Benefits and Risks of Smallholder Livestock Production on Child Nutrition in Low- and Middle-Income Countries.
Livestock production may improve nutritional outcomes of pregnant women and children by increasing household income, availability of nutrient-dense foods, and women's empowerment. Nevertheless, the relationship is complex, and the nutritional status of children may be impaired by presence of or proximity to livestock and their pathogens. In this paper, we review the benefits and risks of livestock production on child nutrition. Evidence supports the nutritional benefits of livestock farming through income, production, and women's empowerment. Increasing animal source food consumption requires a combination of efforts, including improved animal management so that herd size is adequate to meet household income needs and consumption and addressing sociocultural and gendered norms. Evidence supports the inclusion of behavior change communication strategies into livestock production interventions to facilitate the sustainability of nutritional benefits over time, particularly interventions that engage women and foster dimensions of women's empowerment. In evaluating the risks of livestock production, evidence indicates that a broad range of enteric pathogens may chronically infect the intestines of children and, in combination with dietary deficits, may cause environmental enteric dysfunction (EED), a chronic inflammation of the gut. Some of the most important pathogens associated with EED are zoonotic in nature with livestock as their main reservoir. Very few studies have aimed to understand which livestock species contribute most to colonization with these pathogens, or how to reduce transmission. Control at the point of exposure has been investigated in a few studies, but much less effort has been spent on improving animal husbandry practices, which may have additional benefits. There is an urgent need for dedicated and long-term research to understand which livestock species contribute most to exposure of young children to zoonotic enteric pathogens, to test the potential of a wide range of intervention methods, to assess their effectiveness in randomized trials, and to assure their broad adaptation and sustainability. This review highlights the benefits and risks of livestock production on child nutrition. In addition to identifying research gaps, findings support inclusion of poor gut health as an immediate determinant of child undernutrition, expanding the established UNICEF framework which includes only inadequate diet and disease.


Rupture of Arteriovenous Fistula After Transplant Kidney's Biopsy: A Case Report.
To comment on the diagnosis and management of a rupture of arteriovenous fistula which is a rare but serious complication after transplant kidney's biopsy. The report was performed on a serious case with rupture of arteriovenous fistula after transplant kidney's biopsy in 108 Military Central Hospital. On the 7th day after biopsy, after moving out of the technical room for double J-stent removal, the patient suddenly felt a sharp pain in the transplanted kidney, followed by constant and increasing pain, also complete anuria. We revealed an arteriovenous fistula at the lower pole causing the parenchymal rupture and a large hematoma surround the graft and occupying the retroperitoneum. The emergency operation was done to remove the hematoma and suture the graft's wound containing the arteriovenous fistula to stop the bleeding and eventually salvage the graft. Rupture of arteriovenous fistula after transplant kidney's biopsy is a rare but severe complication likely lead to graft loss. The patient should be carefully monitored with blood tests and Doppler ultrasound as a routine at least 2 weeks after biopsy.


Drosophila hybrids in nature: proof of gene exchange between sympatric species.
Genetic studies of two closely related endemic Hawaiian species show that in one area of sympatry about 2 percent of the naturally occurring individuals are hybrids. More than 20 times this many would be expected if the population consisted of a single panmictic unit. Despite hybridization, natural selection appears to maintain the essential integrity of each separate gene pool.


Experimental data of bio self-healing concrete incubated in saturated natural soil.
The provision of suitable incubation environments is vital for successful implementation of bio self-healing concrete (bio-concrete). We investigated the effect of soil incubation to examine if the self-healing process can be activated in comparison with the conventional incubation environment (water). The data was collected from laboratory-scale experiments conducted on mortar specimens. The mortar was impregnated with Bacillus subtilis and this bacteria was encapsulated in calcium alginate for protection from the production process. The mortar specimens were mechanically cracked and then incubated within fine-grained fully saturated natural soil for about 4 weeks. The cracks were inspected before and after incubation by light microscopy to evaluate the healing ratio. The mineral precipitations on crack surfaces were examined by Scanning Electron Microscope (SEM) and Energy Dispersive X-Ray Spectrometry (EDX). The data reflects the efficiency of bio-concrete for certain structures such as tunnels and deep foundation, where concrete elements are exposed to ground conditions.


[Electrocardiographic criteria of probable localization of coronary arteriosclerosis].
Forty-nine patients with coronary atherosclerosis (according to the results of selective angiography), whose ages ranged from 29 to 59 years, were examined. Comparison with the results of ECG at rest and the findings of coronarography showed no changes in the QRS complex in 16% of patients with lesions of two and in 10% of those with obstructive changes in three main coronary artery. Displacement of the ST segment as a sign of myocardial ischemia during physical exercise tests in leads V5--V6 of the ECG coincided with obstructive lesions of the left coronary artery in 91% of cases. Patients suffering from obstructive lesions of the right coronary artery with or without atherosclerotic changes in the left coronary artery reacted by depression of the ST segment in the II, III, and aVF leads of the ECS. The authors suggest that there exists a mechanism of "intracoronary steal" of perfusion blood supply when the ischemic changes on the ECG do not coincide with the localization of coronary atherosclerosis.


SOX9 predicts progression toward cirrhosis in patients while its loss protects against liver fibrosis.
Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study, we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression toward cirrhosis. Inactivation of Sox9 in mice protected against both parenchymal and biliary fibrosis, and improved liver function and ameliorated chronic inflammation. SOX9 was downstream of mechanosignaling factor, YAP1. These data demonstrate a role for SOX9 in liver fibrosis and open the way for the transcription factor and its dependent pathways as new diagnostic, prognostic, and therapeutic targets in patients with liver fibrosis.


Effects of hypochlorous acid exposure on the rejection of salt, polyethylene glycols, boron and arsenic(V) by nanofiltration and reverse osmosis membranes.
The separation layer of polyamide-based (PA) thin film composite (TFC) membranes can be modified by active chlorine species. The PA-TFC membranes, NF90, BW30 and NF270, were exposed to different concentrations of sodium hypochlorite (NaOCl) at pH 5 for 24 h. Elemental composition obtained from X-ray Photoelectron Spectroscopy (XPS) showed that the chlorine content in the PA layer increased with the chlorine concentrations. Treatment of membranes with 10 ppm Cl increased the membrane hydrophilicity. By contrast, when treated with 1000 ppm Cl or more, the membranes became less hydrophilic. Water permeability values for all 3 membrane types declined with increased chlorine concentrations. Filtration of polyethylene glycols (PEGs) with molecular weights of 200, 400 and 600 Daltons (Da) was performed to investigate the influence of chlorine treatment on membrane molecular weight cut off (MWCO) and rejection by size exclusion. Treatment with 10 and 100 ppm Cl lowered the MWCO while treatment with higher concentrations increased the MWCO. All chlorinated membranes experienced higher NaCl rejection compared to virgin ones. The performance of NF90 was tested with respect to the rejection of inorganic contaminants including boron (H(3)BO(3)) and arsenic (H(2)AsO(4)(-)). The boron rejection results paralleled PEG rejection whereas those for arsenic followed NaCl rejection patterns. The changes in membrane performance due to chlorine treatment were explained in terms of competing mechanisms: membrane tightening, bond cleavage by N-chlorination and chlorination promoted polyamide hydrolysis.


Fluctuation of latent inhibition along the estrous cycle in the rat: modeling the cyclicity of symptoms in schizophrenic women?
Latent inhibition (LI) is a cross-species selective attention phenomenon manifested as poorer conditioning of stimuli that had been experienced as irrelevant prior to conditioning. Disruption of LI by pro-psychotic agents such as amphetamine and its restoration by antipsychotic drugs (APDs) is a well-established model of psychotic symptoms of schizophrenia. There is evidence that in schizophrenic women symptom severity and treatment response fluctuate along the menstrual cycle. Here we tested whether hormonal fluctuation along the estrous cycle in female rats (as determined indirectly via the cellular composition of the vaginal smears) would modulate the expression of LI and its response to APDs. The results showed that LI was seen if rats were in estrus during pre-exposure stage and in metestrus during the conditioning stage of the LI procedure (estrus-metestrus) but not along the remaining sequential phases of the cycle (metestrus-diestrus, diestrus-proestrus and proestrus-estrus). Additionally, the efficacy of typical and atypical APDs, haloperidol and clozapine, respectively, in restoring LI depended on estrous condition. Only LI disruption in proestrus-estrus exhibited sensitivity to both APDs, whereas LI disruption in the other two phases was alleviated by clozapine but not haloperidol. Our results show for the first time that both the expression of LI and its sensitivity to APDs are modulated along the estrous cycle, consistent with fluctuations in psychotic symptoms and response to APDs seen along women's menstrual cycle. Importantly, the results indicate that although both low and high levels of hormones may give rise to psychotic-like behavior as manifested in LI loss, the pro-psychotic state associated with low hormonal level is more severe due to reduced sensitivity to typical APDs. The latter constellation may mimic states of increased vulnerability to psychosis coupled with reduced treatment response documented in schizophrenic women during periods associated with low levels of hormones.


Status of anatomic pathology data management systems.
Criteria are presented for selecting and evaluating anatomic pathology computer systems, along with a definition of critical performance areas. Also included are a review of factors in computer technology and coding of diagnoses that are leading to increasing use of computers in anatomic pathology and a list of current systems, some of which are available commercially. A suggested outline of pathologists' data management requirements to facilitate communication with computer marketing personnel and systems developers, and a classification of anatomic pathology data management systems are also presented.


Periadventitial inducible nitric oxide synthase expression and intimal thickening.
Positioning a silicone collar around the rabbit carotid artery induces a smooth muscle cell-rich intimal thickening. We investigated the localization of inducible nitric oxide synthase (iNOS) during thickening of the intima, the effect of iNOS inhibition on intimal thickness, and the effect of oxidized LDL (ox-LDL) on iNOS expression in the vessel wall. Collars were positioned for 18 hours or for 3, 7, or 14 days. Arterial cross sections were immunostained for iNOS, including naïve, sham-operated, and carotid arteries in which ox-LDL had been infused locally for 14 days. Furthermore, collars were connected to osmotic minipumps for local delivery (5 microL. h(-1), 14 days, n=12) of saline or the iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine-HCl (L-NIL, 10 mmol/L). In the adventitia and the periadventitial granulation tissue of collared arteries, iNOS-positive macrophages and T lymphocytes were present from 18 hours onward. The media and intima were negative for iNOS. Reverse transcription-polymerase chain reaction revealed iNOS mRNA in collared but not in sham-operated arteries. Local inhibition of iNOS doubled the intimal thickness and decreased nitrotyrosine staining. Ox-LDL-treated arteries, which had a thicker intima, showed a pronounced influx of macrophages and T lymphocytes in all layers of the vessel wall, accompanied by iNOS expression in a subpopulation of these cells. Our study indicates that iNOS was not induced in intimal thickenings predominantly consisting of smooth muscle cells. However, iNOS was expressed in (peri)adventitial tissue and counteracted the progression of intimal thickening. Ox-LDL treatment was accompanied by an abundant influx of iNOS-positive macrophages and T lymphocytes in the vessel, but this could not prevent the progression of intimal thickening.


[Laparoscopic surgery for endoscopically irretrievable colonic polyps].
The vast majority of benign colorectal neoplasms can be safely removed by colonoscopic polypectomy; while peduncolated polyps can be easily endoscopically excised, the removal of sessile polyps may be more difficult. Between January 1997 and December 1998, 12 patients underwent laparoscopic or laparoscopic-assisted colonic resection for treatment of endoscopically irretrievable colonic polyps; this group was compared to 12 patients who underwent a laparotomic approach for polyps in the same period of time and to 23 patients who previously underwent similar laparoscopic resections. There were no significant differences between laparoscopic and laparotomic groups. Laparoscopic or laparoscopic-assisted colonic resection for treatment of endoscopically irretrievable colonic polyps remains our preferred method of treating these lesions.


Prevalence of atopic symptoms among blood donor carriers of mannose-binding lectin variant alleles.
Mannose-binding lectin (MBL) is a C-type soluble collectin involved in the innate immune response. Carriers of MBL gene variant alleles (MBLva) have decreased plasma concentrations of MBL and increased susceptibility to bacterial and viral infections. The aim of the present study is to test the hypothesis that carriers of MBLva could have a different frequency of atopic symptoms as compared to wild-type carriers. A total of 385 consecutively enrolled Caucasian blood donors were studied. Blood specimens underwent genomic analysis and genotyping for MBLva by polymerase chain reaction (PCR). MBLva carrier status was associated with a reduced frequency of allergic rhinitis (OR 0.41 [95% CI 0.2 to 0.8], chi2 = 6.98, p =.008). No relationship was found between MBLva carrier status and asthma or atopic skin symptoms. MBLva might be one of the host-related genetic factors involved in atopic disorders, namely allergic rhinitis.


Variable Projection Support Vector Machines and Some Applications Using Adaptive Hermite Expansions.
In this paper, we develop the so-called variable projection support vector machine (VP-SVM) algorithm that is a generalization of the classical SVM. In fact, the VP block serves as an automatic feature extractor to the SVM, which are trained simultaneously. We consider the primal form of the arising optimization task and investigate the use of nonlinear kernels. We show that by choosing the so-called adaptive Hermite function system as the basis of the orthogonal projections in our classification scheme, several real-world signal processing problems can be successfully solved. In particular, we test the effectiveness of our method in two case studies corresponding to anomaly detection. First, we consider the detection of abnormal peaks in accelerometer data caused by sensor malfunction. Then, we show that the proposed classification algorithm can be used to detect abnormalities in ECG data. Our experiments show that the proposed method produces comparable results to the state-of-the-art while retaining desired properties of SVM classification such as light weight architecture and interpretability. We implement the proposed method on a microcontroller and demonstrate its ability to be used for real-time applications. To further minimize computational cost, discrete orthogonal adaptive Hermite functions are introduced for the first time.


The immune system profoundly restricts intratumor genetic heterogeneity.
Tumors develop under the selective pressure of the immune system. However, it remains critical to establish how the immune system affects the clonal heterogeneity of tumors that often display cell-to-cell variation in genetic alterations and antigenic expression. To address these questions, we introduced a multicolor barcoding strategy to study the growth of a MYC-driven B cell lymphoma harboring a large degree of intratumor genetic diversity. Using intravital imaging, we visualized that lymphoma subclones grow as patches of sessile cells in the bone marrow, creating a spatially compartmentalized architecture for tumor diversity. Using multicolor barcoding and whole-exome sequencing, we demonstrated that immune responses strongly restrict intratumor genomic diversity and favor clonal dominance, a process mediated by the selective elimination of more immunogenic cells and amplified by epitope spreading. Anti-PD-1 treatment also narrowed intratumor diversity. Our results provide direct evidence that immune pressure shapes the level of intratumor genetic heterogeneity and have important implications for the design of therapeutic strategies.


Implementing a patient education intervention about Methicillin-resistant Staphylococcus aureus prevention and effect on knowledge and behavior in veterans with spinal cord injuries and disorders: a pilot randomized controlled trial.
To assess the feasibility and effect of a nurse-administered patient educational intervention about Methicillin-resistant Staphylococcus aureus (MRSA) prevention on knowledge and behavior of Veterans with spinal cord injuries and disorders (SCI/D). Blinded, block-randomized controlled pilot trial. Two Department of Veterans Affairs (VA) SCI Centers. Veterans were recruited March-September 2010 through referral by a healthcare provider from inpatient, outpatient, and residential care settings. Thirty participants were randomized to the nurse-administered intervention and 31 to the usual care group. The intervention included a brochure and tools to assist nurses in conducting the education. Pre- and post-intervention measurement of knowledge and behaviors related to MRSA and prevention strategies and feasibility measures related to implementation. Participants were primarily male (95.1%), white (63.9%), with tetraplegia (63.9%) and mean age and duration of injury of 64.3 and 20.5 years, respectively. The intervention groups mean knowledge score significantly increased between pre- and post-test (mean change score = 1.70, 95% confidence interval, CI 0.25-3.15) while the usual care groups score did not significantly change (mean change score = 1.45, 95% CI -0.08-2.98). However, the mean knowledge change between intervention and usual care groups was not significantly different (P = 0.81). Overall behavior scores did not significantly differ between treatment groups; however, the intervention group was more likely to report intentions to clean hands (90.0% vs. 64.5%, P = 0.03) and asking providers about MRSA status (46.7% vs. 16.1%, P = 0.01). Nurse educators reported that the quality of the intervention was high and could be implemented in clinical care. A targeted educational strategy is feasible to implement in SCI/D clinical practices and may improve some participants' knowledge about MRSA and increase intentions to improve hand hygiene and engagement with providers about their MRSA status.


On non-invasive measurement of gastric motility from finger photoplethysmographic signal.
This article investigates the possibility of extracting gastric motility (GM) information from finger photoplethysmographic (PPG) signals non-invasively. Now-a-days measuring GM is a challenging task because of invasive and complicated clinical procedures involved. It is well-known that the PPG signal acquired from finger consists of information related to heart rate and respiratory rate. This thread is taken further and effort has been put here to find whether it is possible to extract GM information from finger PPG in an easier way and without discomfort to the patients. Finger PPG and GM (measured using Electrogastrogram, EGG) signals were acquired simultaneously at the rate of 100 Hz from eight healthy subjects for 30 min duration in fasting and postprandial states. In this study, we process the finger PPG signal and extract a slow wave that is analogous to actual EGG signal. To this end, we chose two advanced signal processing approaches: first, we perform discrete wavelet transform (DWT) to separate the different components, since PPG and EGG signals are non-stationary in nature. Second, in the frequency domain, we perform cross-spectral and coherence analysis using autoregressive (AR) spectral estimation method in order to compare the spectral details of recorded PPG and EGG signals. In DWT, a lower frequency oscillation (≈0.05 Hz) called slow wave was extracted from PPG signal which looks similar to the slow wave of GM in both shape and frequency in the range (0-0.1953) Hz. Comparison of these two slow wave signals was done by normalized cross-correlation technique. Cross-correlation values are found to be high (range 0.68-0.82, SD 0.12, R = 1.0 indicates exact agreement, p < 0.05) for all subjects and there is no significant difference in cross-correlation between fasting and postprandial states. The coherence analysis results demonstrate that a moderate coherence (range 0.5-0.7, SD 0.13, p < 0.05) exists between EGG and PPG signal in the "slow wave" frequency band, without any significant change in the level of coherence in postprandial state. These results indicate that finger PPG signal contains GM-related information. The findings are sufficiently encouraging to motivate further exploration of finger PPG as a non-invasive source of GM-related information.


Calcineurin inhibitor-free immunosuppression in kidney transplantation.
The introduction of calcineurin inhibitors (CNI) revolutionized kidney transplantation (KTx). Exceptionally low acute rejection rates and excellent graft survival could be achieved with CNI-based (cyclosporine and tacrolimus) immunosuppressive protocols. However, despite short-term success, long-term graft attrition continues to be a significant problem, thus leaving clinicians looking for possible interventions. CNI nephrotoxicity is but one of numerous factors that may be contributing to long-term damage in transplant kidneys. Therefore, newer immunosuppressive agents such as mycophenolate mofetil and sirolimus (Rapa) have raised the possibility of withdrawing or avoiding CNIs altogether. Protocols exploring these options have gained greater attention over the last few years. Herein, we review studies addressing either CNI withdrawal or CNI avoidance strategies as well as discuss the risks versus benefits of these protocols. Given the accumulated experience to date, in our opinion, the use of CNIs as a part of immunosuppressive regimens remains the proven standard of care for renal transplant patients. The long-term safety and efficacy of CNI withdrawal and avoidance strategies need to be further validated in controlled clinical trials.


Neointima characteristics as a prognostic marker for drug-coated balloon angioplasty in patients with in-stent restenosis: an optical coherence tomography study.
Research has shown that the prognosis of in-stent restenosis (ISR) lesions after drug-coated balloon (DCB) angioplasty can differ in relation to in-stent neointimal characteristics. However, changes in neointima characteristics after DCB have not been studied. This study sought to investigate changes in neointima characteristics after DCB for ISR. From the Yonsei Optical Coherence Tomography (OCT) registry, data on DCBs performed in patients with ISR were collected. Neointima characteristics were categorized as homogeneous, heterogeneous, layered neointima, and neoatherosclerosis in each OCT procedure. Homogeneous and layered neointima were classified as a favorable neointima, while heterogeneous neointima and neoatherosclerosis were classified as an unfavorable neointima. The data of 67 ISR patients were analyzed. The median duration between initial and follow-up OCT was 9.6 months. Patients with homogeneous and layered neointima on the initial OCT before DCB mostly appeared as homogeneous (66.7 and 68.2%, respectively) on the follow-up OCT, whereas most of the patients with heterogeneous neointima on the initial OCT remained unaltered (70%). Patients with unfavorable neointima at either the initial (P = 0.023) or the follow-up OCT (P = 0.037) had a worse major adverse cardiovascular event-free survival than the other patients. Patients who showed unfavorable neointima at both the initial and the follow-up OCT had the worst event-free survival (P = 0.038). The follow-up OCT neointimal characteristics after DCB for ISR was associated with initial OCT characteristics. Sustained unfavorable neointima in serial OCT imaging may reflect poor prognosis in patients with ISR treated with DCB.


Android Fat Deposition and Its Association With Cardiovascular Risk Factors in Overweight Young Males.
Excess adiposity increases the risk of type-2 diabetes and cardiovascular disease development. Beyond the simple level of adiposity, the pattern of fat distribution may influence these risks. We sought to examine if higher android fat distribution was associated with different hemodynamic, metabolic or vascular profile compared to a lower accumulation of android fat deposits in young overweight males. Forty-six participants underwent dual-energy X-ray absorptiometry and were stratified into two groups. Group 1: low level of android fat (<9.5%) and group 2: high level of android fat (>9.5%). Assessments comprised measures of plasma lipid and glucose profile, blood pressure, endothelial function [reactive hyperemia index (RHI)] and muscle sympathetic nerve activity (MSNA). There were no differences in weight, BMI, total body fat and lean mass between the two groups. Glucose tolerance and insulin resistance (fasting plasma insulin) were impaired in group 2 (p < 0.05). Levels of plasma triglycerides and 5 lipid species were higher in group 2 (p < 0.05). Endothelial function was less in group 2 (RHI: 1.64 vs. 2.26, p = 0.003) and heart rate was higher (76 vs. 67 bpm, p = 0.004). No difference occurred in MSNA nor blood pressure between the 2 groups. Preferential fat accumulation in the android compartment is associated with increased cardiovascular and metabolic risk via alteration of endothelial function.


Myeloperoxidase and its products in synovial fluid of patients with treated or untreated rheumatoid arthritis.
Plasma and synovial myeloperoxidase (MPO) and its products were strongly associated with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, it is well known that there is a link between oxidative stress and cytokines. The present study aims at investigating the link between synovial MPO (and its products), interleukin (IL)-18, which is involved in the degradation of articular cartilage in RA, and IL-8, which is involved in recruitment and activation of neutrophils during inflammation. Effects of the treatment of RA on the biological parameters were also investigated. Patients (n = 105) were studied including 39 patients with OA, 33 with RA and 33 with RA receiving a specific treatment. Disease activity score (DAS-28) was calculated whereas MPO antigen/activity, neutrophils, chloro-tyrosine (Cl-Tyr), homocitrulline (Hcit), IL-8, and IL-18 were measured in synovial fluid (SF) and CRP was measured in serum. DAS-28 and CRP levels were not significantly different between groups. MPO activity, and MPO, Cl-Tyr, and Hcit levels were significantly higher in SF of RA patients than OA patients. MPO specific activity (MPO activity/antigen ratio) was significantly lower in treated than in untreated RA patients as was IL-8. MPO activity and concentration were correlated with IL-8 and IL-18 in untreated but not in treated RA patients. MPO level is related to IL-8 and IL-18 levels in untreated RA patients. A link has been shown between treatment and decrease of IL-8, MPO specific activity and Hcit in SF. The causal role of MPO in SF inflammation and how treatment can affect MPO specific activity need further investigations.


pH effects on red cell deformability.
The effect of pH on erythrocyte deformability was determined in the ektacytometer. In isotonic solutions, cell deformability was essentially unaltered at pH values from 6.44 to 7.7, despite the known cell volume changes that occur over this pH range. Analysis by osmotic scan ektacytometry showed that erythrocyte deformability is homeostatically maintained constant during acidosis and alkalosis because of a balance between the countervailing effects of changes in intracellular viscosity and in the surface to volume ratio. This balance is perturbed in the sickle erythrocyte, so that acidosis improves deformability.


Drug like HSP27 cross linkers with chromenone structure ameliorates pulmonary fibrosis.
Background: Pulmonary fibrosis (PF) is a progressive lung disease characterized by fibroblast accumulation and collagen deposition, resulting in lung scarring and impaired gas exchange. Current treatments for idiopathic pulmonary fibrosis (IPF) have limited efficacy and significant side effects. Heat shock protein 27 (HSP27) has emerged as a potential therapeutic target for PF due to its involvement in fibrotic processes. However, effective HSP27 inhibitors for PF treatment are still lacking. Methods: To assess the anti-fibrotic effects of NA49, we utilized murine PF models induced by radiation (IR) or bleomycin (BLM). We administered NA49 to the PF mice and evaluated its impact on lung fibrosis progression. We also investigated the molecular mechanisms underlying NA49's effects, focusing on its inhibition of EMT-related signaling pathways. Results: In our study, we evaluated the potential of a novel HSP27 inhibitor, NA49, in preclinical models of PF. NA49 effectively suppressed PF development in radiation and bleomycin-induced PF models. It reduced fibrosis, inhibited NFkB signaling, and downregulated EMT-related molecules. Importantly, we evaluated the safety profile of NA49 by assessing its impact on DNA strand breakage. Compared to previous HSP27 inhibitors, NA49 showed lower levels of DNA damage in human lung epithelial cells, and suggests that NA49 may have reduced toxicity compared to other HSP27 inhibitors. Overall, our results demonstrate that NA49 effectively inhibits PF development in preclinical models. It reduces lung fibrosis, inhibits EMT-related signaling pathways, and exhibits improved safety profiles. These findings highlight the potential of NA49 as a promising candidate for the treatment of PF. Conclusion: NA49 exhibited significant anti-fibrotic effects, inhibiting fibrosis development and EMT-related signaling pathways. Moreover, NA49 showed improved safety profiles compared to previous HSP27 inhibitors.


Assessing the latent structure of the intolerance of uncertainty construct: an initial taxometric analysis.
Researchers have increasingly suggested that people with anxiety disorders share a common fear that the uncertain future will be catastrophic. Intolerance of uncertainty (IU) - the tendency to consider possible negative events as unacceptable and threatening, irrespective of probabilities - is representative of such fears. A key role has been indicated for IU in several anxiety and mood disorders; however, the present study appears to be the first latent structure examination of IU. Responses were obtained from a large sample (n=977; 65% women) unselected with regard to IU level, comprising anxiety disorder outpatients (i.e., putative taxon members), and community residents (i.e., putative complement class members). MAXEIG, MAMBAC, and L-Mode were performed with indicator sets drawn from the Intolerance of Uncertainty Scale-12. Assessments also included objective Comparison Curve Fit Indices. Results yielded converging evidence that IU symptoms have a dimensional latent structure. Comprehensive findings, implications, and future research directions are discussed.


Microneurography in relation to intraneural topography: somatotopic organisation of median nerve fascicles in humans.
Microneurography was performed in median nerve sensory fascicles with concentric needle electrodes and with conventional tungsten microneedles. The latter electrodes preferentially recorded activity from the myelinated fibres in the whole fascicle. By contrast, due to its special design, a concentric needle can record activity selectively from even a small part of a fascicle. High amplitude signals in C fibres can be discriminated close to Schwann cells that envelope unmyelinated axons. Apart from being biased for activity in thin fibres, the concentric needles can also record signals from nearby myelinated fibres. The palmar receptive fields of such fibre groups were not congruent with the areas traditionally attributed to multiunit skin afferents in humans, namely the innervation zone(s) of one or two adjacent digital nerve(s). Instead, the multiunit fields often comprised small parts of a digital nerve innervation area, frequently only the pulp of a finger. Single units were always localised within previously screened multiunit areas. Contrary to some previously accepted tenets it is probable that single unit activity in myelinated fibres in these studies is recorded extra-axonally near to a node of Ranvier. The findings also suggest the presence of a somatotopy in human limb nerve fascicles, comparable to that previously established in the spinal cord and the somatosensory cortex.


Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFalpha). Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFalpha drug in the treatment of RA, would modulate systemic and local bone resorption and reduce cartilage degradation. We performed a prospective study of a multicentric cohort of 48 women, mean (SD) age 54.2 (12.1) years old, with severe RA for 11.4 (7.8) years, who started infliximab after failure of other disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54 weeks after initiating Infliximab therapy we measured the following biochemical markers: pro-collagen serum type I N-terminal propeptide (PINP), a marker of bone formation; serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of cathepsin K-mediated bone collagen degradation believed to reflect systemic bone resorption; serum C-terminal cross-linked telopeptide of type I collagen (ICTP), an index of matrix metalloprotease (MMP) mediated type I collagen degradation reflecting preferential joint metabolism; and urinary CTX-II a biochemical markers of cartilage degradation. Total hip and lumbar spine bone mineral density (BMD) was assessed at baseline, and after 6 and 12 months by dual-energy x-ray absorptiometry (DXA). No patient received bisphosphonates while 77% were under oral glucocorticoids. BMD remained stable over 1 year. Serum CTX-I levels rapidly decreased by 19% and 28% at week 6 and week 22, respectively (analysis of variance (ANOVA) p = 0.032) values returning to pre-treatment level at week 54. By contrast, ICTP levels progressively declined with a maximal 25% decrease at week 54 (ANOVA p = 0.028). By contrast, PINP levels remained stable over time, which led to a 30 to 40% improvement in bone remodelling balance, as assessed by the ratios PINP/CTX and PINP/ICTP (p<0.05). There was no significant change of urinary CTX-II in the whole population, but a slight decrease (ANOVA p = 0.041) in those with pre-treatment levels above the upper limit of normal range. In summary, the improvement in the formation/resorption marker ratio suggests beneficial systemic and local bone effects of infliximab in patients with RA.


Right Ventricular Response to Acute Hypoxia Exposure: A Systematic Review.
Background: Acute hypoxia exposure is associated with an elevation of pulmonary artery pressure (PAP), resulting in an increased hemodynamic load on the right ventricle (RV). In addition, hypoxia may exert direct effects on the RV. However, the RV responses to such challenges are not fully characterized. The aim of this systematic review was to describe the effects of acute hypoxia on the RV in healthy lowland adults. Methods: We systematically reviewed PubMed and Web of Science and article references from 2005 until May 2021 for prospective studies evaluating echocardiographic RV function and morphology in healthy lowland adults at sea level and upon exposure to simulated altitude or high-altitude. Results: We included 37 studies in this systematic review, 12 of which used simulated altitude and 25 were conducted in high-altitude field conditions. Eligible studies reported at least one of the RV variables, which were all based on transthoracic echocardiography assessing RV systolic and diastolic function and RV morphology. The design of these studies significantly differed in terms of mode of ascent to high-altitude, altitude level, duration of high-altitude stay, and timing of measurements. In the majority of the studies, echocardiographic examinations were performed within the first 10 days of high-altitude induction. Studies also differed widely by selectively reporting only a part of multiple RV parameters. Despite consistent increase in PAP documented in all studies, reports on the changes of RV function and morphology greatly differed between studies. Conclusion: This systematic review revealed that the study reports on the effects of acute hypoxia on the RV are controversial and inconclusive. This may be the result of significantly different study designs, non-compliance with international guidelines on RV function assessment and limited statistical power due to small sample sizes. Moreover, the potential impact of other factors such as gender, age, ethnicity, physical activity, mode of ascent and environmental factors such as temperature and humidity on RV responses to hypoxia remained unexplored. Thus, this comprehensive overview will promote reproducible research with improved study designs and methods for the future large-scale prospective studies, which eventually may provide important insights into the RV response to acute hypoxia exposure.


Posterior tibial nerve somatosensory cortical evoked potentials in adolescent idiopathic scoliosis.
Somatosensory-evoked potentials were used to evaluate neurologic function in patients with adolescent idiopathic scoliosis. To compare the somatosensory-evoked potentials between patients with adolescent idiopathic scoliosis and healthy control individuals, and to determine the incidence of abnormal somatosensory function in patients with adolescent idiopathic scoliosis. Somatosensory-evoked potentials are sensitive in detecting structural lesions in the somatosensory pathway. Previous studies on somatosensory function in patients with idiopathic scoliosis have demonstrated statistical differences in somatosensory-evoked potential latency between scoliotic and normal groups. However, no documentation of the actual incidence of abnormal somatosensory-evoked potentials is available. Posterior tibial nerve somatosensory cortical evoked potentials were evaluated on 147 young patients with adolescent idiopathic scoliosis and 31 healthy control individuals. Seventeen patients with idiopathic scoliosis showed pathologic evoked potentials. Among them were seven with absent somatosensory-evoked potential waveform and 10 with delayed latency. The results were reproducible on repeated measurement. Adolescent idiopathic scoliosis could be subdivided according to the somatosensory-evoked potential findings into two subgroups, those with and those without a somatosensory pathologic process. Potential clinical significance in predicting curve progression in idiopathic scoliosis could be pursued further.


Determinants of caregiver burden of patients with haemorrhagic stroke in China.
The aim of this study was to assess the caregiver burden over time of patients with haemorrhagic stroke and the determinants of this. Identification of the predictors for caregiver burden can be used to improve the outcomes of stroke survivors and caregivers. Few studies focus on the caregiver burden of patients with haemorrhagic stroke and how this changes over time. This was a prospective longitudinal study. A convenience sample of 202 stroke survivor/caregiver pairs were recruited in the neurosurgery unit from March 2015 to March 2016. The participants were assessed at three different times by face to face or telephone interview. Caregiver burden was assessed using the Bakas Caregiver Outcomes Scale. Sociodemographic data and other characteristics of the pairs were also collected. Multiple linear regression was performed to identify the determinants. Caregiver burden decreased from T1 to T3 significantly. The physical function, depression of stroke survivors, and self-rated burden of caregivers were the most important determinants for overall caregiver burden. The factors identified explained 41.6% to 67.4% of overall burden. Caregiver burden decreased over time, affected by factors from patients and caregivers. More professional caregivers are needed to support informal carers.


Understanding the societal factors of vaccine acceptance and hesitancy: evidence from Hong Kong.
Vaccination is considered to be an important public health strategy for controlling the COVID-19 pandemic. Besides subjective evaluations of the vaccine and the health threat, societal factors have been seen as crucial to vaccination decisions. Based on a socioecological perspective, this study examines the role of societal factors in COVID-19 vaccine hesitancy in Hong Kong. An online survey was fielded between 25 and 28 June 2021, collecting 2753 complete responses. Multinomial logistic regression was conducted to examine how subjective evaluations of the vaccine (summarised by the 5C model - Confidence, Collective responsibility, Constraints, Complacency and Calculation), threat perception, interpersonal influences and institutional trust contribute to explaining three types of decision - acceptant (vaccinated, scheduled or indicated 'Yes'), hesitant (unvaccinated and indicated 'Maybe' on intention) and resistant (unvaccinated and indicated 'No'). A total of 43.2%, 21.7% and 35.1% of respondents were acceptant, hesitant and resistant. Although the 5C model remained useful in explaining vaccination decisions, respondents were heavily influenced by the decisions of their family, although they were less influenced by friends. Second, respondents tended to accept the vaccine when they had a weaker perception that the act is supportive of the government and were less resistant if they had stronger institutional trust. Under the low-incidence and low-trust environment such as Hong Kong, vaccination decisions are heavily influenced by family's decision and the perception of vaccination as socially and politically desirable. Our findings highlight the importance of a nuanced conception of interpersonal and political influence towards vaccine acceptance/hesitancy.


The STR252-IVS10nt546-VNTR7 phenylalanine hydroxylase minihaplotype in five Mediterranean samples.
IVS10nt546 (IVS10nt-11g-->a) is the most common molecular defect of the phenylalanine hydroxylase gene causing phenylketonuria in Mediterranean populations. Previous studies have proposed various and alternative hypotheses concerning the geographical origin and pattern of diffusion of this mutation in this area. In this study, this issue was re-examined on a large sample (149) of "Mediterranean" IVS10nt546 mutant alleles analysed with multiallelic intragenic polymorphisms. The analysis of intragenic microsatellite (STR) and minisatellite (VNTR) polymorphisms shows allelic heterogeneity of the IVS10nt546 mutation. Eight STR and three VNTR alleles were found in association with the splicing defect. Of the ten detected STR-VNTR combinations ("minihaplotypes"), we identified a predominant allelic association (VNTR7-STR252) embedded in a RFLP-haplotype 6 background, which seems to correspond to the ancestral gene originating in the Turkey-Israel area. Analysis of both absolute and relative gene frequencies of the STR252-IVS10nt546-VNTR7 minihaplotypes, shows statistically significant (P < 0.02) variations and may suggest gene flow from Turkey and/or Israel to Italy and Spain. The associated migratory events need not be unique in time (and people) but seem to suggest they may be traced back to the expansion of the Neolithic culture and people, thus allowing dating of the origin of this mutation to at least 5000-10000 years ago. Alternative hypotheses are discussed to explain, in light of the available historical and pre-historical evidence, the pattern of diffusion of the IVS10nt546 mutation in the Mediterranean basin.


Oral immunization against experimental salmonellosis I. Development of temperature-sensitive mutant vaccines.
Mutant strains of Salmonella enteritidis were selected for their inability to proliferate at 37 C; when exposed to this temperature, these organisms formed tangled masses of long filaments in liquid media, presumably as a result of their inability to form cross septa. The mutants were also incapable of synthesizing flagella protein. A study of the biological charateristics of the mutants indicated that in most respects they resembled the parent strain of S. enteritidis; however, they were avirulent for mice, presumably because of the restriction of growth imposed by the body temperature of the animal. Preliminary studies have suggested that these mutants are highly effective in inducing protection against severe challenge infections of S. enteritidis; of especial interest is the fact that, when given orally, the mutants conferred a substantial degree of protection against oral infection with the virulent strain.


An evolutionarily conserved RNA stem-loop functions as a sensor that directs feedback regulation of RNase E gene expression.
RNase E is a key regulatory enzyme that controls the principal pathway for mRNA degradation in Escherichia coli. The cellular concentration of this endonuclease is governed by a feedback mechanism in which RNase E tightly regulates its own synthesis. Autoregulation is mediated in cis by the 361-nucleotide 5' untranslated region (UTR) of rne (RNase E) mRNA. Here we report the determination of the secondary structure of the rne 5' UTR by phylogenetic comparison and chemical alkylation, together with dissection studies to identify the 5' UTR element that mediates autoregulation. Our findings reveal that the structure and function of the rne 5' UTRs are evolutionarily well conserved despite extensive sequence divergence. Within the rne 5' UTRs are multiple RNA secondary structure elements, two of which function in cis to mediate feedback regulation of rne gene expression. The more potent of these two elements is a stem-loop structure containing an internal loop whose sequence is the most highly conserved of any region of the rne 5' UTR. Our data show that this stem-loop functions as a sensor of cellular RNase E activity that directs autoregulation by modulating the degradation rate of rne mRNA in response to changes in RNase E activity.


ANMCO/SIT Consensus Document: telemedicine for cardiovascular emergency networks.
Telemedicine has deeply innovated the field of emergency cardiology, particularly the treatment of acute myocardial infarction. The ability to record an ECG in the early prehospital phase, thus avoiding any delay in diagnosing myocardial infarction with direct transfer to the cath-lab for primary angioplasty, has proven to significantly reduce treatment times and mortality. This consensus document aims to analyse the available evidence and organizational models based on a support by telemedicine, focusing on technical requirements, education, and legal aspects.


Fecal occult blood screening for colorectal cancer.
Fecal occult blood testing with guaiac gum is a simple, safe, and cheap method for screening for colorectal cancer. In the office setting, compliance is good. Asymptomatic colorectal cancers are detected at a more favourable pathologic stage than those detected in symptomatic patients. Because of the low positive predictive value of the test, many persons testing positive undergo unnecessary bowel examinations. As yet, randomized controlled studies have not shown that fecal occult blood screening reduces mortality from colorectal cancer. At present, screening with this test is left to the judgement of the individual physician.


Impaired SHP2-mediated extracellular signal-regulated kinase activation contributes to gefitinib sensitivity of lung cancer cells with epidermal growth factor receptor-activating mutations.
Most non-small cell lung cancers (NSCLC) display elevated expression of epidermal growth factor receptor (EGFR), but response to EGFR kinase inhibitors is predominantly limited to NSCLC harboring EGFR-activating mutations. These mutations are associated with increased activity of survival pathways, including phosphatidylinositol 3-kinase/AKT and signal transducer and activator of transcription 3/5. We report that EGFR-activating mutations also surprisingly lead to decreased ability to activate extracellular signal-regulated kinase (ERK) compared with wild-type EGFR. In NSCLC cells and mouse embryonic fibroblasts expressing mutant EGFR, this effect on ERK correlates with decreased EGFR internalization and reduced phosphorylation of SHP2, a tyrosine phosphatase required for the full activation of ERK. We further show that ERK activation levels affect cellular response to gefitinib. NSCLC cells with EGFR mutation display reduced gefitinib sensitivity when ERK activation is augmented by expression of constitutively active mutants of mitogen-activated protein kinase/ERK kinase (MEK). Conversely, in a NSCLC cell line expressing wild-type EGFR, gefitinib treatment along with or following MEK inhibition increases death response compared with treatment with gefitinib alone. Our results show that EGFR-activating mutations may promote some survival pathways but simultaneously impair others. This multivariate alteration of the network governing cellular response to gefitinib, which we term "oncogene imbalance," portends a potentially broader ability to treat gefitinib-resistant NSCLC.


Associations between self-reported physical activity, quality of life, and emotional well-being in men with prostate cancer on active surveillance.
The relationship between physical activity (PA) and quality of life (QOL) relative to active treatment for prostate cancer (PCa) has been well-studied; however, little is known about this relationship during active surveillance (AS). Moreover, whether PA is associated with better emotional well-being (EWB) in men with low-risk PCa requires further investigation. Accordingly, we examined the association between self-reported PA and the average change in QOL and EWB over time during AS. A total of 630 men on AS were included in this retrospective, longitudinal study from AS initiation until AS discontinuation. Generalized estimated equations were used to determine the association between self-reported PA (independent variable) and QOL and EWB (dependent variables) over time, adjusting for participants' age. QOL was higher over time in active ( β^ (95%CI) = 1.14 (0.11, 2.16), P = .029) and highly active participants ( β^ (95%CI) = 1.62 (0.58, 2.67), P = .002) compared to their inactive counterparts. Highly active participants had 55% greater odds of experiencing high EWB relative to inactive participants (OR (95%CI) = 1.55 (1.11, 2.16), P = .010). In men with low EWB at baseline (median = 3 months after diagnosis), the highest levels of PA (>1000 metabolic equivalent-minutes per week) were associated with high EWB over time (OR (95%CI) = 2.17 (1.06, 4.46), P = .034). These data further support the importance of PA as a supportive care strategy for men on AS. Our findings suggest that engaging in higher volumes of PA post-diagnosis may be beneficial particularly for men exhibiting low emotional well-being early on during AS.


Provision of dental care for medically compromised children in the UK by General Dental Practitioners.
The aim of this study was to investigate the views of General Dental Practitioners (GDPs) regarding their provision of dental treatment for medically compromised children. A questionnaire to assess confidence, experience and willingness to treat eight specific groups of medically compromised children was sent to 524 GDPs. Information is based on 271 completed questionnaires. The median number of children treated by GDPs in each of the eight groups over the previous 5 years was 0-2. Eighty percent of respondents stated that they would value further training in the provision of dental care for medically compromised children. Confidence was highest in providing dental treatment for children with three conditions: congenital heart disease (37% very confident), diabetes (39% very confident) and epilepsy (41% very confident). These were also the conditions that the GDPs reported as presenting most frequently in the dental surgery. GDPs reported least confidence in providing dental care for children with haemophilia (12% very confident) and organ transplants (14% very confident). Only 30% of GDPs wanted to be routinely involved with the provision of dental care for medically compromised children. The results indicate that medically compromised children may have problems accessing dental care and expertise. A system of integrated medical and specialised dental care is suggested.


Soybeans as bioreactors for biopharmaceuticals and industrial proteins.
Plants present various advantages for the production of biomolecules, including low risk of contamination with prions, viruses and other pathogens, scalability, low production costs, and available agronomical systems. Plants are also versatile vehicles for the production of recombinant molecules because they allow protein expression in various organs, such as tubers and seeds, which naturally accumulate large amounts of protein. Among crop plants, soybean is an excellent protein producer. Soybean plants are also a good source of abundant and cheap biomass and can be cultivated under controlled greenhouse conditions. Under containment, the plant cycle can be manipulated and the final seed yield can be maximized for large-scale protein production within a small and controlled area. Exploitation of specific regulatory sequences capable of directing and accumulating recombinant proteins in protein storage vacuoles in soybean seeds, associated with recently developed biological research tools and purification systems, has great potential to accelerate preliminary characterization of plant-derived biopharmaceuticals and industrial macromolecules. This is an important step in the development of genetically engineered products that are inexpensive and safe for medicinal, food and other uses.


Clinical Trials Targeting Aging and Age-Related Multimorbidity.
There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans. Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design. Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging. Accumulation and incidence rates of multimorbidity outcomes were developed by selecting at-risk subsets of individuals from three large cohort studies of older individuals. These provide representative benchmark data for decisions on eligibility, duration, and assessment protocols. Monitoring rules should be sensitive to targeting aging-related, rather than disease-specific, outcomes. Clinical trials targeting aging are feasible, but require careful design consideration and monitoring rules.


The usefulness of serum albumin and urinary creatinine as biochemical indices for monitoring the nutritional status of Nigerians with pulmonary tuberculosis.
The objective is to evaluate the relative roles of urinary creatinine and serum albumin as biochemical markers for monitoring the nutritional status of pulmonary tuberculosis patients during treatment. Thirty-one newly diagnosed pulmonary tuberculosis patients were placed on six months short course regimen. Their weight, body mass index, serum albumin and 24-hour urinary creatinine excretion were determined before treatment, at the end of the 1st, 2nd, 4th and 6th month of treatment. Subjecting the mean values of the weight, BMI and Urinary Creatinine excretion and serum albumin to Friedman test showed significant changes for all the four indices. Further analysis with paired student t-test of the pre-treatment values with end of 6th month values confirmed significant changes in the mean values of weight, BMI and serum albumin. Of these three indices serum albumin with chi-square value of 103.515 demonstrated the most significant changes, while the minimal change observed in urinary creatinine excretion could not be confirmed with paired t-test. We recommend serum albumin (as a more sensitive index) for monitoring the nutrition of patient with pulmonary tuberculosis.


Reversible inactivation of the isocitrate dehydrogenase of Escherichia coli ML308 during growth on acetate.
During aerobic growth of Escherichia coli ML308 on acetate as sole carbon source, the apparent synthesis of isocitrate dehydrogenase was repressed relative to cultures on other carbon sources, such as glucose, which do not employ the glyoxylate bypass as an anaplerotic sequence. When cells were removed from an acetate medium, or when compounds were added which made the operation of the glyoxylate bypass unnecessary, the activity of isocitrate dehydrogenase rapidly increased 3- to 4-fold but fell again on restoration to an acetate medium. Changes in activity were rapid and, furthermore, could be demonstrated in the absence of protein synthesis. It is thus improbable that the mechanism involved degradation or de novo synthesis of the enzyme protein. Oxaloacetate and glyoxylate showed concerted inhibition of isocitrate dehydrogenase which could be relieved by dialysis. Because extracts of low enzyme activity, derived from acetate-metabolizing cells, could not be stimulated by dialysis or by addition of a wide range of metabolites, it is unlikely that low molecular weight, freely dissociable effectors were responsible for stimulation or inhibition of activity. Control of isocitrate dehydrogenase permitted the efficient utilization of acetate as sole source of carbon and energy but perserved the capacity of the cell to respond rapidly to an improvement in nutritional conditions. A limited survey showed that the mechanism is common but not universal among strains of E. coli and occurs in at least one strain each of Klebsiella aerogenes, Salmonella typhimurium and Serratia marcescens.


Effect of the Pacing Strategies on the Open-Water 10-km World Swimming Championships Performances.
To (1) compare the pacing strategies of different-level open-water swimmers during the 10-km race of the FINA 2015 Swimming World Championships and (2) relate these pacing strategies to the race performance. Final and intermediate split times, as well as intermediate race positions, from the 10-km race participants (69 men and 51 women) were collected from the public domain and were divided into 5 groups (G1-G5) depending on their finishing positions. Medalists and finalists (G1 and G2, respectively) presented an even pacing profile with swimming velocities similar to those of the less successful swimmers (G3-G5) on the initial and middle stages of the race but a 1.5-3% increase in swimming velocity in the last quarter of the race. This acceleration toward the end of the race, or "end spurt," was largely related to the race performance and was not observed in the G3 and G4 (even-paced profile) or G5 (positive pacing profile) groups. Intermediate race positions and lap rankings were negatively related to finishing position, indicating a delayed positioning of the most successful swimmers at 25%, 50%, and 75% of race distance. The adoption of a conservative starting strategy by open-water swimmers with a negative pacing profile and delayed partial positioning seems to increase the chances of overall race success, as it allows a fast end spurt that is closely related to successful finishing race positions.


RpoS-mediated growth-dependent expression of the Escherichia coli tkt genes encoding transketolases isoenzymes.
Escherichia coli tktA and tktB genes encode two transketolase isoenzymes involved in the pentose-phosphate pathway, In this study, two reporter lacZ fusions, tktA- and tktB-lacZ, were constructed to examine their transcriptional regulation on the E. coli chromosome. The tktA gene was induced in the exponential growth phase and suppressed in the stationary growth phase. However, the genetic elimination of the rpoS, whose product is an alternative sigma factor (RpoS), derepressed the tktA gene expression in the stationary growth phase, indicating that the RpoS sigma factor negatively regulates the tktA gene expression in the stationary growth phase. On the contrary, the tktB gene expression showed the highest value in the stationary growth phase and the RpoS positively regulated the tktB gene expression in the stationary growth phase. We also verified the role of the RpoS affecting the regulation of the tktA and tktB gene expression by the reverse transcription (RT)-PCR experiments. These results suggest that the differential growth-dependent expressions of the tktA and tktB genes are caused by the RpoS action.


Clinical significance of the combination of preoperative SUVmax and CEA in patients with clinical stage IA lung adenocarcinoma.
Preoperative maximum standardized uptake value (SUVmax) of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography and serum carcinoembryonic antigen (CEA) have been reported as prognostic factors for lung adenocarcinoma. However, the significance of combined SUVmax and CEA in early-stage lung adenocarcinoma is not well known. We retrospectively evaluated the relationship between the combination of SUVmax and CEA and the prognosis of 410 patients with clinical stage IA lung adenocarcinoma who underwent resection. The cutoff values for SUVmax and CEA were determined by receiver operating characteristic curve analysis, and patients were categorized into high SC (SUVmax and CEA) group (SUVmax ≥2.96 and CEA ≥5.3), moderate SC group (either SUVmax <2.96 and CEA ≥5.3 or SUVmax ≥2.96 and CEA <5.3) and low SC group (SUVmax <2.96 and CEA <5.3). Kaplan-Meier curve analysis showed that patients with clinical stage IA lung adenocarcinoma in the high SC group had significantly shorter overall survival (OS) and recurrence-free survival (RFS) than the other groups (p = 0.011 and p < 0.0001, respectively). Multivariate analysis showed that high SC was an independent prognostic factor of OS (p = 0.029) and RFS (p < 0.0001). High values of SUVmax and CEA were associated with poor OS and RFS in patients with stage IA lung adenocarcinoma. Simultaneous evaluation of SUVmax and CEA may be an effective prognostic marker to determine the optimal treatment strategy of early-stage lung adenocarcinoma.


Secondary thrombotic microangiopathy and eculizumab: A reasonable therapeutic option.
Understanding the role of the complement system in the pathogenesis of atypical haemolytic uraemic syndrome and other thrombotic microangiopathies (TMA) has led to the use of anti-complement therapy with eculizumab in these diseases, in addition to its original use in patients with paroxysmal nocturnal haemoglobinuria andatypical haemolytic uraemic syndrome. Scientific evidence shows that both primary and secondary TMAs with underlying complement activation are closely related. For this reasons, control over the complement system is a therapeutic target. There are 2scenarios in which eculizumab is used in patients with TMA: primary or secondary TMA that is difficult to differentiate (including incomplete clinical presentations) and complement-mediated damage in various processes in which eculizumab proves to be efficacious. This review summarises the evidence on the role of the complement activation in the pathophysiology of secondary TMAs and the efficacy of anti-complement therapy in TMAs secondary to pregnancy, drugs, transplant, humoral rejection, systemic diseases and glomerulonephritis. Although experience is scarce, a good response to eculizumab has been reported in patients with severe secondary TMAs refractory to conventional treatment. Thus, the role of the anti-complement therapy as a new treatment option in these patients should be investigated.


PDL1-status predicts primary resistance of metastatic, EGFR-mutated non small cell lung cancers to EGFR tyrosine-kinase inhibitors.
EGFR tyrosine-kinase inhibitors (TKIs) are the reference treatment for metastatic, EGFR-mutated, non-small-cell lung cancers (EGFRm NSCLCs). However, 16-20% of those tumors progress early (3-6 months) and factors predicting that resistance are unknown. This study was undertaken to examine PDL1 status as such a factor. This retrospective analysis included metastatic, EGFRm-NSCLC patients who received first-line 1st-, 2nd- or 3rd-generation EGFR TKIs with PDL1 expression determined in pretreatment biopsies. Kaplan-Meier estimations of probabilities of progression-free survival (PFS) and overall survival (OS) were compared with log-rank test, and logistic-regression analyses. PDL1 status of the 145 included patients was ≥1% (47%), 1-49% (33%) or ≥50% (14%). For PDL1-positive vs PDL1-negative patients, respectively, median PFS lasted 8 (95% CI: 6-12) vs 12 (95% CI: 11-17) months (p = 0.008), with 18% vs. 8% (NS) of NSCLCs progressing at 3 months, and 47% vs. 18% (HR 0.25 [95% CI 0.10-0.566], p<0.001) at 6 months. Multivariate analysis retained 1st- or 2nd-generation EGFR TKI, brain metastases and albuminemia <35 g/L at diagnosis as significantly associated with shorter PFS, but not PDL1 status, which was independently associated with progression at 6 months (HR 3.76 [1.23-12.63], p = 0.02). PDL1-negative and PDL1-positive patients' OS lasted 27 (95% CI 24-39) and 22 (95% CI 19-41) months, respectively (NS). Multivariate analysis retained only brain metastases or albuminemia <35 g/L at diagnosis as being independently associated with OS. PDL1 expression ≥1% seems to be associated with early progression during the first 6 months of first-line EGFR-TKI treatment of metastatic EGFRm NSCLCs, without impacting OS.


Multiple Primary Dedifferentiated Liposarcoma of the Jejunal Mesentery: A Case Report and Review of Literature.
Liposarcoma arising primarily from the intestinal mesentery is a rare malignancy. Malignancy is said to be synchronous when there is occurrence of two or more tumours that have not spread from a common site or recurred and show no evidence of metastasis. Multiple synchronous primary liposarcoma of the mesentery is a very unusual clinical finding. Here, we report a rare case of synchronous multiple primary dedifferentiated liposarcoma of jejunal mesentery in a 36-year-old female patient. Radiological investigations aided in making a provisional diagnosis of an ovarian malignancy. A staging laparotomy was performed and general surgeon's help was sought due to the presence of three separate jejunal mesenteric masses of sizes 8x6 cms, 6x6 cms and 25x20 cms respectively. Complete excision of mesenteric masses with one feet of involved jejunum was done and a jejuno-jejunal anastomosis made. The histopathology report was indicative of multiple dedifferentiated liposarcoma of jejunal mesentery. Postoperatively patient received Doxorubicin, Dacarbazine and Ifosfamide based adjuvant chemotherapy in view of poorly differentiated tumour. Patient remains tumour free for the last 12 months of follow up.


Introducer Design Concepts for an Epicardial Parallel Wire Robot.
Cardiac gene therapies lack effective delivery methods to the myocardium. While direct injection has demonstrated success over a small region, homogenous gene expression requires many injections over a large area. To address this need, we developed a minimally invasive flexible parallel wire robot for epicardial interventions. To accurately deploy it onto the beating heart, an introducer mechanism is required. Two mechanisms are presented. Assessment of the robot's positioning, procedure time, and pericardium insertion forces are performed on an artificial beating heart. Successful positioning was demonstrated. The mean procedure time was 230 ± 7 seconds for mechanism I and 259 ± 4 seconds for mechanism II. The mean pericardium insertion force was 2.2 ± 0.4 N anteriorly and 3.1 ± 0.4 N posteriorly. Introducer mechanisms demonstrate feasibility in facilitating the robot's deployment on the epicardium. Pericardium insertion forces and procedure times are consistent and reasonable.


The impact of progress indicators on task completion.
A near ubiquitous feature of user interfaces is feedback on task completion or progress indicators such as the graphical bar that grows as more of the task is completed. The presumed benefit is that users will be more likely to complete the task if they see they are making progress but it is also possible that feedback indicating slow progress may sometimes discourage users from completing the task. This paper describes two experiments that evaluate the impact of progress indicators on the completion of on-line questionnaires. In the first experiment, progress was displayed at different speeds throughout the questionnaire. If the early feedback indicated slow progress, abandonment rates were higher and users' subjective experience more negative than if the early feedback indicated faster progress. In the second experiment, intermittent feedback seemed to minimize the costs of discouraging feedback while preserving the benefits of encouraging feedback. Overall, the results suggest that when progress seems to outpace users' expectations, feedback can improve their experience though not necessarily their completion rates; when progress seems to lag behind what users expect, feedback degrades their experience and lowers completion rates.


Engaging doctors in the health care revolution.
A health care revolution is under way, and doctors must be part of it. But many are deeply anxious and angry about the transformation, fearing loss of autonomy, respect, and income. Given their resistance, how can health system Leaders engage them in redesigning care? In this article, Dr. Thomas H. Lee, Press Ganey's chief medical officer, and Dr. Toby Cosgrove, the CEO of the Cleveland Clinic, describe a framework they've developed for encouraging buy-in. Adapting Max Weber's "typology of motives," and applying behavioral economics and other motivational principles, they describe four tactics leadership must apply in concert: engaging doctors in a noble shared purpose; addressing their economic self-interest; leveraging their desire for respect; and appealing to their sense of tradition. Drawing from experiences at the Mayo Clinic, Geisinger Health System, Partners HealthCare, the Cleveland Clinic, Ascension Health, and others, the authors show how the four motivational levers work together to bring this critical group of stakeholders on board.


Colonic motility diagnosis based on colonic pressure.
Manometry of the alimentary tract is a valuable and widely used means to evaluate and diagnose the function of the alimentary tract. However, the measurement can be inconvenient due to the invasive method used, and the many factors affecting results. Research on colonic pressure data is even more insufficient. This paper deals with colonic pressure data via an improved method ensuring that pressure data of the whole colon is available. The data is analysed based on the learning vector quantization (LVQ) method. Testing results show that this method distinguishes the normal data and the abnormal data, consistently with the original diagnoses. This method can serve as an assistant diagnosis of colonic motility and contributes to further research on colonic motility based on pressure data.


Reliable indexing using unreliable recognition devices.
A new method is described and tested for using an unreliable character recognition device to produce a reliable index for a collection of documents. All highly likely substitution errors of the recognition device are handled by transforming characters which confuse readily into the same pseudocharacter. An analysis of the method is done showing the expected precision (fraction of words correctly found to words present) and recall (fraction of words retrieved properly to those which were retrieved). Published substitution error matrices were employed, along with a large file of words and word frequencies to evaluate the method. Performance was surprisingly good. Suggestions for further enhancements are given.


[Generalized epileptic seizures in an infant due to passive exposure to cocaine].
The differential diagnosis of afebrile seizures in the first year of life is extensive. A 7-month old infant presented two afebrile generalized tonic-clonic seizures in 23 hours; her psychomotor and growth development followed a normal course. Laboratory analysis, cerebral echography and electroencephalogram were normal. Urine toxicology was positive for cocaine on two occasions. A negative urine sample was obtained 48 hours later. The parents denied drug abuse but explained a recent exposure to smoke some hours before the episode. The patient had no seizures in the following six months, with normal psychomotor development. Passive inhalation of cocaine is associated with seizures in infants. There is no perception of the risk of passive exposure to cocaine in our country, despite the increasing consumption of crack in young adults. Urine toxicology should be systematically included in the study of a first afebrile seizure in an infant.


Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively.
Mitochondrial dysfunction may contribute to dopaminergic (DAergic) cell death in Parkinson's disease and GABAergic cell death in Huntington's disease. In the present work, we tested whether blocking A1 receptors could enhance the damage to DAergic and GABAergic neurons caused by mitochondrial inhibition, and whether blocking A2a receptors could protect against damage in this model. Animals received an intraperitoneal injection of 8-cyclopentyl-1,3-dipropylxanthine (CPX) (A1 antagonist) or 3,7-dimethyl-1-propargylxanthine (DMPX) (A2a antagonist) 30 min before intrastriatal infusion of malonate (mitochondrial complex II inhibitor). Damage was assessed 1 week later by measuring striatal dopamine, tyrosine hydroxylase (TH), and GABA content. In mice and rats, malonate-induced depletion of striatal dopamine, TH, or GABA was potentiated by pretreatment with 1 mg/kg CPX and attenuated by pretreatment with 5 mg/kg DMPX. To determine the location of the A1 and A2a receptors mediating these effects, CPX or DMPX was infused directly into the striatum or substantia nigra of rats 30 min before intrastriatal infusion of malonate. When infused into the striatum, CPX (20 ng) potentiated, whereas DMPX (50 ng) prevented malonate-induced GABA loss, but up to 100 ng of CPX or 500 ng of DMPX did not alter malonate-induced striatal dopamine loss. Intranigral infusion of CPX (100 ng) or DMPX (500 ng), however, did exacerbate and protect, respectively, against malonate-induced striatal dopamine loss. Thus, A1 receptor blockade enhances and A2a receptor blockade protects against damage to DAergic and GABAergic neurons caused by mitochondrial inhibition. Interestingly, these effects are mediated by A1 and A2a receptors located in the substantia nigra for DAergic neurons and in the striatum for GABAergic neurons.


Including Children with Developmental Disabilities in the Equation During this COVID-19 Pandemic.
Amidst the ongoing novel Coronavirus disease pandemic, children with developmental disabilities warrant specific attention to minimise having disproportionate consequences. These children are especially vulnerable to the effects of the pandemic due to (1) Greater healthcare needs, (2) Dependency on community-based services and (3) Mental health concerns. Healthcare professionals, public health systems and the society needs to come together to advocate for these children by optimising access to healthcare and community intervention services, promoting mental well-being and caregiver welfare. The consequences of missed present-day opportunities might only be evident in the years to come in these children. Hence, despite the prolonged pandemic, with consequent limitations in availability of resources, children with developmental disabilities should continue to be supported.


Carboxy-terminal dendrimers with phenylalanine for a pH-sensitive delivery system into immune cells including T cells.
Although T cells play important roles in various immune reactions, there are only a few reports on delivery systems into T cells. Our previous study showed that carboxy-terminal phenylalanine (Phe)-modified polyamidoamine (PAMAM) dendrimers have both temperature- and pH-sensitive properties, which are affected by the chemical structure. The self-assembled structures of Phe, observed in phenylketonuria, enhance the protein aggregation, the association with the cell membrane and the membrane permeability. In this study, we applied the Phe-modified dendrimers to a pH-sensitive drug delivery system into T cells. Dendrimers with different amino acids and acid anhydrides were synthesized, and their pH-responsive association with T cells and their subsets was investigated. The dendrimers modified with Phe and cyclohexanedicarboxylic acid (CHex) showed higher uptake into various cells, including Jurkat cells, CD3+ T cells, CD3 + CD4+ helper T cells and CD3 + CD8+ killer T cells. These dendrimers were internalized into T cells via endocytosis, and their cellular uptake was enhanced under weak acidic conditions (pH 6.5). Our results showed that Phe- and CHex-modified dendrimers have a delivery potential to T cells and their subsets, which may be useful for cancer immunotherapy.


Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells.
Because of the many energy-demanding functions they perform and their physical location in the lung, alveolar epithelial type II (ATII) cells have a rapid cellular metabolism and the potential to influence substrate availability and bioenergetics both locally in the lung and throughout the body. A thorough understanding of ATII cell metabolic function in the healthy lung is necessary for determining how metabolic changes may contribute to pulmonary disease pathogenesis; however, lung metabolism is poorly understood at the cellular level. Here, we examine lactate utilization by primary ATII cells and the ATII model cell line, MLE-15, and link lactate consumption directly to mitochondrial ATP generation. ATII cells cultured in lactate undergo mitochondrial respiration at near-maximal levels, two times the rates of those grown in glucose, and oxygen consumption under these conditions is directly linked to mitochondrial ATP generation. When both lactate and glucose are available as metabolic substrate, the presence of lactate alters glucose metabolism in ATII to favor reduced glycolytic function in a dose-dependent manner, suggesting that lactate is used in addition to glucose when both substrates are available. Lactate use by ATII mitochondria is dependent on monocarboxylate transporter (MCT)-mediated import, and ATII cells express MCT1, the isoform that mediates lactate import by cells in other lactate-consuming tissues. The balance of lactate production and consumption may play an important role in the maintenance of healthy lung homeostasis, whereas disruption of lactate consumption by factors that impair mitochondrial metabolism, such as hypoxia, may contribute to lactic acid build-up in disease.


Effects of Klebsiella pneumoniae carbapenemase subtypes, extended-spectrum β-lactamases, and porin mutations on the in vitro activity of ceftazidime-avibactam against carbapenem-resistant K. pneumoniae.
Avibactam is a novel β-lactamase inhibitor with affinity for Klebsiella pneumoniae carbapenemases (KPCs). In combination with ceftazidime, the agent demonstrates activity against KPC-producing K. pneumoniae (KPC-Kp). KPC-Kp strains are genetically diverse and harbor multiple resistance determinants, including defects in outer membrane proteins and extended-spectrum β-lactamases (ESBLs). Mutations in porin gene ompK36 confer high-level carbapenem resistance to KPC-Kp strains. Whether specific mechanisms of antimicrobial resistance also influence the activity of ceftazidime-avibactam is unknown. We defined the effects of ceftazidime-avibactam against 72 KPC-Kp strains with diverse mechanisms of resistance, including various combinations of KPC subtypes and ESBL and ompK36 mutations. Ceftazidime MICs ranged from 64 to 4,096 μg/ml and were lowered by a median of 512-fold with the addition of avibactam. All strains exhibited ceftazidime-avibactam MICs at or below the CLSI breakpoint for ceftazidime (≤4 μg/ml; range, 0.25 to 4). However, the MICs were within two 2-fold dilutions of the CLSI breakpoint against 24% of the strains, and those strains would be classified as nonsusceptible to ceftazidime by EUCAST criteria (MIC > 1 μg/ml). Median ceftazidime-avibactam MICs were higher against KPC-3 than KPC-2 variants (P = 0.02). Among KPC-2-Kp strains, the presence of both ESBL and porin mutations was associated with higher drug MICs compared to those seen with either factor alone (P = 0.003 and P = 0.02, respectively). In conclusion, ceftazidime-avibactam displays activity against genetically diverse KPC-Kp strains. Strains with higher-level drug MICs provide a reason for caution. Judicious use of ceftazidime-avibactam alone or in combination with other agents will be important to prevent the emergence of resistance.


Use of echocardiography for predicting myocardial viability in patients with reperfused anterior wall myocardial infarction.
Dobutamine stress echocardiography (DSE), myocardial contrast echocardiography (MCE), and ultrasonic tissue characterization with integrated backscatter are useful methods for assessing myocardial viability in acute myocardial infarction. In this study, we compared the potential of 3 methods for predicting myocardial viability in 38 patients with reperfused anterior wall acute myocardial infarction. We performed MCE shortly after coronary reperfusion with an intracoronary injection of microbubbles. We recorded 2-dimensional integrated backscatter images at rest and, then, performed low-dose (10 microg/kg/min) DSE 3 days later. In integrated backscatter images, we placed the region of interest in the midwall of the myocardial segment to reconstruct the cyclic variation of myocardial integrated backscatter. The myocardial segment was judged viable when it showed active contraction 3 months later. Among 74 segments analyzed, 34 were judged viable. Presence of contractile response during DSE predicted segmental viability with 91% sensitivity and 78% specificity. Intense and homogenous contrast enhancement with MCE predicted viability with 82% sensitivity and 73% specificity. The presence of synchronous contraction of cyclic variation predicted myocardial viability with 79% sensitivity and 83% specificity. There were no differences in sensitivity and specificity among the 3 methods. Thus, MCE and ultrasonic tissue characterization can predict myocardial viability as accurately as DSE in patients with acute myocardial infarction. The logistics of the methods may determine clinical application.


Catalytic Asymmetric [4+2]-Cycloaddition of Dienes with Aldehydes.
Despite its significant potential, a general catalytic asymmetric [4+2]-cycloaddition of simple and electronically unbiased dienes with any type of aldehyde has long been unknown. Previously developed methodologies invariably require activated, electronically engineered substrates. We now provide a general solution to this problem. We show that highly acidic and confined imidodiphosphorimidates (IDPis) are extremely effective Brønsted acid catalysts of the hetero-Diels-Alder reaction of a wide variety of aldehydes and dienes to give enantiomerically enriched dihydropyrans. Excellent stereoselectivity is generally observed and a variety of scents and natural products can be easily accessed.


Malignant neoplasms after radiation therapy for peptic ulcer.
Most information on radiation-related cancer risk comes from the Life Span Study (LSS) of the Japanese atomic bomb survivors. Stomach cancer mortality rates are much higher in Japan than in the U.S., making the applicability of LSS findings to the U.S. population uncertain. A unique cohort of U.S. patients who were irradiated for peptic ulcer to control gastric secretion provides a different perspective on risk. Cancer mortality data were analyzed and relative risks estimated for 3719 subjects treated by radiotherapy (mean stomach dose 14.8 Gy) and/or by surgery and medication during the period 1936-1965 and followed through 1997 (average 25 years). Compared to the U.S. rates, stomach cancer mortality was significantly increased for irradiated and nonirradiated patients (observed/expected = 3.20 and 1.52, respectively). We observed strong evidence of exposure-related excess mortality from cancer of the stomach (RR 2.6, 95% CI 1.3, 5.1), pancreas (RR 2.7, 95% CI 1.5, 5.1), and lung (RR 1.5, 95% CI 1.1, 2.1), with commensurate radiation dose responses in analyses that included nonexposed patients. However, the dose responses for these cancers were not significant when restricted to exposed patients. Our excess relative risk per gray estimate of 0.20 at doses <or=10 Gy (95% CI 0, 0.73) is consistent with the estimate of 0.24 (95% CI 0.10, 0.40) obtained from the LSS study with the linear model.


Further assessment of the reliability and validity of a Nutritional Risk Index: analysis of a three-wave panel study of elderly adults.
This paper reports on the further assessment of the reliability and validity of a short (16-item), portable method for assessing nutritional risk which is easily administered in the typical social survey setting. Data were obtained from a three-wave panel study of 401 randomly selected, noninstitutionalized elderly persons (age 65 and over) in St. Louis. Reliability was assessed by both internal consistency and test-retest methods. Reliability coefficients (internal consistency) of .603, .544, and .515 were obtained at T-1, T-2, and T-3, respectively. Cross-panel intercorrelations (test-retest) ranged between .67 and .71. Validity was assessed using factor analysis and various outcome measure comparisons for those at risk versus those not at risk. A five-factor orthogonally rotated solution explained 47.9 percent of the variance in the 16 items. Individuals with higher risk scores had significantly poorer health as measured by other standard indexes, and used significantly more health services than those with lower risk scores. These results underscore the potential of the Nutritional Risk Index (NRI) as a screening device for use among the elderly.


Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization.
Blockade of the platelet glycoprotein IIb/IIIa receptor with abciximab (a monoclonal-antibody Fab fragment directed against the receptor) has been shown to diminish ischemic complications among patients undergoing high-risk coronary angioplasty or directional atherectomy but increases bleeding complications. The widespread applicability of this treatment is unknown, particularly in view of the observed risk of hemorrhage. In a prospective, double-blind trial, we randomly assigned patients undergoing urgent or elective percutaneous coronary revascularization at 69 centers to receive abciximab with standard-dose, weight-adjusted heparin (initial bolus of 100 U per kilogram of body weight); abciximab with low-dose, weight-adjusted heparin (initial bolus of 70 U per kilogram); or placebo with standard-dose, weight-adjusted heparin. The primary efficacy end point was death from any cause, myocardial infarction, or urgent revascularization within 30 days of randomization. The trial was terminated at the first interim analysis, with 2792 of the planned 4800 patients enrolled. At 30 days, the composite event rate was 11.7 percent in the group assigned to placebo with standard-dose heparin; 5.2 percent in the group assigned to abciximab with low-dose heparin (hazard ratio, 0.43; 95 percent confidence interval, 0.30 to 0.60; P<0.001); and 5.4 percent in the group assigned to abciximab with standard-dose heparin (hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.63; P<0.001). There were no significant differences among the groups in the risk of major bleeding, although minor bleeding was more frequent among patients receiving abciximab with standard-dose heparin. Inhibition of the platelet glycoprotein IIb/IIIa receptor with abciximab, together with low-dose, weight-adjusted heparin, markedly reduces the risk of acute ischemic complications in patients undergoing percutaneous coronary revascularization, without increasing the risk of hemorrhage.


Perceived motion direction during smooth pursuit eye movements.
Although many studies have been devoted to motion perception during smooth pursuit eye movements, relatively little attention has been paid to the question of whether the compensation for the effects of these eye movements is the same across different stimulus directions. The few studies that have addressed this issue provide conflicting conclusions. We measured the perceived motion direction of a stimulus dot during horizontal ocular pursuit for stimulus directions spanning the entire range of 360 degrees. The stimulus moved at either 3 or 8 degrees/s. Constancy of the degree of compensation was assessed by fitting the classical linear model of motion perception during pursuit. According to this model, the perceived velocity is the result of adding an eye movement signal that estimates the eye velocity to the retinal signal that estimates the retinal image velocity for a given stimulus object. The perceived direction depends on the gain ratio of the two signals, which is assumed to be constant across stimulus directions. The model provided a good fit to the data, suggesting that compensation is indeed constant across stimulus direction. Moreover, the gain ratio was lower for the higher stimulus speed, explaining differences in results in the literature.


Fully solution-processed low-voltage aqueous In2O3 thin-film transistors using an ultrathin ZrO(x) dielectric.
We reported here "aqueous-route" fabrication of In2O3 thin-film transistors (TFTs) using an ultrathin solution-processed ZrOx dielectric thin film. The formation and properties of In2O3 thin films under various annealing temperatures were intensively examined by thermogravimetric analysis, Fourier transform infrared spectroscopy, and atomic force microscopy. The solution-processed ZrOx thin film followed by sequential UV/ozone treatment and low-temperature thermal-annealing processes showed an amorphous structure, a low leakage-current density (∼1 × 10(-9) A/cm(2) at 2 MV/cm), and a high breakdown electric field (∼7.2 MV/cm). On the basis of its implementation as the gate insulator, the In2O3 TFTs based on ZrOx annealed at 250 °C exhibit an on/off current ratio larger than 10(7), a field-effect mobility of 23.6 cm(2)/V·s, a subthreshold swing of 90 mV/decade, a threshold voltage of 0.13 V, and high stability. These promising properties were obtained at a low operating voltage of 1.5 V. These results suggest that "aqueous-route" In2O3 TFTs based on a solution-processed ZrOx dielectric could potentially be used for low-cost, low-temperature-processing, high-performance, and flexible devices.


Myoplasty in chronic osteomyelitis and other postoperative defects of the lower jaw.
Mandibular chronic osteomyelitis is a complicated therapeutical problem in the oral and maxillofacial surgery. While the principles of conservative and radical treatments are generally widely accepted by all authors, the repair of the defects by plastic surgery is inadequately developed. Eleven patients with chronic osteomyelitis, odontogenic cysts and benign tumors of the mandible were treated by filling the osseous defect with a muscle flap from the adjacent m. masseter, m. buccinatorius and m. platysma. The clinical and X-ray examinations showed that a successful outcome without complications was achieved in all treated patients. There was no recurrence of the underlying disease in the five-year follow-up period. Use of muscle pedicle flaps for plastic reconstruction of osteomyelitic cavities and other osseous defects improves the effect of the treatment, shortens its duration and reduces the possibility of further recurrences of the disease.


Role of CD204-positive tumor-associated macrophages in adult T-cell leukemia/lymphoma.
Adult T-cell leukemia/lymphoma (ATLL) is endemic in southwestern Japan, the Caribbean basin, and parts of central Africa, and is considered to be caused by long-term infection with human T-cell leukemia virus type I. CD204 is a scavenger receptor that is overexpressed on alternatively activated macrophages and is known to be overexpressed in tumor-associated macrophages (TAMs). CD206 is also considered a marker of alternatively activated macrophages. However, no studies have investigated CD206 and TAMs. In the present study, we investigated the significance of CD204(+) and CD206(+) TAMs in ATLL tissue samples. We also investigated the correlations with the Ki-67 labeling index (Ki-67LI) and the number of CD31(+) vessels. We found that the number and ratio of CD204(+) TAMs were closely associated with the Ki-67LI, which reflects lymphoma cell proliferation. The number of CD31(+) vessels was not correlated with the number or ratio of CD204(+) and CD206(+) TAMs. The number and ratio of CD204(+) and CD206(+) TAMs, number of CD31(+) vessels, and the Ki-67LI were not associated with the clinical outcome of patients with ATLL. Although further studies are necessary to uncover the detailed mechanisms of CD204 and lymphoma proliferation, these data may provide novel insight into the pathogenesis of ATLL.


Glutamatergic medications for the treatment of drug and behavioral addictions.
Historically, most pharmacological approaches to the treatment of addictive disorders have utilized either substitution-based methods (i.e., nicotine replacement or opioid maintenance) or have targeted monoaminergic or endogenous opioidergic neurotransmitter systems. However, substantial evidence has accumulated indicating that ligands acting on glutamatergic transmission are also of potential utility in the treatment of drug addiction, as well as various behavioral addictions such as pathological gambling. The purpose of this review is to summarize the pharmacological mechanisms of action and general clinical efficacy of glutamatergic medications that are currently approved or are being investigated for approval for the treatment of addictive disorders. Medications with effects on glutamatergic transmission that will be discussed include acamprosate, N-acetylcysteine, d-cycloserine, gabapentin, lamotrigine, memantine, modafinil, and topiramate. We conclude that manipulation of glutamatergic neurotransmission is a relatively young but promising avenue for the development of improved therapeutic agents for the treatment of drug and behavioral addictions.


Zeatin modulates flower bud development and tocopherol levels in Cistus albidus (L.) plants as they age.
In a previous study we showed that Cistus albidus (L.) experiences an age-dependent decay in flower vigour correlated with a decline in trans-zeatin (tZ) levels. In the present study we aimed to establish a causal relationship between these two phenomena. Exogenous tZ applied to plants grown under semi-controlled conditions did not rescue flower vigour; however, it accelerated flower development, but only in younger individuals. Older plants showed lower tocopherol levels in flower buds, which were restored by exogenous tZ, suggesting that a loss of antioxidant defences may underlie the age-dependent decay in flower vigour. We conclude that declining tZ levels may not be directly responsible for the age-associated loss of floral vigour; that tZ modulates the speed of flower development as plants age; and that flower buds alter their sensitivity to tZ as plants age.