Overexpression of metadherin (MTDH) has been reported in many solid tumors and implicated in chemoresistance. This study aimed to examine MTDH expression in cervical cancer tissues and explore its role in chemoresistance of cervical cancer. MTDH expression in cervical cancer biopsies and several cervical cancer cell lines was detected by immunoblotting and immunohistochemisty. MTDH expression level was experimentally modulated in HeLa cells to determine the effects on chemoresistance to cisplatin. The results showed that MTDH expression was higher in tissues from both cervical squamous carcinoma and cervical adenocarcinoma, compared to normal cervical tissues. MTDH expression was not correlated to patient age or cervical cancer grade, although nuclear MTDH expression was correlated with poor differentiation of cervical cancer. In SiHa, HeLa, CasKi, and C33A cells, MTDH expression level was positively correlated with chemoresistance to cisplatin. MTDH increased autophagy in HeLa cells, which was associated with decreased cleavage of Caspase-3 and the activation of EER/NF-κB pathway. In conclusion, MTDH expression is high in cervical cancer, and it contributes to chemoresistance of cervical cancer. MTDH could be utilized as a therapeutic target to overcome chemoresistance of cervical cancer.


[Results of surgical treatment of acute gastro-duodenal ulcers and erosions complicated by profuse hemorrhage].
25 cases were operated upon at the climax of a massive gastrointestinal bleeding from acute ulcers and erosions. Among them 20 patients underwent stomach resection. One patient died from pancreonecrosis within the early postoperative period. There were no cases of the recurrence of bleeding. Excellent late results were found in 12 of 17 cases, in other 5 cases the results were good.


Successful injection of the acromioclavicular joint with use of ultrasound: anatomy, technique, and follow-up.
Injection into the acromioclavicular (AC) joint is often inaccurate (approximately 50%) even in experienced hands. In light of new anatomic observations, we evaluate accuracy of an innovative ultrasound-guided method and follow the clinical course of successful therapeutic injections. Relevant anatomy was investigated in 200 three-dimensional computed tomography scans, 100 magnetic resonance images, and 14 cadavers. Baseline measurements of joint depth and width were performed ultrasonically in 100 normal volunteers; 50 symptomatic patients were injected. Uniquely in a clinical ultrasound study, injection success was documented by arthrography. Outcomes after concomitant steroid instillation were observed for 6 months by visual analog scale (VAS) scores and pain provocation test results. Anatomic studies showed that the widest area for joint penetration was anterior superior. Injection success rate was 96%, overwhelmingly on the first needle pass. Shallow joint depth allowed access with a standard 3-cm needle. Joint width diminished with age but did not reduce injection success. Cadaveric joints admitted 1.2 ± 0.5 mL, but fluid ingress was initially blocked by soft tissues in one third of both cadaveric and clinical cases. Diligent follow-up after steroid injection showed sustained pain relief in the majority with isolated AC disease but significantly less in those with concomitant shoulder disorders. This high level of clinical injection success, irrefutably substantiated with arthrography, has not been previously demonstrated. The anterior superior aspect of the joint is the preferred place for entry. Initial intra-articular blockage to fluid inflow is common but can be surmounted. Encouraging 6-month results of steroid instillation in isolated AC disease do not apply to patients with coexisting shoulder pathologic processes.


Watershed wash-off of atmospherically deposited radionuclides: a review of normalized entrainment coefficients.
Radionuclide wash-off is the transport of activity by flowing water over the soil surface (runoff). To complete existing reviews on long-term removal rates, this paper focuses on short-term wash-off fluxes, quantified in the literature by soil-runoff transfer factors called normalized liquid and solid entrainment coefficients (noted K(l)(*), K(s)(*)). Compiled data concerned essentially (137)Cs and (90)Sr wash-off measured under simulated rainfalls on small experimental plots after Chernobyl fallout in the exclusion zone. K(l)(*) and K(s)(*) values span approximately one order of magnitude. Their validity is limited to a season, and their representativeness is limited by restricted studied situations, notably dominant unsoluble forms in fallout, light soils and intense rainfalls. Formulas based on a simplified representation of the soil-runoff system were proposed to generalize the existing values for other conditions. However, their implementation requires a more systematic compilation of the available information, including decisive influence factors such as the fraction of exchangeable form, distribution coefficient, suspended matter enrichment ratio. Entrainment coefficients K(l)(*) and K(s)(*) were mathematically related to the transfer function approach. The proposed relationships proved their complementarity in terms of time support and captured fluctuations. Both approaches should be used in assessments to estimate average fluxes and their variability.


Improving facilities for children in an accident department.
A separate waiting and treatment area for children was established within an existing general accident and emergency department at relatively little cost. We describe how this was achieved and how it has benefited the children attending the department.


Advances in neuromagnetic topography and source localization.
The development of ultra-low noise instrumentation for neuromagnetic mapping has yielded significant progress in the study of brain function and pathology. New multi-channel systems, belonging to an "intermediate" generation, are already in use, or are going to become operative in the near future. These systems permit simultaneous field mapping over a relatively large area of the scalp, and allow source localization on the basis of a single trial, although they still do not permit topographic mapping over the whole scalp. Significant improvements are being made also in realistic modeling of the human head and brain, with the aim at increasing the accuracy of source localization. Finally, a few examples of recent studies on normal brain function and application of the technique in the clinical field will be illustrated.


Ketoacids and the insulin receptor.
The binding of insulin to a specific receptor on IM-9-cultured human lymphocytes was studied in vitro under conditions simulating diabetic ketoacidosis. Compared with control incubations at pH 7.4, binding was reduced by 19 per cent at pH 7.1 and by 48 per cent at pH 6.8. Addition of beta-hydroxybutyrate, at concentrations similar to those seen clinically, "restored" insulin binding toward normal. We suggest that, by counteracting the effects of acidosis, ketoacids themselves maintain normal insulin-receptor binding in diabetic ketoacidosis. These data also illustrate that small molecules, present in vivo, can significantly alter the interactions between a hormone and its receptor in vitro.


[Update on regulatory framework and certification process].
Patients receiving blood transfusion must benefit from the same quality of care, no matter where they are treated. In an effort to enhance transfusion safety, regulations applicable to blood depot facilities have been considerably reinforced over the last few years. At the present time, facilities authorized to store and distribute labile blood products are subject to the same principles of good practice as transfusion centers. A series of regulations published in 2007 established the duties and responsibilities of depot facilities according to category (emergency, intermediary or distribution) and set out the conditions for certification.


Chemoenzymatic Synthesis of Amphiphilic Core-Shell TMP-(PCL-b-PGMA2)3 Star-Block Copolymer.
A novel well-defined amphiphilic Core-Shell star-block copolymer was synthesized from trimethylolpropane, ε-caprolactone, and glycidyl methacrylate by a combination of enzymatic ring-opening polymerization and atom transfer radical polymerization. The structure and molecular weight of the macroinitiator and the star-block copolymer were confirmed by means of nuclear magnetic resonance and gel permeation chromatography. The effects of the glycidyl methacrylate sequence length on the hydrodynamic diameter and morphology of the polymer micelles were investigated by dynamic light scattering and transmission electron microscopy, respectively.


Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain.
Naked mole-rats (Heterocephalus glaber) are eusocial rodents that live in large subterranean colonies including a single breeding female and 1-3 breeding males; all other members of the colony, known as subordinates, are reproductively suppressed. We recently found that naked mole-rats lack many of the sex differences in the brain and spinal cord commonly found in other rodents. Instead, neural morphology is influenced by breeding status, such that breeders, regardless of sex, have more neurons than subordinates in the ventromedial nucleus of the hypothalamus (VMH), and larger overall volumes of the bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN) and medial amygdala (MeA). To begin to understand how breeding status influences brain morphology, we examined the distribution of androgen receptor (AR) immunoreactivity in gonadally intact breeders and subordinates of both sexes. All animals had AR+ nuclei in many of the same regions positive for AR in other mammals, including the VMH, BST, PVN, MeA, and the ventral portion of the premammillary nucleus (PMv). We also observed diffuse labeling throughout the preoptic area, demonstrating that distribution of the AR protein in presumptive reproductive brain nuclei is well-conserved, even in a species that exhibits remarkably little sexual dimorphism. In contrast to other rodents, however, naked mole-rats lacked AR+ nuclei in the suprachiasmatic nucleus and hippocampus. Males had more AR+ nuclei in the MeA, VMH, and PMv than did females. Surprisingly, breeders had significantly fewer AR+ nuclei than subordinates in all brain regions examined (VMH, BST, PVN, MeA, and PMv). Thus, social status is strongly correlated with AR immunoreactivity in this eusocial species.


Shaped DNA origami carrier nanopore translocation influenced by aptamer based surface modification.
DNA origami is widely used as a translocation carrier to assist solid-state nanopore analysis, e.g., soft linear origami carrier and special-shaped origami structures. In the linear origami carriers based nanopore sensing, molecular modifications induced tiny structural and charge changes, can result in significant variations on translocation signals to facilitating single-molecule sensing. However, an understanding on the influences of surface modifications on special-shaped DNA origami structures during solid-state (SS) nanopores translocation is still far elusive. Herein, we reported a surface modification strategy using aptamer/target-binding to influence the translocation of the shaped origami ribbon carrier through SS-nanopore. Our measurements indicate that the translocation signal variations can respond to ATP/aptamer binding on the carrier surface, even to the surface modifications induced by spatial distributions and enzyme catalysis. Meanwhile, the results also suggest a possibility to identify small spatial and electronic changes on DNA origami by using SS-nanopore. We envision that the surface aptamer-binding influenced origami translocation strategy could find more applications in origami carrier assisted SS-nanopore sensing and detection.


Adverse Childhood Experiences and Health and Wellness Outcomes among Black Men Who Have Sex with Men.
Black men who have sex with men (BMSM) are a population at the intersection of two minority statuses-racial minority and sexual minority. Membership in either group, compared to white or heterosexual group membership, may increase one's risk of negative childhood and adult experiences. Baseline data from an HIV intervention efficacy trial (the Black Men Evolving Study) were used to explore the prevalence of adverse childhood experiences (ACEs) among 536 BMSM and associations between ACEs and adult mental and physical health outcomes. Overall, the prevalence of ACEs was high among this sample of BMSM with almost 90% experiencing at least one ACE. Findings revealed that ACE score was significantly associated with adult mental health (AOR = 1.21, 95% CI [1.12, 1.30]), but not with adult physical health. All ACEs were significantly associated with mental health, but only physical neglect and household substance abuse were significantly associated with physical health (AOR = 1.69, 95% CI [1.02, 2.74] and AOR = 1.57, 95% CI [1.03, 2.40], respectively). The findings support the need for interventions targeting improved adult health outcomes, particularly for minority groups, to consider the impact of early adversity on health and wellness.


Regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing: a comparison with stress echocardiography and perfusion scintigraphy.
We evaluated regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing. Evaluation and quantification of diastolic myocardial function remain a challenge for imaging techniques in stress tests. A prospective study compared the detection of coronary artery stenosis: 1) by pulsed Doppler myocardial mapping, 2) by two-dimensional echocardiographic dobutamine stress test, and 3) by perfusion scintigraphy in 64 patients using coronary angiography for reference. An age matched subgroup of 10 patients with normal angiograms and two-dimensional echocardiographic stress test served as control group. Peak myocardial contraction velocity (Vc) and lengthening rate during early diastolic left ventricular (LV) filling (VE) were measured in 12 LV segments from three apical views. In controls, myocardial velocities increased during stress by > or =3.6 cm/s (p < 0.001). In LV segments depending on a stenosed artery (n = 70), VE decreased by > or =1 cm/s and, thus, was different from control segments (n = 112, p < 0.001) and from scar segments (n = 13, p < 0.01), whereas the change of Vc was similar to that in scar segments. A stress induced 2 cm/s reduction of VE discerned the best diagnostic accuracy (sensitivity 84%, specificity 93%) in comparison with two-dimensional echocardiography (78% and 71%) and perfusion scintigraphy (61% and 86%). Using receiver operating curves at incremental levels of luminal narrowing, these relations persisted. Quantification of diastolic myocardial function by pulsed Doppler myocardial mapping during dobutamine stress test was shown to be a feasible, accurate, reproducible, noninvasive technique that should be considered to be a sensitive alternative to the present echocardiographic and scintigraphic imaging techniques for stress tests.


Clinical significance of the quantitative assessment of the cytosolic concentration of HER-2/neu protein in breast cancer by immunoenzymatic assay (ELISA).
Retrospective analysis to assess the prognostic and predictive value of HER-2/ neu expression in breast tumors, quantified by enzyme immunoassay (ELISA). Quantification of HER-2/neu was performed on cytosolic extracts from 914 cases of primary invasive breast carcinomas. Relapse-free and overall survival data were available from 889 patients. The prognostic value of HER-2/neu levels was assessed considering them as a continuous, dichotomic or quartile variable. Cytosolic HER-2/neu levels ranged widely in breast carcinomas (median: 746.5 NHU/mg; range: 2.8-80,000 NHU/mg protein). HER-2/neu protein levels were significantly higher in either moderately or poorly differentiated tumors, as well as in those showing a ductal histological type, aneuploidy or a high S-phase fraction. There was a significant and positive association between cytosolic and membranous HER-2/neu levels (n=162, r sub S=0.53; P<0.0001). In addition, cytosolic HER-2/neu level correlated weakly with progesterone receptors but not with estrogen receptors. Elevated cytosolic HER-2/neu levels (> or =1,400 NHU/mg protein) were associated with a high probability of both shortened relapse-free survival and overall survival. This same cut-off value was obtained when we divided the overall group of patients in a training set. However, this HER-2/neu value did not achieve any statistical significance in a validation set used to make sure that the cut-off was correct. Nevertheless, when we divided the obtained data into three different groups with respect to the quartile values (Q) of the intratumoral oncoprotein levels (< or = Q1 vs Q1-Q2 vs > Q3), we observed that patients with either low HER-2/ neu levels (< or = Q1) or high HER-2/neu levels (> Q3) had shorter both relapse-free survival and overall survival curves than those patients with intermediate HER-2/neu levels. On the other hand, high HER-2/neu levels predicted a poor response to adjuvant chemotherapy but not to adjuvant hormonal therapy with tamoxifen. The results of the present investigation indicate that by quantitatively determining the content of HER-2/neu oncoprotein, groups of high-risk breast cancer patients could be identified, for a more effective clinical management.


Closed and open conformations of the lid domain induce different patterns of human pancreatic lipase antigenicity and immunogenicity.
Epitope mapping was performed on human pancreatic lipase (HPL) using the SPOTscan method. A set of 146 short (12 amino acid residues) synthetic overlapping peptides covering the entire amino acid sequence of HPL were used to systematically assess the immunoreactivity of antisera raised in rabbits against native HPL, HPL without a lid (HPL(-lid)) and HPL covalently inhibited by diethyl p-nitrophenyl phosphate (DP-HPL). In the latter form of HPL, the lid domain controlling the access to the active site was assumed to exist in the open conformation. All the anti-lipase sera were tested in a direct ELISA, anti-HPL serum showing the greatest antibody titer. Although from the structural point of view, the differences between the various forms of HPL were restricted to the lid domain, differences in the antigenic properties of HPL were observed with the SPOTscan method, and the anti-DP-HPL antibodies showed the strongest reactivity. Most of the peptide stretches recognized included amino acid residues which are accessible at the surface of the lipase, except for those located near the active site. Two small peptides (T173-P180, V199-A207) were identified in the vicinity of the active site, their antipeptide antibodies were produced and their reactivity towards the various forms of HPL was tested in a double sandwich ELISA. No reactivity was observed under these conditions. Two antipeptide antibodies directed against two other selected peptides, P208-V221 (belonging to the beta9 loop) and I245-F258 (belonging to the lid domain) were prepared and found to react much more strongly with DP-HPL than with HPL or HPL(-lid) in a double sandwich ELISA. These antibodies should provide useful tools for monitoring the conformational changes taking place during the opening of the HPL lid domain.


Dephosphorylation of p-ERK1/2 in relation to tumor remission after HER-2 and Raf1 blocking therapy in a conditional mouse tumor model.
Several studies have shown that HER-2/neu (erbB-2) blocking therapy strategies can cause tumor remission. However, the responsible molecular mechanisms are not yet known. Both ERK1/2 and Akt/PKB are critical for HER-2-mediated signal transduction. Therefore, we used a mouse tumor model that allows downregulation of HER-2 in tumor tissue by administration of anhydrotetracycline (ATc). Switching-off HER-2 caused a rapid tumor remission by more than 95% within 7 d of ATc administration compared to the volume before switching-off HER-2. Interestingly, HER-2 downregulation caused a dephosphorylation of p-ERK1/2 by more than 80% already before tumor remission occurred. Levels of total ERK protein were not influenced. In contrast, dephosphorylation of p-Akt occurred later, when the tumor was already in remission. These data suggest that in our HER-2 tumor model dephosphorylation of p-ERK1/2 may be more critical for tumor remission than dephosphorylation of p-Akt. To test this hypothesis we used a second mouse tumor model that allows ATc controlled expression of BXB-Raf1 because the latter constitutively signals to ERK1/2, but cannot activate Akt/PKB. As expected, downregulation of BXB-Raf1 in tumor tissue caused a strong dephosphorylation of p-ERK1/2, but did not decrease levels of p-Akt. Interestingly, tumor remission after switching-off BXB-Raf1 was similarly efficient as the effect of HER-2 downregulation, despite the lack of p-Akt dephosphorylation. In conclusion, two lines of evidence strongly suggest that dephosphorylation of p-ERK1/2 and not that of p-Akt is critical for the rapid tumor remission after downregulation of HER-2 or BXB-Raf1 in our tumor model: (i) dephosphorylation of p-ERK1/2 but not that of p-Akt precedes tumor remission after switching-off HER-2 and (ii) downregulation of BXB-Raf1 leads to a similarly efficient tumor remission as downregulation of HER-2, although no p-Akt dephosphorylation was observed after switching-off BXB-Raf1.


Changes in phrenic nerve compound muscle action potential in streptozotocin-induced diabetic rats.
To evaluate the phrenic nerve compound muscle action potential (CMAP) in rats after diabetes mellitus (DM) induction. Twenty DM animals (intravenous streptozotocin, 45 mg.kg-1) and 25 controls underwent CMAP analysis before and 30, 60 and 90 days after DM induction. Amplitude (mV) progressively declined in DM group after 30 (Mean difference (MD): -0.915, 95 % Confidence interval (CI) -1.580 to -0.250, p < 0.01), 60 (MD: -1.122, 95 % CI -1.664 to -0.581, p < 0.001) and 90 days (MD: -2.226, 95 % CI -3.059 to -1.393, p < 0.001); as well as the area (mV.ms) after 30 (MD: -3.19, 95 % CI -5.94 to -0.44, p < 0.05), 60 (MD: -3.94, 95 % CI -6.24 to -1.64, p < 0.001) and 90 days (MD: -8.64, 95 % CI -12.08 to -5.21, p < 0.001). Transient differences were observed in latency and duration at 60 days. The progressive changes in phrenic nerve CMAP observed during DM suggest a decrement in axonal function rather than substantial demyelination.


Stannous chloride induces alterations in enzyme activities, lipid peroxidation and histopathology in male rabbit: antioxidant role of vitamin C.
Stannous chloride (SnCl2) is widely used in daily human life to conserve soft drinks, in food manufacturing and biocidal preparations. It had genotoxicity, immunotoxicity, neurotoxicity and oxidative stress. Therefore, the present experiment was carried out to determine the effectiveness of l-ascorbic acid (AA) in alleviating the toxicity of SnCl2 on some enzyme activities and oxidative damage in male New Zealand white rabbits. Six rabbits per group were assigned to 1 of 4 treatment groups: 0 mg AA and 0 mg SnCl2/kg BW (control); 40 mg AA/kg BW; 20 mg SnCl2/kg BW (1/500 LD50); 20 mg SnCl2 plus 40 mg AA/kg BW. Rabbits were orally administered the respective doses every other day for 12 weeks. Liver and kidney specimens were processed for histopathologic studies. Results obtained showed that SnCl2 significantly (P < 0.05) induced free radicals in rabbit liver, testes, kidney, lung, brain and heart. While, the activity of glutathione S-transferase (GST) and the level of sulfhydryl groups (SH-group) were decreased (P < 0.05) in all tested organs except brain and heart. Aspartate aminotransferase (AST) activity was increased (P < 0.05) in liver and decreased in testes, but alanine aminotransferase (ALT) did not change. The activities of alkaline phosphatase (AlP) and acid phosphatase (AcP) were decreased (P < 0.05) in liver, testes, kidney and lung. Also, the activity of acetylcholinesterase (AChE) was significantly decreased in brain and plasma of rabbits treated with SnCl2 compared to control group. Histopathologic studies showed marked changes in hepatocytes as well as proliferation of duct epithelium, dilatation and congestion of blood vessels as well as mononuclear inflammatory infiltrate. The kidney were also severely affected by SnCl2 the Bowman's space was increased, with infiltration of renal parenchyma by mononuclear inflammatory infiltrate and changes in cells lining convoluted tubule. Ascorbic acid alone significantly decreased the levels of free radicals, and increased the activity of GST and the levels of SH groups in tested organs except brain and heart. While, the rest of the tested parameters were not affected. Results showed that AA alleviated the harmful effects of SnCl2. This was proved histopathologically by the great improvement in liver and kidney histology where hepatocytes retained normal architecture with mild dilatation and congestion of blood vessels. Bowman's space of kidney was almost normal, with normal lining of proximal and distal convoluted tubules. In conclusion AA could be effective in the protection against stannous chloride toxicity.


Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model.
Overexpression of the crbB-2 gene-encoded p185(c-erbB-2) is correlated with early onset of metastasis in breast cancer patients. Furthermore, the detection of blood-borne epithelium-derived clustered cells expressing p185(c-erbB-2) was related to advanced stages in breast cancer. To further elucidate the receptor's function in the metastatic process of human breast cancers, we analyzed disaggregated cells and cell clusters from freshly dissected breast cancer tissues. We studied whether their capability of extravasation is correlated with their expression of c-erbB-2. A model for the venular wall was constructed by growing human umbilical vein endothelial cells (HUVECs) on porous membranes coated with basement membrane extracellular matrix. In four control breast cancer cell lines (SK-BR-3, MCF-7, MDA-MB-468, and MDA-MB-468, the latter transfected with a full-length c-erbB-2 cDNA vector) producing different levels of the c-erbB-2 receptor, the expression level correlated positively with the invasiveness of the cells. The invasive, predominantly clustered cells from 14 of 23 tumors were positively stained for p185(c-erbB-2) by immunocytochemistry. Furthermore, we show that the invasive cell populations express the metastasis-associated proteins matrix metalloproteinase MMP-2, CD44, and integrins alpha(v)beta3 and alpha6. In this first study on the behavior of cells and cell clusters from disaggregated operated cancers in an extravasation model, we could demonstrate the presence of c-erbB-2-expressing cell subpopulations within the individual breast cancers that are presumably of high metastatic potential.


Neuroendoscopy in the youngest age group.
The aim of this report is to review current data on the role of neuroendoscopy in infants. Specific emphasis will be given to the International Infant Hydrocephalus Study (IIHS). Previous studies, available information, and future directions are discussed. The IIHS is a major international endeavor comparing the results of endoscopic third ventriculostomy (ETV) to ventriculoperitoneal shunting in infants younger than 2 years of age. It is a prospective, randomized study, with a "parental preference" option, that recruits infants with aqueductal stenosis without a history of prematurity or other associated brain anomalies. The primary outcome measure is neurocognitive outcome at 5 years of age. In addition to IIHS data, we also looked at results of neuroendoscopy in infants with other indications, such as fourth ventricular outlet obstruction, Dandy Walker syndrome, etc. The IIHS study includes more than 40 centers on all continents. To date, we have recruited more than 150 infants to the study. At this point we can only release limited data, namely that the complication rates are similar between the two arms. More patients are needed to finalize the study, with an endpoint of 250 children. Neuroendoscopy in infants can be performed with reasonable morbidity. The preferred indications in infants are still not totally refined, especially vis-a-vis shunting procedures. More international, multicenter efforts are required to clarify these points.


Potential of phytohormones as a strategy to improve microalgae productivity for biotechnological applications.
Microalgae have many commercial applications including biofuel production, use in human and animal nutrition, as pharmaceuticals and therapeutic compounds, in beauty-related products and as biofertilizers in the agricultural sector. However, more research needs to be directed to reducing production costs in an environmentally friendly way before their commercial potential can be fully realized. This review discusses the current knowledge on the occurrence and physiological roles of phytohormones in microalgae and explores the potential of phytohormone treatments to improve cultivation practices, including increasing lipid content and productivity for biofuel production. Microalgae synthesize a wide array of phytohormones and are able to regulate the levels of active phytohormones. Biosynthetic and conversion pathways share some key components but are more rudimentary compared to vascular plants and are likely to have some unidentified conjugation mechanisms. Phytohormones have a dual function in microalgae. Specific phytohormones are involved in the regulation of the cell cycle and other metabolic processes, influencing biomass and primary metabolite accumulation. They are also involved in responses to abiotic stresses, allowing microalgae to adapt to the prevailing conditions. Phytohormones provide a promising strategy to improve mass culture biotechnology due to their intrinsic role in microalgal growth and survival, increasing lipid productivity and improving their tolerance to more extreme environmental changes. This makes them less susceptible to environmental fluctuations. This improves the productivity of the cultures for biofuel production and would be beneficial in a biorefinery approach. Overall, phytohormones provide an exciting and promising avenue of research to improve microalgae cultivation, taking it a step closer to successful commercialization.


[Effect of lighting oscillations on growth and energetics of the goldfish Carassius auratus].
Periodic oscillations of illumination exert a positive, rather than negative, effect on goldfish growth and energetics. In a variable light regime, the fishes grow of a higher rate, have decreased oxygen and food requirements, improve the utilization of consumed food for growth, and decrease the oxygen expenditure per increment of unit body mass. The goldfish reactions to the frequency of illumination oscillation and the succession of the stationary light regime by the oscillatory regime were described.


Spontaneous neoplastic transformation of WB-F344 rat liver epithelial cells.
Several studies have shown that cultured rat liver epithelial cells transform spontaneously after chronic maintenance in a confluent state in vitro. In the present study, multiple independent lineages of low-passage WB-F344 rat liver epithelial stem-like cells were initiated and subjected in parallel to selection for spontaneous transformation to determine whether spontaneous acquisition of tumorigenicity was the result of events (genetic or epigenetic) that occurred independently and stochastically, or reflected the expression of a pre-existing alteration within the parental WB-F344 cell line. Temporal analysis of the spontaneous acquisition of tumorigenicity by WB-F344 cells demonstrated lineage-specific differences in the time of first expression of the tumorigenic phenotype, frequencies and latencies of tumor formation, and tumor differentiations. Although spontaneously transformed WB-F344 cells produced diverse tumor types (including hepatocellular carcinomas, cholangiocarcinomas, hepatoblastomas, and osteogenic sarcomas), individual lineages yielded tumors with consistent and specific patterns of differentiation. These results provide substantial evidence that the stochastic accumulation of independent transforming events during the selection regimen in vitro were responsible for spontaneous neoplastic transformation of WB-F344 cells. Furthermore, cell lineage commitment to a specific differentiation program was stable with time in culture and with site of transplantation. This is the first report of a cohort of related, but independent, rat liver epithelial cell lines that collectively produce a spectrum of tumor types but individually reproduce a specific tumor type. These cell lines will provide valuable reagents for investigation of the molecular mechanisms involved in the differentiation of hepatic stem-like cells and for examination of potential causal relationships in spontaneously transformed rat liver epithelial cell lines between molecular/cellular alterations and the ability to produce tumors in syngeneic animals.


Qindan capsule changes adventitial collagen synthesis in spontaneously hypertensive rats.
To investigate the effect of Qindan capsule (QC) on collagen synthesis and the mechanism underlying the process in spontaneously hypertensive rats (SHRs). Twentyfour SHRs were divided into three groups: the hypertension model group, the QC treatment group, and the losartan treatment group. Eight Wistar Kyoto (WKY) rats were used as the normal control group. The systolic blood pressure (SBP) of the rats was monitored, and the thoracic aorta adventitia of the rats was segregated. The expressions of transforming growth factor 1 (TGF-β1), Smad3, and collagens I and were measured by histological staining and reverse transcription polymerase chain reaction. The SBP was significantly higher in the model group than in the normal control group (P<0.01). However, a significant SBP-lowering effect was observed in QC or losartan treatment groups (P<0.05 or P<0.01) after 3 weeks of treatment. QC-treated rats showed a decrease of approximately 40 mm Hg, and the losartan-treated rats showed a decrease of approximately 50 mm Hg at the end of treatment compared with the beginning of treatment. The protein and gene levels of TGF-β1, Smad3, and collagens I and in the model group were significantly increased compared with those in the normal control group (P<0.01). However, the levels were significantly decreased in the QC or losartan treatment group compared with the model group (P<0.05 or P<0.01). However, there was no significant difference between the QC and losartan treatment groups (P<0.05). QC could exert its antihypertensive effect through down-regulating TGF-β1-stimulated collagen expressions. The TGF-β1/Smad3 signaling pathway may be involved in this process.


Hiking in suicidal patients: neutral effects on markers of suicidality.
Regular physical activity promotes physical and mental health. Psychiatric patients are prone to a sedentary lifestyle, and accumulating evidence has identified physical activity as a supplemental treatment option. This prospective, randomized, crossover study evaluated the effects of hiking in high-risk suicidal patients (n = 20) who performed 9 weeks of hiking (2-3 hikes/week, 2-2.5 hours each) and a 9-week control period. All patients participated in the required 2 hikes per week and thus showed a compliance of 100%. Regular hiking led to significant improvement in maximal exercise capacity (hiking period Δ: +18.82 ± 0.99 watt, P < .001; control period: P = .134) and in aerobic capability at 70% of the individual heart rate reserve (hiking period Δ: +8.47 ± 2.22 watt; P = .010; control period: P = .183). Cytokines, associated previously with suicidality (tumor necrosis factor-α, interleukin-6, S100), remained essentially unchanged. Hiking is an effective and safe form of exercise training even in high-risk suicidal patients. It leads to a significant improvement in maximal exercise capacity and aerobic capability without concomitant deterioration of markers of suicidality. Offering this popular mode of exercise to these patients might help them to adopt a physically more active lifestyle.


Oxidation-reduction potentials of the hemes in cytochrome C3 from Desulfovibrio gigas in the presence and absence of ferredoxin by EPR spectroscopy.
1. Ferricytochrome c3 from D. gigas exhibits two low-spin ferric heme EPR resonances with gz-values at 2.959 and 2.853. Ferrocytochrome c3 is diamagnetic based on the absence of any EPR signals. 2. EPR potentiometric titrations result in the resolution of the two low-spin ferric heme resonances into two additional heme components representing in total the four hemes of the cytochrome, with EM values of -235 mV and -315 mV at heme resonance I and EM values of -235 mV and -306 mV at heme resonance II. 3. EPR spectroscopy has detected a significant diminution of intensity (approx. 60 p. 100) in the gx amplitude of ferricytochrome c3 in the presence of D. gigas ferredoxin II. The presence of ferredoxin II also causes a more negative shift in the EM of the second components of the signals at heme resonances I and II of cytochrome C3. Both observations suggest that an interaction has occurred between cytochrome C3 and ferredoxin II. 4. The results presented suggest that the heme ligand environment of ferricytochrome c3 from D. gigas is less perturbed and/or less asymmetric than environment for ferricytochrome c3 from D. vulgaris whose EPR behavior indicates the non-equivalence of all four hemes.


Exchange of Coordinated Solvent During Crystallization of a Metal-Organic Framework Observed by In Situ High-Energy X-ray Diffraction.
Using time-resolved monochromatic high energy X-ray diffraction, we present an in situ study of the solvothermal crystallisation of a new MOF [Yb2(BDC)3(DMF)2]⋅H2O (BDC=benzene-1,4-dicarboxylate and DMF=N,N-dimethylformamide) under solvothermal conditions, from mixed water/DMF solvent. Analysis of high resolution powder patterns obtained reveals an evolution of lattice parameters and electron density during the crystallisation process and Rietveld analysis shows that this is due to a gradual topochemical replacement of coordinated solvent molecules. The water initially coordinated to Yb(3+) is replaced by DMF as the reaction progresses.


Effects of a Potential Probiotic Strain Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-Induced Inflammatory Response and Gene Expression in Coinfected Gastric Epithelial Cells.
In the present study, we aimed to investigate the modulatory effects of a potential probiotic bacterium Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-induced inflammatory response and gene expression in human gastric adenocarcinoma (AGS) cell line. The gastric epithelial cells were coinfected with a collection of H. pylori clinical strains alone or in combination with L. gasseri at a multiplicity of infection (MOI) of 1:100 for each bacterium, and incubated for different time points of 3, 6, and 12 h. IL-8 secretion from coinfected AGS cells after incubation at each time point was measured by an enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-8, Bcl-2, β-catenin, integrin α5, and integrin β1 genes was determined by quantitative RT-PCR amplification of total RNA extracted from coinfected epithelial cells. L. gasseri significantly (P < 0.05 and P < 0.01) decreased the production of IL-8 in AGS cells coinfected with H. pylori strains at 6 h post-infection. We also detected that L. gasseri significantly (P < 0.05) down-regulated the gene expression level of IL-8 in H. pylori-stimulated AGS cells after 6 and 12 h of coinfection. Similarly, L. gasseri caused a significant decrease (P < 0.05) in mRNA expression of Bcl-2, β-catenin, integrin α5, and integrin β1 genes in AGS cells at 3 and 6 h after infection with H. pylori strains as compared with non-infected control cells. In conclusion, our results demonstrated that L. gasseri ameliorates H. pylori-induced inflammation and could be developed as a supplementation to the current treatment regimens administrated against H. pylori infection.


Exploring the inhibitory potential of novel piperidine-derivatives against main protease (Mpro) of SARS-CoV-2: A hybrid approach consisting of molecular docking, MD simulations and MMPBSA analysis.
In the current study, a hybrid computational approach consisting of different computational methods to explore the molecular electronic structures, bioactivity and therapeutic potential of piperidine compounds against SARS-CoV-2. The quantum chemical methods are used to study electronic structures of designed derivatives, molecular docking methods are used to see the most potential docking interactions for main protease (MPro) of SARS-CoV-2 while molecular dynamic and MMPBSA analyses are performed in bulk water solvation process to mimic real protein like aqueous environment and effectiveness of docked complexes. We designed and optimized piperidine derivatives from experimentally known precursor using quantum chemical methods. The UV-Visible, IR, molecular orbitals, molecular electrostatic plots, and global chemical reactivity descriptors are carried out which illustrate that the designed compounds are kinetically stable and reactive. The results of MD simulations and binding free energy revealed that all the complex systems possess adequate dynamic stability, and flexibility based on their RMSD, RMSF, radius of gyration, and hydrogen bond analysis. The computed net binding free energy ( Δ G b i n d ) as calculated by MMPBSA method for the complexes showed the values of -4.29 kcal.mol-1 for P1, -5.52 kcal.mol-1 for P2, -6.12 kcal.mol-1 for P3, -6.35 kcal.mol-1 for P4, -5.19 kcal.mol-1 for P5, 3.09 kcal.mol-1 for P6, -6.78 kcal.mol-1 for P7, and -6.29 kcal.mol-1 for P8.The ADMET analysis further confirmed that none of among the designed ligands violates the Lipinski rule of five (RO5). The current comprehensive investigation predicts that all our designed compounds are recommended as prospective therapeutic drugs against Mpro of SARS-CoV-2 and it provokes the scientific community to further perform their in-vitro analysis.


Gamma/delta T lymphocytes in viral infections.
T lymphocyte progenitors differentiate into two distinct T cell lineages. Although the alpha beta and gamma delta T cell lineages resemble each other phenotypically and functionally, there are some striking differences. Some gamma delta T cells recognize, similarly to alpha beta T cells, peptides presented by major histocompatibility complex (MHC) proteins or MHC-like molecules. However, there are gamma delta T cells that recognize MHC molecules in a fundamentally different manner in comparison with alpha beta T cells. Also in contrast recognizing nonpeptide antigens. Most responses of gamma delta T cells appear to be directed against microbial pathogenic agents including bacteria, parasites, and viruses. In particular, the potent cytotoxic responses of gamma delta T cells against cells infected with, for example, herpesviruses or lentiviruses may be essential for the overall antiviral defense of vertebrates. The analysis of antiviral immunosurveillance by gamma delta T cells is crucial for understanding the unique biological role of this lymphocyte subset.


Neuropharmacological activities of the crude alkaloidal fraction from stems of Tabernaemontana pandacaqui Poir.
The crude alkaloidal (CA) fraction from the stem of Tabernaemontana pandacaqui Poir. was studied for its pharmacological activity on the central nervous system (CNS) of animals. The CA fraction was found to produce symptoms of CNS depression in conscious rats and mice, viz. reduction in spontaneous motility, potentiation of pentobarbital sleeping time, prolongation of latency of convulsions induced by pentylenetetrazole and antinociception. However, the fraction could not antagonize oxotremorine-induced tremor. The observations suggest that the CA fraction possesses a CNS depressant activity.


TBL2 methylation is associated with hyper-low-density lipoprotein cholesterolemia: a case-control study.
HMGCR, SCAP, SREBF1, SREBF2 and TBL2 are well-known genes that are involved in the process of lipid metabolism. However, it is not known whether epigenetic changes of these genes are associated with lipid metabolism. In this study, the methylation levels of the HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes were analyzed between samples from a hyper-low-density lipoprotein cholesterolemia (hyper-LDL) group and a control group to examine the association between the methylation levels of these genes and the risk of hyper-LDL. In this study, a case-control approach was used to explore the association between DNA methylation and hyper-LDL. The DNA methylation levels of HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes and 231 CpG sites in the promoter regions of these genes were measured in 98 hyper-LDL participants and 89 participants without hypo-LDL. Compared with participants without hyper-LDL, patients with hyper-LDL TBL2 gene had lower methylation levels (11.93 vs. 12.02, P = 0.004). The methylation haplotypes with significant abundance in the TBL2 gene are tcttttttttt (P = 0.034), ctttttttcct (P = 0.025), ctctttctttt (P = 0.040), ccttttttttt (P = 0.028), and tctttttttttttttt. The study demonstrates that participants with hyper-LDL have lower methylation of TBL2. The results suggest that DNA methylation of TBL2 can decrease the risk for hyper-LDL in humans.


Enrichment of antibiotic resistance genes in roots is related to specific bacterial hosts and soil properties in two soil-plant systems.
Soil microorganisms carrying antibiotic resistance genes (ARGs) can colonize plants as endophytes, posing a huge risk to human health. However, the distribution and transmission patterns of ARGs in different soil-plant systems are unclear. Here, we investigated the distribution of ARGs and the microbial communities in the soil-wheat and soil-cucumber systems by quantitative PCR (qPCR) and 16S rRNA gene sequencing. The results showed that the relative abundances of seven ARGs and intI1 in roots were higher than those of other samples in both soil-plant systems. Pseudomonas, Enterobacteriaceae, Rhizobiales and Gammaproteobacteria were dominant potential bacterial hosts of endophytic ARGs, with enrichment patterns similar to that of ARGs in roots. In addition, more ARGs were significantly positively correlated with intI1 in roots, indicating that ARGs may be more prone to horizontal gene transfer (HGT). Variation partitioning analysis (VPA) and structural equation models (SEM) revealed that the variations of ARGs were mainly directly affected by the HGT of intI1 and indirectly affected by soil properties in roots. These results demonstrated that root could have a strong proliferative effect on ARGs entering host plant endophytes. Overall, our findings enhanced the understanding distribution patterns of ARGs in different soil-plant systems, and provided an effective basis for developing measures to minimize the spread of ARGs.


Association between loneliness and psychological distress: A cross-sectional study among Japanese workers during the COVID-19 pandemic.
The purpose of this study was to examine the association between loneliness and psychological distress during the COVID-19 pandemic in Japan. We conducted a cross-sectional online study from 22 to 26 December 2020. A total of 27,036 participants, all employed at the time, were included in the analysis. Participants were asked if they felt loneliness in a single-item question. The Kessler 6 (K6) was used to assess psychological distress, defined as mild for K6 scores of 5 to 12 and severe for 13 or higher. The odds ratios (ORs) of psychological distress associated with loneliness were estimated using a multilevel logistic model nested in the prefecture of residence, with adjustment for age, sex, marital status, equivalent income, educational level, smoking, alcohol consumption, job type, number of workplace employees, and cumulative incidence rate of COVID-19 in the prefecture. Communication with friends, acquaintances, and family was strongly associated with psychological distress, so we adjusted for these factors and eating meals alone. Results showed a significant association between loneliness and psychological distress (OR = 36.62, 95% CI = 32.95-40.69). Lack of friends to talk to, lack of acquaintances to ask for help, and lack of people to communicate with through social networking sites were all strongly associated with psychological distress, as were family time and solitary eating. Even after adjusting for these factors, loneliness remained strongly associated with psychological distress (OR = 29.36, 95% CI = 26.44-32.98). The association between loneliness during the COVID-19 pandemic and psychological distress indicates the need for intervention.


Extended reality in musculoskeletal rehabilitation and injury prevention - A systematic review.
Unlike in neurological patient populations, the effects of Extended Reality within the context of sports medicine have rarely been studied. This systematic review was conducted to investigate the value of Extended Realty-assisted rehabilitation and injury prevention strategies on injury rehabilitation and prevention outcomes. PubMed and Web of Science databases were consulted. The search strategy consisted of the terms Virtual Reality (Intervention), rehabilitation and injury prevention (Outcome) and healthy athletes or athletes with a musculoskeletal sports injury (Population). After eligibility and Risk of Bias screening, ten articles were included. Risk of Bias analysis resulted in a level of evidence varying between C (three articles), B (six articles) and A2 (one article) scores. Extended Reality was found to provide an added value for both sports injury prevention and rehabilitation outcomes. It particularly provides clinicians with the opportunity to address the underlying biomechanical risk profile for common sports injuries, allowing the athletes to train protective movement patterns more effectively. More large-scale high-quality prospective research is needed in order to determine whether Extended Reality-assisted therapy is superior to conventional therapy in sports rehabilitation and injury prevention circles with strong conclusive evidence.


Long-Term Retrospective Clinical and Radiographic Follow-up of 205 Brånemark System Mk III TiUnite Implants Submitted to Either Immediate or Delayed Loading.
Studies are needed to evaluate long-term performance of immediately loaded implants with moderately rough surface. This retrospective study evaluated long-term survival and periimplant soft and hard tissue conditions in patients treated with TiUnite implants. Forty-one consecutive patients (mean age, 52.6 years) received 205 Brånemark System Mk III TiUnite implants (145 maxillary, 60 mandibular). The indication was single tooth (n = 7 implants), partial (n = 94), or full arches (n = 104). One hundred thirteen implants were immediately loaded. Cumulative survival rate (CSR) of implants was assessed. Long-term marginal bone remodeling, probing pocket depth (PPD), and periimplant mucosa conditions were assessed. Follow-up averaged 8.8 years (range, 6.6-10.6 years). Eight implants in 5 patients failed. CSR was 96.1% (implant basis) and 87.8% (patient basis) up to 10 years. At the longest follow-up, bone loss averaged 0.43 ± 1.15 mm (n = 173), PPD averaged 3.64 ± 0.74 mm, and periimplant mucosa was healthy in 74.6% of cases. Furthermore, 50.3% and 35.5% of implants scored negative for plaque and bleeding, respectively. No significant difference in CSR and hard and soft tissue conditions was found in the long term between immediately and delayed loaded implants. Implants with TiUnite surface demonstrated excellent long-term survival, marginal bone response, and soft tissue conditions, despite a nonoptimal level of oral hygiene.


A case of hyperinsulinism/hyperammonaemia syndrome with reduced carbamoyl-phosphate synthetase-1 activity in liver: a pitfall in enzymatic diagnosis for hyperammonaemia.
We report a patient who was first diagnosed as having congenital carbamoyl-phosphate synthetase-1 (CPS-1) deficiency on the basis of significantly low CPS-1 activity in the liver at 1 year of age. We then started therapy against hyperammonaemia with little effect and, at the age of 15 years, we analysed the GLUD1 gene and found a previously reported gain-of-function mutation in the gene, resulting in a change of her diagnosis to hyperinsulinism/hyperammonaemia (HI/HA) syndrome. This case demonstrates that low CPS-1 activity in liver, however significant it might be, does not always come from a primary CPS-1 deficiency and that we have to take into consideration the possibility of a secondary CPS-1 deficiency, such as HI/HA syndrome.


Overlapping expression patterns of the multiligand endocytic receptors cubilin and megalin in the CNS, sensory organs and developing epithelia of the rodent embryo.
Cubilin and megalin are multiligand epithelial endocytic receptors well characterized in the adult kidney and ileum where they form a complex essential for protein, lipid and vitamin uptake. Although inactivation of the megalin gene leads to holoprosencephaly and administration of anti-cubilin antibodies induces fetal resorptions or cranio-facial malformations their function in the developing embryo remains unclear. We recently showed that both proteins are strongly expressed by the maternal-fetal interfaces and the neuroepithelium of the early rodent embryo where they co-localize and form a complex important for nutrient uptake. The aim of the present study was the further investigation of cubilin expression at later developmental stages of the rodent embryo and its correlation to that of megalin. Immunohistochemical and in situ hybridization analysis showed striking similarities in the spatial and temporal expression patterns of cubilin and megalin. The electrophoretic mobility of both proteins was identical to that of the adult as revealed by Western blot analysis. Cubilin and megalin were strongly expressed in the sensory organs, the central nervous system, the respiratory and urogenital tracts as well as in the thymus, parathyroids and thyroid. In each site, the expression mainly concerned epithelial structures and correlated with the onset of epithelial induction. Depending on the site, a decreased or restricted expression was observed by the end of the gestation for both proteins.


Incorrect position of Essure microinserts 3 months after successful bilateral placement.
To describe incorrect positions of Essure microinserts detected at 3 months' follow-up. Case report. Outpatient department of obstetrics and gynecology in a Dutch teaching hospital. Initial series of 100 patients who underwent hysteroscopic sterilization using Essure between December 2003 and June 2004. Hysteroscopic placement of the Essure System, follow-up at 3 months with transvaginal ultrasound (TVU), and hysterosalpingography. Bilateral placement rate, tubal obstruction, and detection of incorrect Essure microinsert localization at follow-up after apparent successful bilateral placement. Bilateral placement of Essure microinserts in one session was successful in 93 women (93%). In 90 of these women (96.8%), tubal obstruction was proven at follow-up 3 months later. Three incorrect positions of an Essure insert were seen: two expulsions and one perforation into the abdominal cavity. Incorrect position of Essure microinserts was seen only when the initial placement procedure was difficult. When a placement procedure was difficult or other suboptimal conditions are present during the procedure, we advise performing a TVU or pelvic X-ray in these women 4 weeks after the procedure or after the first vaginal bleeding, instead of waiting for follow-up after 3 months.


Levodopa or D2 agonist induced dyskinesia in MPTP monkeys: correlation with changes in dopamine and GABAA receptors in the striatopallidal complex.
Dopamine D1 and D2 receptors as well as the GABA/benzodiazepine receptor complex in the striatum and the globus pallidus (internal: GPi and external: GPe) were studied by autoradiography using [3H]SCH 23390, [3H]spiperone, and [3H]flunitrazepam ([3H]FNZ) respectively, in five groups of cynomolgus monkeys. These included (i) untreated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-monkeys; (ii) MPTP monkeys treated chronically with levodopa injections; (iii) MPTP monkeys treated chronically with injections of the novel D2 agonist U91356A; (iv) MPTP monkeys treated chronically with U91356A delivered through an osmotic mini-pump; and (5) naive controls. Animals treated in a pulsatile mode with U91356A or levodopa injections showed progressive sensitization to their respective drug and developed choreic dyskinesia. In contrast, animals treated in a continuous mode with U91356A showed behavioral tolerance but did not develop dyskinesia. A trend for a down-regulation of putaminal D2 receptors was observed following D2 agonist stimulation with U913356A. Striatal [3H]FNZ binding was significantly decreased only in animals treated in a continuous mode with U91356A. The dopamine receptor decrease in the striatum could be implicated with the development of tolerance but cannot explain the appearance of dyskinesia. Denervation by MPTP was associated with a decrease of the GPe/GPi [3H]FNZ binding ratio which reflects an imbalance of striatal output pathways; this ratio was not reversed by any of the treatments although changes were observed in the GPe and GPi. Indeed, pulsatile U91356A treatment restored the decreased [3H]FNZ binding in the GPe near control values and levodopa showed a similar tendency. A significant increase of [3H]FNZ binding in the GPi only of dyskinetic monkeys, namely those treated with pulsatile U91356A or levodopa was seen compared to untreated MPTP or naive controls. This GABAA receptor up-regulation might lead to a supersensitive state of the GPi to gabaergic input which may be involved in the mechanism underlying the development of dopaminomimetic-induced dyskinesia.


Synergistic Anti-Tumor Activity by Targeting Multiple Signaling Pathways in Ovarian Cancer.
More effective therapy is needed to improve the survival of patients with advanced and recurrent ovarian cancer. Preclinical and early clinical studies with single molecular targeted agents have shown limited antitumor activity in ovarian cancer, likely due to compensation by alternative growth/survival pathways. An emerging strategy in overcoming resistance is to combine inhibitors targeting multiple pathways. In this study, we used a novel strategy of combining several FDA-approved targeted drugs, including sunitinib, dasatinib, and everolimus, in human ovarian cancers. Combination of the tyrosine kinase inhibitor sunitinib with the SRC inhibitor dasatinib showed synergistic anti-tumor activity in human ovarian cancer cells. The increased activity was associated with inhibition of the STAT3, SRC, and MAPK signaling pathways, but not AKT signaling. To inhibit the PI3K/AKT/mTOR pathway, we added the mTOR inhibitor everolimus, which further increased anti-tumor activity in cells. Combined treatment with sunitinib, dasatinib, and everolimus also resulted in greater inhibition of human ovarian tumor growth in mice. Furthermore, the triple combination also synergistically increased the anti-tumor activity of paclitaxel, both in vitro and in vivo. Taken together, our results demonstrate that simultaneous inhibition of several signaling pathways results in better anti-tumor activity compared to inhibiting any of these signaling pathways alone.


Dyslexia detection using 3D convolutional neural networks and functional magnetic resonance imaging.
Dyslexia is a disorder of neurological origin which affects the learning of those who suffer from it, mainly children, and causes difficulty in reading and writing. When undiagnosed, dyslexia leads to intimidation and frustration of the affected children and also of their family circles. In case no early intervention is given, children may reach high school with serious achievement gaps. Hence, early detection and intervention services for dyslexic students are highly important and recommended in order to support children in developing a positive self-esteem and reaching their maximum academic capacities. This paper presents a new approach for automatic recognition of children with dyslexia using functional magnetic resonance Imaging. Our proposed system is composed of a sequence of preprocessing steps to retrieve the brain activation areas during three different reading tasks. Conversion to Nifti volumes, adjustment of head motion, normalization and smoothing transformations were performed on the fMRI scans in order to bring all the subject brains into one single model which will enable voxels comparison between each subject. Subsequently, using Statistical Parametric Maps (SPMs), a total of 165 3D volumes containing brain activation of 55 children were created. The classification of these volumes was handled using three parallel 3D Convolutional Neural Network (3D CNN), each corresponding to a brain activation during one reading task, and concatenated in the last two dense layers, forming a single architecture devoted to performing optimized detection of dyslexic brain activation. Additionally, we used 4-fold cross validation method in order to assess the generalizability of our model and control overfitting. Our approach has achieved an overall average classification accuracy of 72.73%, sensitivity of 75%, specificity of 71.43%, precision of 60% and an F1-score of 67% in dyslexia detection. The proposed system has demonstrated that the recognition of dyslexic children is feasible using deep learning and functional magnetic resonance Imaging when performing phonological and orthographic reading tasks.


Intracellular Ca modulates K-inward rectification in cardiac myocytes.
In cardiac myocytes, instantaneous inward rectification of the K-rectifying channel is abolished by removal of divalent cations from the intracellular environment and can be restored by addition of Mg ions at submillimolar concentrations, which has led to the proposal that Mg ions regulate inward rectification in these cells (Matsuda et al., 1987; Vandenberg, 1987; Matsuda, 1988). Here we report that Ca, too, reduces outward current flow through single inward rectifier channels in cell-free inside-out patches at much lower (submicromolar) concentrations. Intracellular Ca induces rectification by decreasing the probability of the main open channel state and by favouring the opening of channel substrates. Ca concentrations generating rectification are in the range of the Ca transient during activity, suggesting that Ca ions can contribute to K-rectification during cardiac muscle contraction.


Electronic clinical reminder and quality of primary diabetes care.
To study the association of EMR's clinical reminder use on a comprehensive set of diabetes quality metrics in U.S. office-based physicians and within solo- versus multi-physician practices. We conducted a retrospective cohort study on visits made by adults with diabetes identified from the National Ambulatory Medical Care Survey (2012-2014). Multiple logistic regression is used to test for associations between clinical reminder use and recommended services by the American Diabetes Association. Of 5508 visits, nationally representing 112,978,791 visits, 31% received HbA1c tests, 13% received urinalysis test, and <10% received retinal or foot exams. Main effects of practice size and clinical reminder use were found for HbA1c, urinalysis, and foot exams. We find no statistically significant relationship to suggest that clinical reminder use improve diabetes process guidelines for solo practices. Resource efforts, beyond clinical reminders, are needed to reduce gaps in primary diabetes care between solo and non-solo practices.


Smoking as an independent risk factor for severe skin reactions due to adjuvant radiotherapy for breast cancer.
Risk factors for severe acute radiation skin reactions (ARSR) have been described with conflicting results. The aim of this study was to identify risk factors for the development of severe ARSR in women undergoing adjuvant radiotherapy (RT) for breast cancer. 390 women were assessed at the first and final RT sessions and at followup. ARSR were measured by the Radiation Therapy Oncology Group/The Organization for Research and Treatment of Cancer, Acute Radiation Morbidity Scoring Criteria (RTOG/EORTC scale). Patients reported symptoms using visual analogue scale (VAS). Health related quality of life was assessed by EORTC QLQ-C30 and sleep disturbances by the MOS-Sleep questionnaire. Clinical data included smoking status (carbon monoxide in expired air), body mass index (BMI) and treatment data. RT dose, ≥ 50 Gy (mean difference 1.9 CI: 1.0 to 3.5, p = 0.040), high BMI (mean difference 4.3 CI: 2.2 to 8.3, p < 0.001) and smoking (mean difference 2.5 CI. 1.1 to 5.7, p = 0.027) were the factors strongest related to severe ARSR. Patients' with severe ARSR reported higher levels of pain and increased sleeping problems. To stop smoking during RT is the best decision patients can make to reduce the risk for severe ARSR since smoking is an independent risk factor.


Improved use of SNP information to detect the role of genes.
A topical question in genetic association studies is the optimal use of the information provided by genotyped single-nucleotide polymorphisms (SNPs) in order to detect the role of a candidate gene in a multifactorial disease. We propose a strategy called "combination test" that tests the association between a quantitative trait and all possible phased combinations of various numbers of SNPs. We compare this strategy to two alternative strategies: the association test that considers each SNP separately, and a multilocus genotype-based test that considers the phased combination of all SNPs together. To compare these three tests, a quantitative trait was simulated under different models of correspondence between phenotype and genotype, including the extreme case when two SNPs interact with no marginal effects of each SNP. The genotypes were taken from a sample of 290 independent individuals genotyped for three genes with various number of SNPs (from 5-8 SNPs). The results show that the "combination test" is the only one able to detect the association when the two SNPs involved in disease susceptibility interact with no marginal effects. Interestingly, even in the case of a single etiological SNP, the "combination test" performed well. We apply the three tests to Genetic Analysis Workshop 12 (Almasy et al. [2001] Genet. Epidemiol. 21:332-338) simulated data, and show that although there was no interactions between the etiological SNPs, the "combination test" was preferable to the two other compared methods to detect the role of the candidate gene.


Comparison of performance between an F 18 -FDG PET normal brain template and a commercial template using the MIMneuro software.
The aim of this study was to create and validate a normal brain template of F 18 -fluorodeoxyglucose ( F 18 - FDG ) uptake using the MIMneuro software to improve clinical practice. One hundred and nine volunteers underwent an F 18 - FDG positron emission tomography/computed tomography scan. Sixty-three participants with normal Alzheimer's disease (AD) biomarkers were used to create a template. A group of 23 participants with abnormal AD biomarkers and an additional group of 23 participants with normal AD biomarkers were used to validate the performance of the generated template. The MIMneuro software was used for the analysis and template creation. The performance of our newly created template was compared with that of the MIMneuro software template in the validation groups. Results were confirmed by visual analysis by nuclear medicine physicians. Our created template provided higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV; 90%, 97.83%, 100%, and 100%, respectively) than did the MIMneuro template when using the positive validation group. Similarly, slightly higher performance was observed for our template than for the MIMneuro template in the negative validation group (the highest specificity and NPV were 100% and 100%, respectively). Our normal brain template for F 18 - FDG was shown to be clinically useful because it enabled more accurate discrimination between aging brain and patients with AD. Thus, the template may improve the accuracy of AD diagnoses.


The phosphoinositide 3-kinase and p70 S6 kinase regulate long-term potentiation in hippocampal neurons.
The mechanisms by which long-term changes in synaptic efficacy (e.g., long-term potentiation) are maintained are not well understood. There is evidence that reorganization of the neuronal actin cytoskeleton is important for consolidation of long-term potentiation. In non-neuronal cells, phosphoinositide 3-kinase and p70 S6 kinase have been shown to regulate actin polymerization. We have investigated the subcellular localization of these enzymes in cultured hippocampal pyramidal neurons and their possible role in hippocampal long-term potentiation. Immunohistochemical analysis revealed enrichment of both enzymes in the growth cones and filopodia of extending neurites, whereas p70 S6 kinase was also present at the soma. Antibodies to the phosphorylated form of p70 S6 kinase confirmed its activity in these locations. Interestingly, both enzymes displayed strong colocalization with F-actin in discrete regions of developing neurites. In hippocampal slices, the maintenance of long-term potentiation was attenuated by either rapamycin or 2-(4-morpholinyl)-8-phenyl-1(4H)-1-benzopyran-4-one, inhibitors of p70 S6 kinase and phosphoinositide 3-kinase, respectively. Our findings provide evidence for a novel biochemical pathway involving phosphoinositide 3-kinase and p70 S6 kinase that is important for the maintenance of hippocampal long-term potentiation, possibly via regulation of actin dynamics.


In vivo effects of partial electrothermal shrinkage on mechanical properties of the anterior cruciate ligament in rabbits.
No studies have been conducted to clarify an in vivo remodeling of the radiofrequency-treated lesion of the anterior cruciate ligament. The purpose was to determine in vivo effects of radiofrequency shrinkage on mechanical properties of the anterior cruciate ligament. Thirty skeletally mature rabbits were used. In each group, radiofrequency energy set at non-ablative levels was applied to the posterolateral bundle of the anterior cruciate ligament with a bipolar radiofrequency generator. All animals were sacrificed at 0, 6, and 12 weeks after surgery, respectively. In each group, 7 and 3 out of the 10 specimens were used for biomechanical and histological evaluations. After shrinkage treatment, the anterior-posterior translation of the knee and the length of the posterolateral bundle were significantly reduced immediately after surgery, but that this effect disappeared at 6 weeks. The tensile strength and the tangent modulus of the treated bundle were significantly lower than that of the normal control bundle at each period. In addition, the tensile strength and the tangent modulus measured at 12 weeks were significantly lower than that at 0 week. Histological examination showed granulation-like tissues with numerous plump fibroblasts and inflammatory cells were dominantly found in the midsubstance of the posterolateral bundle at 12 weeks. This result suggested that the anterior cruciate ligament tissue shortened with the radiofrequency treatment is elongated gradually over time. The mechanical properties of the posterolateral bundle of the anterior cruciate ligament reduced by the radiofrequency shrinkage are not restored in vivo, but significantly deteriorated with time.


Pregnancy outcomes after preterm premature rupture of membranes: The Japan Environment and Children's Study.
To evaluate the pregnancy outcomes of preterm premature rupture of membranes (preterm PROM; PPROM) by gestational age. This cohort study analyzed data from the Japan Environment and Children's Study. Pregnancy outcomes were documented using descriptive statistics. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of complications. Data were collected for 104 062 fetuses, and 99 776 were eligible for inclusion. The incidences of early (18-23 weeks) and late (24-36 weeks) PPROM were 0.1% (n = 102) and 1.2% (n = 1205), respectively. Of the 1307 cases, 66 (5.0%) resulted in miscarriage or stillbirth. Overall, 85.6% (1119/1307) resulted in preterm births, and 9.3% (122/1307) in term births. There was a higher incidence of oligohydramnios (OR 6.82, 95% CI 4.07, 11.4; OR 2.42, 95% CI 1.72, 3.40), intrauterine infection (OR 11.9, 95% CI 7.06, 19.9; OR 4.39, 95% CI 3.01, 6.41), cesarean delivery (OR 3.31, 95% CI 2.32, 4.71; OR 1.34, 95% CI 0.97, 1.85), placental abruption (OR 5.57, 95% CI 2.30, 13.5; OR 5.40, 95% CI 3.58, 8.14), and 5-min Apgar score <7 (OR 35.3, 95% CI 21.5, 57.9; OR 2.66, 95% CI 1.75, 4.05) for early and late, compared to no, PPROM, respectively. Miscarriage or stillbirth was higher in early (OR 5.84, 95% CI 3.72, 9.15) and lower in late (OR 0.21, 95% CI 0.06, 0.68) compared to those without PPROM. This study described the epidemiology of pregnancy outcomes of early (occurring at the limit of viability) and late PPROM.


Understanding consumer participation in managing ICT waste: Findings from two-staged Structural Equation Modeling-Artificial Neural Network approach.
For environmental management, the role of consumers is extremely important in the settings of reverse logistics. Though it is a manufacturer's extended responsibility to handle the waste however by becoming the supplier of the end of life products, consumers' participation needed to be encouraged and hence require proper attention. For the said purpose, the present study is conducted whereby crucial determinants of consumer reversing behavior were identified and analyzed by the help of a unique two-staged methodology of partial least square-structural equation modeling and artificial neural network. The data comprised of 746 collected by the survey from ICT users whereby the findings reported to have significant relationships of return intention and reversing behavior with their determinants. Moreover, the aforementioned unique methodology helps in generating more robust results as findings from ANN reported to have moral norm as most important variable which according to PLS-SEM was second most significant construct, whereas attitude was found to be second most important as per ANN which according to PLS-SEM is the most significant construct. Nevertheless, the study offers insights which contributes in the literature of environmental management, reverse logistics, and consumer behavior. Lastly, based on the findings, the managerial implications and recommendations are accordingly discussed.


Antibacterial efficiency over time and barrier properties of wood coatings with colloidal silver.
This work aims to represent a standard application for understanding the extent of the antibacterial efficacy of coatings with different amounts of colloidal silver on wooden surfaces over time. The key variable that was intended to be evaluated in this study was the "time efficiency," with concerns about the possible efficacy in the durability of the surfaces. By highlighting the "expiry date" of the agents, as in the case with other products, the study aimed to confirm the validity of the simulation tests conducted in the laboratory with degradation tests. Furthermore, the role of the silver amount on the barrier performance of the coatings was assessed by liquid resistance, water uptake, and perspiration tests, evaluating the aesthetic durability of the coatings by means of colorimetric analyses. Ultimately, this work demonstrates that these coatings may represent alternatives in terms of prolonged antimicrobial activity when compared with the biocide agents currently in use, capable to offer good resistance to detergent solutions and to water. Nevertheless, due to silver's susceptibility to extended exposure to acidic solutions, the findings of the research discourage the utilization of colloidal silver in wood paints intended for use in public settings. KEY POINTS: • Colloidal silver does not alter the deposition process and does not introduce defects in the wood paint. • Coatings containing silver show high antimicrobial activity over time, against both E.coli and S.aureus. • The silver-based filler resists contact with detergents and aqueous solutions but suffers oxidation processes in acidic environments.


Measures of autonomic nervous system activity and lower urinary tract symptoms.
Autonomic nervous system (ANS) activity may play an important role in the development of lower urinary tract symptoms (LUTS). Men with severe LUTS and men with mild or no LUTS completed the Valsalva maneuver, quantitative sudomotor axon reflex test, tilt-table, and deep breathing tests. There were no differences between men with severe LUTS compared to men with mild or no LUTS (all P values > 0.05). Systemic ANS tests may not be useful in detecting the underlying physiologic changes that lead to LUTS in aging men.


Diagnostic value of dobutamine echocardiography in patients with angina-like symptoms preceding syncope.
Dobutamine echocardiography was performed in 55 patients with syncope which was clinically suspected to be angina-related. We evaluated the value of using a single test, dobutamine echocardiography, in differentiating real ischemia-related from vasovagal syncope which was diagnosed by a tilt test. During testing, supraventricular arrhythmia was provoked in four (7.2%) patients. Dobutamine echocardiography identified all of six (10.9%) patients (sensitivity 100%), who were found with significant coronary stenosis by coronary angiograms. The etiology of syncope in the remaining 45 patients was investigated further by tilt testing, the findings of hypotension and bradycardia during which were compared head to head with those of dobutamine echocardiography. Tilt testing diagnosed vasovagal syncope in 31 patients, in whom only 19 (61.3%) patients developed vasovagal reflex during dobutamine echocardiography. Conclusively, dobutamine echocardiography had a high sensitivity in identifying syncope related to myocardial ischemia in patients with coronary stenosis, but a low sensitivity (61.3%), high specificity (90.5%) and high positive predictive value (81.8%) in detecting the syncope patients with angina caused by vasovagal effect.


Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety.
The study aims at formulation and optimization brain targeted nanoparticles (NP) of Rivastigmine (RT) to improve its therapeutic potential and to verify its safety profile. The NP were optimized using a two factor three level (3(2)) central composite design aiming to minimize particle size; maximize zeta potential and drug entrapment efficiency of NP. The optimized formulation (cRTNP) was evaluated using in vitro drug release study; in vivo behavioral, and biochemical and maximum tolerated dose (MTD) study. The optimized formulation evidenced a significant reversal of scopolamine-induced amnesia by Tween 80(®) coated nanoparticles as compared to both pure RT as well as uncoated nanoparticles. The MTD of RT was increased by 10% by formulating them as cRTNP. Thus, formulation of RT as cRTNP improved the therapeutic and safety profile of RT.


Influence of wafer quality on chip size-dependent efficiency variation in blue and green micro light-emitting diodes.
We propose a key factor associated with both surface recombination velocity and radiative efficiency of an LED to estimate its chip size-dependent radiative efficiencies. The validity of the suggested factor is verified through experimental comparison between various LED wafers. Efficiencies of micro-LEDs from a blue and two green LED wafers are examined by temperature-dependent photoluminescence experiments. Surface recombination velocities are extracted from chip size dependent time-resolved PL results. Possible explanations on the reason why two green wafers show different properties are also given. With the suggested factor, we can provide more accurate prediction on the chip size-dependent efficiency of an LED wafer.


Characterisation of a novel p53 down-regulated promoter in intron 3 of the human MDM2 oncogene.
The MDM2 oncogene exhibits a complex expression pattern partly due to the usage of multiple promoters. Two MDM2 promoters (P1 and P2) have been identified. P1 is located upstream of exon 1 and is modulated by PTEN. P2 sits in intron 1 and is activated by p53. Here we report the discovery of a third promoter (designated P3) in intron 3 of this gene, which contains a TATA-box element and p53-DNA-binding sequences. DNA-protein binding assays indicated that p53 bound to this region specifically. This region also demonstrated promoter activity in a reporter gene system, which was down-regulated by p53. Furthermore, experiments combining P2 and P3 in the same reporter construct indicated that P3 had a suppressive effect on P2 at high levels of p53. These results suggest that one of the P3 functions is to dampen the expression of MDM2 at high levels of p53, adding an additional element to the feedback loop between p53 and MDM2.


Clinical Accuracy of the Lateral-Anterior Drawer Test for Diagnosing Posterior Cruciate Ligament Rupture.
Commonly used clinical posterior cruciate ligament (PCL) tests present with diagnostic weaknesses requiring alternative clinical tests. The Lateral-Anterior Drawer test (LAD-test) is a suggested alternative that previously demonstrated concurrent validity in situ. Further in vivo LAD-test clinical accuracy examination is required prior to any recommendation for clinical adoption. Thus, this case-control study aims to (1) investigate the LAD-test's in vivo interrater and intra-rater reliability; (2) establish LAD-test concurrent validity against MRI as the reference standard; and (3) examine the correspondence between examiners' professional working experience and LAD-test diagnostic accuracy. Three examiners with different professional experience levels, blindfolded during testing, and blinded from subjects' identity, medical history, and reference test outcome performed all LAD-testing twice per subject. Reliability analyses included percent agreement, Fleiss' kappa and Cohen's kappa coefficients with 95% Confidence Intervals (CIs) and prevalence-adjusted bias-adjusted kappa (PABAK) calculations. Validation parameters included sensitivity, specificity, likelihood ratios (LR + ; LR-), and predictive values (PPV; NPV) each accompanied by 95%CIs; each tester's percent agreement with the MRI; and their Youden Index. The study sample was comprised of 31 subjects of which 14 had a history of unilateral full-thickness PCL-rupture. Their 14 contralateral knees and both knees of 17 healthy subjects served as controls. In vivo LAD-test performance did not produce any negative ramifications for the tested subjects. Interrater reliability was moderate (test-1: Fleiss'κ = 0.41; 95% CI 0.40;0.41; test-2:Fleiss'κ = 0.51; 95% CI 0.50;0.51). Pairwise examiner's LAD-test outcome agreement ranged from 74 to 89%. Pairwise interrater reliability was fair-to-substantial (κ = 0.27 to κ = 0.65) with moderate-to-substantial PABAK (0.48-0.77). Intra-rater reliability was substantial-to-almost perfect (PABAK 0.65-0.97). Sensitivity and specificity ranged from 57 to 86% and 83 to 98%, respectively. The advanced and novice clinicians' Youden Indexes were acceptable. The same examiners' positive likelihood ratios revealed important and relative important effects, respectively. Positive predictive values were considerable for the advanced and novice clinicians, while negative predictive values were high for all examiners. Overall, the study results suggested LAD-test practicability. In vivo LAD-test performance did not produce any negative ramifications for the tested subjects. In subjects presenting with a chronic PCL-deficiency (i.e., > 3 months since initial injury), the LAD-test's clinical accuracy was comparable-to-superior to other commonly used clinical PCL-tests. Future studies to establish the LAD-test's usefulness in isolation as well as in combination with other clinical tests for acute PCL-rupture diagnostics are warranted. DRKS00013268 (09. November 2017).


[Fluorimetric determination of tranylcypromine in plasma as its 1-dimethylamino-naphthaline-5-sulfonic acid chloride by direct measurement of TLC-plates (author's transl)].
A fluorimetric method for analysis of tranylcypromine from plasma is described. After extraction from plasma tranylcypromine reacts with 1-dimethylamino-naphthaline-5-sulfonic acid chloride (DANS-Cl) in order to form the highly fluorescent DANS-tranylcypromine. After chromatographic separation on silicagel plates quantitation is achieved by in situ fluorescence determination. The recovery of tranylcypromine from plasma is 64% with a coefficient of variance of about +/- 6%.


LiNbO3 -Type Polar Antiferromagnet InVO3 Synthesized under High-Pressure Conditions.
The ambient pressure cation disordered InVO3 bixbyite has been predicted to form a GdFeO3 -type perovskite phase under high pressure and high temperature. Contrary to the expectation, InVO3 was found to crystallize in the polar LiNbO3 -type structure with a calculated spontaneous polarization as large as 74 μC cm-2 . Antiferromagnetic coupling of V3+ magnetic moments and a cooperative magnetic ground state below about 10 K coupled with a polar structure suggest an intriguing ground state of the novel LiNbO3 -type high-pressure InVO3 structure.


Structure of the capsule and lipopolysaccharide O-antigen from the channel catfish pathogen, Aeromonas hydrophila.
A hypervirulent A. hydrophila (vAh) pathotype has been identified as the etiologic agent responsible for disease outbreaks in farmed carp species and channel catfish (Ictalurus punctatus) in China and the Southeastern United States, respectively. The possible route of infection has previously been unknown; however, virulence is believed to be multifactorial, involving the production/secretion of several virulence factors, including a high molecular weight group 4 capsular polysaccharide. Here we present chemical structural evidence of a novel capsule- and LPS-associated O-antigen found present in vAh isolated during these disease outbreaks. In this study, the chemical structure of the vAh O-antigen was determined by chemical analysis, Smith degradation, mass spectrometry, and 2D proton and carbon nuclear magnetic resonance (NMR) spectroscopy and found to be unique among described bacterial O-antigens. The O-antigen consists of hexasaccharide repeating units featuring a 4)-α-l-Fucp-(1-3)-β-d-GlcpNAc-(1-4)-α-l-Fucp-(1-4)-β-d-Glcp-(1- backbone, substituted with single residue side chains of α-d-Glcp and α-d-Quip3NAc linked to O-3 of the two fucose residues. The polysaccharide is partially O-acetylated on O-6 of the 4-substituted β-Glcp residue.


Effect of high quality nursing and respiratory training on pulmonary function and quality of life in patients with chronic obstructive pulmonary disease.
This research was aimed to evaluate the impact of high-quality nursing (HQN) plus respiratory training on treatment compliance, pulmonary function (PF) and quality of life (QoL) of patients with chronic obstructive pulmonary disease (COPD). We retrospectively analyzed 89 COPD patients who were treated at the affiliated Nanhua Hospital from February 2019 to February 2021. Among them, 40 cases received drug treatment and breathing training as the control group, and 49 cases were supplemented with HQN as the experimental group on the basis of the control group. The changes in PF, quality of life and compliance were compared between the two groups. Vital capacity (VC) and alveolar ventilation (VA) increased in both cohorts after treatment (P < 0.05), and increased more significantly in experimental group compared with control group (P < 0.05). Experimental group also presented markedly higher total effective rate and noticeably lower scores of symptoms, activities and disease impact on daily life than control group (P < 0.05). HQN plus respiratory training can effectively improve the PF, efficacy and QoL of patients with COPD.


Microbiota Imbalance Contributes to COPD Deterioration by Enhancing IL-17a Production via miR-122 and miR-30a.
The changes of microbiota in lungs could change interleukin-17a (IL-17a) expression by altering microRNAs (miRNAs) profile, thus contributing to the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we aimed to study molecular mechanisms' underlying effect of microbiota imbalance on COPD deterioration. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to analyze expression of miRNAs and IL-17a mRNA. ELISA was used to evaluate abundance of IL-17a in plasma, peripheral blood monocyte, and sputum of COPD mice and patients. Luciferase assay was performed to explore underlying molecular mechanisms. The expression of miR-122, miR-30a, and miR-99b were remarkably decreased in COPD mice, while the expression of IL-17a was notably increased in plasma, peripheral blood monocytes, and lung tissues of COPD mice. The levels of Lactobacillus/Moraxella and IL-17a expression were significantly enhanced in sputum of exacerbated COPD patients, along with notably decreased expression of miR-122 and miR-30a. Luciferase assay confirmed that miR-122 and miR-30a played an inhibitory role in IL-17a expression. We identified miR-122 and miR-30a as differentially expressed miRNAs in sputum and plasma of COPD patients in exacerbation-month12 group. Furthermore, downregulated miR-122 and miR-30a expression associated with microbiota imbalance may contribute to COPD deterioration by enhancing IL-17a production.


Resistance and susceptibility in human onchocerciasis--beyond Th1 vs. Th2.
As research progress has led to programs for the elimination of onchocerciasis as a public health problem, research must now be intensified to protect elimination efforts. A profound understanding of the immunology in the human-parasite relationship is required for predicting the impacts of an altered immune response in a population post-microfilaricide treatment, and for the development of a vaccine against onchocerciasis, a highly desirable tool to guarantee sustained elimination success. This article summarizes the recent advancements in understanding the human immune mechanisms against onchocerciasis, and focuses on the new concept of T-cell suppressor responses as a major counterbalance mechanism for effector responses driven by T helper 1 and T helper 2 cells against the filarial worms.


The association and prediction value of acylcarnitine on diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.
Acylcarnitines play a role in type 2 diabetes mellitus (T2DM), but the relationship between acylcarnitine and diabetic nephropathy was unclear. We aimed to explore the association of acylcarnitine metabolites with diabetic nephropathy and estimate the predictive value of acylcarnitine for diabetic nephropathy. A total of 1032 (mean age: 57.24 ± 13.82) T2DM participants were derived from Liaoning Medical University First Affiliated Hospital. Mass Spectrometry was utilized to measure levels of 25 acylcarnitine metabolites in fasting plasma. Diabetic nephropathy was ascertained based on the medical records. Factor analysis was used to reduce the dimensions and extract factors of the 25 acylcarnitine metabolites. Logistic regression was used to estimate the relationship between factors extracted from the 25 acylcarnitine metabolites and diabetic nephropathy. Receiver operating characteristic curves were used to test the predictive values of acylcarnitine factors for diabetic nephropathy. Among all T2DM participants, 138 (13.37%) patients had diabetic nephropathy. Six factors were extracted from 25 acylcarnitines, which account for 69.42% of the total variance. In multi-adjusted logistic regression models, the odds ratio (OR, 95% confidence interval [CI]) of diabetic nephropathy on factor 1 (including butyrylcarnitine/glutaryl-carnitine/hexanoylcarnitine/octanoylcarnitine/decanoylcarnitine/lauroylcarnitine/tetradecenoylcarnitine), factor 2 (including propionylcarnitine/palmitoylcarnitine/hydroxypalmitoleyl-carnitine/octadecanoylcarnitine/arachidiccarnitine), and factor 3 (including tetradecanoyldiacylcarnitine/behenic carnitine/tetracosanoic carnitine/hexacosanoic carnitine) were 1.33 (95%CI 1.12-1.58), 0.76 (95%CI 0.62-0.93), and 1.24 (95%CI 1.05-1.47), respectively. The area under the curve for diabetic nephropathy prediction was significantly increased after the complement of factors 1, 2, and 3 in traditional factors model (P < 0.01). Some plasma acylcarnitine metabolites extracted in factors 1 and 3 were higher in diabetic nephropathy, while factor 2 was lower in diabetic nephropathy among T2DM patients. The addition of acylcarnitine to traditional factors model improved the predictive value for diabetic nephropathy.


Maternal emotional and physical intimate partner violence and early child development: investigating mediators in a cross-sectional study in a South African birth cohort.
This study investigated associations between recent maternal intimate partner violence (IPV) (emotional, physical and sexual) and child development at 2 years as well as whether maternal depression or alcohol use mediated these relationships. Cross-sectional study nested in a South African birth cohort. Two primary care clinics in Paarl, South Africa. 626 mother-child pairs; inclusion criteria for maternal antenatal enrolment were clinic attendance and remaining in the study area for at least 1 year; women were excluded if a minor. Child cognitive, language and motor development composite scores. These were assessed using the Bayley Scales of Infant and Toddler Development, third edition. Emotional IPV was associated with lower cognitive (β=-0.32; 95% CI -0.60 to -0.04), language (β=-0.36; 95% CI -0.69 to -0.01) or motor composite scores (β=-0.58; 95% CI -0.95 to -0.20) in children at 2 years of age. Physical IPV was associated with lower motor scores (β=-0.42; 95% CI -0.75 to -0.09) at 2 years. Sexual IPV was unrelated to developmental outcomes, possibly due to low prevalence. Neither recent maternal depression nor alcohol use were shown to mediate the relationship between IPV and developmental outcomes. Interventions to reduce maternal physical and emotional IPV and early-life interventions for infants and toddlers are needed to promote optimal child development.


Ethical debate: the ethics of not performing extended lymphadenectomy in patients with gastrointestinal cancer.
The ethical debate about performing-or not-extended lymphadenectomy in patients with a gastrointestinal malignancy is approached in this work. It offers a thorough overview of the ethical principles. Problem-solving tools are provided to assist in framing the issues and resolving the conflicts.