Metastasis-enhancing effect of heparin and its relationship to a lipoprotein factor.
The effect of low-dose heparin on spontaneous metastasis formation was studied with the PA-III rat prostate adenocarcinoma cell line model system. In LW rats given heparin iv at a dose of 1,000 U/kg body weight (three times/wk), the metastatic spread of implanted PA-III cells from the footpad through ipsilateral lymphatics to the lungs was enhanced. The weights of the draining lymph nodes (popliteal, inguinal, and axillary) and the number of lung tumor colonies were significantly increased compared with those in the saline-treated control tumor-bearing rats. The growth of the primary tumor was also enhanced. Heparin alone did not induce enlarged lymph nodes in rats nor did it change the growth pattern of PA-III cells in vitro. The accelerated metastatic spread of the PA-III cells was possibly related to the destruction of the oncolytic activity of the very low-density lipoprotein by the lipoprotein lipases induced by the iv administration of heparin. However, the possibility that other mechanisms could be operative in this phenomenon has not been ruled out.


Complications after heavy silicone oil tamponade in complicated retinal detachment.
To observe the complications after heavy silicone oil (HSO) tamponade in complicated retinal detachment. Thirty-three eyes of 33 patients with complicated retinal detachment were included in this retrospective study. Vitrectomy and HSO tamponade were performed in all patients. Other surgical procedures were performed as necessary. The main outcome measures included retinal reattachment, visual acuity, intraocular pressure, intraocular inflammation, lens opacity, and HSO emulsification. The patients were followed up for 3 months to 24 months (average, 8.1 ± 5.3 months). Retinal reattachment was achieved in 29 eyes (87.9%) with a first surgery and in 33 eyes (100%) with a second surgery. In all 33 eyes, HSO had been removed and the visual acuity was improved. Short-term (within 2 weeks after operations) complications included temporarily increased intraocular pressure and mild inflammation in the anterior chamber. Major long-term complications included cataract (100%) and HSO emulsification (42.4%). Other long-term complications included ocular hypertension (12.1%), retinal detachment and proliferative vitreoretinopathy (12.1%), and low intraocular pressure (9.1%). Heavy silicone oil tamponade is safe and effective to treat complicated retinal detachment. The most common complications are cataract and HSO emulsification.


A methodology for the geometric standardization of vehicle hoods to compare real-world pedestrian crashes.
This paper describes a standardization method that allows injury researchers to directly compare pedestrian hood contact points across a variety of hood sizes and geometries. To standardize hood contact locations a new coordinate system was created at the geometric center of the hood. Standardizing hood contact locations was done by turning each coordinate location into a ratio of the entire length or width of the hood. The standardized pedestrian contact locations could then be compared for various hood sizes. The standardized hood was divided into a three-by-three grid to aggregate contact points into hood regions. Data was obtained from the National Highway Traffic Safety Administration's Pedestrian Crash Data Study from 1994 to 1998. To understand injury severity with respect to pedestrian hood contact location, the injuries were narrowed to the single most severe Abreviated Injury Scale injury to the pedestrian and hood location at which that injury was sustained. Of the 97 pedestrian/vehicle cases, pedestrians received 270 injuries from 141 unique hood contact locations. After standardization, 36%, 28%, 36% of all contact points were located on the left, center and right side of the hood respectively. Vertically, 26%, 45%, 28% of contacts occurred at the front, middle, and rear regions of the hood respectively. The middle passenger side of the hood contained the most number of AIS 3+ injuries. By using real-world crash data, engineers can make evidence based decisions to decease the severity of pedestrian injuries.


The contribution of the Grey Nuns to the Development of Nursing in Canada: historiographical issues.
The purpose of this article includes describing the current state of historical knowledge about the Grey Nuns of Montreal, identifying issues which shed light on this state of knowledge and proposing new avenues of scholarship. A review of the literature shows that the nursing role of the Grey Nuns and their national contribution to the development of health care services require examination. The small number of publications about the Grey Nuns, specifically in respect to their role in the development of nursing services, can be linked to issues in Canadian historiography and trends in women's history, health science history, and nursing history.


A nomogram to predict the prognosis of patients with unresected rectal adenocarcinoma undergoing chemoradiotherapy: a population-based study.
Background: Chemotherapy combined with radiotherapy is the main treatment strategy for unresectable rectal cancer. However, the prognostic factors of patients with unresectable rectal cancer treated with radiotherapy and chemotherapy have not been systematically studied. Therefore, this study investigated the prognostic factors and prognosis based on surveillance, epidemiology and final results of the SEER medical insurance database. Methods: Primary rectum patients were selected from the SEER database. The independent prognostic factors associated with overall survival (OS), cancer-specific survival (CSS) and noncancer-related death were evaluated using the Kaplan-Meier method and log-rank test, a competing risk model, and the Cox proportional hazards regression model. Two nomograms were established for predicting the 1- and 3-year OS and CSS of patients. Results: A total of 3,998 rectal adenocarcinoma cancer patients who received chemoradiotherapy but had not undergone surgery were included in this study and divided into training (n = 3559) and validation cohorts (n = 439). Patients in the training cohort had a 1-year OS rate of 65.7±0.8%, a 3-year OS rate of 26.6±0.8%, a 5-year OS rate of 1.6±0.8%, and a median survival rate of 20.0 months (range, 19.22-20.8 months). The following factors were significant prognostic factors of OS: age (p< 0.001); tumour grade (p< 0.001); T stage (p< 0.001); M stage (p< 0.001); bone metastasis (p<0.001); brain metastases (p<0.001); liver metastases (p<0.001); lung metastases (p<0.001); marital status (p<0.001) and insurance status (p=0.005). Age (p< 0.001), tumour grade (p< 0.001), T stage (p< 0.001), M stage (p< 0.001), bone metastasis (p<0.001), brain metastases (p<0.001), liver metastases (p<0.001), lung metastases (p<0.001) and race (p=0.034) were independent prognostic factors of CSS. Age (p< 0.001), T stage (p< 0.001), N stage (p=0.007), M stage (p<0.001), liver metastases (p<0.001), lung metastases (p<0.001), marital status (p<0.001) and insurance status (p=0.019) were independently associated with noncancer-related death. Conclusion: Age, tumour grade, T and M stage, bone, brain, liver and lung metastases, marital status and insurance status are independent risk factors for the OS of rectal adenocarcinoma patients who have undergone chemoradiotherapy but have not undergone surgery. Age, tumour grade, T stage, M stage, bone, brain, liver, lung metastases and race were independent prognostic factors of CSS. Age, T, N and M stage, liver and lung metastases, marital status and insurance status, were independently associated with noncancer-related death. Interestingly, the earlier the T stage was, the higher the rate of noncancer-related death. Two nomograms were developed to predict OS and CSS, and the C-indexes were 0.6776 and 0.6744, respectively. Rectal cancer screening is strongly recommended for patients under the age of 50.


The clinical significance of neutrophil-lymphocyte ratio in patients treated with hemodialysis complicated with lung infection.
The goal of this work was to investigate the potential significance of neutrophil-lymphocyte ratio (NLR) in patients treated with maintenance hemodialysis (MHD).Herein, we retrospectively reviewed the electronic medical records of 100 patients with end-stage renal failure who were treated with MHD. All patients enrolled in this study met the inclusion criteria and were followed. The differences in each indicator between the two groups were compared using the Wilcoxon rank-sum test. On the other hand, Spearman correlation and logistic regression analysis were used to explore the correlation and risk factors for pulmonary infection between NLR and other indicators. Finally, we determined the optimal cut-off values for NLR, hypersensitive c-reactive protein (hs-CRP), and procalcitonin (PCT) diagnosis of pulmonary infection using the receiver operating characteristic curve.We found that NLR was positively correlated with age, PCT, hs-CRP, and hospital stay, but negatively correlated with hemoglobin, red blood cell, and Albumin. The expression levels of PCT, hs-CRP, and NLR in the infected group decreased significantly than those before treatment. Multiple regression analysis revealed that NLR is an important independent risk factor for MHD patients with pulmonary infection. Additionally, receiver operating characteristic curve analysis showed that the sensitivity, specificity, and area under the curve were 87.76%, 100%, and 0.920 when using NLR combined with hs-CRP to predict pulmonary infection in MHD patients, whereas that of NLR combined with PCT were 87.76%, 96.08%, and 0.944, respectively.Findings from this study suggested that NLR is an independent risk factor for MHD patients with pulmonary infection, which can effectively predict pulmonary infection. Moreover, sensitivity and specificity were greatly enhanced when using NLR combined with PCT/hs-CRP to predict pulmonary infection in MHD patients.


Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: determination using a novel oxytocin assay.
Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. As OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not unequivocably demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the intravenous (IV) route, which requires blood-brain barrier penetration. To address these questions, we developed a sensitive and specific quantitative mass spectrometry assay that distinguishes labeled (d5-deuterated) from endogenous (d0) OT. We administered d5 OT (80 IU) to six nonhuman primates via IN and IV routes as well as IN saline as a control condition. We measured plasma and CSF concentrations of administered and endogenous OT before (t=0) and after (t=10, 20, 30, 45 and 60 min) d5 OT dosing. We demonstrate CSF penetrance of d5, exogenous OT delivered by IN and IV administration. Peripheral administration of d5 OT did not lead to increased d0, endogenous OT in the CSF. This suggests that peripheral administration of OT does not lead to central release of endogenous OT. We also did not find that IN administration offered an advantage compared to IV administration with respect to achieving greater CSF concentrations of OT.


Distal anastomotic patency of the Cardica C-PORT(R) xA system versus the hand-sewn technique: a prospective randomized controlled study in patients undergoing coronary artery bypass grafting.
The C-Port® Distal Anastomosis Systems (Cardica, Inc., Redwood City, CA, USA) demonstrated favourable results in feasibility trials. However, distal vein anastomoses created with the C-Port® or C-Port xA® system have never been compared with hand-sewn distal vein anastomoses. The objective of this study was to compare distal end-to-side anastomoses facilitated with the C-Port xA® System with the traditional hand-sewn method. This single-centre prospective randomized controlled study comprised 71 patients (device group n = 35, control group n = 36) who underwent primary elective coronary artery bypass grafting between June 2008 and April 2011. The primary study end-point was 12-month distal anastomotic patency, which was assessed with prospective ECG-gated 256-multislice computed tomographic coronary angiography using a step-and-shoot scanning protocol. For the primary end-point, a per-protocol analysis was used. In the device group, four (11%) anastomoses were converted to hand-sewn anastomoses, and additional stitches to achieve haemostasis were necessary in 22 (76%) patients. There was no hospital mortality in either group. During the 12-month follow-up, a single death occurred in the Device group and was unrelated to the device. Twenty-nine patients in the device group and 32 in the control group completed 12-month CT coronary angiography. The overall patency of 160 studied distal vein graft anastomoses was 93%. Comparison of the end-to-side target anastomosis showed 12-month patencies of 86 and 88% in the device group and the control group, respectively. According to these preliminary results and despite the limited number of patients, the use of the C-Port xA® System is safe enough to perform distal end-to-side vein graft anastomosis, with respect to 12-month end-to-side distal venous anastomotic patency. Although there are some technical challenges with this device, the incidence of complications is comparable to the traditional hand-sewn technique.


Short-duration cassava genotypes for crop diversification in the humid tropics: growth dynamics, biomass, yield and quality.
Short-duration (6-7 months) cassava provides opportunities to smallholder farmers for effective utilisation of resources such as land, moisture and nutrients as well as diversification of enterprise and income. The variation in biomass production and partitioning, seasonal course of growth indices, yield, quality and nutrient uptake of ten short-duration/early-bulking genotypes of cassava and their impact on nutrient contents in soil in a lowland situation akin to rice fallow were examined in this study. Triploid 2-18 gave the highest yield (38.34 t ha(-1)), followed by triploid 4-2, Sree Vijaya, Sree Jaya and Vellayani Hraswa, which were on a par (30-32 t ha(-1)). Vellayani Hraswa, Sree Vijaya and triploid 4-2 had significantly higher tuberous root dry matter content (370-380 mg g(-1)) and fairly higher starch content (270-280 mg g(-1)). All genotypes except triploid 4-2, triploid 2-18 and H-165 had low cyanogen content (29.2-43.8 microg g(-1)), well within the tolerable limit. Tuberous root dry matter and total dry matter production, crop growth rate, tuberous root bulking rate and harvest index at the last phase, number of tuberous roots, mean weight of tuberous roots and nutrient uptake showed significant positive correlations with tuberous root yield. Principal component analysis also showed a similar trend. The diploids Sree Vijaya, Sree Jaya, Vellayani Hraswa and Kalpaka are ideal for cultivation in rice fallow for food use owing to their high yield, good cooking quality and low cyanogen content. The triploids are better suited for industrial use owing to their high tuberous root dry biomass production.


Electron-Transfer Reactions of Electronically Excited Zinc Tetraphenylporphyrin with Multinuclear Ruthenium Complexes.
Transient absorption decay rate constants (kobs) for reactions of electronically excited zinc tetraphenylporphyrin ((3)ZnTPP*) with triruthenium oxo-centered acetate-bridged clusters [Ru3(μ3-O)(μ-CH3CO2)6(CO)(L)]2(μ-pz), where pz = pyrazine and L = 4-cyanopyridine (cpy) (1), pyridine (py) (2), or 4-dimethylaminopyridine (dmap) (3), were obtained from nanosecond flash-quench spectroscopic data (quenching constants, kq, for (3)ZnTPP*/1-3 are 3.0 × 10(9), 1.5 × 10 (9), and 1.1 × 10(9) M(-1) s(-1), respectively). Values of kq for reactions of (3)ZnTPP* with 1-3 and Ru3(μ3-O)(μ-CH3CO2)6(CO)(L)2 [L = cpy (4), py (5), dmap (6)] monomeric analogues suggest that photoinduced electron transfer is the main pathway of excited-state decay; this mechanistic proposal is consistent with results from a photolysis control experiment, where growth of characteristic near-IR absorption bands attributable to reduced (mixed-valence) Ru3O-cluster products were observed.


Construct validity of the Short Form-36 Health Survey and its relationship with BMI in obese outpatients.
To investigate the construct validity of the Short Form-36 (SF-36) Health Survey questionnaire in obese patients. Our series consisted of 1735 obese patients (age, 44.7 +/- 11.0 years; 1346 women) consecutively enrolled in the QUOVADIS study, an observational multicenter study of obese treatment-seeking outpatients. The construct validity of the SF-36 was assessed by main component analysis. Age-, gender-, and education-adjusted general linear models were used to investigate the relationship between BMI and SF-36 domains or factors identified by main component analysis. BMI was significantly associated with poor health-related quality of life in all eight SF-36 domains, and the strongest association was observed with physical activity. Main components analysis generated a six-factor solution explaining 59% of the observed variance. BMI was strongly associated with factors based on the loading of items regarding the physical activity domain and factors based on role-physical and role-emotional items or general health and bodily pain items. In contrast, mental health-, vitality-, and social functioning-based factors were not related to BMI. In obese treatment-seeking outpatients, the clustering of SF-36 items in main components is not significantly different from the domain-based approach generally used, thus confirming the robustness of such a generic questionnaire in this specific condition. However, the peculiar clustering of some SF-36 items and their relationship with BMI suggest that the health-related quality of life profile of subjects belonging to that population may be better described with alternative aggregations of the SF-36 items or with disease-tailored questionnaires.


Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states.
Molecular mechanisms of neuroprotection that lead to ischaemic tolerance are incompletely understood. Identification of genes involved in the process would provide insight into cell survival and therapeutic approaches for stroke. We developed a mouse model of neuroprotection in stroke and did gene expression profiling to identify potential neuroprotective genes and their associated pathways. Eight mice per condition were subjected to occlusion of the middle cerebral artery for 15 min (preconditioning), 60 min (injurious ischaemia), or preconditioning followed 72 h later by injurious ischaemia. RNA was extracted from the cortical regions of the ischaemic and non-ischaemic hemispheres. Three pools per condition were generated, and RNA was hybridised to oligonucleotide microarrays for comparison of ischaemic and non-ischaemic hemispheres. Real-time PCR and western blots were used to validate results. Follow-up experiments were done to address the biological relevance of findings. Microarray analysis revealed changes in gene expression with little overlap among the conditions of injurious ischaemia, ischaemic preconditioning, or both. Injurious ischaemia induced upregulation of gene expression; 49 (86%) of 57 genes regulated showed increased expression in the ischaemic hemisphere. By contrast, preconditioning followed by injurious ischaemia resulted in pronounced downregulation; 47 (77%) of 61 regulated genes showed lower expression. Preconditioning resulted in transcriptional changes involved in suppression of metabolic pathways and immune responses, reduction of ion-channel activity, and decreased blood coagulation. Preconditioning reprogrammes the response to ischaemic injury. Similar changes reported by others support an evolutionarily conserved endogenous response to decreased blood flow and oxygen limitation such as seen during hibernation.


Knowledge of Bahraini women about the menopause and hormone therapy: implications for health-care policy.
To investigate the knowledge of Bahraini women aged 30-64 years about menopause, hormone therapy (HT) and their associated health risks. To examine the relationship between the knowledge of Bahraini women about menopause and their sociodemographic and reproductive characteristics. A cross-sectional study was conducted of 260 Bahraini women attending primary health-care centers. A multistage, stratified and clustered random sampling technique was used. The women were interviewed using a structured questionnaire composed of the Menopause Knowledge Scale and sociodemographics. The mean knowledge percentage of all participants was 59.86, with a standard deviation of 25.77. There were significant differences in the mean knowledge percentages among categories of education (p = 0.025) and employment (p = 0.005). No significant differences in the mean knowledge percentages were found among categories of menopausal status. The statement with the highest percentage of correct answers was 'Pregnancy cannot occur after menopause' (75.8%). Statements regarding risk of cardiovascular diseases had the lowest percentage of correct answers, 'HT increases risk of cardiovascular diseases' (33.8%) and 'Risk of cardiovascular diseases increases with menopause' (40.0%). The knowledge of Bahraini women about menopause and HT is average. Lack of knowledge was greatest in areas related to heart disease. Better education about menopause needs to be achieved regarding the long-term risk associated with menopause and the pros and cons of HT.


Unfounded trust: a constructivist meditation.
From a postmodern standpoint, all trust is ultimately unfounded, in the sense that no authoritative theoretical, empirical or practical foundation exists to ground a unified, explicit, and justified framework for psychotherapeutic practice. Following a constructivist meditation on these themes, I offer five playful prescriptions for addressing this predicament that suggest a provisional way forward in a terrain that offers no firm footholds having bedrock certainty.


Doxorubicin-conjugated mesoporous magnetic colloidal nanocrystal clusters stabilized by polysaccharide as a smart anticancer drug vehicle.
Fabrication of magnetic nanocarriers that demonstrate enhanced biocompatibility and excellent colloidal stability is critical for the application of magnetic-motored drug delivery, and it remains a challenge. Herein, a novel approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (MMCNCs) that are stabilized by agarose is described; these clusters demonstrate high magnetization, large surface area and pore volume, excellent colloidal stability, enhanced biocompatibility, and acid degradability. The hydroxyl groups of agarose, which cover the surface of the magnetic nanocrystals, are modified with vinyl groups, followed by click reaction with mercaptoacetyl hydrazine to form the terminal hydrazide (-CONHNH(2)). The anticancer agent doxorubicin (DOX) is then conjugated to MMCNCs through a hydrazone bond. The resulting hydrazone is acid cleavable, thereby providing a pH-sensitive drug release capability. This novel carrier provides an important step towards the construction of a new family of magnetic-motored drug-delivery systems. The experimental results show that the release rate of DOX from the DOX-conjugated MMCNCs (MMCNCs-DOX) is dramatically improved at low pH (tumor cell: pH 4-5 in the late stage of endolysosome and pH 5-6 from the early to late endosome), while almost no DOX is released at neutral pH (blood plasma). The cell cytotoxicity of the MMCNCs-DOX measured by MTT assay exhibits a comparable antitumor efficacy but lower cytotoxicity for normal cell lines, when measured against the free drug, thus achieving the aim of reducing side effects to normal tissues associated with controlled drug release.


The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae.
Quorum-sensing bacteria communicate with extracellular signal molecules called autoinducers. This process allows community-wide synchronization of gene expression. A screen for additional components of the Vibrio harveyi and Vibrio cholerae quorum-sensing circuits revealed the protein Hfq. Hfq mediates interactions between small, regulatory RNAs (sRNAs) and specific messenger RNA (mRNA) targets. These interactions typically alter the stability of the target transcripts. We show that Hfq mediates the destabilization of the mRNA encoding the quorum-sensing master regulators LuxR (V. harveyi) and HapR (V. cholerae), implicating an sRNA in the circuit. Using a bioinformatics approach to identify putative sRNAs, we identified four candidate sRNAs in V. cholerae. The simultaneous deletion of all four sRNAs is required to stabilize hapR mRNA. We propose that Hfq, together with these sRNAs, creates an ultrasensitive regulatory switch that controls the critical transition into the high cell density, quorum-sensing mode.


Monocyte transferrin-iron uptake in hereditary hemochromatosis.
Transferrin-iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe-labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron-loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin-iron uptake by these cells.


The Development of Environmentally Sustainable Poly(vinyl chloride) Composite from Waste Non-Metallic Printed Circuit Board with Interfacial Agents.
The recycling of non-metallic printed circuit boards (NMPCB) as a filler in poly(vinyl chloride) (PVC) composite would help to encourage the use of waste NMPCB, thus, reducing some environmental concerns with regard to e-waste. The objective of this study was to comprehensively evaluate the effect of different interfacial agents, namely polypropylene grafted maleic anhydride (PP-g-MAH) and ϒ-aminopropyltriethoxy silane (ATPS) on the morphology and properties of PVC/NMPCB composites. A PVC/NMPCB composite was prepared by melt compounding with varying amounts of NMPCB ranging between 10, 20 and 30 wt.%. Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) analysis revealed the interactions between PVC and NMPCB when using both PP-g-MAH and ATPS interfacial agent. The properties and morphology of PVC/NMPCB composites were significantly dependent on the interfacial agent treated on the NMPCB surface. The phase morphology and mechanical properties of PVC/NMPCB composites (30 wt.% of NMPCB) were improved and the result also indicated that the higher compatibility of composites with ATPS as an interfacial agent led to our obtaining the maximum Young's modulus of 484 MPa. The dynamic mechanical analysis revealed the interaction at the interface, with the Tg shifting to a lower temperature in the presence of PP-g-MAH and strong interfacial adhesion noted with the improved Tg in the presence of the ATPS interfacial agent. Further evidence of the improved interaction was observed with the increment in density in the presence of ATPS when compared with PP-g-MAH in PVC/NMPCB composite. Hence, of the two interfacial agents, ATPS showed itself to be more effective when employed as an interfacial agent for NMPCB in PVC composite for industry.


[Determination of the real value of the ventricular volume using angiographic methods].
The developing of cuantitative angiographic procedures for evaluating the left ventricular efficiency have displaced most of the simple hemodynamic methods. The calculation of the left ventricular volume by usual ventriculography yields, as a rule, magnified values. The purpose of this paper is to determine the equation of the regression line means of which the real left ventricular volume can be calculated. A series of 12 normal hearts obtained from accidentaly deceased adult individuals (this necropsy material was afforded by the Forensic Medicine Department of México City). Previously measured amounts of a contrast substance were injected into the left ventricular cavity. The heart was filmed in a position equivalent to the chest RAO. The volume of the left ventricle was calculated using monoplane Sandler and Dodge cineventriculographic method. The results were submitted to statistic analysis. Confrontation of calculated and real values rendered a significative "r" (0.7374) and a non-significant "p" (0.001) the regression equation obteined was: y=36.97 + (0.39 x) in which: y=real left ventricular volume. x=calculated left ventricular volume.


A unified stoichiometric model for oxidative and oxidoreductive growth of yeasts.
Yeasts degrade glucose through different metabolic pathways, where the choice of the pathway is dependent on the nature of the limitation in the various substrates. When oxygen is limiting in addition to glucose, yeasts often grow according to a mixture of oxidative and reductive metabolism. Oxygen may be limiting either by supply or by inherent biological restrictions such as the respiratory bottleneck in Saccharomyces cerevisiae or by both. A unified model incorporating both supply and biological limitations is proposed for the quantitative prediction of growth rates, consumption and production rates, as well as key metabolite concentrations during mixed oxidoreductive metabolism occurring as a result of such oxygen limitations. This simple unstructured model can be applied to different yeast strains while at the same time requiring a minimum number of measured parameters. "Estimators" are utilized in order to predict the presence of supply-side or biological limitations. The values of these estimators also characterize the relative importance of oxidative to total metabolism. Results from the aerobic and oxygen-limited chemostat cultures were used to corroborate the model predictions. During these experiments, the heat released by the yeast cultures was also monitored on-line. The model correctly predicted the overall stoichiometry, steady-state concentrations, and rates including heat dissipation rates measured in the various situations of oxygen limitations. Direct continuous measurements such as heat can be used in conjunction with the unified model for on-line process control.


The RUNX1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasion.
Previously, we have identified the RUNX1 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from epithelial ovarian cancer (EOC) patients, when compared with primary cultures derived from matched primary (prior to CT) tumors. Here we show that RUNX1 displays a trend of hypomethylation, although not significant, in omental metastases compared with primary EOC tumors. Surprisingly, RUNX1 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. The RUNX1 expression levels were almost identical in primary tumors and omental metastases, suggesting that RUNX1 hypomethylation might have a limited impact on its overexpression in advanced (metastatic) stage of the disease. Knockdown of the RUNX1 expression in EOC cells led to sharp decrease of cell proliferation and induced G 1 cell cycle arrest. Moreover, RUNX1 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX1 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX1 gene in EOC progression and suggest that RUNX1 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX1 and other members of the RUNX gene family in ovarian tumorigenesis.


Metastatic malignant melanoma with "rhabdoid" features.
The authors propose the addition of malignant melanoma to the list of extrarenal neoplasms that may be predominantly composed of polygonal cells with the cytologic features of "rhabdoid" tumor. A review of 313 metastatic melanomas disclosed 49 examples with rhabdoid features, from which 31 had sufficient material for further pathologic and immunohistologic characterization. A control group of 46 nonrhabdoid metastatic melanomas was examined in parallel fashion. In 39% of cases, rhabdoid melanomas manifested relative deletion of S100 protein compared with the control tumors. However, there were no differences in staining with HMB-45. Vimentin immunoreactivity was concentrated in the paranuclear cytoplasm of rhabdoid melanoma cells. However, ultrastructural studies of these cases failed to show corresponding whorls of intermediate filaments and instead demonstrated paracrystalline paranuclear inclusions in profiles of rough endoplasmic reticulum. It is concluded that metastatic rhabdoid melanoma exhibits significant morphologic similarity to other rhabdoid tumors at a light-microscopic level. However, it usually retains enough melanocytic attributes to allow for accurate diagnostic recognition. Probably because patients with metastatic melanoma have an extremely poor prognosis overall, no worsening of biologic behavior was associated with rhabdoid cytomorphologic findings in this tumor type when compared with the control cases.


Hyperparathyroidism presenting as brown tumor of the maxilla.
As it becomes common for hyperparathyroidism to be detected earlier in the course of the disease, the bony manifestations of the disease are rarely seen. Presented here is a rare case of brown tumor of the maxilla as the presenting symptom of primary hyperparathyroidism.


Isolated Renal Mucormycosis.
Mucormycosis in humans has been described as early as 1885 in literature. Isolated renal mucormycosis is rare as it has been mainly described in developing countries like India and China. It is rarer still to find this entity in immunocompetent young males without any risk factors. Specific guidelines on the treatment is not yet known but combined surgical and medical therapy is considered the best modality for its management. We describe a young male who presented with bilateral hydroureteronephrosis. He was initially treated as a case renal tuberculosis which is relatively more common in TB endemic country like ours. However when he did not respond to the anti-tuberculosis drug (ATT), a biopsy revealed mucormycosis. He was treated with nephrectomy and liposomal amphotericin B and oral posaconazole. On follow up of 2 years he is healthy and leading his normal life.


Sinus bone grafting procedures using ultrasonic bone surgery: 5-year experience.
Ultrasonic bone surgery was recently introduced as an osteotomic technique; however, documentation is scarce. This article reports on the application of ultrasonic bone surgery for 53 bone-augmentation procedures in the posterior maxilla in 34 patients over 5 years. The initial residual bone height under the sinus varied between 1 and 9 mm (mean: 3.7 mm). Distribution according to residual bone height classes was 7.7% for Class B, 39.3% for Class C, and 53.0% for Class D. The procedures included bony window opening of the sinus, cortical and cancellous bone harvesting, and activation of the sinus wall. During the sinus approach, 2 of 53 membranes (3.8%) were perforated and covered with a membrane made of platelet-poor plasma. Bone grafting was carried out with autologous bone at 22 implant sites (18.8%), with a mixture of autologous bone and anorganic bovine bone mineral (Bio-Oss) at 29 sites (24.8%), and with Bio-Oss alone at 66 sites (56.4%). The perforated membranes healed uneventfully. At second-stage surgery, four implants failed. The survival rate of the 117 placed implants was 96.6%. No implant failed after loading. Performing the sinus grafting procedure with ultrasonic bone surgery limited the occurrence of membrane perforation; by changing the tips, all surgical steps were performed safely and comfortably.


Many facets of chromosome 3p cytogenetic findings in clear cell renal carcinoma: the need for agreement in assessment FISH analysis to avoid diagnostic errors.
Abnormalities of the locus chromosome 3p and the entire chromosome 3 are involved in the cancerogenesis of clear cell renal carcinoma and may be detected by interphase fluorescence in situ hybridization (interphase FISH). We observed a variable detection rate of chromosome 3p/3 abnormalities in different series of clear cell renal carcinoma. Therefore, we focused on problematic issues when performing analysis on routinely available formalin-fixed and paraffin embedded tissue. A group of studies encountered a single approach to chromosome 3p detection, by using probe/s to map different codes of the short arm 3p without a control of the entire chromosome 3. Deletion of chromosome 3p and monosomy of chromosome 3 ranged from 38% to 100% in clear cell renal carcinoma. Cut-off values for the threshold were chosen randomly or obtained by calculation of the mean value plus 1 or 2 or 3 standard deviations. Loss of chromosome 3p was assessed either as the percentage of single signals on the total number of nuclei, or applying a double approach with corrections of control chromosome 3. Moreover, cut off values were sometimes arbitrarily corrected with the findings from normal adjacent renal parenchyma. A consensus of experts in the field is needed in order to define the best methodological approach and the appropriate threshold in assessment 3p deletion when interphase FISH is performed in clear cell renal carcinoma. This harbours relevant diagnostic and therapeutic implications, at light also of targeted therapies recently available to clear cell renal carcinoma.


Raising the awareness of inpatient nursing staff about medication errors.
The study objective was to design and implement an educational programme to raise the awareness of in-patient nursing staff about medication errors and other medication-related safety issues. A sample of in-patient nursing staff in Al Ain hospital (n = 370) was included in the study and completed a self-reported questionnaire about medication errors. A structured program was developed and used by the clinical pharmacists to identify the nursing knowledge on medication errors and other medication-related safety issues. The program consisted of a pre/post self-reported questionnaire, a training service, educational material, successive presentations and handouts. The self-reported questionnaire included twenty closed questions asking nurses opinions about medication errors. A training program on medication safety (Med Safe tool) was carried out by [clinical pharmacy team (n = 2) and quality coordinator nurse (n = 1)], for each group of 10 nurses. Main outcome measure The study outcomes were the change in mean scores pre and post intervention. Findings revealed differences in the knowledge of nurses about the causes and reporting of medication errors. There were statistically significant differences in responses across the participant's years of experience and the current clinical working area. The participant's responses improved significantly [57.4% +/- 8.2, (95%CI: 56.6-58.2) vs. 68.9 +/- 10.3, (95%CI: 67.8-69.9); P < 0.05] pre and post questionnaire respectively. The clinical pharmacist's structured program has improved knowledge of the in-patient nursing staff in terms of raising their awareness about medication errors.


Modulatory effects on proteinase kinetics caused by association of both enzyme and substrate to heparin.
Heparin is shown to produce modulatory effects on the amidolytic activity of trypsin, thrombin and plasmin with various synthetic peptide substrates. Simple Michaelis-Menten kinetics are observed in the absence of heparin. In its presence an enhancement effect is observed at low substrate concentrations, and an inhibitory effect is observed at high substrate concentrations. Other polyanions like dextran sulphate, phosvitin and inositol hexakisphosphate produces a similar effect. The modulatory effect of heparin is abolished when it binds cations. Co-binding of both substrate and enzyme to heparin seems to be a necessary requirement for the effect to occur. A model is proposed which can account semiquantitatively for the kinetics observed. It is suggested that the mechanism, which involves co-binding of substrate and enzyme in an competitive manner to a macromolecular structure, may be of primary importance as a regulatory mechanism in blood coagulation and fibrinolysis.


[Asymptomatic Renal Stones: Do they really Exist?].
Asymptomatic renal calculi without any history of colic, hematuria or infection can be found as an incidental finding during preven-tive check-ups. The aim of our study was to eval-uate whether these stones provoke symptoms with the need for further treatment during the follow-up and whether they cause cortical defects which may consecutively affect the renal func-tion. In a prospective study we evaluated 104 patients with renal calculi. The -medical history, radiological findings and functional imaging as well as urine and blood analyses were recorded and evaluated. The influence of stone size and localisation on the development of acute stone-related symptoms, renal function and renal scarring were evaluated. Furthermore, we analysed whether localised pathological findings in radiographic or functional imaging may influence the creatinine level. The follow-up was be-tween 12 and 48 months (median: 25 months). During the study period 27 / 104 of our patients (26 %) developed symptomatic events (renal colic, hematuria, infection) in which patients with middle pole calculi with a mean -cumulative stone diameter of 9.8 mm had the -highest risk. A localised renal scarring could be found in 36.6 %. These patients had a significantly higher risk in presenting an increased creatinine level. Increasing stone size was diagnosed in 39 cases (37.5 %). Asymptomatic renal stones have to be controlled regularly in order to prevent the -patient from loss of renal function and hypertension caused by increasing stones or urinary tract infection.


Cellular activation mechanisms in septic shock.
Septic shock is an increasingly important clinical condition, characterized by systemic hypotension, ischemia, and ultimately organ failure. In Gram negative infection, the bacterial cell wall component, lipopolysaccharide (endotoxin, LPS), has been strongly linked to the pathophysiological responses that result in septic shock. LPS is bound in plasma to a protein called LPS-binding protein (LBP), which facilitates the binding of LPS to a cell surface receptor, CD14. Binding to CD14 stimulates cell signaling mechanisms that result in the production of inflammatory cytokines. However, the events which follow LPS binding to CD14 and which lead to the production of cytokines remain unclear. It has recently become evident that a number of phosphorylation cascades including MAP kinase pathways and NF-kappaB activation pathway are initiated by exposure of cells to LPS. These cascades act at both the transcriptional and translational levels to regulate cytokine production. This review will focus on the signaling pathways that are initiated by LPS and the cellular effects of the signaling pathways.


Scattering of the fundamental shear horizontal guided wave by a part-thickness crack in an isotropic plate.
The interaction of the fundamental shear horizontal (SH0) guided mode with part-thickness cracks in an isotropic plate is studied as an extension within the context and general framework of previous work ["Short range scattering of the fundamental shear horizontal guided wave mode normally incident at a through thickness crack in an isotropic plate," J. Acoust Soc. Am. 122, 1527-1538 (2007); "Angular influence on scattering when the fundamental shear horizontal guided wave mode is incident at a through-thickness crack in an isotropic plate," J. Acoust. Soc. Am. 124, 2021-2030 (2008)] by the authors with through-cracks. The symmetric incidence case where the principal direction of the incident beam bisects the crack face at 90 degrees is studied using finite element simulations validated by experiments and analysis, and conclusions are inferred for general incidence angles using insights obtained with the through-thickness studies. The influence of the crack length and the monitoring distance on the specular reflection is first examined, followed by a study of the angular profile of the reflected field. With each crack length considered, the crack depth and operating frequencies are varied. For all crack depths studied, the trend of the results is identical to that for the corresponding through-thickness case and the values differ only by a frequency dependent scale factor. Theoretical analysis is used to understand the physical basis for such behavior and estimates are suggested for the scale factor--exact for the high-frequency scattering regime and empirical for the medium- and low-frequency regimes.


Nickel complexes of a binucleating ligand derived from an SCS pincer.
A binucleating ligand has been prepared that contains an SCS pincer and three oxygen donor atoms in a partial crown ether loop. To enable metalation with Ni(0), a bromoarene precursor was used and resulted in the formation of a nickel-bromide complex in the SCS pincer portion of the ligand. Reaction of the nickel complex with a lithium salt yielded a heterobimetallic complex with bromide bridging the two metal centers. The solid-state structures were determined for this heterobimetallic complex and the nickel-bromide precursor, and the two complexes were characterized electrochemically to determine the influence of coordinating the second metal.


The role of foxp3-expressing regulatory T cells and T helpers in immunopathogenesis of multidrug resistant pulmonary tuberculosis.
Subpopulation structure of regulatory T cells and T helpers of peripheral blood in patients with newly diagnosed pulmonary tuberculosis depending on the clinical form of disease and sensitivity of Mycobacterium tuberculosis to antituberculosis drugs has been analyzed in this work. It has been shown that the leading part in immune suppression at infiltrative, dissemination, and fibrosis-cavity pulmonary tuberculosis is played by natural regulatory CD4(+)CD25(+)Foxp3(+)-T lymphocytes. Thus we estimate increase of their number in blood by drug-resistance and drug-susceptible patients. It has been demonstrated that in patients with fibrocavernous and infiltrative form of the disease and drug-resistant pulmonary tuberculosis the number of CD4(+)CD25(-)Foxp3(+)-regulatory T cells was increasing. In patients with infiltrative pulmonary tuberculosis, including multidrug-resistant M. tuberculosis, an increased number of CD3(+)CD4(+)CD25(-) T helpers is determined by the pathogenic features of the development of the tuberculosis infection and is connected with the activation of Th1-dependent immune response. Reduction in the number of T-helpers in the blood of patients with dissemination and fibrosis-cavity pulmonary tuberculosis mediates inefficient implementation of cell-mediated protective immunity.


Early Markers of Tubulointerstitial Fibrosis in Children With Idiopathic Nephrotic Syndrome: Preliminary Report.
Tubulointerstitial fibrosis and tubular atrophy play a crucial role in the pathogenesis of chronic kidney disease (CKD). They are also major determinants in chronic kidney disease development and progression in patients with primary renal diseases characterized by persistent or recurrent proteinuria. The purpose of the study was to assess urinary excretion of alpha-glutathione S-transferase (alpha-GST), pi-glutathione S-transferase (pi-GST), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and serum NGAL level in children with idiopathic nephrotic syndrome (INS). the study group comprised of 39 children with INS and the control group consisted of 20 healthy children. A total of 23 patients were affected with steroid-dependent nephrotic syndrome (SDNS) and 16 with steroid-resistant nephrotic syndrome (SRNS). In the majority of patients, a histopathologic examination revealed minimal change disease (MCD)-25 (64%). Focal segmental glomerulosclerosis (FSGS), mesangioproliferative glomerulonephritis (MesPGN), membranoproliferative glomerulonephritis (MPGN), and membranous glomerulonephritis (MGN) were diagnosed in 4 (10.3 %), 6 (15.5%), 2 (5.1%), and 2 (5.1%) children, respectively. Urinary alpha-GST, urinary pi-GST, urinary KIM-1, and urinary and serum NGAL concentrations were measured using specific enzyme-linked immunosorbent assay. The urinary results were expressed in nanograms per milligram of creatinine (ng/mg). The authors observed significantly higher levels of urinary alpha-GST/creatinine ratio (P = 0.03), urinary KIM-1/creatinine ratio (P < 0.02), serum NGAL level (P < 0.01), and urinary NGAL/creatinine ratio (P = 0.02) in children with INS compared with controls. The median values of urinary pi-GST/creatinine ratio in children with INS and controls did not differ significantly. In children with SRNS, the median values of urinary NGAL/creatinine ratio (P = 0.02) and urinary KIM-1/creatinine ratio (P = 0.02) were significantly higher compared with children with SDNS. The authors noted significant positive correlation between KIM-1/creatinine ratio and proteinuria (r = 0.56, P < 0.05). The analysis of alpha-GST/creatinine ratio, pi-GST/creatinine ratio, sNGAL, and uNGAL/creatinine ratio concerning the histopathologic examination, the duration of the disease, and number of relapses did not show any significant differences. 1. Both children with SDNS and those with SRNS were characterized by increased tubular injury marker levels. 2. Patients with SRNS and higher proteinuria are more susceptible to early kidney damage.


A histologic classification of IgA nephropathy for predicting long-term prognosis: emphasis on end-stage renal disease.
A multicenter case-control study on IgA nephropathy (IgAN) was conducted to develop an evidence-based clinicopathologic classification of IgAN for predicting long-term renal outcome. Two hundred and eighty-seven patients including those with isolated hematuria or very mild proteinuria were enrolled. During a median follow-up of 9.3 years after biopsy, 49 patients (17%) progressed to end stage renal disease (ESRD). The associations between pathological variables and the need for chronic dialysis was examined by multivariate logistic regression analysis separately in patients who required dialysis earlier than 5 years (Early Progressors) and those who required dialysis within 5 to 10 years (Late Progressors) after biopsy. Independent pathological variables predicting progression to ESRD were global sclerosis, segmental sclerosis and fibrous crescents for Early Progressors, and global sclerosis and cellular/fibrocellular crescents for Late Progressors. Four histological grades, HG 1, HG 2, HG 3 and HG 4, were established corresponding to <25%, 25-49%, 50-74% and =75% of glomeruli exhibiting cellular or fibrocellular crescents, global sclerosis, segmental sclerosis or fibrous crescents. Eleven (7%) patients in HG 1, 12 (16%) in HG 2, 13 (31%) in HG 3 and 13 (68%) in HG 4 progressed to ESRD. Multivariate logistic analysis revealed that the risk of progression to ESRD was significantly higher in HG 2, 3 and 4 than in HG 1 (odds ratio, 2.4, 5.7 and 27.6 vs. 1.0). Our evidence-based histologic classification can identify the magnitude of the risk of progression to ESRD and is useful for predicting long-term renal outcome in IgAN.


Novel complexation hydrogels for oral peptide delivery: in vitro evaluation of their cytocompatibility and insulin-transport enhancing effects using Caco-2 cell monolayers.
Poly[methacrylic acid-grafted-poly(ethylene glycol)] [P(MAA-g-EG)] is a complexation hydrogel molecularly designed for oral peptide delivery. In this work, the cytotoxicity and insulin-transport enhancing effect of P(MAA-g-EG) microparticles on intestinal epithelial cells were evaluated using Caco-2 cell monolayers. A series of P(MAA-g-EG) microparticles with different polymer compositions were prepared by a photo-initiated free radical solution polymerization and subsequent pulverization. The hydrogel microparticles were preswollen in either Ca2+-containing (CM+) or Ca2+-free medium (CM-; pH 7.4) and applied to the apical side of the Caco-2 monolayers. No significant cytotoxic effects, as determined by a calorimetric assay with P(MAA-g-EG) microparticles preswollen in the CM+, were observed at doses ranging from 3 to 31 mg/cm2 of cell monolayer. Transepithelial electrical resistance (TEER) measurements showed that the P(MAA-g-EG) microparticles induced a Ca2+ concentration-dependent lowering in TEER values. The reduction effect in CM- media was greater than that in CM+ media (17 +/- 2% reduction in CM+ and 45 +/- 3% reduction in CM-, respectively). Insulin transport in the presence of the preswollen P(MAA-g-EG) microparticles was also strongly depended on the Ca2+ concentration in the medium. The respective estimated permeability for insulin alone and the insulin with hydrogels in CM+ were 0.77 and 1.16 x 10(-8) cm/s, whereas those in CM- were 1.18 and 24.78 x 10(-8) cm/s. The results demonstrate that the P(MAA-g-EG) hydrogel microparticles could be used as a cytocompatible carrier possessing the transport-enhancing effect of insulin on the intestinal epithelial cells.


Hypermutability in carcinogenesis.
The presence of numerous chromosomal changes and point mutations in tumors is well established. At least some of these changes play a role in the development of the tumors. It has been suggested that the number of these genetic changes requires that tumorigenesis involves an increase in mutation rate. However, the presence of numerous changes can also be accounted for by efficient selection. What is required to settle the issue is some measure of nonselected mutations in tumors. In order to determine whether the tumor suppressor TP53 (coding for the protein p53) is hypermutable at some stage of carcinogenesis, the frequency of silent and multiple mutations in this gene has been examined. Silent mutations make up approximately 3% of the total recorded but constitute 9.5% of the mutations found in tumors with multiple mutations. Multiple closely linked mutations are also observed. Such multiple mutations suggest the operation of an error-prone replication process in a subclass of cells. The published data indicate that TP53 is hypermutable at some stage of tumor development. It is not yet clear whether TP53 is unique or whether other genes display a similar pattern of silent and multiple mutations.


Over-expression of human cystatin C in pterygium versus healthy conjunctiva.
A prospective, non-randomised, transversal and comparative study, carried out in INOVA Vision Institute and Autonomous University of Aguascalientes. Pterygium is an important illness that affects 22% people from tropic and equatorial zones. Is an inflammatory process caused by UV rays, and it has a behavior similar to a neoplasm. For this study was taken into consideration 191 samples from the INOVA Vision Institute, Aguascalientes, Mexico. Include 73 pterygia samples, which were obtained during resection under sterile conditions. 44 normal conjunctiva samples were obtained from the same patients when harvesting the conjunctival autograft, or from other patients undergoing extracapsular cataract extraction from the superior bulbar region. Tears from patients with pterygium (n = 50) and normal volunteers (n = 24) were obtained using a calibrated glass micro capillary tube. The surgical conjunctiva and pterygia samples were subjected to reverse-transcription polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. Tears were analyzed by enzyme-linked immunosorbent assays. This was a prospective, non-randomised study involving 191 biological samples taken from patients with pterygium and normal volunteers, whom were operated under local anaesthesia by either complete resection of the lesion with primary closure, or resection with conjunctival autograft. Tissue samples were fixed in 10% formaldehyde. Sections were routinely stained with hematoxylin and eosin. HCC expression was evaluated by reverse-transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and by western blotting. All tears samples were analyzed by enzyme-linked immunosorbent assays (ELISA). Expression levels and distribution patterns of HCC in normal conjunctiva and pterygium. Higher levels of HCC mRNAs and proteins were detected in pterygium compared with a normal conjunctiva. Immunohistochemistry revealed that HCC was localized in the apical cells of the epithelium in the normal conjunctiva. In contrast, HCC was detected in all extension of epithelial tissue, from apical to basal cells in pterygia. The concentration of HCC protein in tears was higher in patients with pterygium versus controls. HCC may play an important role in protecting normal conjunctiva, and regulating inflammatory conditions of the anterior ocular surface.


[Serum cathepsin A activity in pregnant, parturient and puerperal patients].
Cathepsin A activity has been determinal in sera of nonpregnant, pregnant (1st, 2nd and 3rd trimesto), puerperal (first, third and fifth day post partum) and parturient women in second stage (retroplacental blood and blood from umbilical cord) by means of N-Cbz-L-glutamyl-L-tyrosin after incubation with 37 degrees C and pH 5.5. There was an increasing cathepsin A activity with the duration of pregnancy, during labour and in the first puerperal days. Maximum of activity of cathepsin A has been determined in serum of retroplacental blood.


Emergency Palliative Care: Early Assessment of an Older Adult With a Fall and Hip Fracture.
In this segment of the emergency department (ED) palliative care case series, we present a patient who arrives to the ED after a fall resulting in a hip fracture. He is also found to have hypernatremia and an acute kidney injury and develops delirium while in the ED awaiting an inpatient bed. The ED-based integrated geriatric palliative care program is consulted and performs a multidimensional assessment. The geriatric palliative care clinician facilitates discussion with his daughter about surgical intervention based on the patient's goals and values, diagnoses delirium, and worsening depression, creates a plan for delirium and pain management, and accelerates postdischarge planning.


Specific isolation of 3'-terminal exons of human genes by exon trapping.
Exon trapping is a method to functionally clone expressed sequences from genomic DNA. We have previously developed the vector system pETV-SD2, which contains only a splice donor site (SD) followed by a LacZ gene, allowing trapping of internal exons of human genes by blue-white selection. We now describe the adaptation of the same system for the efficient trapping of 3'-terminal exons, by using different RT-PCR primers in a 3' RACE reaction. The addition of a T7 promoter to the RT-PCR products derived from pETV-SD2 allows their amplification in an isothermic amplification reaction called NASBA (nucleic acid sequence-based amplification reaction) and results in a strong signal from amplified 3' exons in addition to a great reduction of non-specific background. As a test for the system, 3' exon trapping was performed using a cosmid containing the alpha-globin gene cluster on chromosome 16. The 3'-terminal exons of the human alpha 1-, zeta 2-, and theta-globin genes were trapped, as well as a correctly spliced and polyadenylated sequence in the 3' flanking region of the alpha 1-globin gene. This exon appears to belong to a previously unidentified gene within the alpha-globin gene cluster. This 3' exon trapping strategy should facilitate the cloning of genes from large genomic regions.


One-electron reduction of kinetically stabilized dipnictenes: synthesis of dipnictene anion radicals.
The redox behavior of kinetically stabilized dipnictenes, BbtE=EBbt [E = P, Sb, Bi; Bbt = 2,6-bis[bis(trimethylsilyl)methyl]-4-[tris(trimethylsilyl)methyl]phenyl], was systematically disclosed using cyclic voltammetry and theoretical calculations. It was found that they showed reversible one-electron redox couples in the reduction region. The anion radical species of the Bbt-substituted diphosphene and distibene were successfully synthesized by the reduction of the corresponding neutral dipnictenes (BbtP=PBbt and BbtSb=SbBbt). Their structures were reasonably characterized by ESR, UV-vis, and Raman spectroscopy, and the distibene anion radical was structurally characterized by X-ray crystallographic analysis.


Structural and Functional Brain Changes in Hemodialysis Patients with End-Stage Renal Disease: DTI Analysis Results and ALFF Analysis Results.
The current study aimed to depict intrinsic structural changes and the spontaneous brain activity patterns in voxel level in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) by using diffusion-tensor imaging and resting-state functional magnetic resonance (MR) imaging with an amplitude of low-frequency fluctuations (ALFF) algorithm and their clinical relevance. In the study, the diffusion-tensor imaging and resting-state functional MR imaging were performed in forty-two hemodialysis patients with ESRD and 42 healthy control subjects. Neuropsychological and laboratory tests were performed in all subjects. ALFF, fraction anisotropy (FA), and mean diffusivity (MD) values were compared between the two groups. Correlations between ALFF, FA or MD values, and clinical markers were analyzed. We found that ESRD patients exhibited significantly lower ALFF values in multiple areas, including medial frontal gyrus, limbic lobe, superior frontal gyrus, bilateral lingual gyri, occipital lobe, parahippocampal gyrus, precuneus, while increased ALFF values in medial frontal gyrus than healthy controls. FA values were decreased in medial frontal gyrus, parietal lobe, and left precuneus regions in the ESRD group compared with controls. Importantly, FA for the frontal and parietal lobes was negatively associated with the dialysis duration of ESRD patients, ALFF z-scores for the medial prefrontal cortex (MPFC) were positively correlated with the dialysis duration of ESRD patients and Serum calcium of ESRD patients negatively correlated with FA values in the frontal and parietal lobes (p<0.05). Our study revealed that both impaired brain structure and function in ESRD patients with routine hemodialysis distributed mainly in the parietal, temporal, and frontal lobes. ESRD patients have cognitive impairment and declined memory ability. Serum calcium and dialysis duration might be associated with the impairment of brain structure and function in patients with ESRD.


ACG clinical guideline: diagnosis and management of achalasia.
Achalasia is a primary motor disorder of the esophagus characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. This results in patients' complaints of dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. Endoscopic finding of retained saliva with puckered gastroesophageal junction or barium swallow showing dilated esophagus with birds beaking in a symptomatic patient should prompt appropriate diagnostic and therapeutic strategies. In this ACG guideline the authors present an evidence-based approach in patients with achalasia based on a comprehensive review of the pertinent evidence and examination of relevant published data.


[Professor Dong Gui-rong's experiences in treatment of child cerebral palsy].
According to the characteristics of the etiology and pathogenesis of child cerebral palsy, on the basis of "regulating the mind in treatment of all kinds of diseases" and "regulating the functions of five zang organs with back-shu points", Professor DONG Gui-rong applied the penetrating needling technique on the scalp points and acupuncture at back-shu points of five zang organs in the treatment of child cerebral palsy. The valuable clinical experiences have been summarized as "regulating the mind with scalp needling technique, benefiting the brain and opening the orifice", "regulating five zang organs with back-shu points" and "integration of acupuncture and rehabilitation, and function reconstruction". Two effective cases were introduced.


PEGylated dextran as long-circulating pharmaceutical carrier.
Dextran-polyethylene glycol (PEG) conjugates were synthesized by activating dextran hydroxy groups with carbonyldiimidazole, introducing amino groups by attaching ethylenediamine, and reacting amino groups with a succinimidyl-activated derivative of PEG. Conjugates with an average of 12 and 21 PEG (5 kDa) residues per single dextran (73 kDa) molecule were prepared. These conjugates have circulation half-lives of 5.3 h and 7.0 h, respectively, compared to 4.0 h for non-PEGylated dextran. The modification of dextran with PEG inhibits the uptake of polymer by the major organ of the reticuloendothelial system, the liver. Dextran-PEG conjugates may represent a convenient platform for long-circulating pharmaceutical preparations.


Role of protein kinase C in ischemic "conditioning": from first evidence to current perspectives.
Since the discovery of ischemic preconditioning (IPC) 26 years ago, numerous studies attempted to determine the mechanism of this powerful form of cardioprotection. One of the first proposed pathways of IPC suggested that the preconditioning stimulus activated phospholipase C via G-protein, and diacylglycerol released from phospholipid moieties activated protein kinase C (PKC) by translocating it from the cytosol to the sarcolemmal membranes. The major protective isoform of PKC was found to be the PKC-∈. Despite some contradictions and controversies, today even the most skeptical opponents acknowledge that PKC plays a significant role in the mechanism of IPC. During recent years, both the role and the place of PKC-∈ in the mechanism of IPC have been revised. The current review presents the evolution of the "PKC theory" and summarizes the most recent data regarding the role of PKC in IPC. In addition to classical IPC, PKC appears to play a role in the mechanisms of newer conditioning protocols, that is, remote IPC and ischemic postconditioning.


Atomic force microscopy under controlled conditions reveals structure of C-terminal region of α-synuclein in amyloid fibrils.
Atomic force microscopy (AFM) is widely used to measure morphological and mechanical properties of biological materials at the nanoscale. AFM is able to visualize and measure these properties in different environmental conditions. However, these conditions can influence the results considerably, rendering their interpretation a matter of some subtlety. We demonstrate this by imaging ~10 nm diameter α-synuclein amyloid fibrils, focusing specifically on the structure of the C-terminal part of the protein monomers incorporated into fibrils. Despite these influences leading to variations in fibril heights, we have shown that by maintaining careful control of AFM settings we can quantitatively compare the morphological parameters of fibrils imaged in air or in buffer conditions. From this comparison we were able to deduce the semiflexible character of this C-terminal region. Fibril height differences measured in air and liquid indicate that the C-terminal region collapses onto the fibril core upon drying. The fibril heights decrease upon increasing ion concentration in solution, suggesting that the C-terminal tails collapse into more compact structures as a result of charge screening. Finally, PeakForce QNM measurements show an apparent heterogeneity of C-terminal packing along the fibril length.


VISUALIZING MULTIVARIATE SELECTION.
Recent developments in quantitative-genetic theory have shown that natural selection can be viewed as the multivariate relationship between fitness and phenotype. This relationship can be described by a multidimensional surface depicting fitness as a function of phenotypic traits. We examine the connection between this surface and the coefficients of phenotypic selection that can be estimated by multiple regression and show how the interpretation of multivariate selection can be facilitated through the use of the method of canonical analysis. The results from this analysis can be used to visualize the surface implied by a set of selection coefficients. Such a visualization provides a compact summary of selection coefficients, can aid in the comparison of selection surfaces, and can help generate testable hypotheses as to the adaptive significance of the traits under study. Further, we discuss traditional definitions of directional, stabilizing, and disruptive selection and conclude that selection may be more usefully classified into two general modes, directional and nonlinear selection, with stabilizing and disruptive selection as special cases of nonlinear selection.


Plasma vasopressin, an etiologic factor of motion sickness in rat and human?
Arginine vasopressin (AVP) is considered as an etiologic hormone in motion sickness. However, the possible role of plasma AVP in motion sickness is still controversial. A number of studies have found a gender difference in susceptibility to motion sickness in humans and experimental animals, with female subjects being more susceptible. However, the existence of a gender difference in the AVP response to motion sickness is not known. This study was designed to verify the assumption that plasma vasopressin plays a role in motion sickness. Changes in plasma vasopressin were observed after motion sickness-inducing rotatory stimuli in both sexes in human subjects and rats receiving or not anti-motion-sickness treatments. Plasma vasopressin levels in motion sickness rats exhibited a decrease after rotation in female, but not in male rats. The vasopressin content of the pituitary increased in both sexes. Plasma vasopressin in rats of both sexes tended to increase after a 15-day adaptive training of rotation, but pituitary vasopressin content was not affected under this condition. In contrast, in human subjects, plasma vasopressin levels increased after rotation in all males, but not in females. When anti-motion-sickness drugs (domperidone 10 mg + flunarizine 5 mg) were administered, plasma vasopressin levels were elevated in both females and males. It is concluded that plasma vasopressin increases after motion sickness-induced stimulation provided subjects have become trained to motion sickness. These results do not support an etiologic role of plasma vasopressin in the genesis of motion sickness.


Increased prevalence of MEFV exon 10 variants in Japanese patients with adult-onset Still's disease.
Autoinflammatory diseases include a large spectrum of monogenic diseases, e.g. familial Mediterranean fever (FMF), as well as complex genetic trait diseases, e.g. adult-onset Still's disease (AOSD). In populations where FMF is common, an increased MEFV mutation rate is found in patients with rheumatic diseases. The aim of this study was to examine MEFV mutations in Japanese patients with AOSD. Genomic DNA was isolated from 49 AOSD patients and 105 healthy controls, and exons 1, 2, 3 and 10 of the MEFV gene genotyped by direct sequencing. MEFV mutation frequencies in AOSD patients were compared with controls. We found no significant difference in overall allele frequencies of MEFV variants between AOSD patients and controls. However, MEFV exon 10 variants (M694I and G632S) were significantly higher in AOSD patients than controls (6.1 versus 0%). In addition, there was no significant difference between MEFV variant carriers and non-carriers with clinical manifestations, but the monocyclic clinical course of the AOSD disease phenotype was observed less frequently in patients without MEFV variants. AOSD patients had significantly higher frequencies of MEFV exon 10 mutations, suggesting that low-frequency variants of MEFV gene may be one of the susceptibility factors of AOSD.


No association between ACE I/D polymorphism and cardiovascular hemodynamics during exercise in young women.
The ACE I/D polymorphism has been shown to interact with habitual physical activity levels in postmenopausal women to associate with submaximal and with maximal exercise hemodynamics. This investigation was designed to assess the potential relationships between ACE genotype and oxygen consumption (VO2), cardiac output (Q), stroke volume (SV), heart rate (HR), blood pressure (BP), total peripheral resistance (TPR), and arteriovenous oxygen difference ([a-v]O2 diff) during submaximal and maximal exercise in young sedentary and endurance-trained women. Seventy-seven 18-35-yr-old women underwent a maximal exercise test and a number of cardiac output tests on a treadmill using the acetylene rebreathing technique. ACE genotype was not significantly associated with VO2max (II 41.4+/-1.2, ID 39.8+/-0.9, DD 39.8+/-1.1 ml/kg/min, p=ns) or maximal HR (II 191+/-2, ID 191+/-1, DD 193+/-2 bpm, p=ns). In addition, systolic and diastolic BP, (a-v)O2 diff, TPR, SV, and Q during maximal exercise were not significantly associated with ACE genotype. During submaximal exercise, SBP, Q, SV, HR, TPR, and (a-v)O2 diff were not significantly associated with ACE genotype. However, the association between diastolic BP during submaximal exercise and ACE genotype approached significance (p=0.08). In addition, there were no statistically significant interactions between ACE genotype and habitual physical activity (PA) levels for any of the submaximal or the maximal exercise hemodynamic variables. We conclude that the ACE I/D polymorphism was not associated, independently or interacting with habitual PA levels, submaximal, or maximal cardiovascular hemodynamics in young women.


Developing an orthopaedic outcomes program.
Over the past several years there has been an increased effort to document outcomes, especially in the area of orthopaedics. Outcomes research is important because it can quantitatively and qualitatively demonstrate changes in a patient's condition, provide validation of clinical procedures, and impact upon patient satisfaction. Outcomes research is similar to traditional research in that it looks at a group of patients or a patient care process and focuses on the outcomes of treatment or care. An outcomes program is the infrastructure necessary to collect and analyze outcomes data within a scientifically sound framework. The steps of developing an outcomes program include identifying key players in the process, identifying the diagnoses and procedures to track in the program, deciding outcomes to measure, identifying instruments to be used, developing the data collection process, establishing a timeline, and developing the data entry and analysis process. A successful outcomes program is the product of a collaborative team effort. With knowledge of the necessary components and effective teamwork, it is relatively simple to establish a successful outcomes program.


Effect of position on pulmonary mechanics in healthy preterm newborn infants.
Preterm infants are often placed in the supine position to facilitate care and observation. Prone positioning may positively affect later neurodevelopmental outcome, but it may also affect pulmonary function. Using a computerized system, we examined the effect of positioning on pulmonary mechanics in spontaneously breathing healthy preterm infants. Eleven infants with a mean birth weight (+/- SD) of 1523 +/- 171 gm and a mean gestational age (+/- SD) of 31.7 +/- 1.5 weeks were studied during the first 2 weeks of life. Pulmonary mechanic measurements were obtained in both supine and prone positions by mask pneumotachography and esophageal balloon technique. Respiratory rate and oxygen saturation were unaffected by positioning. There was a statistically, but not clinically, significant increase in heart rate in the prone position. However, there were no significant differences in tidal volume, minute ventilation, pulmonary resistance, or dynamic compliance between positions. The contribution of intrasubject variability of serial measurements was assessed in a separate group of four infants studied three times in the same position. There was no significant difference in respiratory rate, tidal volume, dynamic compliance per kilogram, or total pulmonary resistance in the same infant when studied in the same position over time (p > or = 0.24). The maximum variability (95% confidence limit) was 25.5% for tidal volume, 21% for dynamic compliance, and 44.3% for resistance. Because prone positioning did not adversely affect pulmonary mechanics or oxygen saturation in these healthy preterm infants, we suggest that prone position be used to facilitate the developmental needs of these infants.


Power Budget of a Skull Unit in a Fully-Implantable Brain-Computer Interface: Bio-Heat Model.
The aim of this study is to estimate the maximum power consumption that guarantees the thermal safety of a skull unit (SU). The SU is part of a fully-implantable bi-directional brain computer-interface (BD-BCI) system that aims to restore walking and leg sensation to those with spinal cord injury (SCI). To estimate the SU power budget, we created a bio-heat model using the finite element method (FEM) implemented in COMSOL. To ensure that our predictions were robust against the natural variation of the model's parameters, we also performed a sensitivity analysis. Based on our simulations, we estimated that the SU can nominally consume up to 70 mW of power without raising the surrounding tissues' temperature above the thermal safety threshold of 1°C. When considering the natural variation of the model's parameters, we estimated that the power budget could range between 47 and 81 mW. This power budget should be sufficient to power the basic operations of the SU, including amplification, serialization and A/D conversion of the neural signals, as well as control of cortical stimulation. Determining the power budget is an important specification for the design of the SU and, in turn, the design of a fully-implantable BD-BCI system.


Differential effects of surgical suture materials in 1,2-dimethylhydrazine-induced rat intestinal neoplasia.
The incidence, distribution, size, and histopathology of rat small and large bowel tumors induced by sequential administration of 1,2-dimethylhydrazine followed by cecal placement of one of six differing types of suture materials were systematically examined. In addition, measurements of beta-glucuronidase activities in large bowel contents followed by fecal trace metal determinations were done. The results indicate that specific slowly absorbed and nonabsorbable suture materials in the absence of a surgical anastomosis promote tumor induction locally in the rat cecum. In addition, cecal suture material composed of multifilament stainless steel wire enhanced tumor development at a "downstream" site in the distal colon, paralleling increased fecal beta-glucuronidase activities at this site and implicating a possible luminally mediated mechanism for colon tumor development in this animal model.


The effect of phototherapy on renal blood flow velocity in preterm infants.
Mean renal blood flow velocity (RBFV) was studied with two-dimensional/ pulsed Doppler ultrasound and relative renal vascular resistance (RVR) was calculated before, during, and after phototherapy treatment in 30 preterm infants (gestational age < or = 32 weeks) who were treated for a minimum of 12 h with phototherapy for nonhemolytic hyperbilirubinemia. RBFV decreased, whereas RVR increased significantly after the initiation of phototherapy. In 'healthy' (nonventilated) infants RBFV and RVR returned to baseline values after discontinuation of phototherapy. Whereas in 'unhealthy' (ventilated) infants, RBFV and RVR did not return to baseline values after discontinuation of phototherapy. In 16 infants (> 50% of the cases) the ductus arteriosus reopened during phototherapy.


The cultural dialogue on the domestic dimension of care to immigrant caregivers in Spain.
to determine how the immigration phenomenon influences the response to informal care in the domestic level through the caregiver activity, and to analyze the cultural dialogue established in the residential area of Murcia (Spain). This is an ethnographic study, conducted in 26 informal immigrant caregivers. As data collection instruments, semi-structured interviews and participant observation were employed. MAXQDA-2 assisted content analysis was also applied. the immigrant caregiver is the main consumer of traditional medicines, extending these health practices to her home group. A cultural dialogue is established on informal care, characterized by interculturalism and mutual adaptation. cultural hybridization was identified for informal caregivers, immigrants and cultural integration: new health care practices and cultural behaviors in informal systems. There is a transformation in the roles of family members attended in domestic environments, increasing quality of life and self care. They represent an alternative to medicalization, promoting self-management of health.


Laparoscopic Duhamel pullthrough procedure for Hirschsprung's disease in childhood.
Advances in instrumentation and technique now make laparoscopic correction of some congenital anomalies possible. We report on a 2-year-old boy with biopsy-proven Hirschsprung's disease successfully treated by a laparoscopic Duhamel pullthrough procedure. The technique and its potential role in the treatment of Hirschsprung's disease are described.


Prophylactic mastectomy--evaluation and treatment of high risk patients.
Prophylactic mastectomy is an aggressive strategy for breast cancer risk reduction. The indications and efficiency of this procedures are not yet clearly defined. Randomized, prospective studies, comparing different surgical procedures with other modalities of breast cancer risk reduction are lacking. The report evaluates the existing controversy, based on Medline search in the following sequence: risk factors, possibilities of risk reduction, effectiveness of risk reduction, technical considerations and recommendations. Patient selection is difficult and needs an interdisciplinary approach. The women have to be well informed about all treatment alternatives and various reconstructive procedures. An appropriate risk reduction strategy should be selected individually for each patient. Up to now, there exist only recommendations from different institutions but no definitive guidelines.


A stereotaxic atlas of the brain of the cynomolgus monkey (Macaca fascicularis).
Outline drawings of representative frontal sections of the Macaca fascicularis brain are presented in stereotaxic coordinates. The levels extend from the rostral tip of the neostriatum to the posterior end of the deep cerebellar nuclei. The illustrations are based on the photographs of unstained frozen sections of three formalin-fixed brains in which stainless steel needles were inserted to mark the horizontal zero and several anteroposterior positions. The sections were not stained in order to prevent shrinkage. Stereotaxic measurements were taken in situ of the highest points on the cortical surface, the position of the central and lunate sulcus, and of certain landmarks at the base of the cranium in a large number of monkeys. These data along with brain dimensions and the weight of animals are displayed in tables to indicate individual variations and to aid investigators in determining the best stereotaxic coordinates for a given structure. It is recommended that the cortical point of entry for an electrode or needle be routinely noted and be compared to the parameters in the atlas to compensate for deviations in the horizontal plane.


Morbidity and mortality of the Confederate generals during the American Civil War.
During the American Civil War (1861-1865), 426 men were commissioned generals by Jefferson Davis and the Confederate Congress. Eighty (19%) died of battle wounds (versus 8% in the Union army) and 3 per cent died of disease. During the war, 211 (49%) were wounded; of these, each was wounded a mean 1.9 times. When noncombatants are excluded, 52 per cent sustained wounds. Of those who served in five or more major engagements, 62 per cent were wounded; of those who fought in more than 10, 71 per cent sustained wounds. Sixty-five per cent of battlefield deaths were immediate and 85 per cent were from gunshot wounds. Mortality did not vary by state of birth, age group, rank (brigadier, major, lieutenant, full), formal military education, or prewar profession. Professional soldiers fared no better or worse than prewar civilians appointed to the rank of general. Of those who survived the war, mean age at death was 68.0 years.


Influence of Relativistic Effects on Assembled Structures of V-Shaped Bispyridine Molecules on M(111) Surfaces Where M = Cu, Ag, Au.
The self-assembly behavior of a V-shaped bispyridine, 1,3-bi(4-pyridyl)benzene (BPyB), was studied by scanning tunneling microscopy on the (111) surfaces of Cu, Ag, and Au. BPyB molecules coordinately bonded with active Cu adatoms on Cu(111) in the form of complete polygonal rings at low coverages. On Ag(111), BPyB molecules aggregated into two-dimensional islands by relatively weak intermolecular hydrogen bonds. The coexistence of hydrogen bonds and coordination interaction was observed on the BPyB-covered Au(111) substrate. Density functional theory calculations of the metal-molecule binding energy and Monte Carlo simulations were performed to help understand the forming mechanism of molecular superstructures on the surfaces. In particular, the comprehensive orbital composition analysis interprets the observed metal-organic complexes and reveals the importance of relativistic effects for the extraordinary activity of gold adatoms. The relativistic effects cause the energy stability of the Au 6s atomic orbital and decrease the energy separation between the Au 6s and 5d orbitals. The enhanced sd hybridization strengthens the N-Au-N bond in BPyB-Au-BPyB complexes.


P076 The Role of Dual Biologic Therapy in Inflammatory Bowel Disease.
As the prevalence of complex inflammatory bowel disease and extraintestinal manifestations continue to rise, more patients are requiring complex treatment regimens. In some cases, patients may require more than one biologic agent to target different areas in the inflammatory cascade. Although a body of data is emerging, there is currently no consensus on patient and agent selection for dual therapy or adverse outcomes of therapy. A retrospective chart review of all patients receiving dual biologic therapy for IBD at a single tertiary care center was conducted. This was exempted by the IRB. Data regarding the patient and disease course, indication for dual biologic use, other concurrent therapies, infections and any adverse events was collected from the EMR. Ten patients (9 Crohn's Disease, 1 Ulcerative Colitis) were identified as receiving dual biologic therapy. The most common combination therapy was ustekinumab with vedolizumab (5) or an anti-TNF (4); one patient was receiving adalimumab with vedolizumab. Nine patients were also on an immunomodulator (6 methotrexate, 2 6-mercaptopurine, 1 azathioprine) and three required steroids in addition to dual biologic therapy. The majority (8) of the patients were started on dual biologic therapy due to refractory GI symptoms, the others were due to extraintestinal manifestations (EIMs) with psoriatic arthritis and ankylosing spondylitis. Nine patients had significant symptomatic improvement on dual biologic regimen and all six patients with follow-up endoscopy demonstrated improvement. Two patients developed infectious diarrhea (C.difficile and e. coli), no other significant infections were noted. No patients were found to have malignancy or any other adverse effects of treatment during the reviewed period. Dual biologic therapy can be used with improvement in symptomatic and endoscopic findings of IBD. The combination use of two biologic agents does not appear to have additional infectious risk compared to single agent and no other adverse events were described. Longer follow-up and larger patient populations are needed to verify the combination of biologic mechanisms for therapy of refractory IBD and EIMs.


Calcium oxalate retention in subjects with crystalluria.
Calcium oxalate retention was studied in non-stone-forming volunteers. All subjects were placed on a constant diet for 5 days. After the oral administration of 10 microCi of [14C]-oxalic acid, the pattern of urinary oxalate excretion was followed for 48 h. Each subject was then given 10 microCi of [14C]-oxalic acid mixed with sufficient sodium oxalate (7.5 mg/kg body weight) to induce calcium oxalate crystalluria. Urinary oxalate excretion was then recorded for 48 h. After the administration of labeled oxalic acid (without additional sodium oxalate), 76.6 +/- 5.9% of the total recovered dose was excreted by 4 h. When the labeled oxalic acid was mixed with a sodium oxalate load, 62.4 +/- 8.8% was excreted by 4 h (p less than 0.01). Induction of calcium oxalate crystalluria results in the retention of oxalate in the kidney. The degree of retention varies among individuals. Differences in particle retention may help explain the differences between stone formers and non-stone formers.


Synthesis and crystal structure of an open capsule-type octanuclear heterometallic sulfide cluster with a linked incomplete double cubane framework without an intramolecular inversion center.
An open capsule-type octanuclear heterometallic sulfide cluster without an intramolecular inversion center [Ru(eta(6)-C(6)Me(6)){P(OMe)(3)}{MoO(mu(3)-S)(3)}(CuI)(2)](2) (5) has been synthesized for the first time by stepwise connection of three mononuclear building blocks, i.e., (i) [RuCl(2)(eta(6)-C(6)Me(6)){P(OMe)(3)}] (1a) as an octahedral terminal building block to control the direction of cluster expansion, (ii) [MoOS(3)](2)(-) as a tetrahedral polydentate building block owing to the strong coordination ability of the S atoms, and (iii) a CuI building block to form a trigonal planar (mu-S)(2)CuI unit or to form a linkage unit of two incomplete cubane-type octanuclear frameworks. The stepwise connection was made in the following order: [RuCl(2)(eta(6)-C(6)Me(6)){P(OMe)(3)}] (1a, mononuclear) --> [Ru(eta(6)-C(6)Me(6)){P(OMe)(3)}{MoOS(mu(2)-S)(2)}] (2a, dinuclear) --> [Ru(eta(6)-C(6)Me(6)){P(OMe)(3)}{MoO(mu(2)-S)(2)(mu(3)-S)}CuI] (3a, butterfly-type trinuclear) --> [Ru(eta(6)-C(6)Me(6)){P(OMe)(3)}{MoO(mu(3)-S)(3)}(CuI)(2)](2) (5). When P(OMe)(3) was replaced by P(OEt)(3), which is more bulky than P(OMe)(3), in the starting ruthenium building block [RuCl(2)(eta(6)-C(6)Me(6)){P(OEt)(3)}] (1b, mononuclear), only the tetranuclear incomplete single cubane cluster [Ru(eta(6)-C(6)Me(6)){P(OEt)(3)}{MoO(mu(3)-S)(3)}(CuI)(2)] (6) was generated, owing to the steric effect of P(OEt)(3).


Adapting Effective mHealth Interventions to Improve Uptake and Adherence to HIV Pre-Exposure Prophylaxis Among Thai Young Men Who Have Sex With Men: Protocol for a Randomized Controlled Trial.
Young men who have sex with men (YMSM) are the fastest-growing HIV-positive population worldwide. Thailand has the highest adult HIV seroprevalence in Asia; over 25% of men having sex with men in Bangkok are HIV positive. Pre-exposure prophylaxis (PrEP) is an efficacious HIV prevention strategy recommended for all at-risk individuals. PrEP is highly effective when taken as prescribed, but PrEP utilization rate has been low, and adherence is often inadequate. We propose to develop and pilot a multicomponent, technology-based intervention to promote motivation to begin PrEP ("uptake") and sustained adherence to PrEP among HIV-negative Thai YMSM. We will adapt an existing 2-session technology-delivered, motivational interviewing-based intervention to focus on PrEP use in YMSM in Thailand. The resulting intervention is called the Motivational Enhancement System for PrEP Uptake and Adherence (MES-PrEP). We will also develop motivational text messaging (MTM) to send two-way motivational messages to promote PrEP use. The proposed study includes 3 phases. Phase 1 includes in-depth interviews with HIV-negative Thai YMSM and providers to explore barriers and facilitators of PrEP initiation and adherence, aiming to inform intervention content. Phase 2 consists of adapting and beta-testing MES-PrEP and MTM for functionality and feasibility using a youth advisory board of Thai YMSM. In Phase 3, we will conduct a pilot randomized controlled trial to evaluate the feasibility, acceptability, and preliminary efficacy of MES-PrEP and MTM to increase PrEP uptake and adherence among Thai YMSM. A total of 60 HIV-negative Thai YMSM who have not started PrEP and 60 YMSM who are on PrEP but not adherent to it will be randomized 2:1 to receive MES-PrEP and MTM (n=40) or standard PrEP counseling (n=20). The feasibility and acceptability of the intervention will be assessed through usage patterns and the System Usability Scale. The preliminary impact will be assessed by evaluating the proportion of PrEP initiation and level of adherence to PrEP. Participants will complete the assessments at baseline and at 1-, 3-, and 6-month postintervention. Biomarkers of adherence to PrEP and biomarkers of HIV and sexually transmitted infections will be collected. Recruitment for this study began in January 2022 for phase 1. Qualitative interviews were completed with 30 YMSM and 5 clinical providers in May 2022. Phase 3, the pilot feasibility and acceptability trial, began in July 2023. Upon project completion, we shall have developed a highly innovative mobile health intervention to support YMSM using PrEP, which will be ready for testing in a larger efficacy trial. This study addresses a critical problem (ie, high HIV incidence and low PrEP use) among Thai YMSM. We are developing 2 potentially synergistic technology-based, theory-driven interventions aimed at maximizing PrEP use. The proposed project has the potential to make significant contributions to advancing HIV prevention research and implementation science. ClinicalTrials.gov NCT05243030; https://clinicaltrials.gov/ct2/show/NCT05243030. DERR1-10.2196/46435.


Pattern formation in the ferrocyanide-iodate-sulfite reaction: the control of space scale separation.
We revisit the conditions for the development of reaction-diffusion patterns in the ferrocyanide-iodate-sulfite bistable and oscillatory reaction. This hydrogen ion autoactivated reaction is the only example known to produce sustained stationary lamellar patterns and a wealth of other spatio-temporal phenomena including self-replication and localized oscillatory domain of spots, due to repulsive front interactions and to a parity-breaking front bifurcation (nonequilibrium Ising-Bloch bifurcation). We show experimentally that the space scale separation necessary for the observation of stationary patterns is mediated by the presence of low mobility weak acid functional groups. The presence of such groups was overlooked in the original observations made with hydrolyzable polyacrylamide gels. This missing information made the original observations difficult to reproduce and frustrated further experimental exploitation of the fantastic potentialities of this system. Using one-side-fed spatial reactors filled with agarose gel, we can reproduce all the previous pattern observations, in particular the stationary labyrinthine patterns, by introducing, above a critical concentration, well controlled amounts of polyacrylate chains in the gel network. We use two different geometries of spatial reactors (annular and disk shapes) to provide complementary information on the actual three-dimensional character of spatial patterns. We also reinvestigate the role of other feed parameters and show that the system exhibits both a domain of spatial bistability and of large-amplitude pH oscillations associated in a typical cross-shape diagram. The experimental method presented here can be adapted to produce patterns in the large number of oscillatory and bistable reactions, since the iodate-sulfite-ferrocynide reaction is a prototype of these systems.


Delayed Subaponeurotic Fluid Collections: A Benign Cause of Scalp Swelling in Infancy.
Delayed subaponeurotic fluid collections (DSFCs) are a recently described cause of idiopathic scalp swelling in young infants. Associated with traumatic birth and the use of vacuum-assisted devices or fetal scalp electrodes, DSFCs can be differentiated from similar causes of neonatal scalp swelling based on characteristic history and physical examination findings. In this article, we highlight 2 cases of young infants presenting to a pediatric emergency department with large, fluctuant scalp swellings, which were appropriately diagnosed as DSFCs; clinical data on an additional eight cases are presented in table format. In cases of isolated DSFCs in otherwise well-appearing infants, further laboratory work, imaging, subspecialty consultation, and child abuse investigation is not necessary. Recommendations for the diagnosis and management of DSFCs presented reflect the clinical experience of the authors in conjunction with a review of the available medical literature on this topic.