AI Risk Score on Screening Mammograms Preceding Breast Cancer Diagnosis.
Background Few studies have evaluated the role of artificial intelligence (AI) in prior screening mammography. Purpose To examine AI risk scores assigned to screening mammography in women who were later diagnosed with breast cancer. Materials and Methods Image data and screening information of examinations performed from January 2004 to December 2019 as part of BreastScreen Norway were used in this retrospective study. Prior screening examinations from women who were later diagnosed with cancer were assigned an AI risk score by a commercially available AI system (scores of 1-7, low risk of malignancy; 8-9, intermediate risk; and 10, high risk of malignancy). Mammographic features of the cancers based on the AI score were also assessed. The association between AI score and mammographic features was tested with a bivariate test. Results A total of 2787 prior screening examinations from 1602 women (mean age, 59 years ± 5.1 [SD]) with screen-detected (n = 1016) or interval (n = 586) cancers showed an AI risk score of 10 for 389 (38.3%) and 231 (39.4%) cancers, respectively, on the mammograms in the screening round prior to diagnosis. Among the screen-detected cancers with AI scores available two screening rounds (4 years) before diagnosis, 23.0% (122 of 531) had a score of 10. Mammographic features were associated with AI score for invasive screen-detected cancers (P < .001). Density with calcifications was registered for 13.6% (43 of 317) of screen-detected cases with a score of 10 and 4.6% (15 of 322) for those with a score of 1-7. Conclusion More than one in three cases of screen-detected and interval cancers had the highest AI risk score at prior screening, suggesting that the use of AI in mammography screening may lead to earlier detection of breast cancers. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Mehta in this issue.


Anodic stripping voltammetry with graphite felt electrodes for the trace analysis of silver.
Graphite felt (GF) is a mass produced porous carbon electrode material commonly used in redox flow batteries. Previous studies have suggested GF may have valuable applications in electroanalysis as a low cost disposable carbon electrode material, although most GF sensors have used flow cell arrangements. In this work, an elegant wetting technique is employed that allows GF electrodes to be used in quiescent solution to detect trace levels of silver in water via anodic stripping voltammetry. GF electrodes display good repeatability and a limit of detection of 25 nM of Ag(+) in 0.1 M HNO3, with a linear range spanning two orders of magnitude. This compares to a value of around 140 nM when using conventional carbon electrodes. Combined with their low cost and disposable nature, the results suggest GF electrodes can make a valuable contribution to electroanalysis.


Mouthwashes: Alternatives and Future Directions.
This narrative review summarises "alternative" or "natural" over-the-counter (OTC) mouthwashes not covered elsewhere in this supplement and newly emerging products, as potential mouthwashes of the future. The "natural" mouthwashes reviewed include saltwater, baking soda, coconut oil, charcoal, propolis, seaweeds, and probiotics. Other than essential oils, it is apparent that their clinical effectiveness is still under debate, but there is some evidence to suggest that propolis reduces plaque and gingivitis. This review also covers the host immune response, via novel anti-inmmunomodulant mouthwashes, such as erythropoietin to reduce inflammation with oral mucositis (OM) after radiotherapy. The emerging concept of nanoparticle-containing mouthwashes, such as iron oxide, is further discussed for OM, this agent having the potential for more targeted delivery of chemical antimicrobials. Unfortunately, there are impacts on the environment of widening mouthwash use with more new products, including increased use of packaging, antimicrobial resistance, and possible detrimental effects on marine life. Further, there are roadblocks, relating to regularly approvals and side effects, that still need to be overcome for any OTC deivered immunomodulant or nanoformulation mouthwashes. Despite these caveats, there are many new mouthwashes under development, which could help manage major oral diseases such as caries, gingivitis, and periodontal disease.


Development and validation of risk prediction and neural network models for dilated cardiomyopathy based on WGCNA.
Dilated cardiomyopathy (DCM) is a progressive heart condition characterized by ventricular dilatation and impaired myocardial contractility with a high mortality rate. The molecular characterization of DCM has not been determined yet. Therefore, it is crucial to discover potential biomarkers and therapeutic options for DCM. The hub genes for the DCM were screened using Weighted Gene Co-expression Network Analysis (WGCNA) and three different algorithms in Cytoscape. These genes were then validated in a mouse model of doxorubicin (DOX)-induced DCM. Based on the validated hub genes, a prediction model and a neural network model were constructed and validated in a separate dataset. Finally, we assessed the diagnostic efficiency of hub genes and their relationship with immune cells. A total of eight hub genes were identified. Using RT-qPCR, we validated that the expression levels of five key genes (ASPN, MFAP4, PODN, HTRA1, and FAP) were considerably higher in DCM mice compared to normal mice, and this was consistent with the microarray results. Additionally, the risk prediction and neural network models constructed from these genes showed good accuracy and sensitivity in both the combined and validation datasets. These genes also demonstrated better diagnostic power, with AUC greater than 0.7 in both the combined and validation datasets. Immune cell infiltration analysis revealed differences in the abundance of most immune cells between DCM and normal samples. The current findings indicate an underlying association between DCM and these key genes, which could serve as potential biomarkers for diagnosing and treating DCM.


Activation of the bile acid receptor TGR5 enhances LPS-induced inflammatory responses in a human monocytic cell line.
Bile acids are recognized as signaling molecules, mediating their effects both through the cell surface receptor TGR5 and the nuclear receptor FXR. After a meal, approximately 95% of the bile acids are transported from terminal ileum and back to the liver via the portal vein, resulting in postprandial elevations of bile acids in blood. During the digestion of fat, components from the microbiota, including LPS, are thought to reach the circulation where it may lead to inflammatory responses after binding TLR4 immune cells. Both LPS and bile acids are present in blood after a high-fat meal; we therefore wanted to study consequences of a possible interplay between TGR5 and TLR4 in human monocytes. The monocytic cell line U937 stably transfected with the NF-κB reporter plasmid 3x-κB-luc was used as a model system to study the effects of TGR5 and TLR4. Activation of MAP kinases was studied to reveal functional consequences of triggering TGR5 in U937 cells. Effects of TGR5 and TLR4 activation were monitored using NF-κB luciferase assay and by quantification of the pro-inflammatory cytokines IL-6 and IL-8 using ELISA. In this study, results show that triggering TGR5 with the specific agonist betulinic acid (BA), and the bile acids CDCA or DCA, activated both the main MAP kinases ERK1/2, p38 and JNK, and the NF-κB signaling pathway. We further demonstrated that co-triggering of TLR4 and TGR5 enhanced the activation of NF-κB and the release of inflammatory cytokines in a synergistic manner compared to triggering of TLR4 alone. Thus, two different and simultaneous events associated with the digestive process coordinately affect the function of human monocytes and contribute to enhanced inflammation. Because elevated levels of circulatory LPS may contribute to the development of insulin resistance, the results from this study suggest that bile acids through the activation of TGR5 may have a role in the development of insulin resistance as well.


Scanning electron microscopy of vascular corrosion casts--standard method for studying microvessels.
Scanning electron microscopy (SEM) of vascular corrosion casts (microvascular corrosion casting/SEM method) is a standard method, which allows three-dimensional visualization with good resolution of the normal and abnormal microvessels, including the capillaries of various organs and tissues. SEM of vascular corrosion casts can obtain qualitative as well as quantitative informations important to anatomists, pathologists and clinicians. Considering these, the history, the advantages and the main steps of this technique including general morphological characteristics of vascular casts observed in SEM are reviewed in this paper. Corrosion casts done by the author representing the microvascular organization of the rat liver and kidney observed in SEM are, also, presented.


How acute care managers can support patients with dementia.
Not all hospital staff have had training in dementia care. This article describes how nurse managers in acute settings can prepare them to manage patients with dementia. It includes advice on identifying patients' diagnosis on admission, working with carers and encouraging activity, and emphasises the importance of establishing a rapport with patients.


Tarsoconjunctival-Skin Flap as Another Option in Correcting Ectropion for Oro-Ocular Cleft Reconstruction: Report of 2 Cases.
Facial clefts are rare facial anomalies. Among them, oro-ocular cleft remains a challenging malformation due to ectropion of the inferior palpebra which can constitute an emergency when the patient's globe is exposed leading to exposure keratitis and blindness. Here we report surgical procedures to correct lower eyelid ectropion using tarsoconjunctival-skin flap performed on 2 cases. In conclusion, tarsoconjunctival-skin flap can be provided to effectively correct lower eyelid ectropion and is a better option when nose correction is not involved simultaneously.


A comparison of two approaches to dynamic prediction: Joint modeling and landmark modeling.
Joint modeling and landmark modeling are two mainstream approaches to dynamic prediction in longitudinal studies, that is, the prediction of a clinical event using longitudinally measured predictor variables available up to the time of prediction. It is an important research question to the methodological research field and also to practical users to understand which approach can produce more accurate prediction. There were few previous studies on this topic, and the majority of results seemed to favor joint modeling. However, these studies were conducted in scenarios where the data were simulated from the joint models, partly due to the widely recognized methodological difficulty on whether there exists a general joint distribution of longitudinal and survival data so that the landmark models, which consists of infinitely many working regression models for survival, hold simultaneously. As a result, the landmark models always worked under misspecification, which caused difficulty in interpreting the comparison. In this paper, we solve this problem by using a novel algorithm to generate longitudinal and survival data that satisfies the working assumptions of the landmark models. This innovation makes it possible for a "fair" comparison of joint modeling and landmark modeling in terms of model specification. Our simulation results demonstrate that the relative performance of these two modeling approaches depends on the data settings and one does not always dominate the other in terms of prediction accuracy. These findings stress the importance of methodological development for both approaches. The related methodology is illustrated with a kidney transplantation dataset.


Acute effects of short-term feed deprivation and refeeding on circulating concentrations of metabolites, insulin-like growth factor I, insulin-like growth factor binding proteins, somatotropin, and thyroid hormones in adult geldings.
Two studies were performed with Standardbred geldings 7 to 21 yr of age to determine the sequence of changes in blood plasma concentrations of some hormones and metabolites during feed deprivation for 48 h and for 12 h after refeeding. Plasma hormone and metabolite concentrations were determined with methods validated for horse plasma. Insulin-like growth factor binding proteins (IGFBP) were determined with radioligand analysis following SDS-PAGE electrophoresis. In both experiments, plasma concentrations of triiodothyronine and thyroxine decreased (P < .01) during feed deprivation and increased (P < .01) during refeeding. Plasma glucose and IGF-I either decreased or were not altered during feed deprivation. In contrast, plasma concentrations of NEFA and urea nitrogen increased (P < .01) during feed deprivation and decreased (P < .01) during the refeeding period. Plasma somatotropin (ST) increased (P < .01) approximately 80% at 24 to 36 h of feed deprivation, declined (P < .01) to control values at 48 h of feed deprivation, increased (P < .01) nearly three fold at 3 h after refeeding, and returned to control values by 6 h after refeeding. We identified five IGFBP, and their plasma concentrations were not significantly altered during feed deprivation or following refeeding. We conclude that metabolite availability during feed deprivation and following refeeding alters the secretion of thyroid hormones, ST, and possibly IGF-I, thereby maintaining homeostasis in horses.


Characterization of amino acid transport system L in HTB-41 human salivary gland epidermoid carcinoma cells.
The amino acid transport system L is a major nutrient transport system that is responsible for transport of neutral amino acids, including several essential amino acids. The current study attempted to investigate the expression and functional characterization of amino acid transport system L in HTB-41 human submaxillary salivary gland epidermoid carcinoma cells. RT-PCR analysis, Western blot analysis and amino acid transport measurements were used. The HTB-41 cells expressed the L-type amino acid transporter 1 (LAT1) together with its associating protein heavy chain of 4F2 antigen (4F2hc) in the plasma membrane, whereas the HTB-41 cells did not express the L-type amino acid transporter 2 (LAT2). The uptakes of [14C]L-leucine were Na+-independent and completely inhibited by a system L selective inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). The affinity of [14C]L-leucine uptake and the inhibition profile of [14C]L-leucine uptake by various L-amino acids in the HTB-41 cells were comparable with those for the LAT1 expressed in Xenopus oocytes. The transport of neutral amino acids including several essential amino acids into the HTB-41 human submaxillary salivary gland epidermoid carcinoma cells are mediated by LAT1.


Hemagglutination-inhibiting antibody in hemorrhagic fever with renal syndrome.
Hemagglutination activity was demonstrated in a Hantaan virus antigen prepared from infected suckling mouse brain by sucrose-acetone extraction. Hemagglutination of goose erythrocytes was pH dependent and was optimal at pH 6.0-6.2. Immunofluorescent and hemagglutination-inhibiting antibodies were significantly correlated in 80 human and 13 animal sera. Hemagglutination-inhibiting antibody was present in some patients 20 years after the onset of hemorrhagic fever with renal syndrome. The hemagglutination inhibition test was useful for confirming that an insectivore, Suncus murinus, may be an animal reservoir host of a Hantaan-like virus.


Successful educational activities in nursing: guidelines for development.
1. Nursing professionals must commit to a lifelong pursuit of continuing education to achieve and maintain competence in their practice. 2. When pursuing quality, cost effective continuing education in times of limited financial resources for professional development, many practitioners must consider their educational requirements for relicensure and certification. 3. Prudent educational sponsors devote adequate resources to accurately assess the needs of potential learners to ensure successful programming and minimize costly marketing failures. 4. Participant evaluation and achievement of outcomes serve as the basis for improving and planning future educational activities.


Effect of arylthiolated 2,3-dimethoxy-1,4-benzoquinones on respiratory activity and lipid peroxidation in bovine heart mitochondria.
A series of arylthiolated 2,3-dimethoxy-1,4-benzoquinones was synthesized and tested for the effect on the respiratory system and the lipid peroxidation in bovine heart mitochondria (BHM). These quinones showed intense inhibitory activities on the respiratory system in BHM. Their inhibitory activity in the succinate oxidase system was greater than that in the NADH oxidase system. No difference between the difference spectra, with and without these quinones, of the reduced minus oxidized forms of cytochromes (cyt.) suggested that these quinones inhibit at the site after cyt. a+a3 in the respiratory chain. Moreover, these quinones were as efficient as exogenous ubiquinone-10 (UQ-10) for the inhibition of lipid peroxidation. 5- And 5,6-di-arylthio groups on the quinone ring were found to be favorable for inhibition of the respiratory system and lipid peroxidation. Our results suggest that arylthiolated 2,3-dimethoxy-1,4-benzoquinones act as antioxidants by increasing the amount of endogenous reduced UQ-10 in BHM.


Fibro-hyaline involution of a papillary thyroid carcinoma metastasis in a lymph node, consecutive to radioiodine therapy, mimicking a parathyroid adenoma. A case presentation.
The aim of the study is to present the unusual changes that a lymph node metastasis of papillary thyroid carcinoma (PTC) underwent after radioiodine therapy, leading to the confusion with a parathyroid adenoma (PA). Eight years after a total thyroidectomy and radioiodine ablation with 73.35 mCurie 131I for PTC, a 67-year-old female presented with an enlarged, painless, nodular mass in the left lateral neck region. Clinical examination revealed a firm nodule located on the site of the left inferior parathyroid gland. Elevated serum parathyroid hormone level (120 pg/mL) and parathyroid scintigraphy led to a suspicion of PA. A minimally invasive surgical procedure was performed to remove the mass, which was sent to the Department of Pathology, Emergency County Hospital, Tirgu Mures, Romania, as left PA. It was fixed and processed for microscopic evaluation. On macroscopic examination, the surgical specimen was oval; it had 13 mm at the largest diameter and weighted 2 g. On microscopy, the lesion appeared as a fibro-hyaline, intensely acidophilic, acellular mass, with calcifications. It was limited by a delicate capsule in which one typical psammoma body was present. At the periphery, on one single level, a small mass of cells of indefinite origin was noticed. Immunohistochemistry (IHC) was done to ascertain the origin of these cells: they were negative for Pan-Cytokeratin AE1/AE2, Parathormone and Thyroglobulin antibodies, but positive for Leukocyte Common Antigen (LCA) antibody, proving that they were lymphocytes, most likely residual from a lymph node. These IHC data, together with the microscopic feature, the presence of the psammoma body and the patient's history, excluded a PA and led to a diagnosis of fibro-hyaline involution of a PTC metastasis in a lymph node, consecutive to radioiodine therapy. Without careful microscopic examination and accurate clinical information, this lesion could represent a real diagnostic challenge.


Visual outcome three and six months after implantation of Acri.LISA 366D lenses.
To evaluate 3 and 6 months binocular visual outcomes after microincision cataract surgery (MICS) with implantation of multifocal, hybrid Acri.LISA 366D 10OLs. Three and six months after bilateral MICS with Acri.Lisa 366D implantation, 40 eyes of 20 patients were evaluated for surgical induced astigmatism (SIA--vector analysis), binocular UDVA, UNVA and UIVA (logMAR), spectacle independence, contrast sensitivities (CS-CSV-1000), subjective symptoms, patient satisfaction (Type Questionnaire) and complications. Three and six months after surgery, SIA was equal 0.55 D and 0.58 D subsequently. Three months postoperatively mean binocular UDVA did not differ significantly from the six-month follow-up (-0.10 +/- 0.17 versus -0.14 +/- 0.11; p = NS). All patients had very good spectacle-free visual function at all distances and were totally spectacle independent. Mesopic distance and photopic distance and near CS were within normal age-matched limits at both follow-ups and did not change during observation time. A low degree of glare/halo was detected in 75% of subjects. Overall patient satisfaction was very high (9.05/10). There were no postoperative complications. Multifocal Acri.LISA 366D IOL implantation in selected cataract patients provides a very good visual outcome, a high level of patient satisfaction and spectacle-free visual function. microincision cataract surgery, Acri.Lisa 3660 101 implantation, visual outcome.


Cell-to-cell contact as an efficient mode of Epstein-Barr virus infection of diverse human epithelial cells.
We show clear evidence for direct infection of various human epithelial cells by Epstein-Barr virus (EBV) in vitro. The successful infection was achieved by using recombinant EBV (Akata strain) carrying a selective marker gene but without any other artificial operations, such as introduction of the known EBV receptor (CD21) gene or addition of polymeric immunoglobulin A against viral gp350 in culture. Of 21 human epithelial cell lines examined, 18 became infected by EBV, as ascertained by the detection of EBV-determined nuclear antigen (EBNA) 1 expression in the early period after virus exposure, and the following selection culture easily yielded a number of EBV-infected clones from 15 cell lines. None of the human fibroblasts and five nonhuman-derived cell lines examined was susceptible to the infection. By comparison, cocultivation with virus producers showed approximately 800-fold-higher efficiency of infection than cell-free infection did, suggesting the significance of direct cell-to-cell contact as a mode of virus spread in vivo. Most of the epithelial cell lines infectable with EBV were negative for CD21 expression at the protein and mRNA levels. The majority of EBV-infected clones established from each cell line invariably expressed EBNA1, EBV-encoded small RNAs, rightward transcripts from the BamHI-A region of the virus genome, and latent membrane protein (LMP) 2A, but not the other EBNAs or LMP1. This restricted form of latent viral gene expression, which is a central issue for understanding epithelial oncogenesis by EBV, resembled that seen in EBV-associated gastric carcinoma and LMP1-negative nasopharyngeal carcinoma. The results indicate that direct infection of epithelial cells by EBV may occur naturally in vivo, and this could be mediated by an unidentified, epithelium-specific binding receptor for EBV. The EBV convertants are viewed, at least in terms of viral gene expression, as in vitro analogs of EBV-associated epithelial tumor cells, thus facilitating analysis of an oncogenic role(s) for EBV in epithelial cells.


Effect of chronic thyroid hormone treatment on cycling, ovulation, serum reproductive hormones and ovarian LH and prolactin receptors in rats.
We studied the effect on cycling, ovulation and hormone secretion of a chronic thyroxine treatment (HT, 1 mg/kg,S.C., daily, initiated at oestrus) on female rats. HT rats showed normal 4-day vaginal cycles on the first three cycles after initiation of the treatment, but on the fourth cycle had a prolonged oestrus and subsequently entered in constant di-oestrus. In spite of the normal vaginal cycles only 66%, 50%, 33% and 10% of the HT rats ovulated on cycles 1 to 4 respectively. In contrast, during cycles 2 and 3, ovulating HT rats shed a significantly greater number of ova than controls. Hormones were measured at 12.00 and 18.00 h (pre-ovulatory) on prooestrus and at 11.00 h on oestrus. HT ovulating rats had normal LH levels on the first two cycles, but low levels on the third one, while non-ovulating HT rats had low preovulatory LH levels. Serum FSH concentrations were elevated in all the HT rats on cycles 1 and 2 and on pro-oestrus morning in cycle 3 and may have been responsible for the increase in ovulation rate. On oestrus, ovulating HT rats had higher FSH values than nonovulating ones. Serum prolactin levels were similar to controls in all the HT rats on cycle 1, but on the subsequent cycles pre-ovulatory levels were lower than controls in all the HT rats, while values were increased in the non-ovulating HT rats on the third and fourth oestrus mornings. Pro-oestrous serum oestradiol concentrations in all the HT rats were not different from controls on cycles 1 and 2 and diminished on 3 and 4. Oestrous levels were significantly lower on the cycle 1 and only on the nonovulating HT rats on cycle 2. Serum progesterone levels had values similar to those of FSH, with increased values in the first two cycles. Serum corticosterone levels were increased in the mornings of cycles 2 and 3, but values were normal on the fourth one. Ovarian prolactin and LH receptor mRNAs, measured on HT rats on the third prooestrus by Northern blotting, showed significant increases in all the majoritary molecular forms (2.5 and 7 kb for LH receptor and 0.9, 2.9-3, 5 and 10 kb for the prolactin receptor) with respect to control pro-oestrous rats. These results show a progressive disruption of cycling, ovulation and hormonal secretion after the initiation of a chronic thyroid hormone treatment in rats, which eventually lead to an anovulatory state. These results may be of importance for the interpretation of the reproductive disfunctions provoked by hyperthyroidism in women.


Caveolin-1 in the Pathogenesis of Diabetic Nephropathy: Potential Therapeutic Target?
Diabetic nephropathy, a major microvascular complication of diabetes and the most common cause of end-stage renal disease, is characterized by prominent accumulation of extracellular matrix. The membrane microdomains caveolae, and their integral protein caveolin-1, play critical roles in the regulation of signal transduction. In this review we discuss current knowledge of the contribution of caveolin-1/caveolae to profibrotic signaling and the pathogenesis of diabetic kidney disease, and assess its potential as a therapeutic target. Caveolin (cav)-1 is key to facilitating profibrotic signal transduction induced by several stimuli known to be pathogenic in diabetic nephropathy, including the most prominent factors hyperglycemia and angiotensin II. Phosphorylation of cav-1 on Y14 is an important regulator of these responses. In vivo studies support a pathogenic role for caveolae in the progression of diabetic nephropathy. Targeting caveolin-1/caveolae would enable inhibition of multiple profibrotic pathways, representing a novel and potentially potent therapeutic option for diabetic nephropathy.


Microsurgical reanastomosis of the fallopian tube: increasingly successful outcome for reversal of previous sterilization procedures.
Reanastomosis of the fallopian tube represents a potential means of restoring fertility to women who have previously had sterilization procedures. During a 40-month period from January 1977 to June 1980, 46 such women had ent-to-end reanastomosis at Vanderbilt University Hospital, 59% after a change in their martial status. The surgical procedure included microsurgical technic, with the use of antibiotics, corticosteroids, intraperitoneal dextran, and postoperative hydrotubation. No stents or splints were used. Tubal patency was demonstrated in 43 patients (93%). Pregnancy was achieved in 25 of the 37 patients (68%) properly followed up for one year. There were no ectopic pregnancies. In three patients who did not conceive, a "second-look' laparoscopy revealed the presence of pelvic adhesions. Such a procedure allows a more accurate assessment of both the cause of the continued infertility and the future prognosis.


Enrichment of Triglyceride-Rich Lipoproteins with Apolipoprotein C-I Is Positively Associated with Their Delayed Plasma Clearance Independently of Other Transferable Apolipoproteins in Postmenopausal Overweight and Obese Women.
Background: The role of plasma apolipoprotein (apo) C-I in cardiometabolic risk in humans is unclear. However, in vitro studies showed a dual role for apoC-I, both protective and harmful, depending on the carrier lipoprotein.Objective: We tested the hypothesis that triglyceride (TG)-rich lipoprotein (TRL) apoC-I, not total or HDL apoC-I, is associated with delayed postprandial plasma clearance of TRLs, independently of apoC-II, apoC-III, and apoE.Methods: This cross-sectional study examines the plasma clearance of a 13C-triolein-labeled high-fat meal (68% fat energy) in 20 postmenopausal overweight and obese women [body mass index (in kg/m2) ≥27; aged 45-74 y] as the increment change in area under the 6-h postprandial curves (iAUC6h) of TRL parameters. Lipoproteins were fractionated by fast-protein LC. Transferable apolipoproteins were measured by ELISA. TRL enrichment with apolipoproteins was calculated by dividing their TRL concentrations by TRL apoB. The effects of human apoC-I and apoC-III on the hydrolysis and storage of 3H-triolein-labeled TRLs were tested in 3T3-L1 adipocytes.Results: TRL apoC-I was positively associated with plasma apo B-48 and total and non-HDL TGs, cholesterol, and apoB (r = 0.52-0.97) and negatively with HDL cholesterol (r = -0.52) and LDL diameter (r = -0.91) (P < 0.05). Total and HDL apoC-I were correlated only with total (r = 0.62) and HDL (r = 0.75) cholesterol. Women with high fasting TRL enrichment with apoC-I (99-365 μmol apoC-I/μmol apoB), but not apoC-II, apoC-III, or apoE, had higher iAUC6h for TGs (+195%), 13C-TGs (+319%), and apo B-48 (+186%) than those with low enrichment (14-97 μmol apoC-I/μmol apoB). The 4-h postprandial increase in TRL apoC-I was associated with a 4-h increase in TRL TGs and iAUC6h for TGs, 13C-TGs, and apo B-48 (r = 0.74-0.86, P < 0.001), independently of 4-h changes in TRL apoB, apoC-II, apoC-III, or apoE. ApoC-I and apoC-III inhibited 3H-TRL clearance by adipocytes by >75% (P < 0.001).Conclusions: TRL enrichment with apoC-I is positively associated with postprandial hypertriglyceridemia and remnant accumulation in postmenopausal overweight and obese women, independently of apoC-II, apoC-III, or apoE, which may be due to inhibiting TRL clearance by adipocytes. Reducing TRL apoC-I may ameliorate delayed postprandial plasma clearance of TRLs and associated risks in humans.


Shift in black rhinoceros diet in the presence of elephant: evidence for competition?
In African large herbivore assemblages, megaherbivores dominate the biomass and utilise the greatest share of available resources. Consequently, they are considered a separate trophic guild that structures the food niches of coexisting large herbivores. However, there exists little empirical evidence on how food resources are shared within this guild, and none for direct competition for food between megaherbivores. Using the histological analysis of faeces, we explore this phenomenon for African elephant Loxodonta africana and black rhinoceros Diceros bicornis in the Addo Elephant National Park, South Africa, where the accumulated impacts of elephant have reduced browse availability. Despite being unable to generalise beyond our study sites, our observations support the predictions of competition theory (as opposed to optimality theory) by showing (1) a clear seasonal separation in resource use between these megaherbivores that increased as resource availability declined, and (2) rhinoceros changed their selectivity in the absence of elephant (using an adjacent site) by expanding and shifting their diet along the grass-browse continuum, and in relation to availability. Although black rhinoceros are generally considered strict browsers, the most significant shift in diet occurred as rhinoceros increased their preferences for grasses in the presence of elephant. We speculate that the lack of specialised grazing adaptations may increase foraging costs in rhinoceros, through reduced harvest- and handling-efficiencies of grasses. In the short-term, this may be off-set by an enhanced tolerance for low quality food and by seasonally mobilising fat reserves; however, the long-term fitness consequences require further study. Our data suggest that managing elephant at high densities may compromise the foraging opportunities of coexisting browsers. This may be particularly important in small, fenced areas and overlapping preferred habitats where impacts intensify.


Alkoxides of Trivacant Lacunary Polyoxometalates.
Lacunary polyoxometalates (POMs) are useful rigid multidentate inorganic ligands to construct multinuclear metal oxo clusters and inorganic-organic hybrid materials. However, the use of multivacant lacunary POMs often suffers from their undesired condensation reactions at the highly reactive vacant sites. Herein, the introduction of alkoxy protecting groups into the vacant sites of lacunary POMs in organic media is reported for the first time. By reacting organic solvent-soluble trivacant lacunary Keggin-type POMs with methanol, six methoxy groups were successfully introduced into the vacant sites, resulting in the formation of the alkoxides TBA4 [A-α-XW9 O28 (OCH3 )6 ] (Ix -OMe; X=Si, Ge). These methoxy groups could protect the reactive vacant sites and suppress the undesired dimerization reaction into the corresponding α-Dawson-type POMs. Since the introduced monodentate methoxy groups could easily be dissociated by hydrolysis, ISi -OMe could be utilized as the precursor for the synthesis of metal-substituted POMs. In addition, by using pentaerythritol as the multidentate alkoxy ligand, the monomeric alkoxide TBA4 [A-α-SiW9 O28 {(OCH2 )2 C(CH2 OH)2 }3 ] (ISi -PE) was successfully synthesized. In particular, these multidentate alkoxy groups showed high resistance against hydrolysis. Moreover, by reacting ISi -PE with trivacant lacunary Keggin-type POMs, the dimeric inorganic-organic-inorganic hybrid structures TBAn H8-n [(A-α-SiW9 O28 ){(OCH2 )2 C(CH2 O)2 }3 (A-α-XW9 O28 )] (IISiX -PE; X=Si, Ge) with the same or different heteroatoms (Si and Ge) were successfully synthesized.


Redescription of the Siberian species Pardosa jeniseica (Araneae: Lycosidae).
The male of Pardosa jeniseica, collected in the East-Kazakhstan Area, was first illustrated in Eskov Marusik (1995). The authorship of the species was given as "Zyuzin, 1991", because A.A. Zyuzin informed the authors in 1990 that a description of the species was in press. Because no such description ever appeared the authorship was given to Eskov Marusik, and a single male specimen from East-Kazakhstan is now considered to be the holotype. It is kept in Zoological Museum of the Moscow State University. Esyunin et al. (1999) illustrated and described a female from the Urals thought to be conspecific with P. jeniseica. Conspecifity of the illustrated specimen with P. jeniseica was doubted by Marusik et al. (2000). Kronestedt (2013) was the first to illustrate the epigyne of P. jeniseica and Azarkina Trilikauskas (2013) provided both verbal and illustrated descriptions of the female, and its epigyne and endogyne. Both sexes taken from one locality were never depicted, nor was peculiar pubescence of the male's leg I. Therefore, I decided to provide detailed illustrations and a verbal description of this species based on specimens from the place considered to be the type locality.Specimens were photographed at the Zoological Museum (University of Turku, Finland) with a Canon EOS 7D camera attached to an Olympus SZX16 stereomicroscope and a SEM JEOL JSM-5200 scanning microscope. Digital images were montaged using Helicon focus 3.10 image stacking software. All measurements are given in millimeters. The following abbreviations are used for leg segments: Fe femur, Pa patella, Ti tibia, Mt metatarsus, Ta tarsus; leg spination abbreviations: d dorsal, p prolateral, r retrolateral, v ventral. Material used in this study is deposited in the Moscow State University (ZMMU) and Zoological Museum of the University of Turku (ZMUT). I thank Seppo Koponen (Turku, Finland) for providing museum facilities and Don Buckle (Saskatoon, Canada) for editing English in the earlier draft of the manuscript.


PRMT1 regulates astrocytic differentiation of embryonic neural stem/precursor cells.
Arginine methylation is a post-translational modification which is catalyzed by protein arginine methyltransferases (PRMTs). Here, we report that PRMT1 is highly expressed in neural stem/precursor cells (NS/PCs) of mouse embryos, and knockdown of PRMT1 in NS/PCs suppresses the generation of astrocytes. The luciferase assay demonstrated that knockdown of PRMT1 inhibits activation of the promoter of a typical astrocytic marker gene, glial fibrillary acidic protein (Gfap), in NS/PCs. The transcription factor signal transducer and activator of transcription 3 (STAT3) is known to generally be critical for astrocytic differentiation of NS/PCs. We found that PRMT1 methylates arginine residue(s) of STAT3 to regulate its activity positively, resulting in the promotion of astrocytic differentiation of NS/PCs.


Neuropsychiatric features in a multi-ethnic population with Alzheimer disease and mild cognitive impairment.
Alzheimer disease (AD) is more prevalent in African American (AA) and Hispanic White (HIW) compared to Non-Hispanic White (NHW) individuals. Similarly, neuropsychiatric symptoms (NPS) vary by population in AD. This is likely the result of both sociocultural and genetic ancestral differences. However, the impact of these NPS on AD in different groups is not well understood. Self-declared AA, HIW, and NHW individuals were ascertained as part of ongoing AD genetics studies. Participants who scored higher than 0.5 on the Clinical Dementia Rating (CDR) Scale (CDR) were included. Group similarities and differences on Neuropsychiatric Inventory Questionnaire (NPI-Q) outcomes (NPI-Q total score, NPI-Q items) were evaluated using univariate ANOVAs and post hoc comparisons after controlling for sex and CDR stage. Our sample consisted of 498 participants (26% AA; 30% HIW; 44% NHW). Overall, NPI-Q total scores differed significantly between our groups, with HIW having the highest NPI-Q total scores, and by AD stage as measured by CDR. We found no significant difference in NPI-Q total score by sex. There were six NPI-Q items with comparable prevalence in all groups and six items that significantly differed between the groups (Anxiety, Apathy, Depression, Disinhibition, Elation, and Irritability). Further, within the HIW group, differences were found between Puerto Rican and Cuban American Hispanics across several NPI-Q items. Finally, Six NPI-Q items were more prevalent in the later stages of AD including Agitation, Appetite, Hallucinations, Irritability, Motor Disturbance, and Nighttime Behavior. We identified differences in NPS among HIW, AA, and NHW individuals. Most striking was the high burden of NPS in HIW, particularly for mood and anxiety symptoms. We suggest that NPS differences may represent the impact of sociocultural influences on symptom presentation as well as potential genetic factors rooted in ancestral background. Given the complex relationship between AD and NPS it is crucial to discern the presence of NPS to ensure appropriate interventions.


Clinical outcome of root-shaped dental implants of various diameters: 5-year results.
The aim of this retrospective study was to evaluate the long-term survival and success rates of screw-type root-shaped (Camlog) implants of various diameters and their implant-prosthodontic reconstructions for more than 5 years of clinical use. A retrospective study of patients receiving root-shaped screw-type dental implants placed between May 2001 and July 2003 was conducted. The cumulative implant survival and success rates and peri-implant conditions (marginal bone loss, pocket depth, Plaque Index, Gingival Index, Bleeding Index) as well as the prosthodontic maintenance requirements were evaluated. In all, 541 implants (3.8 mm: 237 implants; 4.3 mm: 211 implants, 5/6 mm: 93 implants) were placed and restored for implant prosthodontic rehabilitation in 216 patients (134 women, 82 men; mean age 54.3 +/- 9.1 years). Of the original 216 patients enrolled, 198 (91.6%; 510/541 implants [94.2%]) were available for a follow-up evaluation after 5 to 7 years (mean follow-up, 68.8 +/- 7.4 months). The overall cumulative 5-year survival and success rates were 98.3% and 97.3%, respectively. A failure rate of 3.7% (9/237) was seen for 3.8-mm-diameter implants; the corresponding figures for the 4.3-mm and wide-diameter (5.0/6.0-mm) implants were 1.4% (3/211) and 1.0% (1/93), respectively. For implants classified as successful, the average peri-implant marginal bone resorption value was 1.8 +/- 0.4 mm, with no differences among the different implant diameters evaluated. Peri-implant soft tissue conditions such as plaque, bleeding, and pocket depth were also satisfactory. All prostheses were functional throughout the observation period, with no fractures of implants, abutments, or screws. Abutment screw (4.5%) or isolated crown loosening (9.8%) for single-tooth restorations requiring recementation, retightening of screws, and adaptation of removable prostheses were the most frequent prosthodontic maintenance needs. The root-shaped implants and the associated prosthetic constructions used in this study showed excellent survival and success rates.


OPL. Factors affecting OPL performance.
Case study. The CEO of a mid-size community hospital requested a literature search on the standards, costs and regional competition for a pain management center. Results submitted were deemed less than satisfactory. A review of the case suggests numerous elements, listed below, which need to be addressed and revised in order to improve outcome in future interactions.


Interferometric enhancement of x-ray reflectivity from unperturbed Langmuir monolayers of amphiphiles at the liquid-gas interface.
Langmuir monolayers provide an important system for the investigation of the intramolecular structure and intermolecular ordering of organic and bio-organic macromolecular amphiphiles at an interface between polar and nonpolar media, e.g., the liquid-gas interface. Specular x-ray and neutron reflectivity have contributed substantially to these investigations. However, these reflectivity techniques are generally limited by the absence of crucial phase information, the relatively small contribution of the amphiphile to the scattering-length density contrast across the interface, and the relatively limited range of momentum transfer available perpendicular to the interface. Although several procedures have been developed to provide model-independent solutions to the phase problem, there remains a limited ability to distinguish features of slightly differing contrast (i.e., the "sensitivity") as well as their minimum allowable separation (i.e., the "spatial resolution") along the length of the scattering-length density profile derived from the reflectivity data via solution to the phase problem. Here, we demonstrate how the well-known interferometric approach can be extended to the structural investigation of otherwise unperturbed Langmuir monolayers of these amphiphiles to provide a direct solution to the phase problem and importantly, substantially enhance both the sensitivity and the spatial resolution in the derived profiles.


Chitosan green tea polyphenol complex as a released control compound for wound healing.
In recent years, oxidative stress has been implicated in a variety of degenerative process and diseases, including acute and chronic inflammatory conditions such as wound healing. Green tea polyphenols have shown anti-oxidant property. The present study discussed the application of chitosan green tea polyphenol complex on the wound healing. The wound healing effect of chitosan green tea polyphenol complex was studied in ten-week-old healthy male Sherman rats weighing 150-180 g by two wound models. The rats were randomly chosen and divided into four groups (n=5), administered with distilled water in Group A as control group, epigallocatechin-3-gallate (EGCG) in Group B, chitosan-EGCG complex in Group C and chitosan-green tea polyphenols complex in Group D, respectively. In rats'incision wound model, two straight paravertebral incisions were made and skin tensile strength was measured using continuous water flow technology on the 10th day. In rats'excision wound model, wound contraction and period of epithelization were measured. The polyphenols release from the complex was continuously monitored by an elution technique in aqueous solution at different pH values (pH=4, 5, 6, 7). The treatment groups showed significantly enhanced the breaking strength in incision wound (328+/-14.5) g and (421+/-18.5) g compared with control (264+/-16.7) g. In the excision wound model, the wound contraction percentage in treatment groups was relatively increased during the recovery period. Respectively, the percentage of wound contraction ranged from 47.60%+/-2.15% on day 4 to 107.98% +/-1.26% on day 16 compared with control group (8.46%+/-5.42% to 59.80%+/-4.47%). The complex demonstrated a gradual increase in the release rate from the initial stage and slow increase at different pH values. The release rate approximated 0.6-0.7 in the complex and remained stable 6 hours after injury, which may be the end of the release process. In our study, chitosan polyphenol complex has enhanced the healing of incision wounds by increasing the breaking strength of the wounds. In excision wound model, the complex hastens the period of epithelialization. The study on the optimal release of complex among various pH values could be applied in the wound test, which can lead to a gradually active substance(polyphenols) release and efficient coverage of epithelial layers found in the healing of incision and excision wound.


Surgical treatment of left main coronary aneurysm.
Aneurysms of the coronary arteries occur in 0.3% to 4.9% of angiograms. Only 13 cases of left main artery (LMA) aneurysms have been reported. Of these, three were treated by ligation of the aneurysm and coronary revascularization; the others by revascularisation alone. We report the case of a 56 years old man presenting with unstable angina and previous history of myocardial infarction. Coronary angiography confirmed three vessels disease and the presence of an aneurysm of the LMA extending to the proximal part of the left anterior descending artery (LAD). The patient was treated with ligation of the aneurysm and total myocardial revascularization. The clinical and radiological features are reviewed, and the surgical options considered.


Multidetector SPECT scanner for brain and body: system performance and applications.
A multidetector whole-body single photon emission computed tomography (SPECT) scanner has been developed for high-resolution dynamic SPECT imaging. The scanner consists of three detector rings with 128 NaI crystals (14 x 26 x 30 mm) in each ring, providing three tomographic images at 30 mm intervals. This system uses a rotation of collimator around the patient combined with the detector rotation for fine data sampling. The in-plane spatial resolution is 14.2 mm (full width of half maximum) with high-resolution (HR) collimator, 22.0 mm with high-sensitivity (HS) collimator, and 10.6 mm with high-resolution brain (HRB) collimator. The axial resolution is 24.0, 34.0, and 23.5 mm with HR, HS, and HRB collimator, respectively. The sensitivity measured with a 20% energy window for 99mTc in a 20 cm diameter phantom is 5.7, 17.0 and 6.6 kcps/muCi/ml with HR, HS, and HRB collimator, respectively. This scanner allows dynamic SPECT imaging both for brain and body organs with good spatial resolution.


Short-chain fatty acids produced by intestinal bacteria.
The colon is the major site of bacterial colonisation in the human gut and the resident species are predominantly anaerobes. They include potential pathogens but the greater proportion appear to be organisms which salvage energy through the metabolism of undigested carbohydrates and gut secretions. The major products of carbohydrate metabolism are the short chain fatty acids (SCFA), acetate, propionate and butyrate. In addition to general effects (such as lowering of pH) individual acids exert specific effects. All of the major SCFA appear to promote the flow of blood through the colonic vasculature while propionate enhances muscular activity and epithelial cell proliferation. Butyrate appears to promote a normal cell phenotype as well as being a major fuel for colonocytes. Important substrates for bacterial fermentation include non-starch polysaccharides (major components of dietary fibre) but it seems that starch which has escaped digestion in the small intestine (resistant starch) is the major contributor. Oligosaccharides are utilised by probiotic organisms and in the diet, act as prebiotics in promoting their numbers in faeces. High amylose starch is a form of RS and it appears to act as a prebiotic also. Although there is evidence that probiotics such as Bifidobacteria metabolise oligosaccharides and other carbohydrates, there appears to be little evidence to support a change in faecal SCFA excretion. It seems that any health benefits of probiotics are exerted through means other than SCFA.


miR-141 Inhibits Proliferation and Migration of Colorectal Cancer SW480 Cells.
This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC). SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence. Transwell assay was conducted to determine the migration rates of cells. Subcutaneous xenograft models were used to examine the effect of miR-141 on tumorigenicity. Human mitogen-activated protein kinase (MAPK) and receptor tyrosine kinase (RTK) pathway phosphorylation array assays were used to interrogate MAPK and RTK pathway activation. miR-141 directly targeted zinc finger E-box-binding homeobox 1/2 (ZEB1/2). We first determined the expression levels of ZEB1 and ZEB2 in miR-141-expressing cells and miR-141-knockdown cells and found that inhibition of miR-141 significantly increased the expression of ZEB2. In vitro study revealed that miR-141 overexpression inhibited the expression of Ki-67. Furthermore, overexpression of miR-141 led to a significant reduction in the proliferation of SW480 cells via induction of cell-cycle arrest at the G1 stage. In contrast, inhibition of miR-141 markedly promoted the proliferation of SW480 cells by promoting cell-cycle progression. Moreover, overexpression of miR-141 significantly inhibited SW480 cell migration in vitro. In addition, overexpression of miR-141 significantly reduced tumor size and weight, and inhibited the growth of SW480 cell-derived tumor in nude mice. Notably, overexpression of miR-141 also suppressed the liver metastasis of SW480 cells in nude mice. Using RTK and MAPK arrays, we found increased phosphorylation of hepatocyte growth factor receptor (HGFR/c-MET) following inhibition of miR-141, but phosphorylation of P53, AKT, ERK1/2, P38 and mTOR, etc., in SW480 cells was not affected by miR-141. Our results suggest that miR-141 functions as a tumor suppressor through ZEB2 and HGFR in CRC cells.


Kersley lecture: eye believe in contact lenses: contact lenses and/or refractive surgery.
Media publicity has made patients increasingly aware that surgical vision correction is available. This article gives an overview on refractive surgery and contact lenses. Contact lens and refractive surgery possibilities are highlighted for patients with myopia, hyperopia, astigmatism, presbyopia, aphakia, and keratoconus. Therapeutic, pediatric, and cosmetic indications are discussed. Refractive surgery is beneficial for low refractive errors. The use of contact lenses is mandatory in cases of monovision and strabismus before refractive surgery and beneficial for therapeutic use postoperatively. Although many patients are always best corrected with contact lenses, only the right synergism of contact lenses and refractive surgery will benefit patients.


Cellular and Molecular Preconditions for Retinal Pigment Epithelium (RPE) Natural Reprogramming during Retinal Regeneration in Urodela.
Many regeneration processes in animals are based on the phenomenon of cell reprogramming followed by proliferation and differentiation in a different specialization direction. An insight into what makes natural (in vivo) cell reprogramming possible can help to solve a number of biomedical problems. In particular, the first problem is to reveal the intrinsic properties of the cells that are necessary and sufficient for reprogramming; the second, to evaluate these properties and, on this basis, to reveal potential endogenous sources for cell substitution in damaged tissues; and the third, to use the acquired data for developing approaches to in vitro cell reprogramming in order to obtain a cell reserve for damaged tissue repair. Normal cells of the retinal pigment epithelium (RPE) in newts (Urodela) can change their specialization and transform into retinal neurons and ganglion cells (i.e., actualize their retinogenic potential). Therefore, they can serve as a model that provides the possibility to identify factors of the initial competence of vertebrate cells for reprogramming in vivo. This review deals mainly with the endogenous properties of native newt RPE cells themselves and, to a lesser extent, with exogenous mechanisms regulating the process of reprogramming, which are actively discussed.


Enzymatic removal of sialic acid enables iCIEF stability monitoring of charge variants of a highly sialylated bispecific antibody.
Antibody-based therapeutic proteins have highly complex molecular structures. The final therapeutic protein product may contain a wide range of charge variants. Accurate analysis of this charge variant composition is critical to determine manufacturing process consistency and protein stability and ultimately helps to ensure that patients receive a safe and efficacious product. Here, a highly sialylated bispecific antibody (bsAb-1) challenged the ability to monitor stability by imaged capillary isoelectric focusing (iCIEF). This challenge was overcome by optimization of the iCIEF master mix buffer (adjustment of urea concentration, addition of l-arginine) and enzymatic removal of sialic acid. The method was qualified by assessing linearity, precision, LOD, LOQ, accuracy, and robustness in accordance with ICH guidance. Main species loss detectability increased up to approximately fivefold compared to the iCIEF method without desialylation when monitoring changes in stressed samples. Importantly, the results of the iCIEF method with desialylation correlated with results obtained through LC-MS tryptic peptide mapping and enabled analysis of formulation development stability samples. Finally, this analytical method shows the potential to assess low-concentration formulation development samples down to a sample concentration of 0.1 mg/ml.


Substrate independent approach for synthesis of graphene platelet networks.
Graphene platelet networks (GPNs) comprised of randomly oriented graphene flakes two to three atomic layers thick are synthesized using a novel plasma-based approach. The approach uses a substrate capable of withstanding synthesis temperatures around 800 °C, but is fully independent of the substrate material. The synthesis occurs directly on the substrate surface without the necessity of any additional steps. GPNs were synthesized on various substrate materials including silicon (Si), thermally oxidized Si (SiO2), molybdenum (Mo), nickel (Ni) and copper (Cu), nickel-chromium (NiCr) alloy and alumina ceramics (Al2O3). The mismatch between the atomic structures of sp2 honeycomb carbon networks and the substrate material is fully eliminated shortly after the synthesis initiation, namely when about 100 nm thick deposits are formed on the substrate. GPN structures synthesized on a substrate at a temperature of about 800 °C are significantly more porous in comparison to the much denser packed amorphous carbon deposits synthesized at lower temperatures. The method proposed here can potentially revolutionize the area of electrochemical energy storage by offering a single-step direct approach for the manufacture of graphene-based electrodes for non-Faradaic supercapacitors. Mass production can be achieved using this method if a roll-to-roll system is utilized.


[2-axial conformational irradiation for whole-pelvis irradiation of cervical cancer: improvement and evaluation with DVH].
Whole-pelvis irradiation with the two-axial conformation technique has been performed in cervical cancer since 1976. In 1990 this technique was improved by obtaining target areas from serial CT images instead of axial transverse tomograms. The aim of this study was to show the advantage of the new two-axial conformation technique compared with the old type of conformation technique, and also with conventional techniques using DVH of normal tissues. The uniformity of dose within the high dose-region and fit to the target areas observed in the new type were better than those in the old type. This improved result was most remarkable in rectal DVH. The new two-axial conformation technique was also compared with the two-opposed technique and box technique. With the new type, cumulative irradiated volume in rectum of more than 40 Gy was reduced to 37% of that with the two-opposed technique. In bladder and intestine, the smallest volume irradiated to more than 40 Gy was observed using the new two-axial conformation technique. With these results, we conclude that the new two-axial conformation technique for whole-pelvis irradiation is suitable to conform the high dose region with the target region in the pelvis, and at the same time to protect the surrounding normal tissues.


Are increased weight and appetite useful indicators of depression in children and adolescents?
During childhood and adolescence, physiological, psychological, and behavioral processes strongly promote weight gain and increased appetite while also inhibiting weight loss and decreased appetite. The Diagnostic and Statistical Manual-IV (DSM-IV) treats both weight-gain/increased-appetite and weight-loss/decreased-appetite as symptoms of major depression during these developmental periods, despite the fact that one complements typical development and the other opposes it. To disentangle the developmental versus pathological correlates of weight and appetite disturbance in younger age groups, the current study examined symptoms of depression in an aggregated sample of 2307 children and adolescents, 47.25% of whom met criteria for major depressive disorder. A multigroup, multidimensional item response theory model generated three key results. First, weight loss and decreased appetite loaded strongly onto a general depression dimension; in contrast, weight gain and increased appetite did not. Instead, weight gain and increased appetite loaded onto a separate dimension that did not correlate strongly with general depression. Second, inclusion or exclusion of weight gain and increased appetite affected neither the nature of the general depression dimension nor the fidelity of major depressive disorder diagnosis. Third, the general depression dimension and the weight-gain/increased-appetite dimension showed different patterns across age and gender. In child and adolescent populations, these results call into question the utility of weight gain and increased appetite as indicators of depression. This has serious implications for the diagnostic criteria of depression in children and adolescents. These findings inform a revision of the DSM, with implications for the diagnosis of depression in this age group and for research on depression.


Busulfan plus etoposide as a preparative regimen for autologous bone marrow transplantation for acute myelogenous leukemia: an update.
We have used a new preparative regimen prior to autologous bone marrow transplantation in patients in remission of acute myelogenous leukemia (AML). Sixty-two patients were treated with preparative chemotherapy consisting of 1 mg/kg of busulfan every 6 hours for 4 days (total dose 16 mg/kg) on days -7 to -4 followed by an intravenous infusion of 60 mg/kg of etoposide on day -3. Autologous bone marrow that had been purged with 4-hydroperoxycyclophosphamide was infused on day 0. Thirty-five of the treated patients were in first remission, 21 were in second or third remission, and six had primary refractory AML and required aggressive salvage regimens to achieve remission. Among patients in first remission, one treatment-related death and five relapses have occurred. With a median follow-up of 25 months, the actuarial relapse rate is 19% +/- 8% and the disease-free survival rate is 79% +/- 8% at 3 years. The 16 patients with favorable FAB subtypes (M3 or M4E0) showed an excellent response to this treatment protocol, with no relapses after median follow-up of 35 months. Among patients in second or third remission, there were five treatment-related deaths and five relapses. With a median follow-up of 41 months, the actuarial relapse rate is 30% +/- 11% and the disease-free survival rate is 52% +/- 11% at 3 years. Four of six primary refractory patients died during treatment and one remains in remission with short follow-up. These preliminary data indicate that aggressive preparative regimens followed by the infusion of purged autologous bone marrow may be a promising approach to improving the clinical outcome of adult patients with AML.


Blockade of the Human Ether A-Go-Go-Related Gene (hERG) Potassium Channel by Fentanyl.
The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr). Drug-mediated or medical condition-mediated disruption of hERG function is the primary cause of acquired long-QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. Fentanyl abuse poses a serious health concern, with abuse and death rates rising over recent years. As fentanyl has a propensity to cause sudden death, we investigated its effects on the hERG channel. The effects of norfentanyl, the main metabolite, and naloxone, an antidote used in fentanyl overdose, were also examined. Currents of hERG channels stably expressed in HEK293 cells were recorded using the whole-cell voltage-clamp method. When hERG tail currents were analyzed upon -50 mV repolarization after a 50 mV depolarization, fentanyl and naloxone blocked hERG current (IhERG) with IC50 values of 0.9 and 74.3 μM, respectively, whereas norfentanyl did not block. However, fentanyl-mediated block of IhERG was voltage dependent. When a voltage protocol that mimics a human ventricular action potential (AP) was used, fentanyl blocked IhERG with an IC50 of 0.3 μM. Furthermore, fentanyl (0.5 μM) prolonged AP duration and blocked IKr in ventricular myocytes isolated from neonatal rats. The concentrations of fentanyl used in this study were higher than seen with clinical use but overlap with postmortem overdose concentrations. Although mechanisms of fentanyl-related sudden death need further investigation, blockade of hERG channels may contribute to the death of individuals with high-concentration overdose or compromised cardiac repolarization.


Effects of sensorineural hearing loss and personal hearing AIDS on cortical event-related potential and behavioral measures of speech-sound processing.
To systematically investigate the combined effects of sensorineural hearing loss and prescribed personal hearing aid(s) on cortical event-related potentials (ERPs) (waves N1, MMN, N2b, and P3b) and their related behavioral measures of discrimination (d-prime sensitivity and reaction time) to the speech sounds /ba/ and /da/ presented at 65 and 80 dB peak-to-peak equivalent SPL. Cortical ERPs were recorded to /ba/ and /da/ speech stimuli presented at 65 and 80 dB peak-to-peak equivalent SPL from 20 normal-hearing adults and 14 adults with sensorineural hearing losses. The degree of sensorineural impairment at 1000 to 2000 Hz ranged from moderate losses (50 to 74 dB HL) to severe-profound losses (75 to 120 dB HL). The speech stimuli were presented in an oddball paradigm and cortical ERPs were recorded in both active and passive listening conditions at both stimulus intensities. The adults with hearing impairments were tested in the unaided and aided conditions at each stimulus intensity. Electroacoustic and real-ear testing was performed on each subject's hearing aid(s) before electrophysiology testing to ensure that the hearing aids were functioning at the time of testing. The use of personal hearing aids substantially improved the detectability of all the cortical ERPs and behavioral d-prime performance scores at both stimulus intensities. This was especially true for individuals with severe-profound hearing losses. At 65 dB SPL, mean ERP amplitudes and d-prime sensitivity scores were all significantly higher or better in the aided versus unaided condition. At 80 dB SPL, only the N1 amplitudes and d-prime sensitivity scores were significantly better in the aided condition. Even though the majority of the hearing-impaired subjects showed increased amplitudes, decreased latencies, and better waveform morphology in the aided condition, the amount of response change (improvements) seen in these measures showed considerable variability across subjects. When compared with the responses obtained from the normal-hearing subjects, both hearing-impaired groups had significantly prolonged aided RT latencies at both stimulus intensities and N2b latencies at the higher stimulus intensities. These results suggest that hearing-impaired individuals' brains process speech stimuli with greater accuracy and in a more effective manner when these individuals use their personal hearing aids. This is especially true at the lower stimulus intensity. The effects of sensorineural hearing loss and personal hearing aids on cortical ERPs and behavioral measures of discrimination are dependent on the degree of sensorineural loss, the intensity of the stimuli, and the level of cortical auditory processing that the response measure is assessing. The possible clinical significance of these cortical ERP and behavioral findings is discussed.


Use of methyl prednisolone and antioxidants in mercuric chloride-induced experimental vasculitis.
The systemic vasculitides are characterized by necrotizing inflammation of blood vessels. Neutrophils are implicated in tissue damage by their presence at the site of injury. They can mediate injury by release of cellular contents including proteinases, cytokines and reactive oxygen species. Antioxidants such as vitamin E and N-acetyl cysteine (NAC) may therefore be predicted to ameliorate oxidative damage in vivo and could be a cheap and non-toxic form of therapy. We examined this hypothesis in an experimental model of vasculitis which has some similarities to human disease, and in which depletion of neutrophils ameliorates tissue injury. Mercuric chloride (HgCl2) treatment induces an autoimmune syndrome and necrotizing leucocytoclastic vasculitis in the Brown Norway (BN) rat; anti-myeloperoxidase (MPO) and anti-glomerular basement (GBM) antibodies are present, and vasculitis is reduced by antimicrobials. Methyl prednisolone given intravenously was effective in reducing tissue injury, demonstrating that the model was responsive to a treatment used in man. Vitamin E and NAC were given as daily injections intraperitoneally to BN rats either before, during or after HgCl2 administration. Serial blood samples were taken for anti-MPO and IgE antibodies, which were assayed by ELISA. Necropsies were performed on animals killed at peak disease. At doses of 50-200 mg/kg per day vitamin E had no beneficial effect on tissue injury, regardless of timing of treatment. NAC at 100 or 200 mg/kg also had no significant protective effect on vasculitis. Autoantibody and IgE levels were not affected by either methyl prednisolone or the antioxidants. The lack of benefit of vitamin E and NAC suggests that oxidative damage, whether generated by neutrophils or other cells, does not play a major role in the pathogenesis of vasculitis, and that antioxidant therapy is unlikely to be of benefit in systemic vasculitis in man.


Empathy in the Clinician-Patient Relationship: The Role of Reciprocal Adjustments and Processes of Synchrony.
The clinician-patient relationship is asymmetric in the sense that clinicians and patients have different roles in the medical consultation. Yet, there are qualities of reciprocity and mutuality in many clinician-patient encounters, and we suggest that such reciprocity may be related to the phenomenon of empathy. Empathy is often defined as the capacity to place oneself in another's position, but empathy may also be understood as a sequence of reciprocal turns-of talk, starting with the patient's expression of emotion, followed by the perception, vicarious experience, and empathic response by the clinician. These patterns of reciprocity may also include the patient's experience of and response to the clinician's emotions. Researchers in different fields of research have studied how informal human interaction often is characterized by mutuality of lexical alignment and reciprocal adjustments, vocal synchrony, as well as synchrony of movements and psychophysiological processes. A number of studies have linked these measures of reciprocity and synchrony in clinical encounters to the subjective experience of empathy.


Ketamine as potential treatment for postpartum depression: A narrative review.
Postpartum depression (PPD) is a severe, debilitating mood disorder with consequences for both mothers and children, highlighting the need for rapid-acting and effective treatments for PPD. The aim of this narrative review is to synthesize the available literature on the administration of ketamine for PPD and propose ketamine as a viable and advantageous treatment. A search was conducted on MEDLINE/PubMed, PsycInfo, and Embase databases from inception to October 10, 2021 for preclinical studies, interventional studies (ie, open-label and randomized controlled trials), as well as systematic reviews and meta-analyses evaluating the use of ketamine in postpartum populations. Completed and ongoing clinical trials were identified on ClinicalTrials.gov. Four clinical trials were identified. Results from this review support additional investigation into ketamine as a potential treatment for PPD. Ketamine may be a favorable option for treating PPD due to its antidepressive and analgesic effects, short infusion time, and rapid clearance from the maternal bloodstream. However, there is insufficient evidence to support its use in this population, underscoring the importance of additional clinical research investigating ketamine for PPD.


Rhino orbital cerebral mucormycosis in settings of COVID-19 infection: A case series of thirteen patients.
Rhino orbital cerebral mucormycosis (ROCM) is an important infectious disease encountered in large numbers in this recent post-COVID-19 era. An alteration in the defense immune system during COVID-19 illness; in the presence of uncontrolled hyperglycemia has led to the new epidemic of ROCM, especially in developing nations such as India. This case series of thirteen patients illustrates the various clinical presentations, laboratory parameters, imaging features and outcomes of patients with ROCM admitted to a tertiary care hospital in Northern India. In our case series, a total of 13 newly diagnosed cases of rhino-orbital-cerebral mucormycosis were studied. A history of COVID-19 illness was observed in seven cases (53.8%) with a mean duration of mucormycosis after 25 ± 3.6 days, the use of steroids during COVID-19 illness was seen in 5 cases (38.5%), and oxygen therapy was given in 4 cases (30.8%). A comorbid state in the form of diabetes mellitus was present in 12 cases (92.3%) with a mean duration of 16.69 months, with an important finding of seven cases (53.85%) having new-onset diabetes; hypertension was present in three cases (23.1%). Magnetic resonance imaging of paranasal sinuses showed involvement of multiple sinuses in all 13 cases (100%), including maxillary and ethmoidal sinuses, with frontal involvement in 12 cases (92.3%), sphenoidal involvement in 11 cases (84.6%), symmetric involvement in 9 cases (69.2%), mastoiditis in four cases (30.8%), maxillary space involvement in four cases (30.8%), and palatal involvement in one case (7.7%). On statistical analysis, there was a significant association of new-onset diabetes, optic neuropathy and high C reactive protein with blindness (P-value < 0.05) in our study. However, there were no statistically significant association for the involvement of nervous system in our study. Multispecialty approach treatment was given in the liposomal amphotericin B therapy in all the patients along with thorough endo-nasal debridement done in all cases, transcutaneous retrobulbar amphotericin B in six cases (46.2%) with exenteration done in seven patients (53.9%). At 3 months of follow-up, there was substantial clinical improvement in all cases. There should be definite emphasis on high suspicion of mucor clinically for early diagnosis and aggressive management at the initial state of diagnosis for better outcomes. The need for sustained proper glycemic control during the COVID-19 era along with judicious use of steroids and public awareness of early symptoms and manifestations of mucor can curb the magnitude of such potentially opportunistic epidemics to a substantial rate. New-onset diabetes mellitus, optic neuropathy and high C reactive protein (>50 mg/L) showed statistically significant association with blindness. The longer the infection remains undetected, the greater the devastation ROCM can impose, of which blindness is an important hazard.


Genetic Analysis Workshop 18: Methods and strategies for analyzing human sequence and phenotype data in members of extended pedigrees.
Genetic Analysis Workshop 18 provided a platform for developing and evaluating statistical methods to analyze whole-genome sequence data from a pedigree-based sample. In this article we present an overview of the data sets and the contributions that analyzed these data. The family data, donated by the Type 2 Diabetes Genetic Exploration by Next-Generation Sequencing in Ethnic Samples Consortium, included sequence-level genotypes based on sequencing and imputation, genome-wide association genotypes from prior genotyping arrays, and phenotypes from longitudinal assessments. The contributions from individual research groups were extensively discussed before, during, and after the workshop in theme-based discussion groups before being submitted for publication.


Purification, crystallization and preliminary X-ray crystallographic analysis of the ATPase domain of human TAP in nucleotide-free and ADP-, vanadate- and azide-complexed forms.
The human transporter associated with antigen processing (TAP) protein belongs to the ATP-binding cassette (ABC) transporter superfamily and is formed by the heterodimerization of TAP1 and TAP2 subunits. TAP selectively pumps cytosolic peptides into the lumen of the endoplasmic reticulum in an ATP-dependent manner. The catalytic cycle of the ATPase domain of TAP is not understood at the molecular level. The structures of catalytic intermediates of the ATPase domain of TAP will contribute to the understanding of the chemical mechanism of ATP hydrolysis. In order to understand this mechanism, the ATPase domain of human TAP1 (NBD1) was expressed and purified, crystallized in nucleotide-free and transition-state complex forms and X-ray crystallographic studies were performed. The NBD1 protein was crystallized (i) in the nucleotide-free apo form; (ii) in complex with ADP-Mg(2+), mimicking the product-bound state; (iii) in complex with vanadate-ADP-Mg(2+), mimicking the ATP-bound state; and (iv) in complex with azide-ADP-Mg(2+), also mimicking the ATP-bound state. X-ray diffraction data sets were collected for apo and complexed NBD1 using an in-house X-ray diffraction facility at a wavelength of 1.5418 Å. The apo and complexed NBD1 crystals belonged to the primitive hexagonal space group P6(2), with one monomer in the asymmetric unit. Here, the crystallization, data collection and preliminary crystallographic analysis of apo and complexed NBD1 are reported.


Size matters: effects of stimulus size, duration and eccentricity on the visual gamma-band response.
The effects of stimulus size, duration and eccentricity on the visual gamma-band response (GBR) in human EEG were investigated and compared to visual evoked potentials (VEPs) in order to differentiate in future (and past) experiments whether changes in GBRs are due to stimulus-related (exogenous) or cognitive effects. EEG was recorded from 23 subjects while they performed a simple choice reaction time task requiring discrimination of squares and circles. In separate blocks stimulus size, duration, and eccentricity were manipulated. EEG was recorded from 64 electrodes. A wavelet transform based on Morlet wavelets was employed for the analysis of gamma-band activity. Amplitude of the GBR was diminished for small and peripheral stimuli. With short stimulus durations ON and OFF responses of the GBR merged into one peak. In comparison, VEP amplitudes were less susceptible to stimulus features. In contrast to VEP latencies, however, GBR latency did not show a lateralization for eccentric stimuli. In addition to previous experiments which have shown a modulation of the GBR by various cognitive processes, the present results demonstrate the susceptibility of the GBR in human EEG to exogenous factors, as numerous intracortical recordings in non-human primates have shown before. The results suggest that the human GBR resides in early visual areas. The demonstration of the susceptibility of the GBR to stimulus properties implies that studies aimed at exploring the involvement of the GBR in information processing have to be designed carefully. It also constrains the localization of the human GBR.


HPV DNA test and Pap smear in detection of residual and recurrent disease following loop electrosurgical excision procedure of high-grade cervical intraepithelial neoplasia.
We compared the performance of cervical cytology and HPV DNA test in detection of residual or recurrent disease following the treatment of cervical intraepithelial neoplasia (CIN) 2/3 with loop electrosurgical excision procedure (LEEP). A series of 107 women subjected to LEEP due to histologically confirmed CIN 2/3 between March 2001 and December 2002 were followed-up biannually until January 2004. Follow-up visits consisted of interview and gynecological examination including cervical cytology, hybrid capture II (HCII), and colposcopy. Patients presenting with abnormal colposcopy or high-grade squamous intraepithelial lesion (HSIL) smear were subjected to new excision procedure, and presence of histologically confirmed CIN 2/3 or higher was considered as residual or recurrent disease. Performance indicators were calculated for cytology and HCII assay in detecting residual or recurrent disease. Eleven (10.2%) women showed residual or recurrent disease during the follow-up. Considering HCII and Pap smear as stand-alone tests, both techniques showed similar sensitivity, detecting 100% of CIN 2/3 at the first follow-up visit. At the second follow-up visit, Pap smear showed better specificity and positive predictive value (PPV) than HCII, and both tests had fairly the same high negative predictive value (NPV) and sensitivity. The combined positive HCII and abnormal cytology had the same sensitivity as each of the tests alone, but specificity and PPV were significantly higher than those of single tests. When only one of the tests was positive, the sensitivity and the NPV of the combination remained the same, but its specificity and PPV were lower than that of the combined two positive tests and that of the individual test, at both follow-up visits. Both tests performed well in detecting residual or recurrent disease after LEEP and combination of the tests did not increase sensitivity of the single tests.


[Intelligent systems tools in the diagnosis of acute coronary syndromes: A systemic review].
Acute myocardial infarction is the leading cause of non-communicable deaths worldwide. Its diagnosis is a highly complex task, for which modelling through automated methods has been attempted. A systematic review of the literature was performed on diagnostic tests that applied intelligent systems tools in the diagnosis of acute coronary syndromes. A systematic review of the literature is presented using Medline, Embase, Scopus, IEEE/IET Electronic Library, ISI Web of Science, Latindex and LILACS databases for articles that include the diagnostic evaluation of acute coronary syndromes using intelligent systems. The review process was conducted independently by 2 reviewers, and discrepancies were resolved through the participation of a third person. The operational characteristics of the studied tools were extracted. A total of 35 references met the inclusion criteria. In 22 (62.8%) cases, neural networks were used. In five studies, the performances of several intelligent systems tools were compared. Thirteen studies sought to perform diagnoses of all acute coronary syndromes, and in 22, only infarctions were studied. In 21 cases, clinical and electrocardiographic aspects were used as input data, and in 10, only electrocardiographic data were used. Most intelligent systems use the clinical context as a reference standard. High rates of diagnostic accuracy were found with better performance using neural networks and support vector machines, compared with statistical tools of pattern recognition and decision trees. Extensive evidence was found that shows that using intelligent systems tools achieves a greater degree of accuracy than some clinical algorithms or scales and, thus, should be considered appropriate tools for supporting diagnostic decisions of acute coronary syndromes.


Interpreting conflicting findings from clinical trials of auricular acupuncture for cocaine addiction: does treatment context influence outcome?
To compare findings from two consecutive clinical trials of auricular acupuncture for cocaine addiction conducted at the same site in order to explore consistency of treatment effects. One hundred and sixty-five (165) cocaine-dependent, methadone-maintained patients (study 1, n = 82; study 2, n = 83). Subjects in both studies were randomly assigned to auricular acupuncture, a needle insertion control condition, or a no-needle relaxation control. Treatment sessions were offered five times weekly for 8 weeks. The two studies were equivalent in design, except that unlike study 1, study 2 offered subject payments for attendance and did not include weekly group counseling. Cocaine use assessed by three times weekly urine screens constituted the primary outcome. Secondary measures included retention in treatment, treatment attendance, treatment credibility, therapeutic alliance, and acute effects of treatments. Intent-to-treat analysis showed that patients assigned to acupuncture in study 1, but not in study 2, were significantly more likely to provide cocaine-negative urine samples relative to the two control conditions. The positive effect for acupuncture found in study 1 was not found in study 2. Even though the two studies were similar, reasons for this inconsistency cannot be determined definitively, but may be because of differences in psychosocial context and payment contingencies between the two studies, or the lack of effectiveness of acupuncture in this application. The need to critically consider the influence of treatment context and other potential moderating variables on outcome in order to draw conclusions regarding treatment effectiveness is discussed.


Knowledge translation in everyday nursing: from evidence-based to inquiry-based practice.
The interconnection of theory, evidence, and practice is most often conceptualized as an epistemological enterprise. In this article, we shift the discussion from one that is solely concerned with epistemology to one that considers the significance of ontology and the way in which epistemology and ontology are intricately intertwined in every nursing action. Drawing on deconstructive hermeneutics, we contend that to understand and affect the interconnection of theory, evidence, and practice, an ontological inquiry at the action level is required. Using a nursing practice example, we illustrate the complexities of knowledge translation and how effective integration of knowledge into practice involves an embodied process of ontological inquiry and action. This inquiry process draws on theory and evidence to enlarge and imagine possibilities for action in particular moments, situations, and contexts and rests in a way-of-being in which the interconnection of theory, evidence, and practice is embodied.


Robot-Assisted Diagnostic Laparoscopy: A Safe and Feasible Adjunct to the Management of Massive Spontaneous Pneumoperitoneum.
Pneumoperitoneum is the abnormal presence of free air in the peritoneal cavity. Oftentimes, it is a surgical emergency requiring exploratory laparotomy as most cases of pneumoperitoneum are due to perforated hollow viscus. However, not all pneumoperitoneum cases are surgical; nonsurgical pneumoperitoneum can arise from thoracic, abdominal, gynecologic, and other causes. We present a case of a 35-year-old male who developed a non-surgical pneumoperitoneum in the setting of drug overdose. The patient underwent robot-assisted diagnostic laparoscopy without findings of perforation or other pathology. Resolution of pneumoperitoneum was evidenced on follow-up computed tomography scan. This case emphasizes the importance of diagnostic laparoscopy in the setting of a confusing clinical picture and the feasibility of utilizing the robotic approach in hemodynamically stable patients.


The midterm outcomes of ankle Dias-Tachdjian pronation-eversion external rotation physeal fracture in children treated by open reduction internal fixation with one-stage medial-lateral combined incision.
The objective of this study was to report the midterm outcomes and complications of ankle Dias-Tachdjian pronation-eversion external rotation (PEER) physeal fracture in children treated by ORIF with combined medial and lateral incision. A total of 21 children with ankle Dias-Tachdjian PEER physeal fracture underwent open reduction internal fixation treatment with combined medial and lateral incision between January 2015 and October 2017. The lateral distal tibia angle (LDTA) was measured to evaluate angular deformity and the X-rays were taken to evaluate the premature physeal arrest. All patients were followed up for an average time of 20.1 months (ranging from 17 to 25 months). Bone healing was achieved in all cases. American Orthopedic Foot and Ankle Society-Ankle and Hindfoot (AOFAS-AH) score of the patients improved from median 31 (11, 38) preoperation to median 68 (63, 73) postoperation to median score 91 (87, 96) at last follow-up. LDTA of the patients improved from 70.5 ± 4.9 preoperation to 90.0 ± 1.2 postoperation, to measure 90.6 ± 3.7 at last follow-up. The differences were statistically significant (P < 0.05). There is no premature physeal closure, ankle deformity in 19 cases. They could normally exercise and take part in normal sport activities. The remaining two cases had physeal bone bridge and premature physeal closure but could still carry on daily activities and thus were categorized as good. ORIF with one-stage medial-lateral combined incision for ankle Dias-Tachdjian PEER physeal fracture can decrease the rate of premature physeal closure and should be a treatment choice.


A simplified method for fabrication of new complete dentures.
This article discusses a simple technique for fabricating a new set of complete dentures when there is a reasonable existing upper and lower denture pair. This method reduces the number of appointments needed, and may be very helpful in treating patients with transportation difficulties, especially when the dentist is able to perform some simple laboratory procedures such as mounting the case on the articulator. The technique is well-suited for a "worn-out" set of complete dentures.


Selective photodynamic inactivation of bacterial cells over mammalian cells by new triarylmethanes.
Three new triarylmethane dyes (TAMs), MPCV, DPCV, and AEV, were synthesized and their photodynamic inactivation abilities against E. coli and human pulmonary carcinoma A549 cells were compared to two commercial TAMs, CV and EV. The enhanced hydrophilicity of MPCV and AEV decreases their cellular uptake to A549 cells dramatically. However, their binding affinity toward E. coli cells are comparable to that of CV and EV by virtue of the improved electrostatic attraction with highly negatively charged E. coli outer membranes. MPCV and AEV were also found to generate hydroxyl radicals more efficiently upon irradiation than CV and EV. Consequently, MPCV and AEV exhibited markedly improved photodynamic inactivation of E. coli cells but remarkably diminished photodynamic inactivation of A549 cells than CV and EV. The photodynamic inactivation ability of DPCV was much lower than that of CV due to its high propensity for bleaching in neutral aqueous solution. Our work demonstrates that the introduction of protonatable groups in a proper manner into the structures of TAMs may lead to selective binding and photodynamic inactivation toward bacterial cells over mammalian cells. This strategy may be extended to other types of photodynamic antimicrobial chemotherapy (PACT) agents to improve their clinical potential.


Stereopsis: are we assessing it in enough depth?
The assessment of stereoacuity is an integral part of the ophthalmic assessment, with the responses used to inform clinical management decisions. Stereoacuity impacts on many aspects of life, but there are discrepancies reported where people without measurable stereoacuity report appreciating 3-D vision. This could be due, in part, to the presentation of the stimuli. A literature review was undertaken to evaluate current assessment techniques, how they relate to patient outcomes, identify the limitations of current tests and discuss how they could be improved. Recent evidence has been collated on currently available tests, used commonly within vision clinics, with normative data provided allowing responses to the tests to be interpreted. The relevance of the results is evaluated in relation to a range of outcomes, where a reduced level of stereopsis has a negative impact on the ability of an individual to perform many tasks, and can lead to an increase in difficulty interacting in the world. Current tests are limited in the aspects of stereoacuity they assess and their ability to precisely measure stereopsis. The world is not static, yet clinical tests are limited to measuring static stereoacuity, even though higher grades of depth perception can be identified in the presence of changing depth. Presentation methods of stereoacuity tests have remained similar over time, with a limited number of disparity levels assessed. New assessment methods are becoming available that include automated staircase testing to present multiple levels of disparity using digital technology. Current clinical tests are limited in their presentation, and are poor at detecting/measuring stereoacuity in those with limited stereopsis. Given the relevance of the stereoacuity measurement to management choices and functional outcomes, new testing methods would be beneficial to fully assess stereoacuity, both static and dynamic.


Uptake of antigen by afferent lymph dendritic cells mediated by antibody.
Dendritic cells isolated from sheep afferent lymph were examined for their ability to bind soluble protein and peptide antigens labeled with fluorescein both in in vitro assays and following intradermal injection of antigen in vivo. Analysis of dendritic cells by flow cytometry revealed weak direct binding of proteins and peptide antigens. However, the degree of uptake was greatly enhanced in the presence of specific antibody in vitro or if antigen was injected intradermally into antigen-primed sheep. About 60% of dendritic cells possessed the ability to take up antigen in both the in vitro and in vivo experiments. The uptake of antigen occurred very rapidly, reaching maximum values in terms of cell numbers and fluorescence intensity in less than 5 min in vitro and 20-40 min following in vivo challenge. Both sheep IgG subclasses could mediate this effect, but F(ab')2 fragments were ineffective. Procedures adopted to remove complement components from the in vitro test mixtures did not result in any reduction in the binding of antigen by dendritic cells. Two-color flow cytometry analysis of the dendritic cell population further showed that 43% of cells taking up the antigen/antibody complexes were CD1+, suggesting a relationship between these cells and Langerhans' cells or other dendritic cells in skin. The results, thus, indicate that approximately two thirds of sheep afferent lymph dendritic cells bind antigen/antibody complexes via an Fc receptor, a mechanism which could be important in the accentuated accessory function of these cells known to occur following secondary antigen challenge.


Pre-operative differentiation of pediatric ovarian tumors: morphological scoring system and tumor markers.
To investigate the importance of morphological scoring systems in differentiation of ovarian tumors in childhood. Morphological assessment using DePriest's index was performed for all patients with histopathological confirmation of ovarian tumor, with evaluation of tumor markers, from January 1997. Fifty-three girls (age range 13 months to 19 years) were surgically treated for 59 ovarian tumors, including six bilateral. All lesions with cystic appearance on ultrasonography were benign, 23 of 35 semisolid, and four of ten solid tumors were also benign. Stage of malignant disease was as follows: stage I, ten; stage II, two; stage III, six. Sensitivity, positive predictive value and accuracy by DePriest's and Ueland's indexes for benign tumors (score <7) were: 0.88, 0.79; 0.89; and 0.94, 0.84; 0.93; respectively. Elevated levels of tumor markers were observed in 17 patients, including four patients with endocrine manifestations. In 24 patients ovaries were successfully preserved, including two patients with foci of immature teratoma in a dermoid cyst. Ultrasonographic assessment with morphological analysis recommended by DePriest and Ueland is a very useful procedure for differentiating benign from malignant ovarian tumors in children. Tumor markers and endocrinological investigation are also useful for preoperative evaluation.


Generation of MCF-7 cells with aggressive metastatic potential in vitro and in vivo.
Epithelial-mesenchymal transition (EMT) is a cellular development program characterized by loss of cell adhesion and increased cell mobility. It is essential for numerous processes including metastasis. In this study we have generated "aggressive" MCF-7 breast cancer cells (MCF-7-EMT), which show significantly increased invasion in contrast to wild type MCF-7 (MCF-7 WT) cells. In addition, we have analyzed, whether these cell lines differ in their metastatic behavior in vivo and in expression of invasion and/or EMT-relevant genes. Invasive behavior of different human breast cancer cell lines was tested. "Aggressive" MCF-7 cells (MCF-7-EMT) were generated using coculture and mammosphere culture techniques. To analyze whether or not MCF-7-EMT cells in contrast to MCF-7 WT cells form metastases in vivo, we assessed metastases in a nude mouse model. mRNA expression profiles of MCF-7 WT cells and MCF-7-EMT cells were compared using the Affymetrix micro array technique. Expression of selected genes was validated using real-time PCR. In addition, protein expression of epithelial marker E-cadherin (CDH1) and mesenchymal markers N-cadherin (CDH2), Vimentin (VIM), and TWIST was compared. The breast cancer cell lines showed different invasive behavior from hardly any invasion to a stronger cell movement. Coculture with osteoblast-like MG63 cells led to significantly increased cell invasion rates. The highest increase was shown using MCF-7 WT cells. Generated MCF-7-EMT cells showed significantly increased invasion as compared to MCF-7 WT cells. In 8 of 10 mice bearing orthotopically growing MCF-7-EMT tumors, we could detect metastases in liver and lung. In mice bearing MCF-7 WT tumors (n = 10), no metastases were found. MCF-7 WT cells and MCF-7-EMT cells were different in expression of 325 genes. Forty-four of the most regulated 50 invasion and/or EMT-related genes were upregulated and 6 genes were downregulated in MCF-7-EMT cells. Protein expression of mesenchymal markers CDH2, VIM, and TWIST was clearly increased in MCF-7-EMT cells. Protein expression of epithelial marker CDH1 was clearly decreased. With the breast cancer cell lines, MCF-7-EMT and MCF-7 WT cells, we have an excellent model of cells for further studies of EMT and invasion in vitro and in vivo.