The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.
Cerebral ischemia is accompanied by many of the cardinal features of acute inflammation such as neutrophil and platelet activation and accumulation. We sought to determine whether circulating neutrophils or platelets contribute to brain injury in a rabbit model of thromboembolic stroke that includes a fixed duration of superimposed systemic hypotension. We randomized 18 rabbits to receive either antineutrophil antiserum (n = 6), antiplatelet antiserum (n = 5), or nonimmune serum (n = 7). We assessed brain ischemia by measuring cerebral blood flow, intracranial pressure, and infarct size. Following the intracarotid administration of an autologous clot, cerebral blood flow in all groups fell to less than 5 ml/100 g/min during induced hypotension. After restoration of baseline blood pressure, mean cerebral blood flow in neutropenic animals recovered to 20-30 ml/100 g/min while that in control and thrombocytopenic rabbits remained at less than 10 ml/100 g/min. Intracranial pressure in control animals rose steadily to a final value of 241% of baseline, while a much smaller increase (148% of baseline) was noted in the thrombocytopenic group; no change from baseline was evident in the neutropenic group. Infarct size was significantly (p less than 0.05) reduced in the neutropenic group but not in the thrombocytopenic group. These results suggest that neutrophils may be important contributors to ischemia-induced brain injury whereas the role of platelets is more subtle.


Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body.
Sugar overconsumption and chronic stress are growing health concerns because they both may increase the risk for obesity and its related diseases. Rodent studies suggest that sugar consumption may activate a glucocorticoid-metabolic-brain-negative feedback pathway, which may turn off the stress response and thereby reinforce habitual sugar overconsumption. The objective of the study was to test our hypothesized glucocorticoid-metabolic-brain model in women consuming beverages sweetened with either aspartame of sucrose. This was a parallel-arm, double-masked diet intervention study. The study was conducted at the University of California, Davis, Clinical and Translational Science Center's Clinical Research Center and the University of California, Davis, Medical Center Imaging Research Center. Nineteen women (age range 18-40 y) with a body mass index (range 20-34 kg/m(2)) who were a subgroup from a National Institutes of Health-funded investigation of 188 participants assigned to eight experimental groups. The intervention consisted of sucrose- or aspartame-sweetened beverage consumption three times per day for 2 weeks. Salivary cortisol and regional brain responses to the Montreal Imaging Stress Task were measured. Compared with aspartame, sucrose consumption was associated with significantly higher activity in the left hippocampus (P = .001). Sucrose, but not aspartame, consumption associated with reduced (P = .024) stress-induced cortisol. The sucrose group also had a lower reactivity to naltrexone, significantly (P = .041) lower nausea, and a trend (P = .080) toward lower cortisol. These experimental findings support a metabolic-brain-negative feedback pathway that is affected by sugar and may make some people under stress more hooked on sugar and possibly more vulnerable to obesity and its related conditions.


Magnetic resonance energy and topological resonance energy.
Ring-current diamagnetism of a polycyclic π-system is closely associated with thermodynamic stability due to the individual circuits. Magnetic resonance energy (MRE), derived from the ring-current diamagnetic susceptibility, was explored in conjunction with graph-theoretically defined topological resonance energy (TRE). For many aromatic molecules, MRE is highly correlative with TRE with a correlation coefficient of 0.996. For all π-systems studied, MRE has the same sign as TRE. The only trouble with MRE may be that some antiaromatic and non-alternant species exhibit unusually large MRE-to-TRE ratios. This kind of difficulty can in principle be overcome by prior geometry-optimisation or by changing spin multiplicity. Apart from the semi-empirical resonance-theory resonance energy, MRE is considered as the first aromatic stabilisation energy (ASE) defined without referring to any hypothetical polyene reference.


C-reactive protein is a strong independent predictor of death in type 2 diabetes: association with multiple facets of the metabolic syndrome.
It has been suggested that atherosclerotic vascular disease is a chronic inflammatory process. The aim of this study was to investigate the importance of C-reactive protein (CRP) as a cardiovascular risk marker and predictor of death, as well as its relation to other factors of the metabolic syndrome in a cohort of type 2 diabetic patients at high risk of severe macrovascular complications. 592 patients, aged 55 to 74 years (311 men, 281 women), with signs and symptoms of circulation deficits were examined by duplex ultrasound for suspected cerebrovascular and peripheral arterial disease and followed over a period of 5 years. At baseline, 292 patients of the total group had type 2 diabetes (49.3%). Ischemic heart disease was present in 40.2%, internal carotid stenosis in 21.9% and peripheral arterial disease in 39.7% of the subjects. During the observation period, 104 patients had died, 72 (69.2%) due to cardiovascular causes. Non-fatal myocardial infarction occurred in 39 patients (7.4%), non-fatal stroke in 70 patients (13.3%) and amputations because of gangrene were unavoidable in 24 patients (4.6%). In Cox regression analysis, CRP was the strongest predictor of death and cardiovascular death in the total cohort (RR 3.7 [95% CI 1.86-7.50] and 5.4 [2.13-13.76]), as well as in the type 2 diabetic subgroup (RR 3.3 [1.27-8.70] and 5.4 [1.44-20.0]). In contrast neither the traditional cardiovascular risk factors nor the data of diabetic metabolic control were able to improve prediction. CRP was correlated positively with plasma levels of triglycerides (r=0.19, p=0.002), C-peptide (r=0.21, p=0.004), postprandial glucose (r=0.17, p=0.009), albuminuria (r=0.16, p=0.020), and inversely with HDL cholesterol (r=-0.20, p=0.002) in type 2 diabetic patients. CRP seems to be a better predictor of death and cardiovascular events than traditional risk factors or parameters of metabolic control in type 2 diabetic patients at high risk for cardiovascular endpoints. Additionally, CRP is associated with several facets of the metabolic syndrome.


Communicable Disease Surveillance Ethics in the Age of Big Data and New Technology.
Surveillance is essential for communicable disease prevention and control. Traditional notification of demographic and clinical information, about individuals with selected (notifiable) infectious diseases, allows appropriate public health action and is protected by public health and privacy legislation, but is slow and insensitive. Big data-based electronic surveillance, by commercial bodies and government agencies (for profit or population control), which draws on a plethora of internet- and mobile device-based sources, has been widely accepted, if not universally welcomed. Similar anonymous digital sources also contain syndromic information, which can be analysed, using customised algorithms, to rapidly predict infectious disease outbreaks, but the data are nonspecific and predictions sometimes misleading. However, public health authorities could use these online sources, in combination with de-identified personal health data, to provide more accurate and earlier warning of infectious disease events-including exotic or emerging infections-even before the cause is confirmed, and allow more timely public health intervention. Achieving optimal benefits would require access to selected data from personal electronic health and laboratory (including pathogen genomic) records and the potential to (confidentially) re-identify individuals found to be involved in outbreaks, to ensure appropriate care and infection control. Despite existing widespread digital surveillance and major potential community benefits of extending its use to communicable disease control, there is considerable public disquiet about allowing public health authorities access to personal health data. Informed public discussion, greater transparency and an ethical framework will be essential to build public trust in the use of new technology for communicable disease control.


A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons.
Whole-cell patch-clamp recordings were made from cultured rat hippocampal neurons to examine the effects of the steroidal general anesthetic alphaxalone (3 alpha-hydroxy 5 alpha-pregnane 11,20-dione) on responses to pharmacologically applied and physiologically released GABA. At low micromolar concentrations in the anesthetic range, alphaxalone potentiated Cl- conductance responses elicited by GABA and also prolonged evoked GABA-mediated postsynaptic potentials. Under voltage clamp at -40 mV, rapid outwardly directed synaptic currents were evoked that decayed with single exponential kinetics; mean decay time constant was 24 msec at room temperature. Alphaxalone prolonged the decay of these inhibitory postsynaptic currents by 5- to 8-fold, with no increase in peak amplitude or change in growth time. This substantial prolongation of GABA-mediated inhibitory synaptic conductance at clinically effective concentrations may contribute significantly to the anesthetic activity of alphaxalone.


Polyploidy and chromatin remodeling in hepatocytes from insulin-dependent diabetic and normoglycemic aged mice.
Changes in polyploidization, chromatin supraorganization, and chromatin accessibility were investigated in hepatocytes collected from adult, nonobese diabetic (NOD) mice with increasing hyperglycemia and compared with adult normoglycemic controls and 56-week-old normoglycemic BALB/c mice. Our goal was to determine the changes in ploidy degrees and chromatin characteristics in mouse hepatocytes that are associated with insulin-dependent diabetes and to detect similarities in these aspects with those verified with aging, with greater accuracy than previous studies. Image analysis of Feulgen-stained nuclei revealed changes in ploidy degrees and chromatin supraorganization. Chromatin accessibility was assessed with micrococcal nuclease (MNase) digestion. Increased polyploidy was associated with increasing levels of glycemia, and this trend toward polyploidy was found even under normoglycemic conditions in NOD mice. Although high degrees of ploidy were also detected in aged BALB/c mice, the magnitude of polyploidy was not the same magnitude as that in the diabetic mice. While there was increased homogeneity of chromatin packaging with increasing polyploidy under conditions of severe hyperglycemia (and even under conditions of normoglycemia) in NOD mice, an inverse relationship was observed in aged BALB/c mice. Chromatin accessibility to MNase increased under severe hyperglycemia and advanced age, but it was much higher in the diabetic mice. In conclusion, although similarities in polyploidy were observed between the hepatocytes from increasingly hyperglycemic adult mice and those from normoglycemic aged mice, the relationship between chromatin remodeling and increases in ploidy degrees was not the same between the hepatocytes of these two groups. These findings demonstrate that strict similarities between diabetes and aging are not always true at the cellular level. This discordance is likely due to differences in the metabolic state of mouse hepatocytes during aging and diabetic conditions consequent to specificities in their gene regulatory programs.


Mammalian exocrine secretions XVI. Constitutents of secretion of supplementary sacculi of dwarf hamster, Phodopus sungorus sungorus.
As a first step in a study of the role of the secretion of the supplementary sacculi (buccal secretion) of the dwarf hamster, Phodopus sungorus sungorus, almost complete chemical characterization of the secretion was achieved. The 35 compounds identified include carbon dioxide, hydrogen sulfide, a large number of carboxylic acids (representing the bulk of the organic volatile fraction of the secretion), phenol, 2-piperidone, indole, two long-chain hydroxyesters, cholestrol, desmosterol, and lanosterol. The position of the double bonds in gamma-icosadienyl-gamma-butyrolactone and gamma-henicosadienyl-gamma-butyrolactone could not be determined, and these two compounds remained only partially characterized. Large variations were found in the relative concentrations in which the short-chain carboxylic acids are present in the secretions of individual animals, and although this aspect was not investigated in sufficient detail in the present investigation, the difference in the carboxylic acid profiles of the secretions of individual animals could play a role in individual recognition in this animal.


The IP3 receptor as a hub for Bcl-2 family proteins in cell death control and beyond.
Bcl-2 family proteins generally have a proapoptotic or antiapoptotic role. In addition to their known roles at the mitochondria, Bcl-2 family proteins also influence signaling at the endoplasmic reticulum by binding to the inositol 1,4,5-trisphosphate receptor (IP3R), the most ubiquitous intracellular Ca(2+) channel. Surprisingly, multiple Bcl-2 family proteins target different sites on the IP3R to elicit various effects on IP3R function, which suggests that the IP3R is an important hub for Bcl-2 family proteins in various physiological settings.


Mechanism of chimera formation during the Multiple Displacement Amplification reaction.
Multiple Displacement Amplification (MDA) is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2-21 nucleotides (nts) in the new templates. Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.


Viscum album L. Extracts Protects HeLa Cells against Nuclear and Mitochondrial DNA Damage.
Viscum album L. is a semiparasitic plant grown on trees and widely used for the treatment of many diseases in traditional and complementary therapy. It is well known that some activities of Viscum album extracts are varied depending on the host trees, such as antioxidant, apoptosis-inducing, anticancer activities of the plant. The aim of the present study is to examine the comparative effects of methanolic extracts of V. album grown on three different host trees (locust tree, lime tree, and hedge maple tree) on H(2)O(2)-induced DNA damage in HeLa cells. Oxidative damage in mitochondrial DNA and two nuclear regions was assessed by QPCR assay. The cells were pretreated with methanolic extracts (10 μg/mL) for 48 h, followed by the treatment with 750 μM H(2)O(2) for 1 hour. DNA damage was significantly induced by H(2)O(2) while it was inhibited by V. album extracts. All extracts completely protected against nuclear DNA damage. While the extract from lime tree or white locust tree entirely inhibited mitochondrial DNA damage, that from hedge maple tree inhibited by only 50%. These results suggest that methanolic extracts of V. album can prevent oxidative DNA damage, and the activity is dependent on the host tree.


Enterocin P selectively dissipates the membrane potential of Enterococcus faecium T136.
Enterocin P is a pediocin-like, broad-spectrum bacteriocin which displays a strong inhibitory activity against Listeria monocytogenes. The bacteriocin was purified from the culture supernatant of Enterococcus faecium P13, and its molecular mechanism of action against the sensitive strain E. faecium T136 was evaluated. Although enterocin P caused significant reduction of the membrane potential (DeltaPsi) and the intracellular ATP pool of the indicator organism, the pH gradient (DeltapH) component of the proton motive force (Deltap) was not dissipated. By contrast, enterocin P caused carboxyfluorescein efflux from E. faecium T136-derived liposomes.


Hazard-ranking of agricultural pesticides for chronic health effects in Yuma County, Arizona.
With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam-sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk.


Genetics of anisotropy asymmetry: registration and sample size effects.
Brain asymmetry has been a topic of interest for neuroscientists for many years. The advent of diffusion tensor imaging (DTI) allows researchers to extend the study of asymmetry to a microscopic scale by examining fiber integrity differences across hemispheres rather than the macroscopic differences in shape or structure volumes. Even so, the power to detect these microarchitectural differences depends on the sample size and how the brain images are registered and how many subjects are studied. We fluidly registered 4 Tesla DTI scans from 180 healthy adult twins (45 identical and fraternal pairs) to a geometrically-centered population mean template. We computed voxelwise maps of significant asymmetries (left/right hemisphere differences) for common fiber anisotropy indices (FA, GA). Quantitative genetic models revealed that 47-62% of the variance in asymmetry was due to genetic differences in the population. We studied how these heritability estimates varied with the type of registration target (T1- or T2-weighted) and with sample size. All methods consistently found that genetic factors strongly determined the lateralization of fiber anisotropy, facilitating the quest for specific genes that might influence brain asymmetry and fiber integrity.


Immunohistochemical identification of leucocyte populations in normal tissue and inflamed synovium of the rabbit.
A panel of monoclonal antibodies which recognizes well-defined markers of rabbit leucocytes has been used in an immunohistochemical survey of normal rabbit spleen, thymus, and liver, and of inflamed synovial tissue. The results demonstrate that these antibodies are well suited for the identification of leucocytes in frozen sections of rabbit tissues and that T lymphocytes, macrophages, and neutrophils can be readily distinguished. Antibodies to CD44 differentiate between medullary and cortical thymocytes, with the cortical cells being almost entirely negative for this marker. Antibodies to RLA class II show that periportal lymphocytes in the liver express RLA-DR but not RLA-DQ. The type A cells of the synovial lining from inflamed joint tissue are stained by antibodies that recognize macrophages in a manner similar to that found in the human synovial lining.


Is tumor volume an independent prognostic factor in clinically localized prostate cancer?
There continues to be debate regarding the prognostic significance of tumor volume (TV) in radical prostatectomy (RP) specimens. We assessed the prognostic significance of TV in a large series of patients followed for a long time to discover whether the effect of TV has changed with earlier detection of smaller tumors. TV was measured planimetrically in 1,302 consecutive RP specimens with clinical stage T1-3 prostate cancer from 1983 to 2000. We correlated TV with standard clinical and pathological features, and determined the prostate specific antigen nonprogression rate. Median followup was 46 months (range 1 to 202). TV was weakly associated with other clinical and pathological features. Median TV decreased significantly over time (2.16 cm3 before 1995 vs 1.25 cm3 after 1995, p <0.001) and this decrease was also found within each clinical stage. In univariate analysis TV correlated strongly with the probability of progression. However, in multivariate analysis TV was not a significant independent predictor of prognosis, either in the whole cohort of patients or in those with peripheral zone cancer only. Even in univariate analysis TV had no effect on prognosis for patients in whom cancer was either confined to the prostate or was Gleason score 2 through 6. TV provides no independent prognostic information when considered in multivariate analysis with Gleason score and pathological stage. Measurement of TV before treatment is less likely to characterize prostate cancer accurately than assessment of tumor grade and extent. There seems to be little reason to measure TV routinely in RP specimens.


Mast cell tryptase stimulates the synthesis of type I collagen in human lung fibroblasts.
Mast cell activation is a characteristic feature of chronic inflammation, a condition that may lead to fibrosis as a result of increased collagen synthesis by fibroblasts. We have investigated the potential of tryptase, the major protease of human mast cells, to stimulate collagen synthesis in the human lung fibroblast cell line MRC-5. Tryptase was isolated from human lung tissue by ion-exchange and affinity chromatography. At concentrations of 18 and 36 mU/ml, tryptase stimulated both an increase in cell numbers, and a fivefold increase in DNA synthesis as determined by methyl-[3H]thymidine incorporation. Similar concentrations of tryptase resulted in a 2.5-fold increase in collagen synthesis as determined both by incorporation of [3H]proline into collagen, and by assay of hydroxyproline concentrations in the supernatants. There was also a twofold increase in collagenolytic activity in the culture medium after tryptase treatment, indicating that the increase in collagen synthesis was not a consequence of decreased collagenase production. All of these actions of tryptase were reduced in the presence of the protease inhibitors leupeptin and benzamidine hydrochloride, indicating a requirement for an active catalytic site. SDS-PAGE and autoradiographic analysis of the [3H]collagen produced by the cells revealed it to be predominantly type I collagen. Our findings suggest that the release of tryptase from activated mast cells may provide a signal for abnormal fibrosis in inflammatory disease.


Cutaneous myiasis caused by Dermatobia hominis acquired in Jamaica.
The authors describe a case of cutaneous myiasis caused by Dermatobia hominis in a 23-year-old Italian woman who contracted the infestation during a tour in Jamaica. The infestation was located on the back and was characterized clinically by a single inflammatory nodule. To our knowledge, this is the first case of cutaneous myiasis due to Dermatobia hominis acquired in Jamaica.


Epidemiology, Impact and Control of Rabies in Nepal: A Systematic Review.
Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal. We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal. So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10-100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray dog populations and the true contribution of the sylvatic cycle. Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal.


Reprint of: Patient participation in nursing bedside handover: A systematic mixed-methods review.
Numerous reviews of nursing handover have been undertaken, but none have focused on the patient's role. To explore how patient participation in nursing shift-to-shift bedside handover can be enacted. Systematic mixed- methods review. Three search strategies were undertaken in July-August 2016: database searching, backwards citation searching and forward citation searching. To be included, papers had to either be research or quality improvement (QI) projects focusing on the patient role. Fifty-four articles were retrieved, including 21 studies and 25 QI projects. Screening, data extraction and quality appraisal was undertaken systematically by two reviewers. Research studies and QI projects were synthesised separately using thematic synthesis, then the results of this synthesis were combined using a mixed-method synthesis table. Segregated synthesis of research of patients' perceptions revealed two contrasting categories; patient-centred handover and nurse-centred handover. Segregated synthesis of research of nurses' perceptions included three categories: viewing the patient as an information resource; dealing with confidential and sensitive information; and enabling patient participation. The segregated synthesis of QI projects included two categories: nurse barriers to enacting patient participation in bedside handover; and involving patients in beside handover. Once segregated findings were configured, we discovered that the patient's role in bedside handover involves contributing clinical information related to their care or progress, which may influence patient safety. Barriers related to nurses' discomfort encouraging patient participation and worries for sharing confidential and sensitive information. The way nurses approach patients, and how patient-centred they are, constitute further potential barriers. Strategies to improve patient participation in handover include training nurses, making handovers predictable for patients and increasing the interpersonal approach during handover. Using research and QI projects allowed diverse findings to expand each other and identify gaps between research and heuristic knowledge. Our review showed the tension between standardising handovers and making them predictable for patient participation, while promoting tailored and flexible handovers. Further investigation of this issue is required, to understand how to train nurses to achieve this and prepare patients to do this. Many barriers and strategies identified were from QI projects and the nurse perspective, thus caution interpreting results is required. We recommend steps be taken in the future to ensure high quality QI projects.


Endothelium-derived hydrogen peroxide accounts for the enhancing effect of an angiotensin-converting enzyme inhibitor on endothelium-derived hyperpolarizing factor-mediated responses in mice.
Background- We have recently identified that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in animals and humans, for which endothelial nitric oxide synthase (eNOS) is an important source. Angiotensin-converting enzyme (ACE) inhibitors are known to enhance EDHF-mediated responses. In this study, we examined whether endothelium-derived H2O2 accounts for the enhancing effect of an ACE inhibitor on EDHF-mediated responses and, if so, what mechanism is involved. Control and eNOS-/- mice were maintained with or without temocapril (10 mg/kg per day orally) for 4 weeks, and isometric tensions and membrane potentials of mesenteric arteries were recorded. In control mice, temocapril treatment significantly enhanced EDHF-mediated relaxations and hyperpolarizations to acetylcholine (n=8 each). Catalase, a specific scavenger of H2O2, abolished the beneficial effects of temocapril, although it did not affect endothelium-independent relaxations to sodium nitroprusside or NS1619, a direct opener of K(Ca) channels (n=6 each). Western blot analysis demonstrated that the temocapril treatment significantly upregulated the expression of eNOS. By contrast, this enhancing effect of temocapril was absent in eNOS-/- mice (n=6). These results indicate that endothelium-derived H2O2 accounts for the enhancing effect of temocapril on EDHF-mediated responses caused in part by eNOS upregulation, further supporting our H2O2 theory.


[Community participation in health: the challenge in Chile].
Health care reforms implemented in Latin America and the Caribbean over the last 20 years have viewed community participation as a system-wide component. Nonetheless, these reform efforts have yet to break through the conceptual and operational barriers holding back the development and expansion of community participation. In Chile, changes introduced to the health care system are far from achieving any real participation from the community. Therefore, the consumer's role needs to be redefined from merely controlling the parts, to reaching across the whole system in a way that consumer input might identify and quickly correct any possible shortcomings in the health system's design, as well as its operations. With this in mind, the main challenges are to strengthen coordination among the various promotion and participation commitments, as well as community control, and to generate data and other evidence to assess the impact of community participation in health strategies.


Endovascular treatment of basilar tip aneurysms using Guglielmi detachable coils: anatomic and clinical outcomes in 73 patients from a single institution.
Seventy-three consecutive patients with 75 basilar tip aneurysms were treated with Guglielmi detachable coil (GDC) technology. Their anatomic and clinical outcomes are discussed. Seventy-five basilar tip aneurysms were treated with the GDC system at the University of California, Los Angeles Medical Center from 1990 to 1999. The average age of the population was 48.3 years (range, 28-82 yr). Forty-two patients (57.5%) presented with acute subarachnoid hemorrhage, 8 patients (10.9%) had unruptured aneurysms with mass effect, and 23 patients (31.5%) had incidental aneurysms. Thirty-one aneurysms (41.3%) were small with a small neck, 18 (24%) were small with a wide neck, 16 (21.3%) were large, and 10 (13.3%) were giant aneurysms. Immediate anatomic outcomes demonstrated complete or near-complete occlusion in 64 aneurysms (85.3%) and incomplete occlusion in 7 aneurysms (9.3%). Four aneurysms (5.3%) could not be embolized because of anatomic difficulties. Of the 69 patients treated with GDCs, 63 patients (91.3%) remained neurologically intact or unchanged from their initial clinical status. Procedure-related morbidity and mortality were 4.1% and 1.4%, respectively. Long-term follow-up angiograms were obtained in 41 patients with 42 aneurysms. Thirty aneurysms (71.4%) demonstrated complete or near-complete occlusion. One incompletely embolized giant aneurysm ruptured during the follow-up period. In contrast to surgical clipping of basilar tip aneurysms, the main technical challenge of the Guglielmi detachable coiling procedure depends on the shape of the aneurysm, not its location. The results of this study indicate that endovascular GDC technology is an appropriate therapeutic alternative in ruptured or unruptured basilar tip aneurysms regardless of patient age, clinical presentation, clinical status, or timing of treatment.


Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1.
The transmembrane protein amyloid-beta precursor protein (APP) and the vesicle-associated protein c-Jun NH(2)-terminal kinase-interacting protein-1 (JIP-1) are transported into axons by kinesin-1. Both proteins may bind to kinesin-1 directly and can be transported separately. Because JIP-1 and APP can interact, kinesin-1 may recruit them as a complex, enabling their cotransport. In this study, we tested whether APP and JIP-1 are transported together or separately on different vesicles. We found that, within the cellular context, JIP-1 preferentially interacts with Thr(668)-phosphorylated APP (pAPP), compared with nonphosphorylated APP. In neurons, JIP-1 colocalizes with vesicles containing pAPP and is excluded from those containing nonphosphorylated APP. The accumulation of JIP-1 and pAPP in neurites requires kinesin-1, and the expression of a phosphomimetic APP mutant increases JIP-1 transport. Down-regulation of JIP-1 by small interfering RNA specifically impairs transport of pAPP, with no effect on the trafficking of nonphosphorylated APP. These results indicate that the phosphorylation of APP regulates the formation of a pAPP-JIP-1 complex that accumulates in neurites independent of nonphosphorylated APP.


Latent Toxoplasma gondii infection leads to improved action control.
The parasite Toxoplasma gondii has been found to manipulate the behavior of its secondary hosts to increase its own dissemination which is commonly believed to be to the detriment of the host (manipulation hypothesis). The manipulation correlates with an up-regulation of dopaminergic neurotransmission. In humans, different pathologies have been associated with T. gondii infections but most latently infected humans do not seem to display overt impairments. Since a dopamine plus does not necessarily bear exclusively negative consequences in humans, we investigated potential positive consequences of latent toxoplasmosis (and the presumed boosting of dopaminergic neurotransmission) on human cognition and behavior. For this purpose, we focused on action cascading which has been shown to be modulated by dopamine. Based on behavioral and neurophysiological (EEG) data obtained by means of a stop-change paradigm, we were able to demonstrate that healthy young humans can actually benefit from latent T. gondii infection as regards their performance in this task (as indicated by faster response times and a smaller P3 component). The data shows that a latent infection which is assumed to affect the dopaminergic system can lead to paradoxical improvements of cognitive control processes in humans.


Flavonoids: an overview.
Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.


Not Just Participation: The Rise of the Eco-Precariat in the Green Economy.
Despite recent attention to "frontier" green economies and the governance of emerging ecosystem services, the specific division of labour in these economies has been little studied. As many such initiatives are in the global South, labour's marginality potentially contributes to the existing precariousness of those who are more often identified as "participants". This article examines the roles and vulnerabilities of these actors: the carbon counters, species identifiers, GIS mappers, tree planters and others operating in the shadows. We draw on current understandings of labour and precarity to examine the geographical contours of an apparent and emerging "eco-precariat": a socio-economically diverse group of labourers that address the volatile demands of an ever-expanding environmental service-based economy. We illustrate our analysis drawing on examples from a Blue Carbon project in Kenya, ecosystem services project in the Philippines, and REDD+ scheme in Cambodia. We use these examples to theorise the nature of labour in these frontier economies and put forward a framework for analysing the eco-precariat. We highlight the need to understand the precarity and marginalisation potentially created by this green division of labour in the provision of new ecosystem products and services. This framework contributes to ongoing analyses of labour as a central part of the green economy discourse and to larger discussions in the geographies of labour literature around the future of work in the global South and beyond.


Long-term prognosis of patients withJ-wave syndrome.
Limited data are currently available regarding the long-term prognosis of patients with J-wave syndrome (JWS). The aim of this study was to investigate the long-term prognosis of patients with JWS and identify predictors of the recurrence of ventricular fibrillation (VF). This was a multicentre retrospective study (seven Japanese hospitals) involving 134 patients with JWS (Brugada syndrome (BrS): 85; early repolarisation syndrome (ERS): 49) treated with an implantable cardioverter defibrillator. All patients had a history of VF. All patients with ERS underwent drug provocation testing with standard and high intercostal ECG recordings to rule out BrS. The impact of global J waves (type 1 ECG or anterior J waves and inferolateral J waves in two or more leads) on the prognosis was evaluated. During the 91±66 months of the follow-up period, 52 (39%) patients (BrS: 37; ERS: 15) experienced recurrence of VF. Patients with BrS and ERS with global J waves showed a significantly higher incidence of VF recurrence than those without (BrS: log-rank, p=0.014; ERS: log-rank, p=0.0009). The presence of global J waves was a predictor of VF recurrence in patients with JWS (HR: 2.16, 95% CI 1.21 to 3.91, p=0.0095), while previously reported high-risk electrocardiographic parameters (high-amplitude J waves ≥0.2 mV and J waves associated with a horizontal or descending ST segment) were not predictive of VF recurrence. This multicentre long-term study showed that the presence of global J waves was associated with a higher incidence of VF recurrence in patients with JWS.


New reports of Antricola guglielmonei and Antricola delacruzi in Brazil, and a description of a new argasid species (Acari).
Adults of 3 tick species (Acari: Argasidae) identified as Antricola guglielmonei, Antricola delacruzi, and Carios rondoniensis n. sp. were collected on bat guano in a cave in the state of Rondônia, western Amazon, Brazil. Adults of C. rondoniensis possess a unique combination of characters that distinguish them from all described adults in the Argasidae, i.e., a large spiracular plate densely filled with small goblets, a well-developed flap covering the female genital opening, and palpi containing several tufts of long setae on articles 2 and 3. Unlike Ornithodoros or other Carios species, adults of C. rondoniensis have a scooplike hypostome devoid of denticles, as in Antricola spp. Conversely, the presence of a pair of long posthypostomal setae, and a slitlike transverse fissure at the capsule opening of the Haller's organ, are characters of C. rondonensis that are also found in species of Carios and Ornithodoros, but not in Antricola species. Molecular analyses inferred from a portion of the 16S rRNA mitochondrial gene indicate that C. rondoniensis is phylogenetically closest to species of Carios, followed by species of Antricola, and then Ornithodoros. Because the highest bootstrap value linking C. rondoniensis to Carios spp. was 62%, further phylogenetic studies are needed to better evaluate the taxonomic status of the former species.


Decline in intertidal biota after the 2011 Great East Japan Earthquake and Tsunami and the Fukushima nuclear disaster: field observations.
In 2011, 2012, and 2013, in the intertidal zones of eastern Japan, we investigated the ecological effects of the severe accident at the Fukushima Daiichi Nuclear Power Plant that accompanied the 2011 Great East Japan Earthquake and Tsunami. The number of intertidal species decreased significantly with decreasing distance from the power plant, and no rock shell (Thais clavigera) specimens were collected near the plant, from Hirono to Futaba Beach (a distance of approximately 30 km) in 2012. The collection of rock shell specimens at many other sites hit by the tsunami suggests that the absence of rock shells around the plant in 2012 might have been caused by the nuclear accident in 2011. Quantitative surveys in 2013 showed that the number of species and population densities in the intertidal zones were much lower at sites near, or within several kilometers south of, the plant than at other sites and lower than in 1995, especially in the case of Arthropoda. There is no clear explanation for these findings, but it is evident that the intertidal biota around the power plant has been affected since the nuclear accident.


Protein database and quantitative analysis considerations when integrating genetics and proteomics to compare mouse strains.
Decades of genetics research comparing mouse strains has identified many regions of the genome associated with quantitative traits. Microarrays have been used to identify which genes in those regions are differentially expressed and are therefore potentially causal; however, genetic variants that affect probe hybridization lead to many false conclusions. Here we used spectral counting to compare brain striata between two mouse strains. Using strain-specific protein databases, we concluded that proteomics was more robust to sequence differences than microarrays; however, some proteins were still significantly affected. To generate strain-specific databases, we used a complete database that contained all of the putative genetic isoforms for each protein. While the increased proteome coverage in the databases led to a 6.8% gain in peptide assignments compared to a nonredundant database, it also necessitated the development of a strategy for grouping similar proteins due to a large number of shared peptides. Of the 4563 identified proteins (2.1% FDR), there were 1807 quantifiable proteins/groups that exceeded minimum count cutoffs. With four pooled biological replicates per strain, we used quantile normalization, ComBat (a package that adjusts for batch effects), and edgeR (a package for differential expression analysis of count data) to identify 101 differentially expressed proteins/groups, 84 of which had a coding region within one of the genomic regions of interest identified by the Portland Alcohol Research Center.


Effect of temperature on the potential and current thresholds of axon membrane.
The effect of temperature on the potential and current thresholds of the squid giant axon membrane was measured with gross external electrodes. A central segment of the axon, 0.8 mm long and in sea water, was isolated by flowing low conductance, isoosmotic sucrose solution on each side; both ends were depolarized in isoosmotic KCl. Measured biphasic square wave currents at five cycles per second were applied between one end of the nerve and the membrane of the central segment. The membrane potential was recorded between the central sea water and the other depolarized end. The recorded potentials are developed only across the membrane impedance. Threshold current values ranged from 3.2 microa at 267deg;C to 1 microa at 7.5 degrees C. Threshold potential values ranged from 50 mv at 26 degrees C to 6 mv at 7.5 degrees C. The mean Q(10) of threshold current was 2.3 (SD = 0.2), while the Q(10) for threshold potentials was 2.0 (SD = 0.1).


Macrophage apoptosis in tuberculosis.
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects alveolar macrophages following aerosol transmission. Lung macrophages provide a critical intracellular niche that is required for Mtb to establish infection in the human host. This parasitic relationship is made possible by the capacity of Mtb to block phagosome maturation following entry into the host macrophage, creating an environment that supports bacillary replication. Apoptosis is increasingly understood to play a role in host defense against intracellular pathogens including viruses, fungi, protozoa and bacteria. In the last 15 years an understanding of the role that macrophage apoptosis plays in TB has begun to emerge. Here we review the history and current state of the art of this topic and we offer a model of the macrophage-pathogen interaction that takes into the account the complexities of programmed cell death and the relationship between various death signaling pathways and host defense in TB.


Leakage-free solution-processed organic light-emitting diode using a ternary host with single-diode emission area up to 6 × 11.5 cm2.
The electrical current leakage and stability are studied for solution-processed OLEDs with areas of 4.45 mm2, 3 × 3.2 cm2, and 6 × 11.5 cm2. The emission layer of the OLED has a ternary or binary mixed host with hole-transporting molecules tris(4-carbazoyl-9-ylphenyl)amine (TCTA) and 9-(4-tert-butylphenyl)-3,6-bis(triphenylsilyl)-9H-carbazole (CzSi), together with the electron-transporting molecule 2,7-bis(diphenylphosphoryl)-9,9'-spirobi[fluorene] (SPPO13). The phosphorescent emitters are Ir(mppy)3 for green and bis[4-(4-tert-butylphenyl)thieno[3,2-c]pyridine][N,N'-diisopropylbenamidinato]iridium(iii) (PR-02) for orange. Poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(4-sec-butylphenyl))diphenylamine)] (TFB) is used as the hole transport layer and PEDOT:PSS is used as the hole injection layer. On top of the emission layer, CsF/Al is deposited by thermal evaporation as the cathode. All organic layers are deposited by blade coating and the initial current leaking defects can be avoided by careful control of the coating conditions. The detrimental burning point caused by a local current short developed after long-time operation can be avoided by reducing the operation voltage using a ternary mixed host. The operation voltage is only 4 V at 100 cd m-2 and 5 V at 250 cd m-2 for the green emitting device. Furthermore, the crystallization defect is reduced by the ternary host. For the orange emitting device, the binary host is good enough with an operating voltage of 5 V at 100 cd m-2. For an area as large as 6 × 11.5 cm2, the OLED shows good stability and there is no burning point after an operation of over 1600 hours.


Faster progression from MCI to probable AD for carriers of a single-nucleotide polymorphism associated with type 2 diabetes.
Sporadic Alzheimer's disease (AD), as opposed to its autosomal dominant form, is likely caused by a complex interaction of genetic, environmental, and health lifestyle factors. Twin studies indicate that sporadic AD heritability could be between 58% and 79%, around half of which is explained by the ε4 allele of the apolipoprotein E (APOE4). We hypothesized that genes associated with known risk factors for AD, namely hypertension, hypercholesterolemia, obesity, diabetes, and cardiovascular disease, would contribute significantly to the remaining heritability. We analyzed 22 AD-associated single-nucleotide polymorphisms (SNPs), associated with these risk factors, that were included in the sequencing data of the Alzheimer's Disease Neuroimaging Initiative 1 data set, which included 355 participants with mild cognitive impairment (MCI). We built survival models with the selected SNPs to predict progression of MCI to probable AD over the 10-year follow-up of the study. The rs391300 SNP, located on the serine racemase (SRR) gene and linked to increased susceptibility to type 2 diabetes, was associated with progression from MCI to probable AD.


Subwavelength focusing and imaging by a multimode optical waveguide.
A simple subwavelength focusing system formed by a straight or bent multimode waveguide is investigated numerically. The simulation results indicate that an appropriately designed multimode waveguide can focus the outgoing waves of a point source and form an image with a full width at half-maximum of less than half a wavelength in the near-field area at the other side of the waveguide. The physical mechanism of the subwavelength focusing for this imaging system is explained.


Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls.
Chronic use of drugs may alter the brain's reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the 'CannTeen' study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26-29 years) and adolescent (16-17 years) cannabis users (1-7 days/week cannabis use) and gender- and age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.


QTc monitoring in adults with medical and psychiatric comorbidities: Expert consensus from the Association of Medicine and Psychiatry.
Several psychiatric medications have the potential to prolong the QTc interval and subsequently increase the risk for ventricular arrhythmias such as torsades de pointes (TdP). There is limited guidance for clinicians to balance the risks and benefits of treatments. After a review of the existing literature, clinical-educators from the Association of Medicine and Psychiatry developed expert consensus guidelines for ECG monitoring of the QTc interval for patients with medical and psychiatric comorbidities who are prescribed medications with the potential to prolong the QTc interval. A risk score was developed based on risk factors for QTc prolongation to guide clinical decision-making. A baseline ECG may not be necessary for individuals at low risk for arrythmia. Those individuals with a risk score of two or more should have an ECG prior to the start of a potentially QTc-prolonging medication or be started on a lower risk agent. Antipsychotics are not equivalent in causing QTc prolongation. A consensus-based algorithm is presented for the management of those identified at high (QTc >500 msec), intermediate (males with QTc 450-499 msec or females with QTc > 470-499 msec), or low risk. The proposed algorithm can help clinicians in determining whether ECG monitoring should be considered for a given patient. These guidelines preserve a role for clinical judgment in selection of treatments that balance the risks and benefits, which may be particularly relevant for complex patients with medical and psychiatric comorbidities. Additional studies are needed to determine whether baseline and serial ECG monitoring reduces mortality.


Three new species of entimine weevils in Early Miocene amber from the Dominican Republic (Coleoptera: Curculionidae).
Using syntactic and semantic conventions of the taxonomic concept approach (Franz et al. 2015), we describe three newly recognized fossil broad-nosed weevils (Coleoptera: Curculionidae: Entiminae) preserved in Early Miocene amber (ca. 20.4-16.0 mya) from the Dominican Republic: Scelianoma compactasp. n. sec. Franz & Zhang (2017) (henceforth abbreviated as [FZ2017]), Tropirhinus palpebratussp. n. [FZ2017], and Diaprepes anticussp. n. [FZ2017]. The taxonomic assignment of the amber inclusions is grounded in a preceding phylogenetic analysis by Franz (2012). As many as 88 of the 143 therein identified characters were coded for the fossils, whose traits are largely congruent with those present in extant congeners while also differing in ways that justify their new nomenclatural and taxonomic status. We present detailed images, descriptions, and phylogenetically informed diagnoses for the three new species-level entities, along with logically consistent Region Connection Calculus (RCC-5) alignments of the amended genus-level classifications for Scelianoma Franz and Girón 2009 [FZ2017], Tropirhinus Schoenherr 1823 [FZ2017], and Diaprepes Schoenherr 1823 [FZ2017] - in relation to 2-4 preceding classifications published in 1982-2012. The description of Scelianoma compacta [FZ2017] from Hispaniola is indicative of a more widespread historical range of Scelianoma [FZ2017] than reflected in the extant, southwestern Puerto Rican Scelianoma elydimorpha Franz and Girón 2009 sec. Franz and Girón (2009). The presence of Diaprepes anticus [FZ2017] in Hispaniola during the Early Miocene suggests an eastward directed process of island colonization and likely speciation of members of Diaprepes [FZ2017], given that most extant relatives occur throughout the Lesser Antilles. The herein presented data will facilitate more reliable reconstructions of historical biographic processes thought to have played a prominent role in the diversification of the West Indian and Neotropical mainland broad-nosed weevil lineages.


HIV-PULSE: A long-read sequencing assay for high-throughput near full-length HIV-1 proviral genome characterization.
A deep understanding of the composition of the HIV-1 reservoir is necessary for the development of targeted therapies and the evaluation of curative efforts. However, current near full-length (NFL) HIV-1 proviral genome sequencing assays are based on labor-intensive and costly principles of repeated PCRs at limiting dilution, restricting their scalability. To address this, we developed a high-throughput, long-read sequencing assay called HIV-PULSE (HIV P roviral U MI-mediated L ong-read Se quencing). This assay uses unique molecular identifiers (UMIs) to tag individual HIV-1 genomes, allowing for the omission of the limiting dilution step and enabling long-range PCR amplification of many NFL genomes in a single PCR reaction, while simultaneously overcoming poor single-read accuracy. We optimized the assay using HIV-infected cell lines and then applied it to blood samples from 18 individuals living with HIV on antiretroviral therapy, yielding a total of 1,308 distinct HIV-1 genomes. Benchmarking against the widely applied Full-Length Individual Proviral Sequencing assay revealed similar sensitivity (11% vs 18%) and overall good concordance, though at a significantly higher throughput. In conclusion, HIV-PULSE is a cost-efficient and scalable assay that allows for the characterization of the HIV-1 proviral landscape, making it an attractive method to study the HIV-1 reservoir composition and dynamics.


Maximising the global health impact of future HIV cure-related interventions through advance planning.
Thinking about public health impact should inform HIV curative investigations. Should an effective HIV cure or sustained viral remission intervention emerge from ongoing investigations, implementation strategies aimed at ensuring global access will be needed if these approaches are to be impactful, and planning accordingly makes sense now. Specifically, we discuss three key access barriers to future cure-related interventions: high cost of the strategy; non-financial challenges to procurement, distribution and point-of-care delivery; and non-adherence and the need for long-term monitoring. As we argue, plans and decision-making for overcoming each of these barriers will need to be developed in advance. An evaluation of remaining barriers and likely global impact of the leading strategies under investigation should inform decisions on which strategy might receive funding priority. Among the strategies being investigated, implementation barriers for latency-reversing agents, immunotherapy and combination antiretroviral therapy (ART) may be overcome on a global scale with some effort. Overcoming implementation barriers for medically complex and high-risk interventions, such as stem cell and, to some degree, gene therapy, may be less feasible.


Interactions of like-charged rods at low temperatures: analytical theory vs. simulations.
We investigate a system consisting of two like-charged infinitely long rods and neutralizing counterions at low temperatures, using both analytic theory and simulations. With some reasonable approximations we can analytically solve for several ground-state structures of the model, starting with states where all counterions are lined up in the gap between the rods, over planar configurations, where the counterions are divided up into a fraction which resides between the rods, and counterions which are located on the outer surfaces, up to configurations which cover the full rod surfaces. Using parallel tempering simulations, we are able to study the system over a wide range of temperatures. At low temperatures we find good agreement with our T = 0 results. At higher temperatures, the strong coupling (SC) theory delivers qualitatively better results. We furthermore demonstrate that for the SC theory and our ground-state approximations to yield quantitative agreement, three parameters are required to be large, the strong-coupling parameter, the Rouzina-Bloomfield parameter, and the ratio of the average distance of the counterions to the radius of the rods. In the case of the latter ratio being small, our T = 0 results show better agreement with the simulation data at very low temperatures.


Multiple Progressive Thermopreconditioning Improves Cardiac Ischemia/Reperfusion-induced Left Ventricular Contractile Dysfunction and Structural Abnormality in Rat.
Triple progressive thermopreconditioning (3PTP) may induce high Hsp-70 expression to maintain cardiac function. We suggest that 3PTP may reduce myocardial ischemia/reperfusion (I/R) injury during organ transplantation through Bag3/Hsp-70 mediated defense mechanisms. Male Wistar rats were divided into sham control group and 72 h after 3PTP in a 42°C water bath (3PTP) group. Rats underwent 60 min of ischemia by occlusion of the left anterior descending coronary artery followed by 240 min reperfusion. Hemodynamic parameters, including the electrocardiogram, microcirculation, heart rate, left ventricular end-diastolic pressure, maximal rate of rise (+dp/dt), and fall (-dp/dt) in the left ventricular pressure for index of contraction and relaxation were determined. Myocardial infarct size was evaluated by the Evans blue-2,3,5-triphenyltetrazolium chloride method. 3PTP-induced protective mechanisms were determined by Western blot and immunohistochemistry. Cardiac I/R depressed cardiac microcirculation, induced S-T segment elevation, and R-R and P-R interval elongation increased infarct size associated with erythrocyte extravasation, leukocytes and macrophage/monocyte infiltration, granulocyte colony-stimulating factor, poly(ADP-ribose) polymerase 1 stain, and transferase-mediated dUTP-biotin nick end labeling positive cells. However, 3PTP evoked significant cardioprotection against I/R injury, characterized by the increased +dp/dt value and the decreased elevated left ventricular end-diastolic pressure, erythrocyte extravasation, leukocyte and macrophage/monocyte infiltration, granulocyte colony-stimulating factor expression, poly(ADP-ribose) polymerase 1 expression, transferase-mediated dUTP-biotin nick end labeling positive cells, and fragmentation and infarct area. In addition, 3PTP increased Hsp-70 and Bag3 expression and decreased Bax/Bcl-2 ratio, but did not affect the Beclin-1 and LC3-II/LC3-I ratio in the heart with I/R injury. 3PTP therapies may through Bag3 upregulation alleviate I/R injury-induced left ventricular structural deterioration and dysfunction.


Case Studies in Exercise and Sport Sciences: A Powerful Tool to Bridge the Science-Practice Gap.
Despite the progress made by the scientific exercise community in collaborating and communicating with non-scientist coaches, there is room for improvement. Coaches find research difficult to understand, feel that their interests are not being addressed by exercise research, and rely on peer-discussion to further their coaching knowledge base while consuming little peer-reviewed articles. One useful strategy to bridge the science-practice gap is with case-studies. In addition to furthering our understanding of the physiology, psychology, and training schedules of elite athletes, case studies can serve 1) as a useful communication channel with coaches if presented as narratives and 2) to establish and strengthen relationships between scientists and coaches leading to fruitful research collaborations. The purpose of this invited commentary is to discuss these two less-recognized benefits of case-studies, and propose a way to incorporate case-studies more frequently alongside group-based studies.


HIV Related Stigma and Discrimination among People Living with HIV/AIDS in Ernakulam District: A Qualitative Study.
Human immunodeficiency virus (HIV)-related stigma refers to the negative beliefs, feelings, and attitudes, while discrimination is the unfair and unjust treatment of people living with HIV/acquired immunodeficiency syndrome (PLHA). Their manifestations are context-specific and have varied impacts. (1) To determine the different contexts in which PLHA face stigma and discrimination. (2) To study the impact of stigma and discrimination on the health of the PLHA. A qualitative study was conducted among PLHA at the office of the network for positives. Fourteen key informant interviews were conducted on PLHA and the peer counselors to determine the contexts in which they faced stigma and discrimination. To understand its impact on health, two Focus Group Discussions were carried out separately for male and female PLHA. The data were collected using a semi-structured interview guide and were audio recorded. They were then transcribed, manually coded, thematically analyzed, and triangulated. The themes that arose showed that stigma and discrimination were context-specific and were experienced in different levels such as an individual, family, community, health-care system, and media. They experienced violence in addition to the loss of shelter and economic support. Stigma and discrimination was found to have a negative impact on the health of the PLHA. It was a major hindrance to health-care utilization resulting in worsening of health conditions and indirectly contributed to the spread of diseases. PLHA experience different forms of stigma and discrimination which have an adverse impact on their health. Behavior change communication initiatives for the community are required.


Electrochemical investigation of covalently post-synthetic modified SURGEL coatings.
Thiol-yne click chemistry is used to covalently link a ferrocenyl derivative to the pore walls of a fully organic porous polymer coating (SURGEL). By cyclic voltammetry, it is demonstrated that the ferrocene bound to the SURGEL via a flexible alkyl linker can be reversibly reduced and oxidised. Surprisingly, when adding ferrocene as an electrolyte, a Nernstian diffusion limited process is observed. We explain this observation in terms of a high permeability of the SURGELs for ferrocene after the post synthetic modification.


Pipecolic acid, an endogenous mediator of defense amplification and priming, is a critical regulator of inducible plant immunity.
Metabolic signals orchestrate plant defenses against microbial pathogen invasion. Here, we report the identification of the non-protein amino acid pipecolic acid (Pip), a common Lys catabolite in plants and animals, as a critical regulator of inducible plant immunity. Following pathogen recognition, Pip accumulates in inoculated Arabidopsis thaliana leaves, in leaves distal from the site of inoculation, and, most specifically, in petiole exudates from inoculated leaves. Defects of mutants in AGD2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1) in systemic acquired resistance (SAR) and in basal, specific, and β-aminobutyric acid-induced resistance to bacterial infection are associated with a lack of Pip production. Exogenous Pip complements these resistance defects and increases pathogen resistance of wild-type plants. We conclude that Pip accumulation is critical for SAR and local resistance to bacterial pathogens. Our data indicate that biologically induced SAR conditions plants to more effectively synthesize the phytoalexin camalexin, Pip, and salicylic acid and primes plants for early defense gene expression. Biological priming is absent in the pipecolate-deficient ald1 mutants. Exogenous pipecolate induces SAR-related defense priming and partly restores priming responses in ald1. We conclude that Pip orchestrates defense amplification, positive regulation of salicylic acid biosynthesis, and priming to guarantee effective local resistance induction and the establishment of SAR.


Aposematism increases acoustic diversification and speciation in poison frogs.
Multimodal signals facilitate communication with conspecifics during courtship, but they can also alert eavesdropper predators. Hence, signallers face two pressures: enticing partners to mate and avoiding detection by enemies. Undefended organisms with limited escape abilities are expected to minimize predator recognition over mate attraction by limiting or modifying their signalling. Alternatively, organisms with anti-predator mechanisms such as aposematism (i.e. unprofitability signalled by warning cues) might elaborate mating signals as a consequence of reduced predation. We hypothesize that calls diversified in association with aposematism. To test this, we assembled a large acoustic signal database for a diurnal lineage of aposematic and cryptic/non-defended taxa, the poison frogs. First, we showed that aposematic and non-aposematic species share similar extinction rates, and aposematic lineages diversify more and rarely revert to the non-aposematic phenotype. We then characterized mating calls based on morphological (spectral), behavioural/physiological (temporal) and environmental traits. Of these, only spectral and temporal features were associated with aposematism. We propose that with the evolution of anti-predator defences, reduced predation facilitated the diversification of vocal signals, which then became elaborated or showy via sexual selection.


Association of natural fluoride in community water supplies with dental health of children in remote indigenous communities - implications for policy.
To map the geographic distribution of fluoride in water supplies and child dental caries in remote Indigenous communities of the Northern Territory (NT). To examine the association between fluoride levels, household and community factors, access to services and child dental caries in these communities and to model the impact on the caries experience of children of introducing water fluoridation. Fluoride testing was conducted in 80 locations across the NT in 2001. Measures of mean caries experience for six-year-olds and 12-year-olds and community and housing-related infrastructure were obtained from records of the NT School Dental Service. Associations between community fluoride levels, community level variables and childhood caries experience and potential impact of water fluoridation were assessed using linear regression modeling. Mean caries experience for six- and 12-year-olds tended to be higher in northern and eastern areas of the NT, corresponding to the distribution of low levels of natural fluoride. Several-fold more children in remote NT communities are exposed to the risks of inadequate fluoride than are exposed to excessive fluoride. Mean reticulated fluoride level was the only variable significantly associated (p<0.05) with caries experience in both age groups. The potential reduction of caries through introducing water fluoridation is expected to be about 28% for children living in communities with the lowest levels of fluoride (<0.3 mg/L). Introduction of fluoridation of water supplies into communities with inadequate natural fluoride is a vital measure for improving the dental health of children living in remote NT communities.


An Examination of Ability Emotional Intelligence and Its Relationships with Fluid and Crystallized Abilities in a Student Sample.
This study investigated correlative, factorial, and structural relationships between scores for ability emotional intelligence in the workplace (measured with the Geneva Emotional Competence Test), as well as fluid and crystallized abilities (measured with the Intelligence Structure Battery), carried out by a 188-participant student sample. Confirming existing research, recognition, understanding, and management of emotions were related primarily to crystallized ability tests measuring general knowledge, verbal fluency, and knowledge of word meaning. Meanwhile, emotion regulation was the least correlated with any other cognitive or emotional ability. In line with research on the trainability of emotional intelligence, these results may support the notion that emotional abilities are subject to acquired knowledge, where situational (i.e., workplace-specific) emotional intelligence may depend on accumulating relevant experiences.


Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis.
Although a positive association has been established, it is unclear whether lower respiratory tract infections (LRTIs) with respiratory syncytial virus (RSV) cause chronic wheezing illnesses. If RSV-LRTI were causal, we would expect RSV-LRTI prevention to reduce the incidence of chronic wheezing illnesses in addition to reducing acute disease. We aimed to evaluate the strength of evidence for a causal effect of RSV-LRTI on subsequent chronic wheezing illness to inform public health expectations for RSV vaccines. We did a systematic review and meta-analysis of observational studies evaluating the association between RSV-LRTI and subsequent wheezing illness (exposure studies) and studies evaluating the association between RSV immunoprophylaxis and subsequent wheezing illness (immunoprophylaxis studies). Exposure studies were included if the exposure group members had an LRTI with laboratory-confirmed RSV and if the exposure ascertainment period began before 2 years of age and ended before 5 years of age. We required a wash-out period of more than 30 days between the index RSV-LRTI and the outcome measurement to allow for resolution of the acute illness. Comparisons between RSV-LRTI and non-RSV-LRTI were not included. Immunoprophylaxis studies were included if they measured the association with subsequent wheezing illness relative to a control group, either in a randomised controlled trial (RCT) or an observational design. For the immunoprophylaxis drugs in question, we required evidence of efficacy in targeting RSV-LRTI from at least one RCT to ensure biological plausibility. All variations of wheezing illness were combined into a single outcome that refers broadly to asthma or any other respiratory illness with wheezing symptoms. Ovid MEDLINE and Embase databases were searched from inception up to Aug 28, 2018. We evaluated whether data from exposure studies could provide evidence against the most viable non-causal theory that RSV-LRTI is a marker of respiratory illness susceptibility rather than a causal factor. Additionally, we tested whether RSV immunoprophylaxis reduces the odds of subsequent wheezing illnesses. We used a random-effects modelling framework and, to accommodate studies providing multiple correlated estimates, robust variance estimation meta-regressions. Meta-regression coefficients (b) quantify differences between exposure and comparator groups on the loge odds ratio (loge OR) scale. From 14 235 records we identified 57 eligible articles that described 42 studies and provided 153 effect estimates. 35 studies estimated the direct effect of RSV-LRTI on wheezing illnesses (exposure studies) and eight evaluated the effect of RSV immunoprophylaxis (immunoprophylaxis studies). Exposure studies that adjusted for genetic influences yielded a smaller mean adjusted OR estimate (aOR+ 2·45, 95% CI 1·23-4·88) compared with those that did not (4·17, 2·36-7·37), a significant difference (b 0·53, 95% CI 0·04-1·02). Infants who were not protected with RSV immunoprophylaxis tended to have higher odds of subsequent wheezing illness, as we would expect if RSV-LRTI were causal, but the effect was not significant (OR+ 1·21, 95% CI 0·73-1·99). There was generally a high threat of confounding bias in the observational studies. Additionally, in both the observational studies and immunoprophylaxis RCTs, there was high risk of bias due to missing outcome data. Our findings, limited to exposure and immunoprophylaxis studies, do not support basing policy decisions on an assumption that prevention of RSV-LRTI will reduce recurrent chronic wheezing illnesses. Bill & Melinda Gates Foundation.


BNIP-2 induces cell elongation and membrane protrusions by interacting with Cdc42 via a unique Cdc42-binding motif within its BNIP-2 and Cdc42GAP homology domain.
The Cdc42 small GTPase regulates cytoskeletal reorganization and cell morphological changes that result in cellular extensions, migration, or cytokinesis. We previously showed that BNIP-2 interacted with Cdc42 and its cognate inactivator, p50RhoGAP/Cdc42GAP via its BNIP-2 and Cdc42GAP homology (BCH) domain, but its cellular and physiological roles still remain unclear. We report here that following transient expression of BNIP-2 in various cells, the expressed protein was located in irregular spots throughout the cytoplasm and concentrated at the leading edge of cellular extensions. The induced cell elongation and membrane protrusions required an intact BCH domain and were variously inhibited by coexpression of dominant negative mutants of Cdc42 (completely inhibited), Rac1 (partially inhibited), and RhoA (least inhibited). Presence of the Cdc42/Rac1 interactive binding (CRIB) motif alone as the dominant negative mutant of p21-activated kinase also inhibited the BNIP-2 effect. Bioinformatic analyses together with progressive deletional mutagenesis and binding studies revealed that a distal part of the BNIP-2 BCH domain contained a sequence with low homology to CRIB motif. However, in contrary to most effectors, BNIP-2 binding to Cdc42 was mediated exclusively via the unique sequence motif 285VPMEYVGI292. Cells expressing the BNIP-2 mutants devoid of this motif or/and the 34-amino acids immediately upstream to this sequence failed to elicit cell elongation and membrane protrusions despite that the protein still remained in the cytoplasm and interacted with Cdc42GAP. Evidence is presented where BNIP-2 in vivo induces cell dynamics by recruiting Cdc42 via its BCH domain, thus providing a novel mechanism for regulating Cdc42 signaling pathway.


Early events of secretory granule formation in the rat parotid acinar cell under the influence of isoproterenol. An ultrastructural and lectin cytochemical study.
The events involved in the maturation process of acinar secretory granules of rat parotid gland were investigated ultrastructurally and cytochemically by using a battery of four lectins [Triticum vulgaris agglutinin (WGA), Ulex europaeus agglutinin I (UEA-I), Glycine max agglutinin (SBA), Arachys hypogaea agglutinin (PNA)]. In order to facilitate the study, parotid glands were chronically stimulated with isoproterenol to induce secretion. Specimens were embedded in the Lowicryl K4M resin. The trans-Golgi network (TGN) derived secretory granules, which we refer to as immature secretory granules, were found to be intermediate structures in the biogenesis process of the secretory granules in the rat parotid acinar cell. These early structures do not seem to be the immediate precursor of the mature secretory granules: in fact, a subsequent interaction process between these early immature granule forms and TGN elements seems to occur, leading, finally, to the mature granules. These findings could explain the origin of the polymorphic subpopulations of the secretory granules in the normal acinar cells of the rat parotid gland. The lectin staining patterns were characteristic of each lectin. Immature and mature secretory granules were labelled with WGA, SBA, PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi apparatus were labelled with WGA, and trans cisternae with WGA and SBA.


The "bear" essentials: actualistic research on Ursus arctos arctos in the Spanish Pyrenees and its implications for paleontology and archaeology.
Neotaphonomic studies of large carnivores are used to create models in order to explain the formation of terrestrial vertebrate fossil faunas. The research reported here adds to the growing body of knowledge on the taphonomic consequences of large carnivore behavior in temperate habitats and has important implications for paleontology and archaeology. Using photo- and videotrap data, we were able to describe the consumption of 17 ungulate carcasses by wild brown bears (Ursus arctos arctos) ranging the Spanish Pyrenees. Further, we analyzed the taphonomic impact of these feeding bouts on the bones recovered from those carcasses. The general sequence of consumption that we charted starts with separation of a carcass's trunk; viscera are generally eaten first, followed by musculature of the humerus and femur. Long limb bones are not broken open for marrow extraction. Bears did not transport carcasses or carcass parts from points of feeding and did not disperse bones appreciably (if at all) from their anatomical positions. The general pattern of damage that resulted from bear feeding includes fracturing, peeling, crenulation, tooth pitting and scoring of axial and girdle elements and furrowing of the upper long limb bones. As predicted from observational data, the taphonomic consequences of bear feeding resemble those of other non-durophagus carnivores, such as felids, and are distinct from those of durophagus carnivores, such as hyenids. Our results have paleontological and archaeological relevance. Specifically, they may prove useful in building analogical models for interpreting the formation of fossil faunas for which bears are suspected bone accumulators and/or modifiers. More generally, our comparative statistical analyses draw precise quantitative distinctions between bone damage patterns imparted respectively by durophagus (modelled here primarily by spotted hyenas [Crocuta crocuta] and wolves [Canis lupus]) and non-durophagus (modelled here by brown bears and lions [Panthera leo]) carnivorans.


Coronavirus spike glycoprotein, extended at the carboxy terminus with green fluorescent protein, is assembly competent.
Due to the limited ultrastructural information about the coronavirion, little is known about the interactions acting at the interface between nucleocapsid and viral envelope. Knowing that subtle mutations in the carboxy-terminal endodomain of the M protein are already lethal, we have now probed the equivalent domain of the spike (S) protein by extending it terminally with a foreign sequence of 27 kDa: the green fluorescent protein (GFP). When expressed individually in murine cells, the S-GFP chimeric protein induced the formation of fluorescent syncytia, indicating that it was synthesized and folded properly, trimerized, and transported to the plasma membrane, where it exhibited the two key S protein functions, i.e., interaction with virus receptor molecules and membrane fusion. Incorporation into virus-like particles demonstrated the assembly competence of the chimeric spike protein. The wild-type S gene of mouse hepatitis coronavirus (MHV) was subsequently replaced by the chimeric construct through targeted recombination. A viable MHV-SGFP was obtained, infection by which could be visualized by the fluorescence induced. The efficiency of incorporation of the chimeric protein into particles was, however, reduced relative to that in wild-type particles which may explain, at least in part, the reduced infectivity produced by MHV-SGFP infection. We conclude that the incorporation of spikes carrying the large GFP moiety is apparently impaired by geometrical constraints and selected against during the assembly of virions. Probably due to this disadvantage, deletion mutants, having lost the foreign sequences, rapidly evolved and outcompeted the chimeric viruses during virus propagation. The fluorescent MHV-SGFP will now be a convenient tool to study coronaviral cell entry.


Antiendomysium antibodies in Brazilian patients with celiac disease and their first-degree relatives.
Literature data have shown high specificity of antiendomysial antibodies (EmA IgA) in celiac disease. The scarcity of Brazilian reports concerning this subject motivated the present study. To determine the sensitivity and specificity of antiendomysial IgA antibodies in Brazilian celiac patients at diagnosis and after treatment, to confirm patient adherence to a gluten-free diet and to screen first-degree relatives. An extensive clinical and serological study was performed by investigating the presence of these antibodies in 392 individuals from Southern Brazil. Indirect immunofluorescence using human umbilical cord as substrate was employed and the total levels of IgA were determined by turbidimetry in all groups. The study was conducted on 57 celiac patients (18 at diagnosis, 24 who adhered to a gluten-free diet and 15 with marked or slight transgression of the diet), 115 relatives of celiac patients (39 families), 94 patients with other gastrointestinal diseases, and 126 healthy individuals from the general population. The results demonstrated 100% positivity for the recently diagnosed patients and for those consuming gluten, in contrast to the patients who complied with the diet (0%). In the control group one individual was positive, but refused to undergo a biopsy. In the group of other gastrointestinal diseases, one positive patient presented ulcerative colitis, Down's syndrome and epilepsy, and the intestinal biopsy was diagnostic for celiac disease. These data showed 99.3% specificity for the test. Eighteen relatives were positive for antiendomysial antibodies IgA (15.65%), and comparison with the healthy population revealed a significant difference. An intestinal biopsy was obtained from seven subjects (one with total villous atrophy and six without alterations in the mucosal architecture, but all with a high number of intra-epithelial lymphocytes). The method revealed 100% sensitivity and 99.3% specificity. Because it is not an invasive method it can be used for the screening of atypical and latent forms of celiac disease to avoid serial biopsies and to control adherence to a gluten-free diet with implications in the prevention of malignancy in celiac disease.


Plasma homocysteine and restenosis after femoropopliteal angioplasty.
To assess the relationship between plasma homocysteine levels and restenosis after femoropopliteal percutaneous transluminal angioplasty. Over a 10-month period, 128 consecutive, symptomatic patients (72 men; median age 70 years) having successful femoropopliteal angioplasty for atherosclerotic occlusive disease were prospectively enrolled in the study. Plasma homocysteine levels were determined the day before the procedure. The primary endpoint was restenosis >50%, documented by duplex sonography, at up to 12 months' follow-up. Cox proportional hazards analysis was used to determine the risk of restenosis in relation to pretreatment homocysteine levels. The restenosis rate at 12 months was 46%. Median baseline plasma homocysteine levels were not different in patients with and without restenosis (15.4 versus 16.7 micromol/L, p=0.30). Compared to patients with homocysteine levels </=14 micromol/L (lower tertile, n=43), the hazard ratio of incident restenosis was 0.75 (95% CI 0.40 to 1.40) in patients with homocysteine levels from 14.1 to 19.6 micromol/L (middle tertile, n=42) and 0.64 (95% CI 0.33 to 1.22) in patients with homocysteine levels >/=19.7 micromol/L (upper tertile, n=42) (p=0.38). Multivariate analysis showed that lesion length (p<0.0001) and lack of hypertension (p=0.0013) were associated with restenosis. Elevated plasma homocysteine levels are not associated with restenosis after femoropopliteal angioplasty. Therefore, plasma homocysteine cannot be considered as an important risk factor influencing the outcome after initially successful angioplasty in femoropopliteal arteries.


Methodology for assessing rice varieties for resistance to the lesser grain borer, Rhyzopertha dominica.
Several physical and chemical attributes of rice were evaluated to determine which character would be best to use to assess multiple rice varieties for resistance to the lesser grain borer, Rhyzopertha dominica (F.). Laboratory tests were conducted on single varieties of long-, short-, and medium grain-rice to develop procedures and methodologies that could be used for large-scale screening studies. Progeny production of R. dominica was positively correlated with the percentage of broken hulls. Although kernel hardness, amylose content, neonate preference for brown rice, and adult emergence from neonates varied among the three rice varieties tested they did not appear to be valid indicators of eventual progeny production, and may not be useful predictors of resistance or susceptibility. Soundness and integrity seem to be the best characters to use for varietal screening studies with R. dominica.


Early Improvements of Individual Symptoms With Antipsychotics Predict Subsequent Treatment Response of Neuropsychiatric Symptoms in Alzheimer's Disease: A Re-Analysis of the CATIE-AD Study.
The aim of the present study was to identify individual symptoms whose early improvements contributed to subsequent treatment response to antipsychotics for neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD) using the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD). The CATIE-AD study was conducted between April 2001 and November 2004 at 45 sites in the United States. Data for 421 patients with DSM-IV AD with NPSs treated with antipsychotics were analyzed in the present study. Treatment response was defined as a reduction of ≥ 9 points in the Neuropsychiatric Inventory (NPI) score or a reduction of ≥ 25% from baseline in Brief Psychiatric Rating Scale (BPRS) total score at week 8. Logistic regression analyses were performed to examine associations between response and clinical and demographic characteristics, including each total or individual symptom score reduction at week 2. Reduction in NPI or BPRS total score at week 2 and several individual symptom score reductions (euphoria/elation, irritability, hallucinations, anxiety, agitation, apathy, disinhibition, and depression among NPI subitems; excitement, suspiciousness, disorientation, hostility, depressive mood, and emotional withdrawal among BPRS subitems) at week 2 were significantly associated with subsequent treatment response at week 8 (all P values < .05); Early non-improvements of irritability and suspiciousness were shown to be especially influential clinical markers in predicting subsequent treatment nonresponse. Furthermore, healthier condition at baseline was significantly associated with treatment response at week 8 (P < .05). Although further research to validate these preliminary findings is needed, focusing on early improvements of individual symptoms could help identify subsequent treatment responders to antipsychotics in AD patients with NPSs. ClinicalTrials.gov identifier: NCT00015548.


Stepping to an Auditory Metronome Improves Weight-Bearing Symmetry in Poststroke Hemiparesis.
Asymmetry in weight-bearing is a common feature in poststroke hemiparesis and is related to temporal asymmetry during walking. The aim of this study was to investigate the effect of an auditory cue for stepping in place on measures of temporal and weight-bearing asymmetry. A total of 10 community-dwelling adults (6 males and 4 females) with chronic poststroke hemiparesis performed 5 un-cued stepping trials and 5 stepping trials cued by an auditory metronome cue. A Vicon system was used to collect full body kinematic trajectories. Two force platforms were used to measure ground reaction forces. Step, swing, and stance times were used to calculate temporal symmetry ratios. Weight-bearing was assessed using the vertical component of the ground reaction force and center of mass-center of pressure separation at mid-stance. Weight-bearing asymmetry was significantly reduced during stepping with an auditory cue. Asymmetry values for step, swing, and stance times were also significantly reduced with auditory cueing. These findings show that auditory cueing when stepping in place produces immediate reductions in measures of temporal asymmetry and dynamic weight-bearing asymmetry.


Capecitabine plus paclitaxel as front-line combination therapy for metastatic breast cancer: a multicenter phase II study.
The goal of this multicenter, open-label phase II study was the clinical evaluation of combination therapy with the oral fluoropyrimidine capecitabine and the taxane paclitaxel in patients with metastatic breast cancer (MBC). Forty-seven patients with MBC received oral capecitabine at 1650 mg/m(2)/d (825 mg/m(2) twice daily) on days 1 through 14, and intravenous infusion of paclitaxel at 175 mg/m(2) on day 1 of each 21-day treatment cycle. Treatment continued until disease progression, intolerable toxicity, or patient' s decision to discontinue. Patients (35 to 76 years old) had a median Karnofsky performance status of 90%. Forty-four patients (94%) received study treatment as first-line therapy for metastatic disease. Objective responses occurred in 24 (51%) patients; seven (15%) complete responses and 17 (36%) partial responses. Stable disease lasting 180 days or more was observed in nine (19%); the clinical response rate was 70%. Median duration of response was 12.6 months, median time to disease progression was 10.6 months, and median overall survival time was 29.9 months. The most common treatment-related adverse events, regardless of severity, were alopecia, hand-foot syndrome, nausea, and fatigue. Neutropenia (15%), alopecia (13%), and hand-foot syndrome (11%) were the only grade 3 or 4 treatment-related adverse events that occurred in more than 10% of patients. The combination of capecitabine plus paclitaxel is a highly active and generally well-tolerated regimen for first-line treatment of MBC.