Heterogeneity and the interpretation of treatment effect estimates from risk adjustment and instrumental variable methods.
To contrast the interpretations of treatment effect estimates using risk adjustment and instrumental variable (IV) estimation methods using observational data when the effects of treatment are heterogeneous across patients. We demonstrate these contrasts by examining the effect of breast conserving surgery plus irradiation (BCSI) relative to mastectomy on early stage breast cancer (ESBC) survival. We estimated discrete time survival models for 6185 ESBC patients in the 1989-1994 Iowa Cancer Registry via IV estimation using 2 distinct instruments (distance of the patient's residence from the nearest radiation center, and local area BCSI rate) and controlling for cancer stage, grade, and location; age; comorbidity; hospital access; payer; diagnosis year; and area poverty level. We then estimated comparable risk adjustment survival models using linear probability methods with robust standard errors. Risk adjustment models yielded average survival estimates similar to trial results. With favorable BCSI selection, these estimates represent an upper bound of the true effect for patients receiving BCSI. IV estimates showed a BCSI survival risk for patients whose surgery choices were affected by the instruments and these estimates varied with the instrument specification. When treatment benefits are heterogeneous across patients, treatment effect estimates from observational data can still be useful to policymakers, but they must be interpreted correctly. Risk adjustment methods yield estimates that can assess whether the patients who received treatment benefited from the treatment, but the direction of bias must be considered. In contrast, IV estimates can assess the effect of treatment rate changes, but characteristics of patients whose choices were affected by the instruments must be considered when making such inferences.


Colon necrosis in acute severe pancreatitis.
A 78 year-old woman was admitted for biliary acute pancreatitis (AP). Fluid and analgesia were initially administered. Her clinical course was poor with persisting abdominal pain, intestinal paresis and fever development. On her 7th admission day a contrast-enhanced computed tomography scan was performed where a huge necrotic peripancreatic collection was found with gastric compression .


Symptomatic gastrointestinal metastases from malignant melanoma.
Twenty-two patients with symptomatic metastases to the gastrointestinal tract from malignant melanoma who presented to the Roswell Park Memorial Institute during the past 12 years were reviewed. Sixteen of 22 patients underwent abdominal surgery and most received satisfactory palliation. Of the six patients who were considered unsuitable for surgery, two died from perforation of the small bowel. The group had a median survival of 2.2 months. Thirteen patients with symptomatic intestinal metastases had a median survival of 4.5 months following resection of the involved portion of the intestine. One of these patients remains well, and free of disease 15 months later, and two lived more than 33 months after the surgical procedures.


[Pulmonary hydatid cyst: unusual double apical location. About a case].
Hydatid cyst (KH) is still endemic in several areas of Morocco. Pulmonary involvement is a consequence of liver disease. Hydatid cyst is characterized by diverse anatomical and clinical presentations and by the possibility of multiple locations within the lung parenchyma, predominantly involving pulmonary bases. We report the case of Mr J. M, 54 years old, admitted with suspected pulmonary hydatid cyst based on chest pain lasting for six months and an episode of hydatidoptysis. Chest x-ray objectified a double apical location suggesting different stages of evolution for pulmonary hydatid cyst. The diagnosis was confirmed by thoracic CTscan and hydatid serology. Multiple pulmonary hydatid cyst is not rare in areas in which hydatid disease is highly endemic. Our study reports an unusual double apical location of hydatid cyst at various stages of evolution.


PROMISE. Beyond frontiers.
The concepts underlying the PROMISE initiative are described. This initiative to implement more humane healthcare is now developing from a local initiativein Cambridge to a global movement.


Endoscopic ultrasonography using a 15/20 MHz probe in a direct contact technique: evaluation and application in esophageal and gastric varices.
Endoscopic ultrasonography (EUS) has been recently developed as a new diagnostic technique for portal hypertension. However, its conventional water-filled balloon technique is not suitable for the evaluation of esophageal varices, because the vessel lumen is compressed by the inflated balloon. Particularly for small varices, the vessel tends to collapse and is difficult to display. A miniature ultrasonic probe for use via the forceps channel in EUS has been developed and is expected to overcome this difficulty. Here we report the efficacy of this new probe in patients with esophago-gastric varices. Instead of using a water-filled balloon for an acoustic window, we displayed the EUS findings from the new probe in direct contact with gastrointestinal wall by removing air from the lumen under vacuum. Both conventional endoscopy and the new EUS were performed on 3 patients with esophageal varices. The transforceps-channel ultrasonic probe visualized grade 1 varices in addition to the larger varices, confirming this technique to be a useful method for assessing of esophageal varices. Moreover, this method does not require a specially designed endoscope for EUS, rather it can be employed in combination with conventional endoscopy. We conclude that this new technique is a preferred diagnostic technique, and it should become more widely accepted for routine clinical applications.


The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study.
Evaluating measurement equivalence (also known as differential item functioning (DIF)) is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC) model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small.


Efficacy and Nontarget Effects of a Spinosad-Based Larvicide in Minnesota Vernal Pools and Cattail Marshes.
Larvicides that contain spinosad, a bacterial metabolite, are used to control mosquitoes in diverse aquatic habitats. These same habitats are home to other invertebrates, including Crustacea-fairy shrimp, isopods, and amphipods-and mollusks-fingernail clams and freshwater snails. A double-blind study evaluated the effects of Natular® G, a granular treatment containing spinosad, on spring Aedes spp. and nontarget invertebrates in vernal wetlands. Within 14 days after application, Natular G controlled larvae of spring Aedes by 53-84%, depending on species, but had no significant effects on numbers of fairy shrimp, fingernail clams, or freshwater snails. A second double-blind study evaluated effects on Coquillettidia perturbans and nontarget isopods and amphipods in cattail marshes. Treatment reduced emergence of Cq. perturbans by 25% but did not change numbers of isopods or amphipods. The 2 experiments indicate Natular G could be effective against spring Aedes in vernal wetlands, less so against Cq. perturbans in cattail marshes, and yet pose minimal risk to crustaceans and mollusks in either vernal wetlands or cattail marshes.


The calcium channel antagonists receptor from rabbit skeletal muscle. Reconstitution after purification and subunit characterization.
The Ca2+ channel antagonists receptor from rabbit skeletal muscle was purified to homogeneity. Following reconstitution into phosphatidylcholine vesicles, binding experiments with (+)[3H]PN 200-110, (-)[3H]D888 and d-cis-[3H]diltiazem demonstrated that receptor sites for the three most common Ca2+ channel markers copurified with binding stoichiometries close to 1:1:1. Sodium dodecyl sulfate gel analysis of the purified receptor showed that it is composed of only one protein of Mr 170,000 under non-reducing conditions and of two polypeptides of Mr 140,000 and 32,000 under disulfide-reducing conditions. Iodination of the protein of Mr 170,000 and immunoblots experiments with antisera directed against the different components demonstrated that the Ca2+ channel antagonists receptor is a complex of Mr 170,000 composed of a polypeptide chain of Mr 140,000 associated to one polypeptide chain of Mr 32,000 by disulfide bridges. One of the problems concerning this subunit structure of the putative Ca2+ channel was the presence of smaller polypeptide chains of Mr 29,000 and 25,000. Peptide mapping of these polypeptide chains and analysis of their cross-reactivity with sera directed against the proteins of Mr 170,000 and 32,000 demonstrated that they were degradative products of the Mr 32,000 component. Both the large (140 kDa) and the small (32 kDa) component of the putative Ca2+ channel are heavily glycosylated. At least 20-22% of their mass were removed by enzymatic deglycosylation. Finally the possibility that both the 140-kDa and 32-kDa components originate from a single polypeptide chain of Mr 170,000 which is cleaved by proteolysis upon purification is discussed.


Understanding circuit dynamics using the stomatogastric nervous system of lobsters and crabs.
Studies of the stomatogastric nervous systems of lobsters and crabs have led to numerous insights into the cellular and circuit mechanisms that generate rhythmic motor patterns. The small number of easily identifiable neurons allowed the establishment of connectivity diagrams among the neurons of the stomatogastric ganglion. We now know that (a) neuromodulatory substances reconfigure circuit dynamics by altering synaptic strength and voltage-dependent conductances and (b) individual neurons can switch among different functional circuits. Computational and experimental studies of single-neuron and network homeostatic regulation have provided insight into compensatory mechanisms that can underlie stable network performance. Many of the observations first made using the stomatogastric nervous system can be generalized to other invertebrate and vertebrate circuits.


Total laparoscopic aortomesenteric bypass.
We describe what we believe to be the first case of C-loop aortomesenteric total laparoscopic bypass. This bypass was combined with a total laparoscopic aortofemoral bypass. The approach to the superior mesenteric artery used a partial left medial visceral rotation after a left retrocolic dissection.


(Can) Not talk about it - Urinary incontinence from the point of view of stroke survivors: a qualitative study.
The current study intends to gain an in-depth understanding of stroke survivors' lived experience of urinary incontinence and its treatment in an inpatient rehabilitation clinic. A qualitative approach was chosen. Semi-structured individual interviews with ten stroke survivors suffering from urinary incontinence were conducted in an inpatient rehabilitation clinic and analysed using qualitative content analysis with an inductive approach. '(Can) not talk about it' was identified as the first main category. The affected persons do not talk about urinary incontinence because they are ashamed. At the same time, no one asks them about this issue. Psychological strain is so high that patients feel the need to talk about incontinence, but from their point of view, conversations with nurses - if they indeed occur - are superficial or nurses do not listen. Therefore, patients' needs and concerns are not properly considered. 'Trying to command incontinence' was also identified as a main category. Participants reported that they try to command incontinence and to develop their own strategies in order to hide urinary incontinence and prevent shameful situations. However, this proved mostly unsuccessful and resulted in resignation to their condition. It is important to raise awareness within the treatment team of urinary incontinence in stroke survivors. Team members should be able to communicate about urinary incontinence in an open and empathic way. Obviously, there is great potential for supporting stroke survivors in dealing with incontinence.


Hippocampal function during adolescence: a unique target of ethanol effects.
Behaviors mediated by the hippocampus have long been known to be sensitive to the acute, chronic, and prenatal effects of ethanol. It has recently become clear that hippocampal function is uniquely responsive to ethanol during periadolescent development, and that alcohol affects behavior and brain function differently in adolescents and adults. We have used behavioral techniques, as well as extracellular and whole-cell electrophysiological techniques, to assess the effects of acute and chronic ethanol exposure on hippocampal function during adolescence and adulthood. Our results are consistent with the view that the hippocampus is more sensitive to the acute effects of ethanol during adolescence and may be more susceptible to the neurotoxic effects of ethanol during this developmental period. Studies of this type have yielded valuable information for prevention, education, and public policy efforts related to underage drinking.


Comparative Analysis of Water Extracts from Roselle (Hibiscus sabdariffa L.) Plants and Callus Cells: Constituents, Effects on Human Skin Cells, and Transcriptome Profiles.
Roselle (Hibiscus sabdariffa L.) is a plant that has traditionally been used in various food and beverage products. Here, we investigated the potential of water extracts derived from Roselle leaves and callus cells for cosmetic and pharmaceutical purposes. We generated calluses from Roselle leaves and produced two different water extracts through heat extraction, which we named Hibiscus sabdariffa plant extract (HSPE) and Hibiscus sabdariffa callus extract (HSCE). HPLC analysis showed that the two extracts have different components, with nucleic acids and metabolites such as phenylalanine and tryptophan being the most common components in both extracts. In vitro assays demonstrated that HSCE has strong anti-melanogenic effects and functions for skin barrier and antioxidant activity. Transcriptome profiling of human skin cells treated with HSPE and HSCE showed significant differences, with HSPE having more effects on human skin cells. Up-regulated genes by HSPE function in angiogenesis, the oxidation-reduction process, and glycolysis, while up-regulated genes by HSCE encode ribosome proteins and IFI6, functioning in the healing of radiation-injured skin cells. Therefore, we suggest that the two extracts from Roselle should be applied differently for cosmetics and pharmaceutical purposes. Our findings demonstrate the potential of Roselle extracts as a natural source for skincare products.


LncRNA BANCR facilitates vascular smooth muscle cell proliferation and migration through JNK pathway.
Deregulated migration and proliferation of vascular smooth muscle cells (VSMCs) acts a crucial role in the pathogenesis of many cardiovascular diseases such as atherosclerosis, coronary heart disease and hypertension. Long noncoding RNAs (lncRNAs) play crucial functional roles in a lot of biological processes such as cell development, cell proliferation, differentiation and invasion. In our study, we demonstrated that the BANCR expression level was upregulated in the atherosclerotic plaques tissues compared to in the normal vessels tissues. TNF-α could emhance the VSMCs proliferation. The expression level of BANCR and p-JNK were upregulated and activated in the proliferating VSMCs. Overexpression of BANCR enhanced VSMCs proliferation and migration. Elevated expression of BANCR induced JNK activation, which can be decreased by the specific JNK inhibitor SP600125. We demonstrated that ectopic expression of BANCR increased the VSMCs proliferation and migration through activating JNK pathway. These data suggested that lncRNA BANCR acts a crucial role in the regulating VSMCs proliferation and migration partly by activating the JNK pathway.


Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. Stroke Unit Trialists' Collaboration.
To define the characteristics and determine the effectiveness of organised inpatient (stroke unit) care compared with conventional care in reducing death, dependency, and the requirement for long term institutional care after stroke. Systematic review of all randomised trials which compared organised inpatient stroke care with the contemporary conventional care. Specialist stroke unit interventions were defined as either a ward or team exclusively managing stroke (dedicated stroke unit) or a ward or team specialising in the management of disabling illnesses, which include stroke (mixed assessment/rehabilitation unit). Conventional care was usually provided in a general medical ward. 19 trials (of which three had two treatment arms). 12 trials randomised a total of 2060 patients to a dedicated stroke unit or a general medical ward, six trials (647 patients) compared a mixed assessment/rehabilitation unit with a general medical ward, and four trials (542 patients) compared a dedicated stroke unit with a mixed assessment/rehabilitation unit. Death, institutionalisation, and dependency. Organised inpatient (stroke unit) care, when compared with conventional care, was best characterised by coordinated multidisciplinary rehabilitation, programmes of education and training in stroke, and specialisation of medical and nursing staff. The stroke unit care was usually housed in a geographically discrete ward. Stroke unit care was associated with a long term (median one year follow up) reduction of death (odds ratio 0.83, 95% confidence interval 0.69 to 0.98; P < 0.05) and of the combined poor outcomes of death or dependency (0.69, 0.59 to 0.82; P < 0.0001) and death or institutionalisation (0.75, 0.65 to 0.87; P < 0.0001). Beneficial effects were independent of patients' age, sex, or stroke severity and of variations in stroke unit organisation. Length of stay in a hospital or institution was reduced by 8% (95% confidence interval 3% to 13%) compared with conventional care but there was considerable heterogeneity of results. Organised stroke unit care resulted in long term reductions in death, dependency, and the need for institutional care. The observed benefits were not restricted to any particular subgroup of patients or model of stroke unit care. No systematic increase in the use of resources (in terms of length of stay) was apparent.


ADULT syndrome: dental features of a very rare condition.
The Acro-Dermato-Ungual-Lacrimal-Tooth syndrome (ADULT syndrome) is one of the rarest ectodermal dysplasias and it is associated with several malformations involving especially the limbs. The most clinical features are the presence of ectrodactyly, syndactyly, hypermelanosis or multiple lentigines, onhycodysplasia, abnormalities in the lacrimal duct, recurrent conjuntivitis, photophobia, mammarian hypoplasia, hypotrichosis and frontal alopecia, hypohydrosis, cutaneous photosensitivity, nasal bridge prominence, exfoliative dermatitis and xerosis. The ectodermal dysfunction expresses itself with conoid teeth, enamel hypoplasia, dentinal dysplasia and especially hypodontia, with following functional and aesthetic defects. We report the case of an 11-year-old Caucasian girl affected by ADULT syndrome.


The Roles of Arabidopsis CDF2 in Transcriptional and Posttranscriptional Regulation of Primary MicroRNAs.
The precise regulation of microRNA (miRNA) transcription and processing is important for eukaryotic development. Plant miRNAs are first transcribed as stem-loop primary miRNAs (pri-miRNAs) by RNA polymerase II,then cleaved in the nucleus into mature miRNAs by Dicer-like 1 (DCL1). We identified a cycling DOF transcription factor, CDF2, which interacts with DCL1 and regulates the accumulation of a population of miRNAs. CDF2 binds directly to the promoters of some miRNAs and works as a transcription activator or repressor for these miRNA genes. CDF2 binds preferentially to the pri-miRNAs regulated by itself and affects DCL1-mediated processing of these pri-miRNAs. Genetically, CDF2 works in the same pathway as miR156 or miR172 to control flowering. We conclude that CDF2 regulates a group of pri-miRNAs at both the transcriptional and posttranscriptional levels to maintain proper levels of their mature miRNAs to control plant development.


[The frequency of peripheral blood CD14(+)HLA-DR(-/low) MDSCs is negatively correlated with the inflammation in patients with chronic hepatitis B].
To study the frequency of CD14⁺HLA-DR(-/low) myeloid-derived suppressor cells (MDSCs) in the peripheral blood of chronic hepatitis B (CHB) patients and the relationship with biochemical characteristics, viral load and liver pathology. The frequency of CD14⁺HLA-DR(-/low) MDSCs in the peripheral blood of 96 patients with CHB and 20 healthy control cases were detected by flow cytometry. Ultrasound-guided liver biopsies as well as HBV-related serological tests were performed in HBV-infected individuals to analyze the biochemical characteristics, viral load and pathology. The data were assessed using Spearman correlation analysis. The frequency of the peripheral blood CD14⁺HLA-DR(-/low) MDSCs in the 96 CHB cases was (6.03 ± 0.09)%, which was significantly higher than that of the 20 healthy control cases (1.87 ± 0.05)%. The group of HBeAg positive cases had a significantly higher frequency of the peripheral blood CD14⁺HLA-DR(-/low) MDSCs compared with the group of HBeAg negative cases and the healthy control group. The frequency of CD14⁺HLA-DR(-/low) MDSCs in the peripheral blood was negatively correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. There was no correlation between the frequency of peripheral blood CD14⁺HLA-DR(-/low) MDSCs and HBV load. The frequency of CD14⁺HLA-DR(-/low) MDSCs in the peripheral blood was negatively correlated with the liver inflammation grade, but not related with the fibrosis stage in patients with CHB. The frequency of CD14⁺HLA-DR(-/low) MDSCs is negatively correlated with the inflammation of CHB.


A conceptual model for defining and assessing land management units using a fuzzy modeling approach in GIS environment.
Appropriate land management decisions are important for current and future use of the land to ensure its sustainability. This requires that land management units (LMUs) be specified to enable the identification of specific parameters employed in decision making processes. This paper presents the development of a conceptual model, within geographic information systems (GIS), for defining and assessing LMUs from available biophysical information. The model consists of two main components (sub-models): land quality-based suitability analysis and soil erosion estimation. Using a fuzzy set methodology, the first sub-model was constructed to derive a land suitability index (LSI) for a cropping land utilization type. The LSI thus highlights the suitability grades of every pixel in the study area on a continuous basis. A submodel of soil erosion was established based on the Revised Universal Soil Loss Equation (RUSLE) utilising the same spatial data bases employed for structuring the LSI. Using a soil loss tolerance principle, a fuzzy membership function of average annual soil loss (called soil loss index, SLI) was established, leading to compatibility between LSI and SLI for data integration. LMUs were then derived from various combinations of LSI and SLI. The methodology developed shows the significance of the model for refining available land suitability evaluation systems, which take no account of expected land degradation (from erosion) due to a nominated land use. It also provides a valuable guideline for cost-effective GIS applications in the identification and assessment of homogeneous land units, using available spatial information sets, at a finer scale.


Unintentional doping in GaN.
The optimisation of GaN-based electronic and optoelectronic devices requires control over the doping of the material. However, device performance, particular for lateral transport electronic devices, is degraded by the presence of unintentional doping, which for heteroepitaxial GaN layers grown in the polar (0001) orientation is mainly confined to a layer adjacent to the GaN/substrate interface. The use of scanning capacitance microscopy (SCM) has demonstrated that this layer forms due to the high rate of incorporation of gas phase impurities, primarily oxygen, during the early stages of growth, when N-rich semi-polar facets are often present. The presence of such facets leads to additional unintentional doping when defect density reduction strategies involving a three-dimensional growth phase (such as epitaxial lateral overgrowth) are employed. Many semi-polar epitaxial layers, on the other hand, exhibit significant unintentional doping throughout their thickness, except when a three-dimensional growth phase is introduced to aid in defect density reduction resulting in the presence of (0001) and non-polar facets which incorporate less dopant. Non-polar epitaxial samples exhibit behaviour more similar to (0001)-oriented material, but oxygen diffusion from the sapphire substrate along prismatic stacking faults also locally affects the extent of the unintentional doping in this case.


Transcriptional response of Escherichia coli to external zinc.
Transcriptional response of Escherichia coli to extracellular zinc was studied using DNA microarray and S1 mapping assays. Addition of external zinc induced the expression of zinc exporter ZntA and inhibited the expression of zinc importer ZnuC. In the continuous presence of zinc, ZnuC repression took place at lower zinc concentrations than ZntA induction. The microarray assay indicated that the addition of excess external zinc induces the expression of many genes that are organized in the regulon for cysteine biosynthesis, implying that cysteine plays a role in transient trapping of free zinc for maintenance of zinc homeostasis. Besides the RpoE regulon, other genes were also induced by zinc, suggesting that periplasmic proteins denatured by zinc induce the genes for protein repair. The microarray data of the newly identified zinc-responsive promoters were confirmed by S1 mapping.


New insights into intestinal macrophages in necrotizing enterocolitis: the multi-functional role and promising therapeutic application.
Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease that profoundly affects preterm infants. Currently, the pathogenesis of NEC remains controversial, resulting in limited treatment strategies. The preterm infants are thought to be susceptible to gut inflammatory disorders because of their immature immune system. In early life, intestinal macrophages (IMφs), crucial components of innate immunity, demonstrate functional plasticity and diversity in intestinal development, resistance to pathogens, maintenance of the intestinal barrier, and regulation of gut microbiota. When the stimulations of environmental, dietary, and bacterial factors interrupt the homeostatic processes of IMφs, they will lead to intestinal disease, such as NEC. This review focuses on the IMφs related pathogenesis in NEC, discusses the multi-functional roles and relevant molecular mechanisms of IMφs in preterm infants, and explores promising therapeutic application for NEC.


Proteolytic inhibitors as alternative medicines to treat trypanosomatid-caused diseases: experience with calpain inhibitors.
The treatment for tropical neglected diseases, such as Chagas disease (CD) and leishmaniasis, is extremely limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures due to the parasite resistance. Consequently, there is urgency for the development of new therapeutic options to treat such diseases. Since peptidases from these parasites are responsible for crucial functions in their biology, these molecules have been explored as alternative targets. In this context, a myriad of proteolytic inhibitors has been developed against calcium-dependent cysteine-type peptidases, collectively called calpains, which are implicated in several human pathophysiological diseases. These molecules are highly expanded in the genome of trypanosomatids and they have been reported participating in several parasite biological processes. In the present perspective, we discuss our almost two decades of experience employing the calpain inhibitors as an interesting shortcut to a possible repurpose strategy to treat CD and leishmaniasis.


A high-performance "sweeper" for toxic cationic herbicides: an anionic metal-organic framework with a tetrapodal cage.
This communication reports a novel metal-organic framework exhibiting an excellent performance in adsorbing small toxic cationic herbicides, i.e. methyl viologen and diquat, with large adsorption capacities and ultratrace residue levels. To the best of our knowledge, this is the first example of high-performance MOFs trapping toxic cationic herbicides.


Mitral valve endothelial cells with osteogenic differentiation potential.
Cardiac valvular endothelium is unique in its ability to undergo endothelial-to-mesenchymal transformation, a differentiation process that is essential for valve development and has been proposed as mechanism for replenishing the interstitial cells of mature valves. We hypothesized that the valvular endothelium contains endothelial cells that are direct precursors to osteoblastic valvular interstitial cells (VICs). Clonal cell populations from ovine mitral valve leaflets were isolated by single cell plating. Mitral valvular endothelial and mesenchymal clones were tested for osteogenic, adipogenic, and chondrogenic differentiation, determined by the expression of lineage-specific markers. Mitral valvular endothelial clones showed a propensity for osteogenic, as well as chondrogenic differentiation that was comparable to a mitral valvular VIC clone and to bone marrow-derived mesenchymal stem cells. Osteogenic differentiation was not detected in nonvalvular endothelial cells. Regions of osteocalcin expression, a marker of osteoblastic differentiation, were detected along the endothelium of mitral valves that had been subjected in vivo to mechanical stretch. Mitral valve leaflets contain endothelial cells with multilineage mesenchymal differentiation potential, including osteogenic differentiation. This unique feature suggests that postnatal mitral valvular endothelium harbors a reserve of progenitor cells that can contribute to osteogenic and chondrogenic VICs.


Primary pure choriocarcinoma of the ovary.
The authors report a case of pure primary choriocarcinoma of the ovary (FIGO stage III A) in a young patient with 24-month follow-up. The patient, an advanced case of choriocarcinoma, was treated with combination chemotherapy comprising vincristine, bleomycin and cisplatinum. It is stressed that at that stage of the disease it is of prime importance to initiate combination chemotherapy for improvement in survival and prognosis of such cases rather than to distinguish the gestational or nongestational origin of the tumor.


ASSIMILATION OF PHOTOSYNTHETIC PRODUCTS OF ZOOXANTHELLAE BY A REEF CORAL.
1. The hermatypic coral, Pocillopora damicornis was incubated in the laboratory and in its reef habitat with Na214CO3 for 1-24 hours. Controls were incubated in darkness. 14C fixation in light exceeded that in darkness. 2. Fractionation of corals labeled on the reef for 24 hours revealed that 35-50% of the total 14C fixed appeared in the animal tissue lipid (as 14C-glycerol) and protein. From a comparison with dark controls it is concluded that photosynthetic products of zooxanthellae are translocated to host coral tissue. The skeletal organic matrix also acquires 14C. 3. Zooxanthehellae isolated from corals and incubated in a homogenate of host coral tissue selectively release glycerol and traces of other organic material including glucose, alanine, and glycolic acid confirming previous observations.


[The efficacy of botulinotherapy in the correction of the pain syndrome and quality of life of patients with cervical dystonia].
To evaluate the severity of pain, emotional status and humoral serotonin in patients with cervical dystonia (CD) before and after the botulinotherapy. A simple, open, comparative study of clinical characteristics of hyperkinesis, pain and emotional status, quality of life and contents of serum and blood platelet serotonin in 48 patients (32 women and 16 men) with CD, in age from 37 to 53 years, before and one month after the botulinotherapy with disport in dose of 500--1000 U was carried out. A control group included 15 healthy people. All patients (100%) complained of involuntary movements and pain in the neck. The overall score on a scale of dystonic movements in the group of patients was 16,7±7,7 points, on TWSTRS - 46,48±6,2 points, on the Visual Analogue Scale, the average level of pain was 6,4±1,08 points. The degree of depression according to the Hamilton scale was significantly higher (p<0.05) compared to the control group. The level of trait and state anxiety measured with the Spielberger-Khanin scale was significantly higher (p<0.005) in patients with CD than in the controls. The correlation analysis revealed a direct dependence of the intensity of pain subscale TWSTRS with the degree of anxiety on the Hamilton scale and the amount of final points of dystonic movements. The level of serotonin in the serum was significantly lower in patients compared to the controls. After botulinotherapy, pain scores, anxiety and depression have significantly decreased and the level of blood platelet serotonin has increased. Botulinotherapy with dysport in CD patients reduces the degree of pain, depression, improves quality of life and stimulates the serotoninergic system.


Transmission electron microscopic visualization of the degradation and phagocytosis of a poly-L-lactide screw in cancellous bone: a long-term experimental study.
The increasing clinical use of biodegradable implants in orthopedic surgery makes it necessary to determine their long-term behavior in tissues. In this study, a biodegradable screw made of poly-L-lactide (PLLA) was inserted axially into the right distal femur in 18 rabbits. The degradation and phagocytosis process of PLLA was assessed histologically and by transmission electron microscopy (TEM). The follow-up times were 3 and 4.5 years for groups of nine and eight animals, respectively. Abundant birefringent polymeric material was still present in the center of the implant channel in all specimens in both follow-up groups. The PLLA material studied appeared to be a biologically relatively inert material, with only sparse reactive cellular activity at the tissue-implant boundary. In the TEM specimens, polymeric particles of an average area of 2 microm2 were seen to be located intracellularly within phagocytic cells. The spheric and polygonal particles were membrane-bound and to a great extent filled up each phagocyte. In the 4.5-year specimens, the size of the polymeric particles, measured as area and perimeter, was significantly smaller (p < 0.02) than that of the 3-year specimens. The findings indicate that the ultimate degradation process of PLLA is much longer than it previously was thought to be. Complete degradation probably still would have taken years after the 4.5-year span of this study.


Cutaneous wound healing.
The wound healing is a complex process that can be divided into inflammatory reaction, proliferation and maturation of newly formed tissue. The inflammatory phase involves vascular and cellular events and is best characterized by edema, erythema and marked increase of blood supply. During proliferative phase there is formation of the epithelium with concomitant grow of granulation tissue and new blood vessels (angiogenesis). Angiogenesis seems to be strictly coordinated and regulated by multiple grow factors and cytokines released at the wound site. Once the tissue within the wound is formed the maturation phase begins. The synthesis of collagens and other extracellular matrix components increase tensile strength of the wound. Thus, the final result of the process of healing is the formation of tissue able to replace the normal, uninjured skin.


Carbapenem-resistant Klebsiella pneumoniae in Barbados: Driving change in practice at the national level.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is of growing concern globally. The risk for transmission of antimicrobial resistant organisms across several continents to the Caribbean is a real one given its tourism industry. After a cluster of cases of CRKP were detected, several studies detailed in this report were initiated to better characterize the problem. A hospital-wide point prevalence study and active surveillance were performed at Queen Elizabeth Hospital (QEH) in Barbados in 2013 to assess the prevalence of CRKP infection/colonization. Following this, a 1-year longitudinal study measured the prevalence of CRKP isolates in the hospital and across all healthcare facilities in the country. In 2013, eleven viable isolates of CRKP from cluster of cases were sent for molecular epidemiology studies. When sequenced, they were found to be the ST-258 clone. Identification of a cluster of cases of CRKP ST-258/512 clones indicated person-to-person transmission. In September 2013, the hospital-wide point prevalence study revealed 18% of patients (53/299) at the hospital were either colonized or infected with CRKP. The infection to colonization ratio was 1:7. Patients who were infected/colonized vs. non-colonized were older (64.7 vs. 48.7 years, p<0.0001), were hospitalized longer (42.5 days vs. 27 days, p = 0.0042), were more likely to have an invasive device (66% vs. 32%, p<0.0001), especially urinary catheters (55% vs. 24%, p<0.0001), and were more likely to have used antimicrobials within the prior 14 days (91% vs. 46%, p<0.0001). Specific antimicrobials, including fluoroquinolones and piperacillin-tazobactam, were significantly associated with infection/colonization. In 2014, the 12-month period prevalence of CRKP in Barbados was 49.6 per 100,000 population and of blood stream infections was 3.2 per 100,000 population. This point prevalence study identified patients at-risk of acquisition of CRKP and allowed QEH to implement interventions aimed at decreasing the prevalence of CRKP. Organization of a National and regional Infection Prevention and Control Committee in 2014 aimed to strengthen antimicrobial resistance surveillance programs across the English-speaking Caribbean were established.


New concept in external fixation.
A new concept in external skeletal fixation is presented. A 3D unilateral system developed by Mitkovic has widely been investigated biomechanically in AO institute in Davos (Switzerland). Consists of three components only providing extremely simple application and dynamic fixation of bones and different joints. This simple external fixator functions as an accurate reduction device at the same time, minimizing need for fluoroscopy. Clinically this system has been applied to mere then 13 thousand patients in 43 clinics. This paper presents the results of its application for treatment of open fractures, war wounds with fractures and for comminuted and intraarticular closed fractures in the series of 597 patients. Overall average time for union time was 3.2 months. Overall success of fracture healing was 96.8% including open and closed fractures. Our study suggests that the use of this 3D unilateral system is suitable for routine use.


The clinician's approach to the management of headache.
Headache is a ubiquitous complaint, yet it is one that often elicits anxiety in both patients and physicians. When a patient presents with headache, the clinician must answer the following questions: (1) Is the headache "worrisome" (secondary to underlying disease)? (2) If the headache is benign, what type is it? (3) How is the acute headache best treated? and (4) How may future headaches be prevented? The following review is intended to aid primary care physicians in answering these questions.


Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma: with respect to histological subtypes and stages.
Although the mechanism remains obscure, two histological subtypes of gastric carcinoma (GC), the diffuse and intestinal types, differ drastically in epidemiological, clinical, pathological and biological characteristics. We investigated whether the genetic alterations of several oncogenes and tumour suppressor genes could be correlated with the two histological subtypes. In 60 patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochemical stains. Mutations of the p15 and p16 tumour suppressor genes were assessed by polymerase chain reaction, Southern blotting, and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%) and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point mutations of p16 nor alterations of p15 were detected. The frequency of alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter pylori infection. No correlation of genetic changes between any two genes was observed. Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC. Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may function independently of each other in gastric carcinogenesis. The association between genetic alterations and histological subtypes supports the notion that a distinct pathogenesis may exist in different histological subtypes.


Odorization of inert gas for occupational safety: psychophysical considerations.
Odorization of inert gas can serve to warn workers in an enclosed space about gas leaking into the space. This psychophysical investigation, performed under conditions of directed attention, examined two candidates for possible odorization of argon:pyridine and cis-3-hexen-1-ol. Detection thresholds for pyridine and cis-3-hexen-1-ol in argon were 106 ppb and 19 ppb, respectively. Practice over four days yielded modest improvement in the detection of both odorants. For cis-3-hexen-1-ol, smokers had marginally lower thresholds than nonsmokers and older participants had slightly higher thresholds than younger participants. Gender, smoking status and age had no reliable influence on threshold for pyridine. This outcome indicated desirable perceptual stability for pyridine. Additional experiments dealt with the perceived intensity of pyridine and cis-3-hexen-1-ol over time in the realistic setting of an environmental chamber. Visitors to the chamber and occupants in the chamber assessed perceived magnitude at 5-min intervals for up to 60 min during injections of odorized argon into the chamber. Participants could gauge and track the concentration of pyridine much better than that of cis-3-hexen-1-ol. This held true for occupants almost to the same degree as visitors, though occupants inevitably exhibited some olfactory adaptation. Hence, the suprathreshold measurements also gave strong relative endorsement to pyridine. Calculations based on the experimental results indicated that odorization of the inert gas stream with 3 to 10 ppm (v/v) pyridine should suffice to warn occupants or visitors of an argon buildup of any severity. Field studies should permit a definitive judgment of the best concentration to use in practice.


In-Vitro Pulsatile Flow Measurement in Prosthetic Heart Valves: An Inter-Laboratory Comparison.
One of the first steps in qualifying a new prosthetic valve for eventual clinical use is preclinical flow performance testing in vitro. Such testing is typically performed in an in-vitro test system that simulates the pumping mechanics of the left ventricle of the heart, generally referred to as a pulse duplicator or duplicator. Historically, test results in these systems have varied from duplicator to duplicator. This collaborative effort between heart valve manufacturers and the Food and Drug Administration (FDA) was designed to evaluate the variability of the pulse duplicator test technology for pulsatile flow performance measurement in an interlaboratory round robin. The participants jointly developed and followed a limited test protocol based on accepted methods outlined in the International Standards Organization 5840: Cardiovascular Implants - Cardiac Valve Prostheses, and in the FDA Replacement Heart Valve Guidance. One 25 mm valve, each of four basic designs, was circulated to test centers which included four manufacturers and two FDA duplicators. The pressure drop and regurgitation data were then collected and summarized by the FDA. Considerable variation was observed in hydrodynamic performance measures of pressure drop across the valve and back flow leakage through the valve among the different duplicators. Despite the variations seen in these measures, the results from all centers showed that the valves conformed to certain minimum performance criteria. Despite the fact that the valves would have been judged to have met Minimum Performance Requirements of effective orifice area and regurgitant fraction, as specified in the international standard, variations in measurements existed among duplicators. Valve manufacturers should use a reference valve of similar design in hydrodynamic performance testing to assess the individual measurement conditions in the duplicator.


Ribbon modulates apical membrane during tube elongation through Crumbs and Moesin.
Although the formation and maintenance of epithelial tubes are essential for the viability of multicellular organisms, our understanding of the molecular and cellular events coordinating tubulogenesis is relatively limited. Here, we focus on the activities of Ribbon, a novel BTB-domain containing nuclear protein, in the elongation of two epithelial tubes: the Drosophila salivary gland and trachea. We show that Ribbon interacts with Lola Like, another BTB-domain containing protein required for robust nuclear localization of Ribbon, to upregulate crumbs expression and downregulate Moesin activity. Our ultrastructural analysis of ribbon null salivary glands by TEM reveals a diminished pool of subapical vesicles and an increase in microvillar structure, cellular changes consistent with the known role of Crumbs in apical membrane generation and of Moesin in the cross-linking of the apical membrane to the subapical cytoskeleton. Furthermore, the subapical localization of Rab11, a small GTPase associated with apical membrane delivery and rearrangement, is significantly diminished in ribbon mutant salivary glands and tracheae. These findings suggest that Ribbon and Lola Like function as a novel transcriptional cassette coordinating molecular changes at the apical membrane of epithelial cells to facilitate tube elongation.


Stoichiometric modeling of aboveground-belowground interaction of herbaceous plant.
Grassland ecosystems are the most widely distributed terrestrial ecosystems of the world. Many studies focus on aboveground grassland, but the belowground grassland is less explored because of the difficulty of sampling. Furthermore, the above-and-below ground biomass allocation mechanism of herbs is still disputed between the isometric growth hypothesis and the optimal partitioning hypothesis. In this study, a regrowth dynamic model, based on nutrient dynamics and stoichiometry, is proposed and analyzed to investigate the interaction between the aboveground and belowground herbaceous plants. The global dynamics of the belowground and aboveground biomass is well analyzed. Numerical simulations conclude that the herbaceous plant's biomass allocation mechanism for the aboveground and the belowground is in conformity with optimal partitioning at the beginning of growth, when the environment changes, it conforms to the constraints of isometric growth. Moreover, the dynamics of the model agree well with experimental data, which reveals that the model can express the relationship between aboveground and belowground biomass. Finally, a regrowth-herbivore model is established to explore the effects of nutrition and light intensity on the dynamics of plant and herbivore biomass.


Skin barrier in atopic dermatitis.
The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative factors for a number of skin diseases, in particular atopic dermatitis (AD). This review summarizes current knowledge on the role of the skin barrier in AD with regard to pathogenesis and treatment, on the relationship between skin barrier abnormalities and immune aberrations, and on potential therapies aimed at repair of the skin barrier. Furthermore recent advances in the genetics of AD will be addressed.


The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Heart Failure Validation Study: diagnosis and prognosis.
ALLHAT, a randomized, double-blind, active-controlled hypertension treatment trial in 42,418 patients, reported that a thiazide-type diuretic (chlorthalidone) was superior to a calcium channel blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and an alpha1-blocker (doxazosin) in preventing the new onset of heart failure (HF). However, questions have been raised regarding the validity of the HF diagnosis. The ALLHAT HF Validation Study was designed to validate and elucidate the significance of HF events in ALLHAT. Records for 2778 HF hospitalizations in 1935 patients were centrally reviewed using several prespecified algorithms (based on ALLHAT and Framingham criteria) and reviewers' global clinical judgment. Percent agreement with diagnoses assigned by ALLHAT site physicians, relative risks across randomized comparisons, incidence rates, and mortality after HF hospitalization were evaluated for first events validated by each of the criteria sets. Percent agreements with site physician diagnoses were 71%, 80%, and 84% for ALLHAT, Framingham, and reviewers' judgment, respectively. Using these 3 criteria, relative risks (95% CI) for new-onset HF compared with chlorthalidone were, respectively, 1.46 (1.27-1.68), 1.42 (1.25-1.62), and 1.45 (1.28-1.64) for amlodipine; 1.18 (1.02-1.28), 1.13 (0.99-1.30), and 1.15 (1.01-1.32) for lisinopril; and 1.79 (1.51-2.11), 1.71 (1.46-2.00), and 1.80 (1.55-2.10) for doxazosin. An independent review of source documentation showed a high degree of agreement with the HF diagnoses assigned by site physicians and confirmed the higher risk of HF associated with first-step therapy using amlodipine, lisinopril, or doxazosin compared with chlorthalidone. Thiazide-type diuretics should be the preferred first-step therapy for prevention of HF in high-risk patients with hypertension.


[Is the application of CAD useful for radiologists for passing the official tests required for outpatient breast imaging?].
To analyze whether currently available CAD systems meet the diagnostic requirements for passing screening tests (first reader CAD) and to analyze whether the additional usage of CAD systems provides significant support for the diagnosing radiologist on the basis of official screening test cases (second reading by CAD). 200 images of 100 mammographies of 50 patients of an official screening test case collection were analyzed double-blind with and without CAD printouts (iCAD, USA ) by three radiologists: one experienced in breast analysis and CAD application, one experienced in mammography analysis but inexperienced in CAD usage, one with minimal experience with breast analysis and CAD application. All radiologists measured the largest diameter of any malignant mass. The mean value of these calculations was correlated to the largest diameter given by CAD prompts. The mean sensitivity and specificity increased slightly as a result of the additional usage of CAD (1 and 0.6 %, resp.). Both values are not statistically significant. The highest effect was measured for the radiologist with CAD experience, while no effect was measured for the inexperienced radiologist. CAD met the sensitivity requirements but not the specificity criteria (96 and 20.3 %, resp.). The sizes given by CAD prompts corresponded significantly with the real sizes (r = 0.45, p < 0.05). A statistically significant effect of the use of CAD could not been detected dependent on the radiological experience or the CAD experience. The effect of CAD on radiologists is still subtle despite the highly sensitive CAD performance due to the high number of false positive prompts and thus does not reach statistical significance. Sizes given by CAD prompts correlate significantly with the real sizes of malignant lesions.


Red blood cell disorders in Rwandese neonates: screening for sickle cell disease and glucose-6-phosphate dehydrogenase deficiency.
To determine the prevalence of haemoglobin (Hb) variants and glucose-6-phosphate dehydrogenase (G6PD) deficiency in Rwanda. During a two-month period in 2005, 987 cord blood samples were obtained in two hospitals in Kigali and Butare, Rwanda. Screening for sickle cell disorders, other Hb disorders, G6PD deficiency and other rare erythroenzymopathy deficiencies was done using isoelectric focusing techniques and quantitative kinetic assays, respectively. The prevalence of Hb S trait was 2.7% and that of G6PD deficiency was 3.8%. No neonate suffered from a sickle cell disease (homozygous for Hb S or compound heterozygous for Hb S), from another clinically significant haemoglobinopathy, or from pyruvate kinase or glucose phosphate isomerase deficiency. Sickle cell disorders should be considered a public health problem in Kigali and Butare. A systematic neonatal screening programme for those disorders, and to diagnose G6PD deficiency, seems reasonable, but local health priorities must be considered. Adapted management of hereditary sickle cell and G6PD disorders should be available.


Thyroid Volume Assessment in 3-14 Year-Old Spanish Children from an Iodine-Replete Area.
Few data exist on reference thyroid volumes (Tvols) for Spanish children. The standard tables of the World Health Organization (WHO) are only for children older than 6 years. The present cross-sectional study reports the normal Tvols of 3-14 year-old girls and boys living in Madrid (Spain). The study subjects were 217 children aged 3-14 years. Urinary iodine was determined, and, on the same day, cervical ultrasound examinations were performed by a single, experienced paediatric radiologist. The sex-specific, upper normal limits for Tvol were then determined, based on age and body surface area (BSA). The median urinary iodine concentration was 120 µg/L (interquartile range 80-184); the population was therefore deemed to fall within the optimum range for iodine nutritional status. Eight children with heterogeneous glandular parenchyma were detected, as were 6 with increased vascularity, and 22 with intrathyroid cysts. Tvol increased with age and BSA in both sexes from the age of 3 years. In girls aged 11-12 years, Tvol was significantly larger than that in boys of the same age. When comparing children 6 years old and above, the 97th percentile Tvols with respect to gender/BSA were similar to WHO reference values, but by gender/age they were 30% larger. This work proposes reference ultrasound-determined Tvols for 3-14-year-old children living in Madrid.


Visceral Adiposity Is an Independent Determinant of Hypercoagulability as Measured by Thrombin Generation in Morbid Obesity.
Introduction Increased visceral adipose tissue (VAT) has been shown to be associated with the development of insulin resistance, type 2 diabetes, stroke, and ischemic heart disease. It remains unknown whether fat distribution impacts on coagulation markers and/or the risk of venous thrombosis. This study evaluates markers of hypercoagulability in class III obesity (body mass index [BMI] >40 kg/m 2 ) compared with nonobese controls. We further investigated whether hypercoagulability was influenced by VAT, metabolic syndrome, and metabolic markers, including adiponectin. Patients and Methods Ninety patients were recruited from the obesity clinic at King's College Hospital from November 2009 to December 2011. The inclusion criteria were class III obesity (BMI ≥40 kg/m 2 ) and age 18 to 65 years. A control group (healthy ambulatory participants, with a BMI < 30 kg/m 2 ) was recruited from volunteers responding to advertisement. Abdominal VAT and subcutaneous adipose tissue surface areas were determined by evaluation of a single-slice CT at spinal vertebra L4. Results Thrombin generation revealed a significantly increased peak and endogenous thrombin potential in patients compared with controls. Lag time and time to peak (ttP) were also significantly prolonged in patients. VAT was found to have the strongest association with thrombin generation parameters: lag time (β = 0.378; p < 0.001), peak thrombin (0.378; p = 0.04), and ttP (β = 0.373; p = 0.001). BMI was found to be a predictor for lag time only (β = 0.313; p = 0.003). SAT was not associated with any of the thrombin generation parameters (data not shown). VAT was found to be an independent determinant of peak thrombin, lag time, and ttP. The study suggests not only fat mass but also fat distribution, particularly visceral adiposity, mediates hypercoagulability in obesity.


Ising spin-glass transition in a magnetic field outside the limit of validity of mean-field theory.
The spin-glass transition in a magnetic field is studied both in and out of the limit of validity of mean-field theory on a diluted one dimensional chain of Ising spins where exchange bonds occur with a probability decaying as the inverse power of the distance. Varying the power in this long-range model corresponds, in a one-to-one relationship, to changing the dimension in spin-glass short-range models. Evidence for a spin-glass transition in a magnetic field is found also for systems whose equivalent dimension is below the upper critical dimension in a zero magnetic field.


25 years' experience of a gluten-free diet in the treatment of dermatitis herpetiformis.
Gluten-free diets have been used in the treatment of patients with dermatitis herpetiformis in our department since 1967. Of the 212 patients with dermatitis herpetiformis attending between 1967 and 1992, 133 managed to take the diet, and 78 of these achieved complete control of their rash by diet alone. Of the remaining 55 patients taking a gluten-free diet, all but three were taking partial diets; over half of these patients managed to substantially reduce the dose of medication required. Of the 77 patients taking a normal diet, eight entered spontaneous remission, giving a remission rate of 10%; a further two patients who had been taking gluten-free diets were found to have remitted when they resumed normal diets. Loss of IgA from the skin was observed in 10 of 41 (24%) patients taking strict gluten-free diets. These patients had been taking their diets for an average of 13 years (range 5-24 years), and their rash had been controlled by diet alone for an average of 10 years (range 3-16 years). The advantages of a gluten-free diet in the management of patients with dermatitis herpetiformis are: (i) the need for medication is reduced or abolished; (ii) there is resolution of the enteropathy, and (iii) patients experience a feeling of well-being after commencing the diet. Thus, we propose that a gluten-free diet is the most appropriate treatment for patients with dermatitis herpetiformis.


Myocardial creatine kinase isoenzyme in serum after subarachnoid haemorrhage.
The myocardial isoenzyme of creatine kinase (MB CK) has been demonstrated in the serum of seven of 16 patients presenting with acute subarachnoid haemorrhage. All patients with elevated MB CK levels exhibited at some stage either intracranial arterial spasm as demonstrated by cerebral angiography, or a focal reversible neurological deficit not due to direct pressure by either intracranial haematoma or aneurysm. The presence of MB CK isoenzymes in sera of patients with subarachnoid haemorrhage may be an index of cerebral ischaemia, and may thus be of value in determining optimal timing of surgery or, ultimately, the long-term prognosis. Changes in the sympathetic nervous system may be a common factor producing both MB isoenzyme release from the myocardium and intracranial arterial spasm.


Late development of malignant fibrous histiocytoma at the site of a giant cell tumour 38 years after initial surgery.
The authors report on a patient who developed a malignant fibrous histiocytoma at the site of a benign giant cell tumour, which had been treated by curettage 38 years previously. This latency period is, to their knowledge, the longest yet reported. This female patient was initially treated for a benign giant cell tumour of the proximal tibia when she was 33 years old; she underwent curettage and Kiel bone grafting. She had not received radiation therapy. Twenty eight years later, she underwent a second operation due to recurrence of a tumour. No specific histological diagnosis was possible: histology suggested a benign tumour, however compatible with a low-grade malignant potential but not associated with giant cell tumour. The patient underwent a third operation, with extensive curettage and total knee arthroplasty 38 years after the initial surgery, because of progressive knee pain. Postoperative histopathology study showed high-grade malignant fibrous histiocytoma. Finally, she underwent above-knee amputation because of uncontrollable progression of the tumour. The use of xenogenic bone graft, bone cement and associated bone necrosis potentially contributed to the development of a malignant tumour adjacent to the primary giant cell tumour.


Repeat rape and multiple offending among undetected rapists.
Pooling data from four samples in which 1,882 men were assessed for acts of interpersonal violence, we report on 120 men whose self-reported acts met legal definitions of rape or attempted rape, but who were never prosecuted by criminal justice authorities. A majority of these undetected rapists were repeat rapists, and a majority also committed other acts of interpersonal violence. The repeat rapists averaged 5.8 rapes each. The 120 rapists were responsible for 1,225 separate acts of interpersonal violence, including rape, battery, and child physical and sexual abuse. These findings mirror those from studies of incarcerated sex offenders (Abel, Becker, Mittelman, Cunningham-Rathner, Rouleau, & Murphy, 1987; Weinrott and Saylor, 1991), indicating high rates of both repeat rape and multiple types of offending. Implications for the investigation and prosecution of this so-called "hidden" rape are discussed.


Lesions of porcine necrotic ear syndrome.
Porcine necrotic ear syndrome is a disease of swine characterized by large erosive lesions at the margin of the pinna(e). The gross and microscopic characteristics of the lesions were studied in 38 pigs selected from eight affected swine herds. The progression of the lesions was examined in a herd of 174 weaned pigs in a total confinement nursery. The lesions began as a superficial vesicular dermatitis associated with superficial auricular trauma and progressed to become exudative and encrusted. Localized lesions slowly healed or sporadically progressed to deep necrotic ulcers. The early lesions resembled the epidermal changes produced by Staphylococcus hyicus. Deep ulceration and necrosis was attributed to the invasion of streptococci into the dermis resulting in cellulitis, vasculitis, thrombosis, ischemia, and necrosis.


Audit of double-lumen endobronchial intubation.
Many technical variations are possible in the placing and management of a double-lumen tube (DLT). We surveyed our practice to relate these variations to the course of the anaesthetic. We used a questionnaire to obtain details of technique in 506 consecutive double lumen intubations. The details were related to the incidence of secretions, tube displacement, and decreases of oxygen saturation (<88%) during one lung anaesthesia (OLA). Robertshaw tubes were used for 482 of the 506 intubations. During OLA there were 48 instances of desaturation (<88%), 19 cases of upper lobe obstruction, 15 of carinal obstruction, 16 of isolation failure, eight of excessive secretions (none of whom had received an antisialogogue; P<0.01) and 12 miscellaneous events. The experience of the anaesthetist or use of a fibre-optic bronchoscope did not affect these events. Air was of no advantage as a maintenance gas. Atropine 400-600 micro g appeared to prevent desaturation on OLA (P<0.05) but glycopyrrolate 200 micro g did not. Most factors had little effect on the progress of the anaesthetic, but an antimuscarinic usefully reduced secretions, and atropine (but not glycopyrrolate) was associated with less desaturation during OLA.


Failure of rifampin to eradicate methicillin-resistant Staphylococcus aureus colonization.
Four patients with methicillin-resistant Staphylococcus aureus (MRSA) carriage in one body site each (urine, anterior nares, throat, or wound) received 300 mg of oral rifampin twice daily for ten days. Treatment did not eradicate MRSA carriage in any patient, and three of the posttherapy isolates were highly resistant to the drug. Rifampin by itself does not appear to be an effective drug for the eradication of MRSA carriage.


The postsurgical heart. The pathology of cardiac transplantation.
Cardiac transplantation offers an excellent chance of long-term survival and functional rehabilitation for the carefully selected patient with end-stage heart disease. The role played by the pathologist in the management of cardiac transplant recipients is a very important one. Although much work is being carried out currently on noninvasive procedures to predict acute rejection, at this time the morphological index of rejection by endomyocardial biopsy is still the only reliable one. Noninvasive techniques are more sensitive because the whole heart can be studied; however, they are still much less specific and cannot distinguish infection from rejection or ischemia. The current management and survival of cardiac allografts depends as much on the pathologist as on his clinical colleagues.


Oral-Fluid Thiol-Detection Test Identifies Underlying Active Periodontal Disease Not Detected by the Visual Awake Examination.
Periodontal disease in dogs is highly prevalent but can only be accurately diagnosed by performing an anesthetized oral examination with periodontal probing and dental radiography. In this study, 114 dogs had a visual awake examination of the oral cavity and were administered an oral-fluid thiol-detection test prior to undergoing a a full-mouth anesthetized oral examination and digital dental radiographs. The results show the visual awake examination underestimated the presence and severity of active periodontal disease. The thiol-detection test was superior to the visual awake examination at detecting the presence and severity of active periodontal disease and was an indicator of progression toward alveolar bone loss. The thiol-detection test detected active periodontal disease at early stages of development, before any visual cues were present, indicating the need for intervention to prevent periodontal bone loss. Early detection is important because without intervention, dogs with gingivitis (active periodontal disease) progress to irreversible periodontal bone loss (stage 2+). As suggested in the current AAHA guidelines, a thiol-detection test administered in conjunction with the visual awake examination during routine wellness examinations facilitates veterinarian-client communication and mitigates under-diagnosis of periodontal disease and underutilization of dental services. The thiol-detection test can be used to monitor the periodontal health status of the conscious patient during follow-up examinations based on disease severity.


Hypertrophic pyloric stenosis in infants: US evaluation of vascularity of the pyloric canal.
To determine if there is increased flow to the pylorus in infants with hypertrophic pyloric stenosis (HPS) and, if so, whether the flow is localized to the muscle layer, mucosal layer, or both. Seventy-five infants examined for clinical suspicion of HPS were prospectively recruited for the study. Color scale was standardized at 4.2-4.4 cm/sec. Color Doppler flow at ultrasonography (US) was graded as follows: Grade 1 meant no signal; grade 2, two to five flow signals; and grade 3, extensive or continuous flow. Flow to the muscle or mucosal layer was documented and confirmed with spectral analysis. Infants without HPS served as control patients. Descriptive analyses were conducted to assess the demographic data and US results. Significance was assessed with chi2 or t tests. P <.05 was considered to indicate a significant difference. HPS was present in 41 infants with a mean age of 5 weeks +/- 2.0 (SD). Their mean flow grade was 2.80 +/- 0.4 in muscle and 2.88 +/- 0.4 in mucosa. HPS was not present in 34 infants with a mean age of 5.9 weeks +/- 4.5. Their mean flow grade was 1.26 +/- 0.5 in muscle and 1.15 +/- 0.5 in mucosa (P <.001). There was no significant difference in flow grades when the dimensions of the pyloric muscle and mucosa were compared. There was no significant difference in age between the HPS and control patient groups. Increased flow accompanies and may conceivably represent an integral component of the changes that occur with infantile HPS.


Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study.
Mortality rates remain high for human immunodeficiency virus (HIV)-associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects. We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis. HIV-infected outpatients without tuberculosis served as controls. Plasma biomarkers reflecting activation of procoagulation and anticoagulation, fibrinolysis, endothelial cell activation, matricellular protein release, and tissue damage were measured at admission. Cox proportional hazard models were used to assess variables associated with 12-week mortality rates. Of 59 patients with HIV-tuberculosis, 16 (27%) died after a median of 12 days (interquartile range, 0-24 days); 29 (64%) of the 45 not receiving anticoagulants fulfilled criteria for disseminated intravascular coagulation. Decreased survival time was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release, and tissue damage and with decreased concentrations for markers of anticoagulation. In patients who died, coagulation factors involved in the common pathway were depleted (factor II, V, X), which corresponded to increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality. Patients with severe HIV-tuberculosis display a hypercoagulable state and activation of the endothelium, which is associated with mortality.


Burden of cardiovascular morbidity and mortality following humanitarian emergencies: a systematic literature review.
The global burden of cardiovascular mortality is increasing, as is the number of large-scale humanitarian emergencies. The interaction between these phenomena is not well understood. This review aims to clarify the relationship between humanitarian emergencies and cardiovascular morbidity and mortality. With assistance from a research librarian, electronic databases (PubMed, Scopus, CINAHL, and Global Health) were searched in January 2014. Findings were supplemented by reviewing citations of included trials. Observational studies reporting the effect of natural disasters and conflict events on cardiovascular morbidity and mortality in adults since 1997 were included. Studies without a comparison group were not included. Double-data extraction was utilized to abstract information on acute coronary syndrome (ACS), acute decompensated heart failure (ADHF), and sudden cardiac death (SCD). Review Manager 5.0 (Version 5.2, The Nordic Cochrane Centre; Copenhagen Denmark,) was used to create figures for qualitative synthesis. The search retrieved 1,697 unique records; 24 studies were included (17 studies of natural disasters and seven studies of conflict). These studies involved 14,583 cardiac events. All studies utilized retrospective designs: four were population-based, 15 were single-center, and five were multicenter studies. Twenty-three studies utilized historical controls in the primary analysis, and one utilized primarily geographical controls. Conflicts are associated with an increase in long-term morbidity from ACS; the short-term effects of conflict vary by study. Natural disasters exhibit heterogeneous effects, including increased occurrence of ACS, ADHF, and SCD. In certain settings, humanitarian emergencies are associated with increased cardiac morbidity and mortality that may persist for years following the event. Humanitarian aid organizations should consider morbidity from noncommunicable disease when planning relief and recuperation projects.


The effect of cyclic rifaximin therapy on symptoms of diverticular disease from the perspective of the gastroenterology outpatient clinic: a "real-life" study.
Symptomatic uncomplicated diverticular disease of the colon (SUDD) is one of the most common diseases with which patients present to a gastroenterologist. Mild forms of diverticulitis can also be treated using rifaximin. Although numerous randomised controlled trials have already demonstrated the efficacy of rifaximin therapy, there is still a lack of data from daily medical practice. To assess the effect of rifaximin on the symptoms of diverticular disease (SUDD and mild diverticulitis) in patients undergoing routine treatment in gastroenterology outpatient clinics in Poland. The retrospective study included 142 patients with a diagnosis of SUDD and mild diverticulitis, with a mean age of 60-69 years (41%), of whom 65% were women. Patients underwent three cycles of rifaximin therapy at a dose of 2 × 400 mg daily for 7 days over 3 consecutive months. Survey data were collected during monthly clinic appointments using a questionnaire completed by 48 gastroenterologists, and in selected cases standard inflammatory parameters were also determined. After just one cycle of therapy a significant reduction in disease symptoms was observed (abdominal pain, abdominal tenderness, bloating, disturbances in bowel habit), defined over a scale of 0-3 points. The mean intensity of symptoms decreased from 1.7 ±0.7 to 0.8 ±0.3 points (with a maximum symptom intensity of 3.0 points). After three cycles, the severity of symptoms decreased markedly to an average of 0.3 ±0.1, and as many as 75% of patients reported no abdominal pain (previously the percentage was only 4%). These differences were statistically significant, p < 0.001. The decrease in inflammatory parameters (white blood cell count, C-reactive protein and erythrocyte sedimentation rate) was statistically significant. Rifaximin is highly effective in the symptomatic relief of uncomplicated diverticular disease of the large bowel, and it is also effective in the treatment of mild forms of diverticulitis. Although the effects were already visible after the first cycle of therapy, the highest efficacy was obtained after three cycles of therapy. Rifaximin can be successfully used in routine medical practice.


[Urinary iodide assessment of the adult population in Catalonia].
In 1983 goitre prevalence in Catalonia (Spain) was 21% and average urinary iodine (UI) 88.5 microg/l (SD 47.5). Surveys carried out in the nineties, after a campaign promoting the use of iodized salt, showed a significant improvement in UI. In the framework of Catalan Health Examination (2002), the assessment of iodine deficiency was included. The aim of this study was to determine UI and its distribution among a representative sample of population aged 18-74 in Catalonia. A sample of 2,100 people were stratified in accordance with the eight Catalan health areas (CHA). A questionnaire was prepared and urinary samples were collected for iodine testing. 1,115 urinary samples were collected (in 7 of the 8 CHA). Median UI was 147 microg/l and average UI 182.8 (SD 140). UI < 50 microg/l was found in 5% (95% CI, 3.8-6.5) of the sample. No difference in average UI was found between sexes. In fertile women (< 45 years) the 25th percentile of UI was 98 microg/l. Among CHA, average UI ranges from 141 to 159 microg/l. No difference in social class, education or employment was found in average UI. Our results show a significant improvement in iodine level of the Catalan population. Average UI is within the levels recommended by the WHO. However, it must be taken into account that 25% of fertile women have UI < 98 microg/l. This implies a risk in the event of pregnancy.


Rapid signaling to B cells by antigen-specific T cells requires CD18/CD54 interaction.
This study reports early B and T cell signaling events during cognate interactions between a human B cell line pulsed with peptide and an Ag-specific T cell clone. As has been previously reported, peptide in the context of the appropriate class II molecule stimulated a rise in intracellular calcium [Ca2+]i in the Ag-specific T cell clone. The activation of the T cell clone was associated with a reciprocal rise in [Ca2+]i in the B cells. Engagement of receptors on the B cell surface by the T cell also was associated with inositol phospholipid turnover comparable to that elicited by stimulation through sIg. Early signaling events in B cells can therefore be stimulated in cognate interactions with Ag-specific T cells, without the direct engagement of Ig receptors. A class II deficient B lymphoblastoid mutant, 6.1.6, which was incapable of presenting peptide to the T cell clone, could be stimulated to produce a rise in [Ca2+]i if the T cell clone was activated by monoclonal antibodies to CD3. Therefore, the interaction of class II molecules on the B cell with the TCR and/or the CD4 accessory molecule was not essential for T-dependent B cell activation. However, T-dependent signalling of B cells was profoundly inhibited by mAb to CD18 (beta-chain of LFA-1) on the T cell or CD54 (ICAM-1) on the B cell, demonstrating the importance of this pair of adhesion molecules in early T-B cell interactions.


Diabetic ketoacidosis in children in Khartoum city, Sudan.
Ninety episodes of diabetic ketoacidosis (DKA) in 72 Sudanese children seen during a one year period were investigated. The age of the patients ranged from 3 to 16 years with a median of 12 years. Twenty-two episodes (24%) occurred in newly diagnosed patients and 68 (76%) in previously known diabetic children. The mean observation period defined as the number of days from each one of the episodes until next episode or end of survey divided by the total number of the episodes was 180 days. During this short period of observation 18 recurrent episodes were observed giving an annual recurrent rate of 40%. The classical triad of polyuria, polydipsia and weight loss was a presentation in 83 (92%) episodes; acute abdominal pain and/or vomiting were observed in 69 (77%) episodes and drowsiness or deep coma was seen in 31 (34%) episodes. The most common precipitating causes of DKA in the studied patients with known diabetes were acute infections accounting for 38% of episodes, insulin non-availability for 34% of episodes and errors of treatment for 25%. The outcome of treatment in the whole group was good in the 69 (96%) patients who recovered without complications, but 3 (4%) patients died.


The influence of phonotactic probability and neighborhood density on children's production of newly learned words.
A word learning paradigm was used to teach children novel words that varied in phonotactic probability and neighborhood density. The effects of frequency and density on speech production were examined when phonetic forms were non-referential (i.e., when no referent was attached) and when phonetic forms were referential (i.e., when a referent was attached through fast mapping). Two methods of analysis were included: (1) kinematic variability of speech movement patterning; and (2) measures of segmental accuracy. Results showed that phonotactic frequency influenced the stability of movement patterning whereas neighborhood density influenced phoneme accuracy. Motor learning was observed in both non-referential and referential novel words. Forms with low phonotactic probability and low neighborhood density showed a word learning effect when a referent was assigned during fast mapping. These results elaborate on and specify the nature of interactivity observed across lexical, phonological, and articulatory domains.


Unlocking the full potential of conducting polymers for high-efficiency organic light-emitting devices.
By carefully tuning the thicknesses of low-optical index PEDOT:PSS and high-index ITO layers in organic light-emitting devices (OLEDs), very high optical coupling efficiencies can be obtained through the generation of appropriate microcavity effects. These experiments result in an external quantum efficiency (EQE) of 33.7% for green phosphorescent OLEDs and even higher EQEs of 54.3% can be obtained by adopting an external out-coupling lens.


Food and Drug Interactions.
Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions.


New classification of tauopathies.
Tauopathies are a group of neurodegenerative diseases characterized by pathological intracellular deposits of the protein tau. Isoform composition, morphology and anatomical distribution of cellular tau-immunoreactivities are defining distinct tauopathies as molecular pathological disease entities. The clinical spectrum of tauopathies includes syndromes with primary motor symptoms and with primary cognitive dysfunction. The traditional syndrome-based classification is currently being complemented by a molecular-pathological classification. While the syndrome-based classification is helpful to select symptomatic therapies, and to generate clinical working hypotheses about underlying etiologies, the molecular-pathological classification is most important for the development and application of molecularly tailored disease-modifying therapies.


Exome sequencing for simultaneous mutation screening in children with hemophagocytic lymphohistiocytosis.
In the present study, we used exome sequencing to analyze PRF1, UNC13D, STX11, and STXBP2, as well as genes associated with primary immunodeficiency disease (RAB27A, LYST, AP3B1, SH2D1A, ITK, CD27, XIAP, and MAGT1) in Thai children with hemophagocytic lymphohistiocytosis (HLH). We performed mutation analysis of HLH-associated genes in 25 Thai children using an exome sequencing method. Genetic variations found within these target genes were compared to exome sequencing data from 133 healthy individuals. Variants identified with minor allele frequencies <5% and novel mutations were confirmed using Sanger sequencing. Exome sequencing data revealed 101 non-synonymous single nucleotide polymorphisms (SNPs) in all subjects. These SNPs were classified as pathogenic (n = 1), likely pathogenic (n = 16), variant of unknown significance (n = 12), or benign variant (n = 72). Homozygous, compound heterozygous, and double-gene heterozygous variants, involving mutations in PRF1 (n = 3), UNC13D (n = 2), STXBP2 (n = 3), LYST (n = 3), XIAP (n = 2), AP3B1 (n = 1), RAB27A (n = 1), and MAGT1 (n = 1), were demonstrated in 12 patients. Novel mutations were found in most patients in this study. In conclusion, exome sequencing demonstrated the ability to identify rare genetic variants in HLH patients. This method is useful in the detection of mutations in multi-gene associated diseases.


Risk factors for uterine incision extension during cesarean delivery.
Unintentional extension of uterine incision is a known complication during cesarean delivery estimated to occur in 4-8% of cesarean deliveries. The aim of this study was to examine risk factors associated with unintentional uterine incision extension and to assess which of them are independent risk factors for this condition. We conducted a retrospective cohort study at a large public university tertiary referral center between 2003 and 2017. Included were women who underwent cesarean delivery during this time period. Demographic, medical, obstetrical and surgical data were collected. The primary outcome was the presence of uterine incision extension during cesarean delivery. Secondary outcomes included detection of risk factors associated with uterine incision extension. A multivariate analysis was additionally performed to identify general and labor related risk factors for unintentional extension of uterine incision among patients that underwent cesarean delivery during second stage of labor. During the study period, 25,879 cesarean deliveries performed in our medical center were assessed. Out of them, 731 (2.8%) cases of unintended uterine incision extension were identified. Women in this group had high rates of full cervical dilatation and increased maternal hemorrhage. Assessment of incision extension direction revealed that two-thirds of extensions were lateral, mostly unilateral. Median size of the extension was 2.7 ± 1.2 cm.Independent parameters associated with unintended uterine incision extension included nulliparity, vertex presentation, epidural anesthesia and cesarean section indication. Further analysis including cesarean deliveries performed during the second stage of labor revealed 397 (15.3%) cesarean deliveries in which incision extension was noted and 2205 (84.7%) cesarean deliveries without incision extension. Following multivariate analysis performed in women who underwent cesarean delivery during second stage of labor, two independent parameters associated with unintended uterine incision extension remained significant - past cesarean delivery and failed vacuum attempt. Vacuum extraction attempt and previous cesarean delivery are independent risk factors for uterine incision extension in women undergoing cesarean delivery during the second stage of labor. We also showed the majority of these extensions to be lateral.


Computational model of the lower leg and foot/ankle complex: application to arch stability.
The aim of this work was the design and evaluation of a computational model to predict the functional behavior of the lower leg and foot/ankle complex whereby joint behavior was dictated by three-dimensional articular contact, ligamentous constraints, muscle loading, and external perturbation. Three-dimensional bony anatomy was generated from stacked CT images after which ligament mimicking elements were attached and muscle/body loading added to recreate the experimental conditions of selected cadaveric studies. Comparisons of model predictions to results from two different experimental studies were performed for the function of the medial arch in weight bearing stance and the contributions of soft tissue structures to arch stability. Sensitivity simulations evaluated selected in situ strain and stiffness values for ligament tissue. The greatest contributor to arch stability was the plantar fascia, which provided 79.5% of the resistance to arch collapse, followed by the plantar ligaments (12.5%), and finally the spring ligament (8.0%). Strains measured after plantar fasciotomy increased in the remaining plantar ligament by approximately 300% and spring ligament by approximately 200%. Sensitivity tests varying both in situ strain and stiffness across reported standard deviations showed that functional trends remained the same and true to experimental data, although absolute magnitudes changed. While not measured experimentally, the model also predicted that load can increase dramatically in the remaining plantar tissues when one of such tissues is removed. Overall, computational predictions of stability and soft tissue load sharing compared well with experimental findings. The strength of this simulation approach lies in its capacity to predict biomechanical behavior of modeled structures and to capture physical parameters of interest not measurable in experimental simulations or in vivo.


Artificial chordae in the treatment of anterior mitral leaflet pathology.
This report describes the authors' clinical experience with expanded polytetrafluorethylene (e-PTFE) sutures to replace the anterior mitral leaflet chordae for valve repair. Between November 1986 and July 1995, 203 patients underwent operations with e-PTFE chordae insertion. Among these, 122 had artificial chordae utilized for anterior mitral leaflet repair. Four patients had the valve replaced during the same operation because of an unsatisfactory result. One patient died from respiratory insufficiency 16 days after operation. Transoesophageal echocardiography at discharge from hospital showed no evidence of regurgitation in 81 cases, and trivial regurgitation in 36. During a mean follow-up of 36.6 (range 1-106) months two other patients died from causes unrelated to the valve repair, while one patient had a transient ischaemic attack returning to sinus rhythm. Two patients were reoperated on 12 and 18 months respectively after their initial operation for progression of valvular degeneration causing natural chordae rupture. Among the remaining 113 patients, 111 are in New York Heart Association functional class I and yearly transoesophageal echocardiography has shown absent or trivial regurgitation. The utilization of e-PTFE as artificial chordae for anterior mitral leaflet pathology is a safe and reliable procedure, yielding excellent results and increasing the number of candidates for valve repair.


Low temperature Raman spectra of hydrogen in simple and binary clathrate hydrates.
The Raman spectrum of hydrogen clathrate hydrates has been measured, as a function of temperature, down to 20 K. Rotational bands of H(2) and HD, trapped into the small cages of simple (H(2)O-H(2)) and binary (H(2)O-THF-H(2)) hydrates, have been analyzed and the fivefold degeneracy of the molecular J=2 rotational level has been discussed in the light of the available theoretical calculations. The vibrational frequencies of H(2) molecules encapsulated in the large cages of simple hydrates turn out to be well separated from those pertaining to the small cages. Comparison with the equivalent D(2) spectra allowed us to assign the large cavity vibrational frequencies to three couples of Q(1)(1)-Q(1)(0) H(2) vibrational modes. Populations of ortho and para species have been measured as a function of time from rotational spectra and the rate of ortho-para conversion has been estimated for both simple and binary hydrates. We suggest, using the H(2) vibrational spectra, a model to analyze the cage population in simple hydrates.


Anti-Inflammatory Effect of Titrated Extract of Centella asiatica in Phthalic Anhydride-Induced Allergic Dermatitis Animal Model.
Centella asiatica has potent antioxidant and anti-inflammatory properties. However, its anti-dermatitic effect has not yet been reported. In this study, we investigated the anti-dermatitic effects of titrated extract of Centella asiatica (TECA) in a phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. An AD-like lesion was induced by the topical application of five percent PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μL of 0.2% and 0.4% of TECA (40 μg or 80 μg/cm²) was spread on the dorsum of the ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB activity, which were determined by electromobility shift assay (EMSA). We also measured TNF-α, IL-1β, IL-6, and IgE concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). TECA treatment attenuated the development of PA-induced atopic dermatitis. Histological analysis showed that TECA inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. TECA treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as the release of TNF-α, IL-1β, IL-6, and IgE. In addition, TECA (1, 2, 5 μg/mL) potently inhibited Lipopolysaccharide (LPS) (1 μg/mL)-induced NO production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW264.7 macrophage cells. Our data demonstrated that TECA could be a promising agent for AD by inhibition of NF-κB signaling.


Plasma cortisol and cortisone in pregnancies with normal and anencephalic fetuses.
Plasma cortisol (F), cortisone (E), and progesterone (P), were measured in the umbilical vein (UV), umiblical artery (UA), and maternal peripheral vein (MPV) of 17 normal patients, and of 8 patients carying anencephalic fetuses. The plasma F in MPV of patients undergoing vaginal delivery after labor of spontaneous onset was significantly higher than that of patients delivered by elective cesarean section, whereas the plasma F concentrations in the UA or UV of the 2 groups were not statistically different from each other. The anencephalic fetuses had UA plasma F and E concentrations which were significantly lower than those of normal fetuses, suggesting that a main portion of UA cortisol and cortisone originates in the fetal adrenal. The UV and MPV plasma F and E concentrations of patients carrying anencephalic fetuses did not differ, however, from those of normal patients, suggesting that these UV corticoids are derived mainly from maternal sources. The amniotic fluid cortisol levels of the patients carying anencephalic fetuses were lower than those observed in the normal pregnancies, suggesting that amniotic fluid cortisol is derived mainly from fetal sources.


Autoimmunity, infection and adjuvants.
The effect of infection in initiating autoimmune disease has been debated for many years. There are, even now, few instances of a human autoimmune disease clearly caused by prior infection, probably due to the frequent separation in time and space from the clinical outcomes. As our understanding of the immunologic consequences of the infectious process has deepened, we can re-think some of the issues by focusing attention on the varied adjuvant effects of microbial products. We are now able to distinguish some of the critical steps in progression from virus infection to benign autoimmunity to autoimmune disease in an experimental model of myocarditis. Immune regulators, such as cytokines and costimulatory molecules, serve as signposts in the process. The lessons learned may be broadly applicable to autoimmune disorders.