An unusual presentation of secondary involvement of B-cell chronic lymphocytic leukemia. A case report.
Extramammary tumors rarely metastasize to the breast. The commonest tumors to metastasize in breast tissue are lymphoproliferative diseases, melanoma, lung cancer and gynecological malignancies. Primary breast lymphoma has been reported in the literature with a maximum percentage of about 0.5% of all breast malignancies, while secondary localizations of lymphomas in the breast are less well studied in the literature than primary ones. The authors report a rare case of a secondary localization of B-cell chronic lymphocytic leukemia to the breast in which the diagnosis was obtained by histopathology and immunohistochemistry and further confirmed by molecular data. This occurrence must be considered in the differential diagnosis of a breast lump so that the primary hematological disease can be adequately treated and the correct type of breast surgery performed.


Structure and biological functions of human IgD. V. Insulin antibodies of the IgD class in sera from some diabetic patients.
Insulin antibodies were detected in the sera of diabetics who had received injections of animal insulin. The incidence of anti-insulin antibodies varied from 47 to 97% depending upon whether individual diabetic serum samples were compared with the highest 'normal' serum binding value or the mean binding value of all 'normal' nondiabetic sera. Approximately 64 of our diabetic patients had detectable IgD anti-insulin antibodies but only approximately 14% of the patients had values clearly above those found in 'normal' nondiabetic sera.


Canonical transient receptor potential 6 (TRPC6), a redox-regulated cation channel.
This study examined the effect of H(2)O(2) on the TRPC6 channel and its underlying mechanisms using a TRPC6 heterologous expression system. In TRPC6-expressing HEK293T cells, H(2)O(2) significantly stimulated Ca(2+) entry in a dose-dependent manner. Electrophysiological experiments showed that H(2)O(2) significantly increased TRPC6 channel open probability and whole-cell currents. H(2)O(2) also evoked a robust inward current in A7r5 vascular smooth muscle cells, which was nearly abolished by knockdown of TRPC6 using a small interfering RNA. Catalase substantially attenuated arginine vasopressin (AVP)-induced Ca(2+) entry in cells co-transfected with TRPC6 and AVP V1 receptor. N-Ethylmaleimide and thimerosal were able to simulate the H(2)O(2) response. Dithiothreitol or glutathione-reduced ethyl ester significantly antagonized the response. Furthermore, both N-ethylmaleimide- and H(2)O(2)-induced TRPC6 activations were only observed in the cell-attached patches but not in the inside-out patches. Moreover, 1-oleoyl-2-acetyl-sn-glycerol effect on TRPC6 was significantly greater in the presence of H(2)O(2). Biotinylation assays revealed a significant increase in cell surface TRPC6 in response to H(2)O(2). Similarly, in cells transfected with TRPC6-EGFP, confocal microscopy showed a significant increase in fluorescence intensity in the region of the cell membrane and adjacent to the membrane. AVP also increased the fluorescence intensity on the surface of the cells co-transfected with TRPC6-EGFP and V1 receptor, and this response was inhibited by catalase. These data indicate that H(2)O(2) activates TRPC6 channels via modification of thiol groups of intracellular proteins. This cysteine oxidation-dependent pathway not only stimulates the TRPC6 channel by itself but also sensitizes the channels to diacylglycerol and promotes TRPC6 trafficking to the cell surface.


Equine herpesvirus 1 entry via endocytosis is facilitated by alphaV integrins and an RSD motif in glycoprotein D.
Equine herpesvirus 1 (EHV-1) is a member of the Alphaherpesvirinae, and its broad tissue tropism suggests that EHV-1 may use multiple receptors to initiate virus entry. EHV-1 entry was thought to occur exclusively through fusion at the plasma membrane, but recently entry via the endocytic/phagocytic pathway was reported for Chinese hamster ovary cells (CHO-K1 cells). Here we show that cellular integrins, and more specifically those recognizing RGD motifs such as alphaVbeta5, are important during the early steps of EHV-1 entry via endocytosis in CHO-K1 cells. Moreover, mutational analysis revealed that an RSD motif in the EHV-1 envelope glycoprotein D (gD) is critical for entry via endocytosis. In addition, we show that EHV-1 enters peripheral blood mononuclear cells predominantly via the endocytic pathway, whereas in equine endothelial cells entry occurs mainly via fusion at the plasma membrane. Taken together, the data in this study provide evidence that EHV-1 entry via endocytosis is triggered by the interaction between cellular integrins and the RSD motif present in gD and, moreover, that EHV-1 uses different cellular entry pathways to infect important target cell populations of its natural host.


Outcomes of a Quality Improvement Initiative to Prevent Unnecessary Packed Red Blood Cell Transfusions Among Extremely Low Birth-Weight Neonates.
Extremely low birth-weight (ELBW) infants frequently receive packed red blood cell (PRBC) transfusions. Recent studies have shown that more restrictive PRBC transfusion guidelines limit donor exposure and reduce transfusion-related costs without any increase in adverse clinical outcomes. We developed and implemented an evidence-based PRBC transfusion guideline for ELBW infants treated in our unit and then measured provider adherence to this guideline. We performed a retrospective review of all PRBC transfusions given to ELBW infants in 2012 (preguideline) and the first half of 2014 (postguideline). We identified the indication for each transfusion by reviewing physiological/laboratory data and the daily clinical note. We then determine whether each transfusion met criteria according to our new evidence-based guideline. When extrapolating the newly developed protocol to 2012 data, less than 15% of transfusions among ELBW infants would have met the current evidence-based standard. Conversely, during the first 6 months of 2014, 61% of transfusions were administered in adherence to the guideline (P < 001). Using current cost estimates, this represents a projected cost savings of $31,000 in that 6-month period. A multidisciplinary approach to improving PRBC transfusion practices results in potentially safer, more cost-effective care for ELBW infants. Given the frequency, potential harms, and costs associated with PRBC transfusions in ELBW infants, it seems both feasible and important to pursue prospective clinical trials comparing permissive and restrictive approaches to transfusion in this vulnerable population.


Circuit motifs for contrast-adaptive differentiation in early sensory systems: the role of presynaptic inhibition and short-term plasticity.
In natural signals, such as the luminance value across of a visual scene, abrupt changes in intensity value are often more relevant to an organism than intensity values at other positions and times. Thus to reduce redundancy, sensory systems are specialized to detect the times and amplitudes of informative abrupt changes in the input stream rather than coding the intensity values at all times. In theory, a system that responds transiently to fast changes is called a differentiator. In principle, several different neural circuit mechanisms exist that are capable of responding transiently to abrupt input changes. However, it is unclear which circuit would be best suited for early sensory systems, where the dynamic range of the natural input signals can be very wide. We here compare the properties of different simple neural circuit motifs for implementing signal differentiation. We found that a circuit motif based on presynaptic inhibition (PI) is unique in a sense that the vesicle resources in the presynaptic site can be stably maintained over a wide range of stimulus intensities, making PI a biophysically plausible mechanism to implement a differentiator with a very wide dynamical range. Moreover, by additionally considering short-term plasticity (STP), differentiation becomes contrast adaptive in the PI-circuit but not in other potential neural circuit motifs. Numerical simulations show that the behavior of the adaptive PI-circuit is consistent with experimental observations suggesting that adaptive presynaptic inhibition might be a good candidate neural mechanism to achieve differentiation in early sensory systems.


Statistical issues in the evaluation of screening and early detection modalities.
Thorough evaluation of a screening test requires conducting a series of studies to ascertain its ability to detect accurately disease, as well as its benefits and costs. In this article, I review the steps involved in evaluating a screening test, using the case of prostate-specific antigen (PSA) screening for prostate cancer as a case study. I discuss designs for quantifying the diagnostic properties of a screening test and compare several different studies that have produced quite different estimates of the diagnostic accuracy of PSA screening. I also review methods that may be used to combine other markers or tests with PSA to improve test accuracy. Determining the benefits of a screening test is complex, particularly when information from randomized trials is lacking. I review several observational studies of PSA benefit and discuss the use of computer models for inferring the impact of screening from trends in population mortality.


Optical manipulation of micron/submicron sized particles and biomolecules through plasmonics.
Plasmonics, a rapidly emerging subdiscipline of nanophotonics, is aimed at exploiting surface plasmons for important applications, including sensing, waveguiding, and imaging. Parallel to these research efforts, technology yielding enhanced scattering and absorption of localized surface plasmons (LSPs) provides promising routes for trapping and manipulation of micro and nano scale particles, as well as biomolecules with low laser intensity due to high energy conversion efficiency under resonant excitation. In this paper, we show that the LSP-induced scattering field from a self-assembled gold nanoparticle array can be used to sustain trapping of single micron-sized particles with low laser intensity. Moreover, we demonstrate for the first time efficient localized concentration of sub-micron sized particles and DNAs of various sizes through photothermal effect of plasmonics.


3-D computed tomography measurement of mandibular growth after costochondral grafting in growing children with temporomandibular joint ankylosis and jaw deformity.
The aim of this study was to evaluate the long-term results after costochondral grafting (CCG) in growing children with temporomandibular joint ankylosis and jaw deformity by 3-dimensional computed tomography (CT) measurement. Patients with unilateral TMJ ankylosis and jaw deformity treated by CCG from 2010 to 2014 were evaluated. Their CT data within 1 week after operation and after at least 2 years of follow-up were analyzed using ProPlan CMF 1.4 software. Maximal incisal opening (MIO), condyle-ramus heights, chin deviation, and growth of CCG were measured and compared before and after the operation and at the last follow-up. SPSS 17.0 software was used for statistical analysis. Seven patients were included in the study. The mean follow-up period was 46.4 months. Five of 7 patients treated with this protocol experienced good mouth opening and symmetric mandibular growth. One patient achieved good mouth opening but not symmetric growth, and 1 patient experienced ankylosis again. CCG can be a reliable method to treat temporomandibular joint ankylosis with jaw deformity in growing children. Continued growth occurs in the children, but long-term outcomes require further investigation.


Hepatocellular carcinoma in thalassemia: A critical review.
Due to blood transfusions, thalassemics are often infected with either hepatitis C virus (HCV) or hepatitis B virus and often have hemochromatosis. Hepatocellular carcinoma (HCC) has emerged in thalassemics only recently as a result of the improvement in thalassemia outcomes. In fact, a prospective study estimated an HCC incidence in β-thalassemia of about 2%. Although data are scanty, HCC screening in thalassemics with risk factors for HCC should be carried out. HCV treatments have some efficacy in HCV infected thalassemics despite partial contraindication to ribavirin and iron overload. However, there are no data on how HCV treatment translates into HCC prevention. Preliminary data suggest that HCC treatment in thalassemics should generally have the same outcomes as in non-thalassemics. Although coexistence of severe comorbidities makes liver transplantation challenging, this therapeutic possibility should not be precluded for well selected HCC β-thalassemia patients. In fact, 2 transfusion dependent adult HCC β-thalassemia patients have recently undergone successful liver transplantation with a good outcome. In conclusion, HCC seems to be a developing issue in thalassemia and HCC screening should be carried out. HCC treatment, including liver transplantation, can be performed in selected patients. A multidisciplinary effort is needed for management.


Examining protective and buffering associations between sociocultural factors and adverse childhood experiences among American Indian adults with type 2 diabetes: a quantitative, community-based participatory research approach.
The purpose of this study was to determine the frequency of select adverse childhood experiences (ACEs) among a sample of American Indian (AI) adults living with type 2 diabetes (T2D) and the associations between ACEs and self-rated physical and mental health. We also examined associations between sociocultural factors and health, including possible buffering processes. Survey data for this observational study were collected using computer-assisted survey interviewing techniques between 2013 and 2015. Participants were randomly selected from AI tribal clinic facilities on five reservations in the upper Midwestern USA. Inclusion criteria were a diagnosis of T2D, age 18 years or older and self-identified as AI. The sample includes n=192 adults (55.7% female; mean age=46.3 years). We assessed nine ACEs related to household dysfunction and child maltreatment. Independent variables included social support, diabetes support and two cultural factors: spiritual activities and connectedness. Primary outcomes were self-rated physical and mental health. An average of 3.05 ACEs were reported by participants and 81.9% (n=149) said they had experienced at least one ACE. Controlling for gender, age and income, ACEs were negatively associated with self-rated physical and mental health (p<0.05). Connectedness and social support were positively and significantly associated with physical and mental health. Involvement in spiritual activities was positively associated with mental health and diabetes-specific support was positively associated with physical health. Social support and diabetes-specific social support moderated associations between ACEs and physical health. This research demonstrates inverse associations between ACEs and well-being of adult AI patients with diabetes. The findings further demonstrate the promise of social and cultural integration as a critical component of wellness, a point of relevance for all cultures. Health professionals can use findings from this study to augment their assessment of patients and guide them to health-promoting social support services and resources for cultural involvement.


The unilocular fat-cell graft.
Autologous fat grafting has become a common procedure for augmenting soft tissue. However, there are still some problems with resorption and cyst formation after injection, which mainly arise from insufficient nourishment of the transplanted fat tissues. In this study, using a mouse model, we enzymatically digested fat tissues into unilocular fat cells, and then transplanted the unilocular fat cells by sub-dermal injection to allow the transplanted cells to easily spread within the injected area. Fat tissue was harvested from a green fluorescent protein transgenic mouse (C57BL/6), and the optimal digestion time was determined to be 30 min. The fat cells were then injected into the sub-dermal layer of the head skin of a C57BL/6 mouse. As a control, minced fat without digestion was also injected. The animals were sacrificed immediately after injection and on days 1, 2 and 3, as well as at weeks 1, 2 and 4 after injection, and the recipient skins were collected for microscopic observation. The unilocular fat cells were observed to spread in a solitary manner among the recipient tissues, and no necrotic areas or cysts were observed. The minced-fat-graft control showed central necrosis in the transplanted region. In addition, the minced fat tissue needed to be injected with an 18-gauge syringe, but the unilocular fat cells could be injected with a 26-gauge syringe. Thus, the unilocular fat-cell graft was determined to be a superior alternative to conventional fat grafts.


Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac.
Sulindac regresses colorectal adenomas in patients with familial adenomatous polyposis (FAP), although the mechanism of polyp regression is unclear. To determine whether differences occur in alteration of rectal epithelial apoptotic index and expression of apoptosis related proteins in FAP patients treated with sulindac compared with placebo. Twenty one FAP patients; 12 had not undergone colectomy. Patients with FAP were treated with sulindac 150 mg orally twice a day for three months (n=10) or placebo (n=11). Colorectal polyp number was determined and biopsies of the normal rectal mucosa were performed before and after three months of treatment. Response to treatment and alteration of the apoptotic ratio (index in base of crypt divided by index in surface epithelium) were evaluated. Bcl-2, bax, p21/WAF-1, and p53 proteins were assessed semiquantitatively by immunohistochemistry. Significant decreases in polyp number and in the apoptotic ratio were seen in patients treated with sulindac compared with controls. The mean percentage change in polyp number from baseline was -46% in the sulindac group and +13% in the placebo group (p=0.005). Mean percentage change in the apoptotic ratio was -8% and +25% in the sulindac and placebo treated patients, respectively (p=0.004). No differences in expression or compartmentalisation of apoptosis related proteins were noted between treatment groups. Sulindac regression of colorectal adenomas is accompanied by alteration of the rectal epithelial apoptotic ratio with relative increase in apoptosis in surface cells compared with the deeper crypt. The utility of the apoptotic ratio as an intermediate biomarker for colorectal tumorigenesis deserves further study.


Cardiac positron tomography: current status and future directions.
Positron emission tomography (PET) performed after the administration of the positron-emitting radionuclides carbon-11 (11C), nitrogen-13(13N), oxygen-15(15O) and fluorine-18(18F) has permitted the improved noninvasive assessment of the regional myocardial metabolism of normal physiologic substrates and intermediates and their cogeners. In experimental animals, the rate of oxidation of 11C-palmitate correlates closely with other indexes of oxygen consumption, and the extraction of 11 C-palmitate (like that of 18F-fatty acids and 18F-fluordeoxyglucose) is markedly diminished in regions of myocardial ischemia. In both experimental animals and in patients, myocardial infarct site and size, determined by positron emission tomography after the intravenous injection of 11C-palmitate, correlate closely with the electrocardiographic infarct locus and enzymatically estimated infarct size as well as with the location and extent of regional left ventricular wall motion abnormalities. PET offers promise for assessment of flow as well despite the complexities involved. PET with 13NH3 appears to provide one useful qualitative index, although this tracer is actively metabolized. Because of the quantitative capabilities of positron emission tomography and the rapid progress which is being made in the development of fast scan, multi-slice, and gated instrumentation, this technique is likely to facilitate improved understanding and characterization of regional myocardial metabolism and blood flow in man under physiological and pathophysiological conditions.


Influence of Defect Engineering in Nanocrystalline CeO2 for Therapeutics of Reactive Oxygen Species-mediated Disorders.
Intracellular oxidative stress generation is a root cause of the dysfunctioning of mitochondria that is accountable for neurodegenerative disorders. In nano-CeO2, the intrinsic redox cycle (Ce3+ ⇔ Ce4+) confers them with a distinct oxygen buffering ability. Thus, increasing the Ce3+/Ce4+ ratio by preferentially engineering oxygen vacancies is expected to boost the antioxidant characteristics in CeO2 nanocrystals (NCs) and hold promise in nanotherapeutics of neurodegenerative disorders. Here, a pristine, economic, and scalable synthesis route with rapid nucleation-growth to yield monodispersed CeO2 NCs of 4 nm has been employed. The NCs demonstrated sustained colloidal stability (zeta potential ~ -30.3±7.2 mV). The survival rate (~96.1% for 0.1 mg/mL) of healthy L929 cells and cell apoptosis induced on the SH-SY5Y cells (~ 30.2% for 0.1 mg/mL) indicate nano-CeO2s' prospects in nanomedicine. The formulated sustainable synthesis strategy for the enrichment of defects in these NCs is anticipated to pave the way for nanocrystal-based-treatments in smart healthcare.Clinical Relevance-This investigation signifies the oxygen vacancy-dependent therapeutic efficacy of CeO2 NCs by ensuring ~96.1% survival rate of L929 cells while demonstrating cell apoptosis on SH-SY5Y cells (~ 30.2%) to establish newer insights on treatment of neurodegenerative disorders.


Audit of standardized precautionary and contact practices in the Intensive Care Unit.
To evaluate the structure and adherence to the standardized and specific precautionary measures of health professionals in the Intensive Care Unit of a teaching hospital in the Federal District of Brazil. A descriptive, cross-sectional and prospective study. A structured questionnaire was used via observations which recorded the practices of professionals with Individual Protection Equipment and indications of precautions. The chi-square test was applied, and the p-value was calculated. A total of 52 professionals participated in the study, and 445 care procedures were observed in 36 audit sessions. The average adhesion rate for equipment use was 72.72%, with 94.91% for gloves, 91.43% for aprons, 80% for masks and 24.56% for safety glasses. When there was no indication and no personal protective equipment was used, the average rate was 68.01%, with 30.77% for gloves, 87.58% for aprons, 57.58% for masks, and 96.13% for safety glasses. Contact precautions were unnecessarily indicated for 35% of patients. Good adherence to using gloves, aprons and masks were observed, but there was poor adherence to using safety glasses and unnecessary use of masks and admission contact precautions.


Environmental exposure more than plastic composition shapes marine microplastic-associated bacterial communities in Pacific versus Caribbean field incubations.
Microplastics have arisen as a global threat to marine ecosystems. In this study, we explored the role that plastic polymer type, incubation time and geographic location have on shaping the microbial community adhered to the microplastics, termed the plastisphere. We performed detailed bacterial plastisphere community analyses on microplastics of six different household plastic polymers, serving as proxies of secondary microplastics, incubated for 6 weeks in coastal Pacific waters. These bacterial communities were compared to the plastisphere communities grown on identical microplastic particles incubated in the coastal Caribbean Sea at Bocas del Toro, Panama. Ribosomal gene sequencing analyses revealed that bacterial community composition did not exhibit a significant preference for plastic type at either site but was instead driven by the incubation time and geographic location. We identified a 'core plastisphere' composed of 57 amplicon sequence variants common to all plastic types, incubation times and locations, with possible synergies between taxa. This study contributes to our understanding of the importance of geography in addition to exposure time, in the composition of the plastisphere.


Liability for Diagnosing Malingering.
Malingering is a medical diagnosis, but not a psychiatric disorder. The label imputes that an evaluee has intentionally engaged in false behavior or statements. By diagnosing malingering, psychiatrists pass judgment on truthfulness. Evaluees taking exception to the label may claim that the professional has committed defamation of character (libel or slander) when the diagnosis is wrong and costs the claimant money or benefits. Clinicians may counter by claiming immunity or that the diagnosis was made in good faith. This problem has come into focus in military and veterans' contexts, where diagnoses become thresholds for benefits. Through historical and literary examples, case law, and military/veterans' claims of disability and entitlement, the authors examine the potency of the malingering label and the potential liability for professionals and institutions of making this diagnosis.


Global sensitivity analysis of a wave propagation model for arm arteries.
Wave propagation models of blood flow and blood pressure in arteries play an important role in cardiovascular research. For application of these models in patient-specific simulations a number of model parameters, that are inherently subject to uncertainties, are required. The goal of this study is to identify with a global sensitivity analysis the model parameters that influence the output the most. The improvement of the measurement accuracy of these parameters has largest consequences for the output statistics. A patient specific model is set up for the major arteries of the arm. In a Monte-Carlo study, 10 model parameters and the input blood volume flow (BVF) waveform are varied randomly within their uncertainty ranges over 3000 runs. The sensitivity in the output for each system parameter was evaluated with the linear Pearson and ranked Spearman correlation coefficients. The results show that model parameter and input BVF uncertainties induce large variations in output variables and that most output variables are significantly influenced by more than one system parameter. Overall, the Young's modulus appears to have the largest influence and arterial length the smallest. Only small differences were obtained between Spearman's and Pearson's tests, suggesting that a high monotonic association given by Spearman's test is associated with a high linear corelation between the inputs and output parameters given by Pearson's test.


Immunohistochemical demonstration of the expression of CYP2E1 in human breast tumour and non-tumour tissues.
Environmental chemicals are one of the risk factors in breast cancer genesis. Cytochrome P450 2E1 (CYP2E1), a member of multigene superfamily of enzymes, plays a major role in the activation of some of these chemicals such as tobacco-derived N-nitrosamines. Using immunohistochemistry, the cellular distribution and the level of expression of CYP2E1 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP2E1 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 96% (24/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP2E1 was detected in normal epithelial, myoepithelial and to a lesser degree in some of the non-epithelial cells (e.g. endothelial cells). No positive staining was detected in other non-epithelial cells such as fibroblasts in normal breast tissues. When CYP2E1 staining was assessed semiquantitatively the mean staining score values of CYP2E1 was found to be significantly higher in tumours compared to that of normal breast tissues. These results show that CYP2E1 protein is expressed in both tumour and normal breast tissue with an increased expression in breast tumours.


I only have eyes for you: Ovulation redirects attention (but not memory) to attractive men.
A number of studies have found a disjunction between women's attention to, and memory for, handsome men. Although women pay initial attention to handsome men, they do not remember those men later. The present study examines how ovulation might differentially affect these attentional and memory processes. We found that women near ovulation increased their visual attention to attractive men. However, this increased visual attention did not translate into better memory. Discussion focuses on possible explanations, in the context of an emerging body of findings on disjunctions between attention to, and memory for, other people.


Investigating population differentiation in a major African agricultural pest: evidence from geometric morphometrics and connectivity suggests high invasion potential.
The distribution, spatial pattern and population dynamics of a species can be influenced by differences in the environment across its range. Spatial variation in climatic conditions can cause local populations to undergo disruptive selection and ultimately result in local adaptation. However, local adaptation can be constrained by gene flow and may favour resident individuals over migrants-both are factors critical to the assessment of invasion potential. The Natal fruit fly (Ceratitis rosa) is a major agricultural pest in Africa with a history of island invasions, although its range is largely restricted to south east Africa. Across Africa, C. rosa is genetically structured into two clusters (R1 and R2), with these clusters occurring sympatrically in the north of South Africa. The spatial distribution of these genotypic clusters remains unexamined despite their importance for understanding the pest's invasion potential. Here, C. rosa, sampled from 22 South African locations, were genotyped at 11 polymorphic microsatellite loci and assessed morphologically using geometric morphometric wing shape analyses to investigate patterns of population structure and determine connectedness of pest-occupied sites. Our results show little to no intraspecific (population) differentiation, high population connectivity, high effective population sizes and only one morphological type (R2) within South Africa. The absence of the R1 morphotype at sites where it was previously found may be a consequence of differences in thermal niches of the two morphotypes. Overall, our results suggest high invasion potential of this species, that area-wide pest management should be undertaken on a country-wide scale, and that border control is critical to preventing further invasions.


Designing and reporting case series in plastic surgery.
The case series is the most prevalent type of clinical research in the plastic surgery literature. However, this is a lower level study design in the hierarchy of evidence. The case series is nevertheless a useful hypothesis generator for future studies. These in turn can be tested with more robust study designs such as the randomized controlled trial. Because the case series remains the most common study design used to communicate our new innovations, there is a need to improve its reporting so that readers will know why the study was undertaken, what the results were, and how the results affect patient care. The authors provide a guide to help future investigators improve the conduct and the reporting of their case series.


Hepatitis in disseminated bacillus Calmette-Guérin infection.
Local immunotherapy with an attenuated live strain of Mycobacterium bovis, bacillus Calmette-Guérin (BCG), is an effective and frequently used treatment for in situ transitional cell carcinoma (TCC) of the bladder. Success rates are high, and serious side effects are infrequent but can affect every organ system. A 79-year-old patient with recently diagnosed TCC who was treated with intravesical BCG for a recurrence after initial surgical treatment is reported. After unsuccessful attempts at bladder catheterization with the creation of a false passage for his third treatment, BCG was instilled via a suprapubic catheter the same day and again a week later. Two weeks after the third BCG instillation, the patient presented with profound lethargy and weakness to the point of not being able to get up out of a chair. He was febrile, anorexic, icteric and had hepatosplenomegaly. Disseminated BCG infection was suspected on the basis of history, clinical examination and a liver biopsy that showed noncaseating granulomatous hepatitis. Empirical treatment was started with antituberculous combination therapy. A short course of an oral corticosteroid was given. Clinical improvement was marked and sustained so that the patient could be discharged home for the full six-month course of his treatment. Disseminated BCG infection with granulomatous hepatitis can be severe and life-threatening in cases where a large intravascular inoculum of BCG may have been given inadvertently.


Stabilization of alpha-lipoic acid by complex formation with octenylsuccinylated high amylose starch.
The thermal and oxidative stability of alpha-lipoic acid (ALA) in aqueous dispersions containing beta-cyclodextrin (CD), native high amylose (HA) and octenylsuccinylated high amylose (OS) starches (0.1% ALA and 1.0% CD or starch solids) were compared. Both native and modified starches increased the stability of ALA against thermal degradation and oxidation at higher degrees than CD. The OS was more effective in stabilizing ALA than HA. The ALA loss in the dispersions occurred mainly in the supernatant, suggesting that the complex formation of ALA with amylose played a key role in the stabilization. In an in vitro digestion test, the release of ALA from OS dispersion was less than that of HA dispersion, indicating that ALA complexed with OS amylose was most stable against digestion. The octenylsuccinylated high amylose starch was an effective protecting agent for ALA in aqueous media, as well as a delivery carrier for ALA in digestive tract.


The selectivity of K+ ion channels: testing the hypotheses.
How K(+) channels are able to conduct certain cations yet not others remains an important but unresolved question. The recent elucidation of the structure of NaK, an ion channel that conducts both Na(+) and K(+) ions, offers an opportunity to test the various hypotheses that have been put forward to explain the selectivity of K(+) ion channels. We test the snug-fit, field-strength, and over-coordination hypotheses by comparing their predictions to the results of classical molecular dynamics simulations of the K(+) selective channel KcsA and the less selective channel NaK embedded in lipid bilayers. Our results are incompatible with the so-called strong variant of the snug-fit hypothesis but are consistent with the over-coordination hypothesis and neither confirm nor refute the field-strength hypothesis. We also find that the ions and waters in the NaK selectivity filter unexpectedly move to a new conformation in seven K(+) simulations: the two K(+) ions rapidly move from site S4 to S2 and from the cavity to S4. At the same time, the selectivity filter narrows around sites S1 and S2 and the carbonyl oxygen atoms rotate 20 degrees -40 degrees inwards toward the ion. These motions diminish the large structural differences between the crystallographic structures of the selectivity filters of NaK and KcsA and appear to allow the binding of ions to S2 of NaK at physiological temperature.


Spinopelvic Changes Based on the Simplified SRS-Schwab Adult Spinal Deformity Classification: Relationships With Disability and Health-Related Quality of Life in Adult Patients With Prolonged Degenerative Spinal Disorders.
Cross-sectional, observational study. To study the occurrence of sagittal malalignment, the adaptability of a simplified sagittal modifiers grading of the Scoliosis Research Society (SRS)-Schwab adult spinal deformity (ASD) classification, and the deformity-specific SRS questionnaire version 30 (SRS-30) in an unselected adult cohort with symptomatic degenerative spinal disorders. The sagittal modifiers of the SRS-Schwab ASD classification correlate with health-related quality of life (HRQoL) measures in patients with ASD. The deformities and disabilities caused by sagittal malalignment in patients with common degenerative spinal disorders of multiple etiologies are rarely studied. A simplified and categorizing version of the SRS-Schwab ASD classification in relation to the Oswestry Disability Index (ODI) and the SRS-30 outcomes has not yet been developed. We recruited 874 consecutive patients with degenerative spinal disorders between March 2013 and February 2014. Full spine radiographs were taken and the patients divided into sagittal deformity severity groups: mild or none, moderate, and marked deformity. Participants completed the ODI, SRS-30, and a general health questionnaire. We included 637 patients in the analysis. The severity of sagittal deformity was mild or none in 407 (63.9%) patients, moderate in 159 (25.0%), and marked in 71 (11.1%). Linearity across the modifier grades and deformity classes was found for ODI total score (P = 0.033), and the function/activity (P = 0.004) and self-image/appearance (P = 0.030) domains of the SRS-30. Age, body mass index, duration of symptoms, and the use of painkillers increased while physical activity, working, and educational status decreased significantly with deformity severity. Sagittal spinopelvic malalignment is significantly related to deterioration of the ODI and the SRS-30 in symptomatic adults with degenerative spinal disorders. The SRS-Schwab classification sagittal modifiers categorized into three groups is a practical tool to detect various clinically significant grades of deformity in a cohort with no recognized ASD. 3.


Effect of Melatonin and Caffeine Supplementation to Freezing Medium on Cryosurvival of Peruvian Paso Horse Sperm Using a Two-Step Accelerating Cooling Rate.
This research examined the antioxidant and cryoprotective effects of melatonin (ME) and caffeine (CAF) supplementation in freezing medium on the cryosurvival of Peruvian Paso horse sperm using a two-step accelerating cooling rate. Twenty ejaculates from four adult and fertile stallions were recovered, initially diluted with INRA-96®, and finally frozen with INRA-Freeze® with either no supplementation (as control), 1 μM ME, or 2 mM CAF using a two-ramp freezing system content inside a cryogenic-box and liquid nitrogen vapors. The sperm kinematic parameters and integrity of the plasma and acrosomal membranes of fresh semen and cryopreserved samples were evaluated using the CASA system (SCA-Evolution® 2018) and PI/fluorescein isothiocyanate-conjugated peanut (Arachis hypogaea) agglutinin double fluorescent test, respectively. The oxidative stress of post-thaw sperm samples was also assessed using the CellRox Deep Red fluorescence test. The results showed that curvilinear velocity and average-path velocity were greater (p < 0.05) after freezing with CAF than the control group. In addition, there were significance differences (p < 0.01) between stallions (1-4) in post-thaw kinematic parameters regardless of ME or CAF addition. Both ME and CAF improved (p < 0.05) the proportion of sperm with intact plasma membranes and intact acrosomes. Nevertheless, neither CAF nor ME improved the oxidative stress after the cryopreservation process.


Reliability of Transcallosal Inhibition in Healthy Adults.
Transcallosal inhibition (TCI), assessed using transcranial magnetic stimulation, can provide insight into the neurophysiology of aging and of neurological disorders such as stroke. However, the reliability of TCI using the ipsilateral silent period (iSP) has not been formally assessed, despite its use in longitudinal studies. This study aimed to determine the reliability of iSP onset latency, duration and depth in healthy young and older adults. A sample of 18 younger (mean age 27.7 years, range: 19-42) and 13 older healthy adults (mean age 68.1 years, range: 58-79) attended four sessions whereby the iSP was measured from the first dorsal interosseous (FDI) muscle of each hand. 20 single pulse stimuli were delivered to each primary motor cortex at 80% maximum stimulator output while the participant maintained an isometric contraction of the ipsilateral FDI. The average onset latency, duration of the iSP, and depth of inhibition relative to baseline electromyography activity was calculated for each hand in each session. Intraclass correlation coefficients (ICCs) were calculated for all four sessions, or the first two sessions only. For iSP onset latency the reliability ranged from poor to good. For iSP duration there was moderate to good reliability (ICC > 0.6). Depth of inhibition demonstrated variation in reproducibility depending on which hand was assessed and whether two or four sessions were compared. Bland and Altman analyses showed wide limits of agreement between the first two sessions, particularly for iSP depth. However, there was no systematic pattern to the variability. These results indicate that although iSP duration is reliable in healthy adults, changes in longitudinal studies should be interpreted with caution, particularly for iSP depth. Future studies are needed to determine reliability in clinical populations.


Expression of vasoactive intestinal peptide and functional VIP receptors in human prostate cancer: antagonistic action of a growth-hormone-releasing hormone analog.
Vasoactive intestinal peptide (VIP) functions as a mitogenic agent in the human prostate gland acting by autocrine/paracrine mechanisms. Here we extend knowledge on the VIP system (expression of VIP and VIP receptors, functionality of VIP receptors) at this level by analyzing the differences between human normal prostate and prostate carcinoma specimens. RT-PCR showed the expression of mRNA for VIP in normal and malignant tissues, whereas VIP levels, as measured by enzyme immuno-analysis, were about two times higher in adenocarcinoma samples. Real-time RT-PCR indicated a minor expression of VPAC2 receptors in the prostate gland, as well as the overexpression of VPAC1 and PAC1 receptors in malignant tissue specimens. Radio-labeled binding experiments with [125I]VIP showed an increased number of VIP binding sites (2.5 times for the high- and 1.7 times for the low-affinity sites) during malignant transformation, whereas the affinity values were unaffected. The receptors were functional in control and cancer tissues as shown by the ability of increasing VIP doses to stimulate adenylate cyclase activity. Interestingly, JV-1-53 (a GHRH-related peptide analog) (at 0.1 microM) behaved as a potent VIP antagonist since it inhibited by 60% the maximal VIP effect upon the enzyme activity. The results further explain the mechanisms of the autocrine/paracrine actions of VIP in human prostate and prostatic carcinoma through the observation of differences between healthy tissue and malignant transformation. Moreover, present data support the potential usefulness of VIP and/or synthetic peptide analogs for diagnostic or radiotherapeutic purposes as well as for long-term peptide therapy in this malignancy.


[The detection of spores of the bacillus species within the scope of the hygienic control of water pollution (author's transl)].
Due to their differentiated nutritional requirements the species of the genus Bacillus found in large number in the waste matter and the upper layers of the soil and consequently in the surface water cannot multiply in biotopes of low nutritive content. However, they are spread to these areas as spores and are of extraordinary tenacity if not eliminated. Consequently, in the ground water and within the range of its utilization they represent an indicator of the degree of purification or contamination of the water with waste products or surface impurities; their number does not depend on the phase of self-purification (as e.g. the number of colonies) in the sense of the degradation of remaining substances still utilizable by pseudomonads. The concentration of spores of the Bacillus species in the surface water ranges from 1000-10000 per 50 ml of water. In undisturbed ground water 0-5 per 50 ml are found; in filtered ground water from near the banks and in such water that has been exposed to surface contamination 1000 per 50 ml have been found or even more; in the direction of infiltration - proportionate to the purification effect in the ground - decreasing numbers of spores of the Bacillus species are detectable. In "areas of subsequent germination" of the water supply and water utilization no multiplication of spores of the Bacillus species has been observed - provided no additional contamination occurs.


Resiniferatoxin induces paradoxical changes in thermal and mechanical sensitivities in rats: mechanism of action.
Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, has been used as a tool to study the role of capsaicin-sensitive C fibers in pain. Recently, we found that RTX diminished the thermal sensitivity but unexpectedly increased the sensitivity to tactile stimulation in adult rats. In this study, we explored the potential mechanisms involved in RTX-induced changes in somatosensory function. An intraperitoneal injection of 200 microg/kg RTX, but not its vehicle, rapidly produced an increase in the paw withdrawal latency to a heat stimulus. Also, profound tactile allodynia developed in all the RTX-treated rats in 3 weeks. This paradoxical change in thermal and mechanical sensitivities lasted for at least 6 weeks. Electron microscopic examination of the sciatic nerve revealed a loss of unmyelinated fibers and extensive ultrastructural damage of myelinated fibers in RTX-treated rats. Immunofluorescence labeling showed a diminished vanilloid receptor 1 immunoreactivity in dorsal root ganglia neurons and the spinal dorsal horn of RTX-treated rats. Furthermore, two transganglionic tracers, horseradish peroxidase conjugates of cholera toxin B subunit (CTB) and isolectin-B(4) of Bandeiraea simplicifolia (IB(4)), were injected into the opposite sides of the sciatic nerve to trace myelinated and unmyelinated afferent terminations, respectively, in the spinal dorsal horn. In RTX-treated rats, IB(4)-labeled terminals in the dorsal horn were significantly reduced, and CTB-labeled terminals appeared to sprout into lamina II of the spinal dorsal horn. Thus, this study demonstrates that systemic RTX diminishes the thermal pain sensitivity by depletion of unmyelinated afferent neurons. The delayed tactile allodynia induced by RTX is likely attributable to damage to myelinated afferent fibers and their abnormal sprouting in lamina II of the spinal dorsal horn. These data provide new insights into the potential mechanisms of postherpetic neuralgia.


Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species.
Studies on human LH receptors are difficult due to the limited availability of clinical samples. Recent cloning of rat and porcine LH receptor cDNAs indicated that these binding sites are single polypeptides of the G-protein-coupled receptor family with seven transmembrane domains. Based on the conserved sequences of rat and porcine receptors, we performed reverse transcription polymerase chain reaction, using human ovarian mRNA as template and obtained partial human LH receptor cDNA clones. Further screening of a human ovary cDNA library and subsequent ligation of individual cDNA clones generated a human LH receptor cDNA containing the entire amino acid-coding region. Sequence analysis indicated that the human receptor cDNA displays 89% and 82% homology at the nucleotide level with its porcine and rat counterparts, respectively. A region spanning the second extracellular and third transmembrane domains is highly conserved among the human LH, FSH, and TSH receptors. The ovarian LH receptor clone is, however, significantly different from an incompletely spliced LH receptor cDNA recently obtained from a human thyroid library. Unlike the thyroid clone, the ovarian LH receptor cDNA could be expressed in the human fetal kidney cell line (293), and radioligand receptor assay identified high affinity (Kd, 1.2 x 10(-10) M) LH/hCG-binding sites on the plasma membrane. Binding specificity of the human LH receptor was studied using recombinant human CG, LH, and FSH secreted by CHO cells transfected with the respective genes. Human CG and LH displaced [125I]hCG binding with an ED50 of 4.3 and 4.8 ng/ml, respectively. In contrast, recombinant FSH was not effective. Treatment of transfected cells with recombinant gonadotropins also induced dose-dependent increases in extracellular cAMP production (hCG = LH much greater than FSH; ED50 25, 10, and greater than 3000 ng/ml). Although equine, rat, and ovine LH as well as equine CG competed effectively for rat testicular LH receptor binding, these hormones were unable to displace [125I]hCG binding to the human receptor, suggesting evolutionary changes in receptor binding specificity and the importance of using human receptors for clinical studies. Thus, the cloning and expression of the human LH receptor cDNA allowed analysis of interactions between human LH receptor and gonadotropins from diverse species. The present work should provide the basis for future design of therapeutic agents capable of interacting with the human receptor and for understanding the structural basis for LH receptor binding to different gonadotropins.


Synthesis and evaluation of new salicylaldehyde-2-picolinylhydrazone Schiff base compounds of Ru(II), Rh(III) and Ir(III) as in vitro antitumor, antibacterial and fluorescence imaging agents.
Reaction of salicylaldehyde-2-picolinylhydrazone (HL) Schiff base ligand with precursor compounds [{(p-cymene)RuCl2}2] 1, [{(C6H6)RuCl2}2] 2, [{Cp*RhCl2}2] 3 and [{Cp*IrCl2}2] 4 yielded the corresponding neutral mononuclear compounds 5-8, respectively. The in vitro antitumor evaluation of the compounds 1-8 against Dalton's ascites lymphoma (DL) cells by fluorescence-based apoptosis study and by their half-maximal inhibitory concentration (IC50) values revealed the high antitumor activity of compounds 3, 4, 5 and 6. Compounds 1-8 render comparatively lower apoptotic effect than that of cisplatin on model non-tumor cells, i.e., peripheral blood mononuclear cells (PBMC). The antibacterial evaluation of compounds 5-8 by agar well-diffusion method revealed that compound 6 is significantly effective against all the eight bacterial species considered with zone of inhibition up to 35 mm. Fluorescence imaging study of compounds 5-8 with plasmid circular DNA (pcDNA) and HeLa RNA demonstrated their fluorescence imaging property upon binding with nucleic acids. The docking study with some key enzymes associated with the propagation of cancer such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II revealed strong interactions between proteins and compounds 5-8. Conformational analysis by density functional theory (DFT) study has corroborated our experimental observation of the N, N binding mode of ligand. Compounds 5-8 exhibited a HOMO (highest occupied molecular orbital)-LUMO (lowest unoccupied molecular orbital) energy gap 2.99-3.04 eV. Half-sandwich ruthenium, rhodium and iridium compounds were obtained by treatment of metal precursors with salicylaldehyde-2-picolinylhydrazone (HL) by in situ metal-mediated deprotonation of the ligand. Compounds under investigation have shown potential antitumor, antibacterial and fluorescence imaging properties. Arene ruthenium compounds exhibited higher activity compared to that of Cp*Rh/Cp*Ir in inhibiting the cancer cells growth and pathogenic bacteria. At a concentration 100 µg/mL, the apoptosis activity of arene ruthenium compounds, 5 and 6 (~30 %) is double to that of Cp*Rh/Cp*Ir compounds, 7 and 8 (~12 %). Among the four new compounds 5-8, the benzene ruthenium compound, i.e., compound 6 is significantly effective against the pathogenic bacteria under investigation.


Early response evaluation and prediction in neoadjuvant-treated patients with esophageal cancer.
Since the introduction of multimodal therapy regimens, the prognosis of esophageal cancer has improved. There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or chemoradiation. Important conclusions can be drawn from this regarding the indication for perioperative therapies, the radicality of surgery, or the surgical indications. Thus, most of the current research in this field is aimed at the early identification of this subset of patients, at the beginning of, or even before, neoadjuvant treatment. Conventional staging tools have failed to predict responses to neoadjuvant therapy. However, molecular imaging methods, e.g. positron emission tomography (PET)-scans, have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy, allowing physicians to alter the treatment plan accordingly. Even more desirable is the identification of potential responders before the start of neoadjuvant therapy. Preliminary molecular data on biopsy specimens demonstrate the possibility of early response prediction in these patients. We present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review.


Principles of clinical medicine: Oregon Health Sciences University School of Medicine.
In 1992, the School of Medicine at Oregon Health Sciences University inaugurated a Principles of Clinical Medicine (PCM) course as part of an overall curricular revision. The PCM course, which covers the first and second years of medical school, integrates material from ten separate courses in the previous curriculum. Students learn longitudinally over the two years, rather than "cramming" discrete areas of knowledge and then moving on. Course sessions are related to concurrently taken basic science classes. Meeting two afternoons per week, the PCM course offers preceptorships, health care issues sessions, and patient examination sessions. The PCM course aims to encompass the body of knowledge, skills, and attitudes necessary to become a competent physician. First- and second-year students have more opportunities than previously to interact with patients and practicing physicians in the community. Competition between learning areas, student perceptions of "soft" and "hard" courses, teacher recruitment, and administrative burnout are ongoing difficulties, while faculty recognition and development, administrative commitment and flexibility, and student and faculty feedback all contribute to the success of the course. The PCM course is now the backbone of the first two years of medical school and creates a solid foundation for the third and fourth years.


Brief pitch-priming facilitates infants' discrimination of pitch-evoking noise: evidence from event-related potentials.
Pitch is derived by the auditory system through complex spectrotemporal processing. Pitch extraction is thought to depend on both spectral cues arising from lower harmonics that are resolved by cochlear filters in the inner ear, and on temporal cues arising from the pattern of action potentials contained in the cochlear output. Adults are capable of extracting pitch in the absence of robust spectral cues, taking advantage of the temporal cues that remain. However, recent behavioral evidence suggests that infants have difficulty discriminating between stimuli with different pitches when resolvable spectral cues are absent. In the current experiments, we used the mismatch negativity (MMN) component of the event related potential derived from electroencephalographic (EEG) recordings to examine a cortical representation of pitch discrimination for iterated rippled noise (IRN) stimuli in 4- and 8-month-old infants. IRN stimuli are pitch-evoking sounds generated by repeatedly adding a segment of white noise to itself at a constant delay. We created IRN stimuli (delays of 5 and 6ms creating pitch percepts of 200 and 167Hz) and high-pass filtered them to remove all resolvable spectral pitch cues. In experiment 1, we did not find EEG evidence that infants could detect the change in the pitch of these IRN stimuli. However, in Experiment 2, after a brief period of pitch-priming during which we added a sine wave component to the IRN stimulus at its perceived pitch, infants did show significant MMN in response to pitch changes in the IRN stimuli with sine waves removed. This suggests that (1) infants can use temporal cues to process pitch, although such processing is not mature and (2) that a short amount of pitch-priming experience can alter pitch representations in auditory cortex during infancy.


Antitrypanosomal effects of polyamine biosynthesis inhibitors correlate with increases in Trypanosoma brucei brucei S-adenosyl-L-methionine.
We reported recently that administration of ([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine (MDL 73811), an enzyme-activated irreversible inhibitor of S-adenosyl-L-methionine decarboxylase (AdoMetDC; EC 22.214.171.124), a key enzyme in the synthesis of spermidine, cures African trypanosome infections in mice. The precise mechanism of action of MDL 73811 was not clear because a rapid disappearance of trypanosomes from the bloodstream of treated rats occurred before significant depletion of spermidine. Administration of MDL 73811 to Trypanosoma brucei brucei-infected rats resulted in a 70% decrease in parasitaemia within 1 h and a complete disappearance of parasites by 5 h. The reduction in parasitaemia was accompanied by complete inhibition of AdoMetDC activity by 10 min after injection of MDL 73811; inhibition was sustained for at least 4 h. Polyamine levels in trypanosomes were unaffected during the first 1 h in which the marked decrease in parasitaemia was observed, but parasite AdoMet levels increased 20-fold within this time. In contrast, exposure of cultured mammalian cells to MDL 73811 resulted in only a 1.5-2-fold increase in AdoMet levels over a 6 h time course. Experiments with inhibitors of ornithine decarboxylase (ODC) also suggested that the increased AdoMet levels might be an important factor for antitrypanosomal efficacy. Trypanosomes taken from rats treated for 36 h with eflornithine, an inhibitor of ODC, were depleted of putrescine and had markedly decreased spermidine levels. These organisms also had less than 10% of control AdoMetDC activity, and had elevated decarboxy AdoMet (greater than 4000-fold) and AdoMet (up to 50-fold) levels. The methyl ester of alpha-monofluromethyl-3,4-dehydro-ornithine (delta-MFMO-CH3), which cures murine T. b. brucei infections, and the ethyl ester analogue of this compound (delta-MFMO-C2H5), which does not cure this infection, become ODC inhibitors upon hydrolysis and thus were tested for their effects on trypanosomal polyamines, AdoMet and decarboxy AdoMet levels. Although both esters of delta-MFMO depleted trypanosomal polyamines, AdoMet and decarboxy AdoMet levels were elevated in T. b. brucei from infected mice treated with delta-MFMO-CH3 but not in parasites from mice treated with the delta-MFMO-C2H5. These data suggest that inhibition of AdoMetDC, either directly with MDL 73811 or indirectly with inhibitors of ODC, apparently leads to a trypanosome-specific elevation of AdoMet. It is possible that major changes in AdoMet, rather than changes in polyamines, may be responsible for the antitrypanosomal effects of these drugs.


Demonstrations of Cooperative Perception: Safety and Robustness in Connected and Automated Vehicle Operations.
Cooperative perception, or collective perception (CP), is an emerging and promising technology for intelligent transportation systems (ITS). It enables an ITS station (ITS-S) to share its local perception information with others by means of vehicle-to-X (V2X) communication, thereby achieving improved efficiency and safety in road transportation. In this paper, we present our recent progress on the development of a connected and automated vehicle (CAV) and intelligent roadside unit (IRSU). The main contribution of the work lies in investigating and demonstrating the use of CP service within intelligent infrastructure to improve awareness of vulnerable road users (VRU) and thus safety for CAVs in various traffic scenarios. We demonstrate in experiments that a connected vehicle (CV) can "see" a pedestrian around the corners. More importantly, we demonstrate how CAVs can autonomously and safely interact with walking and running pedestrians, relying only on the CP information from the IRSU through vehicle-to-infrastructure (V2I) communication. This is one of the first demonstrations of urban vehicle automation using only CP information. We also address in the paper the handling of collective perception messages (CPMs) received from the IRSU, and passing them through a pipeline of CP information coordinate transformation with uncertainty, multiple road user tracking, and eventually path planning/decision-making within the CAV. The experimental results were obtained with manually driven CV, fully autonomous CAV, and an IRSU retrofitted with vision and laser sensors and a road user tracking system.


Micronutrient levels and nutritional status of school children living in Northwest Ethiopia.
Several micronutrients are essential for adequate growth of children. However, little information is available on multiple micronutrient status of school children in Ethiopia. The present study was designed to evaluate the relationship between multiple micronutrient levels and nutritional status among school children. In this cross-sectional study, anthropometric data, blood and stool samples were collected from 100 children at Meseret Elementary School in Gondar town, Northwest Ethiopia. Serum concentration of magnesium, calcium, iron, copper, zinc, selenium and molybdenum were measured by inductively coupled plasma mass spectrometer. Anthropometric indices of weight-for-age, height-for-age and BMI-for-age were used to estimate the children's nutritional status. Stool samples were examined by standard microscopic methods for intestinal parasites. The prevalence of stunting, underweight, wasting and intestinal parasitoses among school children was 23%, 21%, 11% and 18%, respectively. The mean serum levels of magnesium, calcium, iron, copper, zinc, selenium and molybdenum were 2.42±0.32 (mg/dl), 15.31±2.14 (mg/dl), 328.19±148.91 (μg/dl), 191.30±50.17 (μg/dl), 86.40±42.40 (μg/dl), 6.32±2.59 (μg/dl), and 0.23±0.15 (μg/dl), respectively. Selenium deficiency, zinc deficiency and magnesium deficiency occurred in 62%, 47%, and 2% of the school children, respectively. Height-for-age showed significant positive correlation with the levels of copper and molybdenum (p = 0.01) and with the levels of magnesium (p = 0.05). Deficiencies of selenium and zinc were high among the school children although the deficiencies were not significantly related with their nutritional status. The prevalence of both malnutrition and intestinal parasitism was not negligible. These calls for the need to undertake multicentre studies in various parts of the country to substantiate the data obtained in the present study so that appropriate and beneficial strategies for micronutrient supplementation and interventions on nutritional deficiencies can be planned.


Inhibition of chronic ulcerative colitis-associated colorectal adenocarcinoma development in a murine model by N-acetylcysteine.
Long-term ulcerative colitis (UC) patients are at increased risk for developing colorectal cancer. In order to develop strategies for preventing UC-associated carcinogenesis, we studied the effect of the antioxidant N-acetylcysteine (NAC) on UC-associated cancer development in a mouse model. Female C57BL/6J mice were subjected to long-term administration of dextran sulfate sodium (DSS) in the drinking fluid and 2-fold iron-enriched AIN76A diet, with or without NAC. In the DSS-plus-2-fold iron positive control group, gross tumor incidence was 88.5% (23/26 mice) after 12 DSS cycles (1 DSS cycle = 7 day DSS treatment period followed by 10 day recovery period). The tumor multiplicity was 2.1 +/- 0.2 tumors/tumor-bearing mouse, and the tumor volume was 0.054 +/- 0.019 cm3. With 0.2% NAC administration, tumor incidence was significantly reduced (68%, 17/25 mice; P < 0.05), as was the tumor multiplicity (1.5 +/- 0.1 tumors/tumor-bearing mouse; P < 0.05). The tumor volume was lower (0.014 +/- 0.004 cm3), but not significantly decreased. The proliferation index was significantly decreased in non-cancerous epithelia (48.5 +/- 6.0% vs 32.0 +/- 3.7%; P < 0.05), but not in tumor cells. NAC significantly induced apoptosis in both non-cancerous epithelia and colorectal adenocarcinoma. The number of cells immunostained-positive for nitrotyrosine was markedly decreased in the non-cancerous mucosa of NAC-treated mice (102.4 +/-16.6 positive cells/mm2 mucosa vs 53.6 +/- 14.9 cells/mm2; P < 0.05). In addition, the number of inducible nitric oxide synthase (iNOS)-positive inflammatory cells in the non-cancerous mucosa of the distal colon was markedly decreased by NAC. This study indicates that the antioxidant NAC has the potential to serve as a preventive agent for UC-associated colorectal cancer, possibly via inhibition of cellular proliferation and nitrosative stress-caused cellular damage.


Implementing tobacco use treatment guidelines in public health dental clinics in New York City.
In this study we evaluated the effect of a multicomponent intervention to implement the Public Health Service (PHS) guideline Treating Tobacco Use and Dependence in six randomly selected dental clinics in New York University's College of Dentistry. The main outcome measure-provider adherence to tobacco use treatment guidelines-was assessed by auditing a random selection of patient charts pre (698) and post (641) intervention. The intervention components included a chart reminder and referral system, free nicotine replacement therapy (NRT), and provider training and feedback. The results showed that rates of screening for tobacco use did not change between pre and post test chart audits. However, providers were significantly more likely to offer advice (28.4 percent pre, 49 percent post), assess readiness to quit (17.8 percent pre, 29.9 percent post), and offer assistance (6.5 percent pre and 15.6 percent post) in the post test period. Increases in NRT distribution were associated with booster training sessions but declined in the time periods between those trainings. Research is needed to further define sustainable strategies for implementing tobacco use treatment in dental clinics. The results of this study suggest the feasibility and effectiveness of using a tailored multicomponent approach to implement tobacco use treatment guidelines in dental clinics.


Cinmethylin controls multiple herbicide-resistant Lolium rigidum and its wheat selectivity is P450-based.
Multiple-herbicide resistance in Lolium rigidum and other weed species is increasingly exerting pressure on herbicide discovery research for solutions against resistance-prone weeds. In this study we investigate: (i) the responses of L. rigidum populations and wheat to the new herbicide cinmethylin in comparison with other pre-emergence herbicides, (ii) the effect of seed burial depths on cinmethylin efficacy and crop selectivity, and (iii) the basis of cinmethylin selectivity in wheat. Cinmethylin at 400 g ha-1 controls herbicide-susceptible and multiple-resistant L. rigidum, with a reduction of >85% in plant emergence and 90% in aboveground biomass. Cinmethylin provides effective control of a large number of field populations of L. rigidum with evident resistance to trifluralin. When the wheat seed is buried ≥1 cm below the cinmethylin-treated soil surface, the emergence of crop seedlings is not different from the untreated control. The organophosphate insecticide phorate synergizes cinmethylin toxicity in wheat, with an LD50 of 682 g ha-1 in the absence of phorate versus 109 g ha-1 in the presence of phorate (84% reduction). The synergistic effect of phorate with cinmethylin on herbicide-susceptible L. rigidum appears smaller (a 44% reduction in the LD50 of cinmethylin). Cinmethylin is effective in controlling multiple-resistant L. rigidum and appears safe for wheat when the seed is separated at depth from the herbicide applied to the soil surface. The basis of this metabolism-based selectivity is likely regulated by cytochrome P450 monooxygenases. © 2020 Society of Chemical Industry.


Outcome of Single- vs Multiple-visit Endodontic Therapy of Nonvital Teeth: A Meta-analysis.
Endodontic therapy is a specialized procedure more demanded by patients within public oral health care in the country. Then, single-visit endodontic therapy may offer advantages to the health care services, to the professionals, and to the patients by reducing access barriers. A meta-analysis was done and the variables evaluated were periapical repair, microbiological control, and postobturation pain in randomized clinical trials (RCTs) involving endodontic treatment of nonvital teeth at single- or multiple visits. About 17 RCTs were included. There were no differences found in periapical repair or microbiological control in single- and multiple-visit therapy. Single-visit endodontic therapy resulted in 21% less postobturation pain (relative risks = 0.79; 95%, confidence interval: 0.66-0.94). There was less postobturation pain in the single-visit endodontic therapy group. In the public dental care, this analysis favors the adoption of this one therapy because it will be possible to increase the patient access and the supply of this therapy. It is possible to get a better cost-effectiveness for the patients and the health care service. This is very important because the reduction of the cost to the patient allows it to become a complete treatment. The health service, in turn, is able to be better used, with a greater supply of this service.


MRI phenotypes of the brain are related to future stroke and mortality in patients with manifest arterial disease: The SMART-MR study.
Neurodegenerative and neurovascular diseases lead to heterogeneous brain abnormalities. A combined analysis of these abnormalities by phenotypes of the brain might give a more accurate representation of the underlying aetiology. We aimed to identify different MRI phenotypes of the brain and assessed the risk of future stroke and mortality within these subgroups. In 1003 patients (59 ± 10 years) from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, different quantitative 1.5T brain MRI markers were used in a hierarchical clustering analysis to identify 11 distinct subgroups with a different distribution in brain MRI markers and cardiovascular risk factors, and a different risk of stroke (Cox regression: from no increased risk compared to the reference group with relatively few brain abnormalities to HR = 10.34; 95% CI 3.80↔28.12 for the multi-burden subgroup) and mortality (from no increased risk compared to the reference group to HR = 4.00; 95% CI 2.50↔6.40 for the multi-burden subgroup). In conclusion, within a group of patients with manifest arterial disease, we showed that different MRI phenotypes of the brain can be identified and that these were associated with different risks of future stroke and mortality. These MRI phenotypes can possibly classify individual patients and assess their risk of future stroke and mortality.


SH2-B and APS are multimeric adapters that augment TrkA signaling.
Neurotrophins influence growth and survival of sympathetic and sensory neurons through activation of their receptors, Trk receptor tyrosine kinases. Previously, we identified Src homology 2-B (SH2-B) and APS, which are structurally similar adapter proteins, as substrates of Trk kinases. In the present study, we demonstrate that both SH2-B and APS exist in cells as homopentamers and/or heteropentamers, independent of Trk receptor activation. Structure-function analyses revealed that the SH2-B multimerization domain resides within its amino terminus, which is necessary for SH2-B-mediated nerve growth factor (NGF) signaling. Overexpression of SH2-B enhances both the magnitude and duration of TrkA autophosphorylation following exposure of PC12 cells to NGF, and this effect requires the amino-terminal multimerization motif. Moreover, the amino terminus of SH2-B is necessary for TrkA/SH2-B-mediated morphological differentiation of PC12 cells. Together, these results indicate that the multimeric adapters SH2-B and APS influence neurotrophin signaling through direct modulation of Trk receptor autophosphorylation.


Ethnic inequalities in psychological distress among urban residents in the Netherlands: A moderating role of neighborhood ethnic diversity?
The main purpose of this study was to investigate whether neighborhood ethnic diversity moderated the association between ethnicity and psychological distress in the four largest cities of Netherlands. Multilevel linear regression analysis was used to assess whether the association between ethnicity and psychological distress differed by levels of neighborhood ethnic diversity. Results showed that the Turkish and Moroccan residents reported significantly higher psychological distress than native Dutch and Surinamese residents. In high ethnic diverse neighborhoods Turkish residents reported significantly less psychological distress than in low ethnic diverse neighborhoods. Ethnic diversity amplifies the risk of depression for some but not all ethnic minorities.


Phaeocystidibacter marisrubri sp. nov., a member of the family Cryomorphaceae isolated from Red Sea sediment.
Strain G18(T), a Gram-stain-negative, aerobic, rod-shaped, motile, non-fermentative, yellow-pigmented bacterium, was isolated from Red Sea sediment. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain G18(T) was most closely related to Phaeocystidibacter luteus PG2S01(T) with 95.3% similarity. Growth of strain G18(T) occurred at 10-42 °C (optimum 28-37 °C), pH 5.0-9.0 (optimum pH 6.0-8.0) and in the presence of 0.5-10% NaCl (optimum 2-5%). The major fatty acids of strain G18(T) were iso-C15 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 1 G and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, unidentified aminolipids, phospholipids and other lipids. The predominant quinone was menaquinone 6 (MK-6). The G+C content of the genomic DNA from strain G18(T) was 39.0 mol%. Based on the phylogenetic and phenotypic properties, strain G18(T) represents a novel species of the genus Phaeocystidibacter, for which the name Phaeocystidibacter marisrubri sp. nov. is proposed. The type strain is G18(T) ( = CGMCC 1.14954(T)= JCM 30614(T)).


Portal vein or hepatic vein? A curious aberrant vasculature in the liver with idiopathic portal hypertension.
The existence of aberrant vasculatures has been described as one of the characteristic findings in the liver with idiopathic portal hypertension (IPH). In this paper, the morphological features and the genesis of aberrant vasculatures were studied on the basis of autopsy and biopsy materials of IPH and animal experiments. Aberrant vasculatures in IPH livers are characterized as thin-walled vessels located mainly adjacent to the portal tracts and at times in the hepatic lobules. Although some of them are morphologically very similar to hepatic vein branches, they are portal in nature. These aberrant vessels develop in order to compensate for portal circulatory insufficiency due to obliteration of portal vein branches, and play an important role in maintaining an adequate blood supply to the parenchyma. It is predicted that decrease of these intrahepatic collateral vessels is responsible for or related to parenchymal atrophy and deterioration of liver function in the advanced stage of this disease. We regard these vasculatures as characteristic of the intrahepatic portal venous obstruction, particularly with portal hypertension accompanied by increased portal blood flow.


Novel chyme reinfusion device for gastrointestinal fistulas and stomas: feasibility study.
High-output enterostomies and enteroatmospheric fistulas are common causes of intestinal failure, and may necessitate parenteral nutrition and prolonged hospital stay. Reinfusing lost chyme into the distal gut is known to be beneficial, but implementation has been limited because manual reinfusion is unpleasant and labour-intensive, and no devices are available. A new device is presented for reinfusing chyme easily and efficiently, with first-in-human data. The device comprises a compact centrifugal pump that fits inside a standard stoma appliance. The pump is connected to an intestinal feeding tube inserted into the distal intestinal limb. The pump is activated across the appliance by magnetic coupling to a hand-held driver unit, effecting intermittent bolus reinfusion while avoiding effluent contact. Safety, technical and clinical factors were evaluated. Following microbiological safety testing, the device was evaluated in ten patients (median duration of installation 39·5 days; total 740 days). Indications included remediation of high-output losses (8 patients), dependency on parenteral nutrition (5), and gut rehabilitation before surgery (10). Reinfusion was well tolerated with use of regular boluses of approximately 200 ml, and no device-related serious adverse events occurred. Clinical benefits included resumption of oral diet, cessation of parenteral nutrition (4 of 5 patients), correction of electrolytes and liver enzymes, and hospital discharge (6 of 10). Of seven patients with intestinal continuity restored, one experienced postoperative ileus. A novel chyme reinfusion device was developed and found to be safe, demonstrating potential benefits in remediating high-output losses, improving fluid and electrolyte balance, weaning off parenteral nutrition and improving surgical recovery. Pivotal trials and regulatory approvals are now in process.


[Brain death: biological and ethical aspects].
The article presents briefly historical development of death criteria from the modern times to the present. The criteria which are used for identification and diagnosing death on the base of respiratory and circulatory death definition are described. This work underlines the inadequacy of the definition of the brain death in relation to patients with persistent vegetative state and in relation to anencephalic newborns. The author describes the pathology and clinical and laboratory evidence of the brain stem death, which gave the possibility to justify the thesis that in case of the brain stem death ontological arguments are sufficient for diagnosing the death of a human being. The attention of the ethic of the life sanctity (on the base of halachic's law) and its opposing influence on the evolution of the medical definition of death has been paid. The recognition of the brain as the death of an individual is a cultural shock, which from scientific point of view changed the ways of thinking, almost immediately but did not in the awareness of the society. The work also underlies the fact that utilitarian argumentation can not be a criterion for making a decision concerning the life of an individual.


Helicobacter pylori infection promotes methylation and silencing of trefoil factor 2, leading to gastric tumor development in mice and humans.
Trefoil factors (TFFs) regulate mucosal repair and suppress tumor formation in the stomach. Tff1 deficiency results in gastric cancer, whereas Tff2 deficiency increases gastric inflammation. TFF2 expression is frequently lost in gastric neoplasms, but the nature of the silencing mechanism and associated impact on tumorigenesis have not been determined. We investigated the epigenetic silencing of TFF2 in gastric biopsy specimens from individuals with Helicobacter pylori-positive gastritis, intestinal metaplasia, gastric cancer, and disease-free controls. TFF2 function and methylation were manipulated in gastric cancer cell lines. The effects of Tff2 deficiency on tumor growth were investigated in the gp130(F/F) mouse model of gastric cancer. In human tissue samples, DNA methylation at the TFF2 promoter began at the time of H pylori infection and increased throughout gastric tumor progression. TFF2 methylation levels were inversely correlated with TFF2 messenger RNA levels and could be used to discriminate between disease-free controls, H pylori-infected, and tumor tissues. Genome demethylation restored TFF2 expression in gastric cancer cell lines, so TFF2 silencing requires methylation. In Tff2-deficient gp130(F/F)/Tff2(-/-) mice, proliferation of mucosal cells and release of T helper cell type-1 (Th-1) 1 cytokines increased, whereas expression of gastric tumor suppressor genes and Th-2 cytokines were reduced, compared with gp130(F/F)controls. The fundus of gp130(F/F)/Tff2(-/-) mice displayed glandular atrophy and metaplasia, indicating accelerated preneoplasia. Experimental H pylori infection in wild-type mice reduced antral expression of Tff2 by increased promoter methylation. TFF2 negatively regulates preneoplastic progression and subsequent tumor development in the stomach, a role that is subverted by promoter methylation during H pylori infection.


Mediation of macrophage collagenase production by 3'-5' cyclic adenosine monophosphate.
The production of collagenase by lipopolysaccharide-(LPS) activated guinea pig macrophages is mediated by prostaglandins (PG) of the E series. After stimulation of guinea pig macrophages with LPS, extracellular PGE levels and cellular cAMP levels are elevated. Indomethacin inhibits not only PG synthesis, but also cAMP and collagenase production in LPS-stimulated macrophage cultures. In these indomethacin-inhibited cultures containing LPS, dibutyryl (dB) cAMP, or cholera toxin can restore macrophage collagenase production but not PG synthesis. Moreover, dBcAMP and cholera toxin enhance collagenase production in LPS-activated cultures. Initial activation of the macrophages by an agent such as LPS is a prerequisite for synthesis of collagenase, since in the absence of LPS, dBcAMP or cholera toxin alone are ineffective stimuli. These findings clearly demonstrate a role for PG-induced elevations of cAMP in the production of collagenase by LPS-activated macrophages.


Conserved aromatic residues of the C-terminus of human butyrylcholinesterase mediate the association of tetramers.
Human butyrylcholinesterase (BChE) in serum is composed predominantly of tetramers. The tetramerization domain of each subunit is contained within 40 C-terminal residues. To identify key residues within this domain participating in tetramer stabilization, the interaction between C-terminal 46 residue peptides was quantitated in the yeast two-hybrid system. The wild-type peptide interacted strongly with another wild-type peptide in the yeast two-hybrid system. The C571A mutant peptides interacted to a similar degree as the wild-type. However, the mutant in which seven conserved aromatic residues (Trp 543, Phe 547, Trp 550, Tyr 553, Trp 557, Phe 561, and Tyr 564) and C571 were altered to alanines showed only 12% of the interaction seen with the wild-type peptide. The seven mutations (aromatics-off) were incorporated into the complete BChE molecule, with or without the C571A mutation, and expressed in 293T and CHO-K1 cells. Expression of wild-type BChE in these cell lines yielded 10% tetramers. The aromatics-off mutant formed dimers and monomers but no tetramers. The aromatics-off/C571A mutant yielded only monomers. Addition of poly-L-proline to culture medium, or coexpression with the N-terminus of COLQ including the proline-rich attachment domain (Q(N)PRAD), increased the amount of tetrameric wild-type BChE from 10 to 70%, but had no effect on the G534stop (lacking 41 C-terminal residues) and the aromatics-off mutants. Recombinant BChE produced by coexpression with Q(N)PRAD was purified by column chromatography. The purified tetramers contained the FLAG-tagged Q(N)PRAD peptide. These observations suggest that the stabilization of BChE tetramers is mediated through the interaction of the seven conserved aromatic residues and that poly-L-proline and PRAD act through these aromatic residues to induce tetramerization.


Randomized trial of working memory training as an adjunct to inpatient substance use disorder treatment.
Despite interest in computerized working memory training as a transdiagnostic intervention, little is known about its feasibility and efficacy in addiction treatment settings. This double-blind, randomized controlled trial examined the efficacy of working memory training for improving performance on standardized measures of executive function during inpatient substance use disorder treatment. Secondary outcomes included delay discounting, adherence to cognitive training, and posttreatment relapse. Adults (N = 110) entering inpatient alcohol or drug treatment were randomized to active (adaptive) or control (nonadaptive) training conditions, with up to 25 training sessions spanning inpatient and postdischarge phases. In generalized estimating equation (GEE) analyses, the experimental group showed relatively greater improvements on the primary outcome (digit span performance) based on Time × Treatment interactions in per-protocol (p < .05) and intent-to-treat (p = .07) models. Similar results were observed for one secondary outcome. Lower working memory performance at baseline predicted significantly greater delay discounting; however, no time or treatment effects on discounting were observed. Adherence to cognitive training was generally good during inpatient treatment, but suboptimal overall. These results suggest that implementing cognitive training is feasible in inpatient settings, and that adaptive working memory training can potentially lead to near-transfer effects for select cognitive outcomes. However, further work is necessary to establish training effects on clinical outcomes and to improve adherence in outpatient contexts. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Resonating models for the electric power market.
This paper describes the economic phenomenon of price spiking in electric power markets and introduces an alternative way to model it. A stochastic FitzHugh-Nagumo dynamics in a special regime is proposed as a basic model for the power market, and an extension of the FitzHugh-Nagumo system is introduced to improve the statistical features of the basic model. Ideas from stochastic and coherence resonance are used to discuss the models.


The ftsA* gain-of-function allele of Escherichia coli and its effects on the stability and dynamics of the Z ring.
Formation of the FtsZ ring (Z ring) in Escherichia coli is the first step in the assembly of the divisome, a protein machine required for cell division. Although the biochemical functions of most divisome proteins are unknown, several, including ZipA, FtsA and FtsK, have overlapping roles in ensuring that the Z ring assembles at the cytoplasmic membrane, and that it is active. As shown previously, a single amino acid change in FtsA, R286W, also called FtsA*, bypasses the requirement for either ZipA or FtsK in cell division. In this study, the properties of FtsA* were investigated further, with the eventual goal of understanding the molecular mechanism behind the bypass. Compared to wild-type FtsA, the presence of FtsA* resulted in a modest but significant decrease in the mean length of cells in the population, accelerated the reassembly of Z rings, and suppressed the cell-division block caused by excessively high levels of FtsZ. These effects were not mediated by Z-ring remodelling, because FtsA* did not alter the kinetics of FtsZ turnover within the Z ring, as measured by fluorescence recovery after photobleaching. FtsA* was also unable to permit normal cell division at below normal levels of FtsZ, or after thermoinactivation of ftsZ84(ts). However, turnover of FtsA* in the ring was somewhat faster than that of wild-type FtsA, and overexpressed FtsA* did not inhibit cell division as efficiently as wild-type FtsA. Finally, FtsA* interacted more strongly with FtsZ compared with FtsA in a yeast two-hybrid system. These results suggest that FtsA* interacts with FtsZ in a markedly different way compared with FtsA.


Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris.
Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz, the acute phase reaction, total fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the fibrinogen beta-gene. The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers, selected on genotype of the Bcl] polymorphism of the fibrinogen beta-gene, and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study. Functional plasma fibrinogen levels were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and TDP levels were measured using an enzyme immuno assay (EIA). In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p = 0.005 using the paired Student l-test) after 4 weeks of 250 mg bid ticlopidine administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP and TDP levels were significantly higher than in the volunteer group. After four weeks 250 mg bid ticlopidine administration the functional fibrinogen levels had decreased by 0.38 g/l (11%, p < 0.005), whereas the fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels of functional and antigen fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen beta-gene polymorphisms. Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen beta-gene polymorphisms.


A novel test reliably captures hip and knee kinematics and kinetics during unanticipated/anticipated diagonal hops in individuals with anterior cruciate ligament reconstruction.
Unanticipated land-and-cut maneuvers might emulate lower limb mechanics associated with anterior cruciate ligament (ACL) injury. Reliability studies on landing mechanics of such maneuvers are however lacking. This study investigated feasibility and within-session reliability of landing mechanics of a novel one-leg double-hop test, mimicking a land-and-cut maneuver, in individuals with ACL reconstruction (ACLR). Our test comprised a forward hop followed by a diagonal hop in either of two directions (medial/lateral) under anticipated and unanticipated conditions. Twenty individuals with a unilateral ACLR (aged 24.2 ± 4.2 years, 0.7-10.8 years post-surgery) performed three successful hops/direction per leg. We determined reliability (intraclass correlation coefficient [ICC]) and agreement (standard error of measurement [SEM]) of 3-dimensional hip and knee angles and moments during the deceleration phase of the land-and-cut maneuver (vulnerable for non-contact ACL injuries). Mean success rate for unanticipated hops was 71-77% and for anticipated hops 91-95%. Both limbs demonstrated moderate-excellent reliability (ICC 95% confidence intervals: 0.50-0.99) for almost all hip and knee peak angles and moments in all planes and conditions, with a few exceptions: poor-good reliability for hip and knee frontal and/or transverse plane variables, especially for lateral diagonal hops. The SEMs were ≤5° and ≤0.23 N·m/kg·m for most peak angles and moments, respectively. Our test seems feasible and showed satisfactory reliability for most hip and knee angles and moments; however, low knee abduction and internal rotation angles and moments, and moderate reliability of these moments deserve consideration. The test appears to challenge dynamic knee control and may prove valuable in evaluation during knee rehabilitation.


Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae.
Cdc45, which binds to the minichromosomal maintenance (Mcm) proteins, has a pivotal role in the initiation and elongation steps of chromosomal DNA replication in eukaryotes. Here we show that throughout the cell cycle in Saccharomyces cerevisiae, Cdc45 forms a complex with a novel factor, Sld3. Consistently, Sld3 and Cdc45 associate simultaneously with replication origins in the chromatin immunoprecipitation assay: both proteins associate with early-firing origins in G(1) phase and with late-firing origins in late S phase. Moreover, the origin associations of Sld3 and Cdc45 are mutually dependent. The temperature-sensitive sld3 mutation confers a defect in DNA replication at the restrictive temperature and reduces an interaction not only between Sld3 and Cdc45, but also between Cdc45 and Mcm2. These results suggest that the Sld3-Cdc45 complex associates with replication origins through Mcm proteins. At the restrictive temperature in sld3-5 cells, replication factor A, a single-strand DNA binding protein, does not associate with origins. Therefore, the origin association of Sld3-Cdc45 complex is prerequisite for origin unwinding in the initiation of DNA replication.


[Study of nucleoside phosphorescence with a phosphorescent microscope].
Phosphorescence of ribonucleosides and desoxyribonucleosides is studied. The phosphorescence spectra of polycrystalline powders of adenosine, guanosine, thymidine, uridine, cytidine, desoxyadenosine, desoxyguanosine and desoxycytidine are recorded at -175 degrees C as well as the decay curves at -175 degrees C. The phosphorescence spectrum of guanosine is also recorded at room temperature. The decay times of phosphorescence of adenosine and cytidine are determined at room temperature too. Obtained values of pi for nucleosides are shorter than those for nucleic acid bases.


Drosophila Myc is oncogenic in mammalian cells and plays a role in the diminutive phenotype.
Biochemical and biological activities of Myc oncoproteins are highly dependent upon their association with another basic region helix-loop-helix/leucine zipper (bHLH/LZ) protein, Max. Our previous observation that the DNA-binding/dimerization region of Max is absolutely conserved throughout vertebrate evolution provided the basis for a yeast two-hybrid interaction screen that led to the isolation of the Drosophila Myc (dMyc1) protein. Structural conservation in regions of known functional significance is consistent with the ability of dMyc1 to interact with vertebrate Max, to transactivate gene expression in yeast cells, and to cooperate with activated H-RAS to effect the malignant transformation of primary mammalian cells. The ability of P-element-mediated ectopic expression of dmyc1 to reverse a subset of the phenotypic alterations associated with the diminutive mutation suggests that diminutive may correspond to dmyc1. This finding, along with the localization of dmyc1 expression to zones of high proliferative activity in the embryo, implicates dMyc1 as an integral regulator of Drosophila growth and development.


Never in care: characteristics of HIV-infected crack cocaine users in 2 US cities who have never been to outpatient HIV care.
There are very limited data available of the correlates of HIV-infected crack users who have never been to HIV care. Interviews were conducted at bedside with HIV-infected crack cocaine users who were recruited from the inpatient wards at Jackson Memorial Hospital in Miami, FL, and Grady Memorial Hospital in Atlanta, GA, between August 2006 and July 2009. Participants were asked about their sociodemographic characteristics, drug use, drug/alcohol treatment history, use of HIV care, perceived social support, and mental health status. Multiple logistic regression was performed to identify factors associated with never having been to HIV care. Among 355 study participants, 21% reported never having been to a doctor or clinic for HIV care. Higher adjusted odds of never having been in care were associated with an annual income of less than $5000 [adjusted odds ratio (AOR) = 8.17, 95% confidence interval (CI) = 3.35 to 19.94], residence in Atlanta compared with Miami (AOR = 2.57, 95% CI = 1.36 to 4.83), no history of drug treatment (AOR = 4.13, 95% CI = 2.24 to 7.62), and not being helped into care at the time of HIV diagnosis (AOR = 2.83, 95% CI = 1.56 to 5.15). Our data show that a significant proportion of HIV-infected crack cocaine users in 2 city hospitals have never been to HIV care. Interventions at the time of HIV diagnosis and drug treatment participation may facilitate linkage to care.