The impact of health behaviours on incident cardiovascular disease in Europeans and South Asians--a prospective analysis in the UK SABRE study.
There is consistent evidence on the impact of health behaviours on risk of cardiovascular disease (CVD) in European populations. As South Asians in the UK have an excess risk of CVD and coronary heart disease (CHD) compared to Europeans, we investigated whether a similar association between combined health behaviours and risk of CVD and CHD among this high-risk group exists, and estimated the population impact. In a prospective cohort of 1090 Europeans and 1006 South Asians (40-69 y) without prevalent CVD at baseline (1988-1990), followed up for 21 years to 2011, there were 601 incident CVD events [Europeans n = 255; South Asians n = 346] of which 520 were CHD events [n = 207 and 313 respectively]. Participants scored between 0 to 4 points for a composite score including four baseline healthy behaviours (non-smoker, moderate alcohol intake, physically active, frequent fruit/vegetable intake). Adjusted hazard ratios (95% confidence intervals) for incident CHD in Europeans who had three, two, one, and zero compared to four health behaviours were 1.33 (0.78-2.29), 1.96 (1.15-3.33), 1.36 (0.74-2.48) and 2.45 (1.18-5.10), respectively, p-trend = 0.025. In South Asians, corresponding HRs were 2.88 (1.33-6.24), 2.28 (1.06-4.91), 3.36 (1.53-7.39) and 3.48 (1.38-8.81), p-trend = 0.022. The results were similar for incident CVD; Europeans HR 2.12 (1.14-3.94), p-trend = 0.014; South Asians HR 2.73 (1.20-6.21), p-trend = 0.018. The population attributable fraction in Europeans was 43% for CHD and 28% for CVD. In South Asians it was 63% and 51% respectively. Lack of adherence to four combined health behaviours was associated with 2 to 3-fold increased risk of incident CVD in Europeans and South Asians. A substantial population impact in the South Asian group indicates important potential for disease prevention in this high-risk group by adherence to healthy behaviours.


Simulation of a radiobiology facility for the Centre for the Clinical Application of Particles.
The Centre for the Clinical Application of Particles' Laser-hybrid Accelerator for Radiobiological Applications (LhARA) facility is being studied and requires simulation of novel accelerator components (such as the Gabor lens capture system), detector simulation and simulation of the ion beam interaction with cells. The first stage of LhARA will provide protons up to 15 MeV for in vitro studies. The second stage of LhARA will use a fixed-field accelerator to increase the energy of the particles to allow in vivo studies with protons and in vitro studies with heavier ions. BDSIM, a Geant4 based accelerator simulation tool, has been used to perform particle tracking simulations to verify the beam optics design done by BeamOptics and these show good agreement. Design parameters were defined based on an EPOCH simulation of the laser source and a series of mono-energetic input beams were generated from this by BDSIM. The tracking results show the large angular spread of the input beam (0.2 rad) can be transported with a transmission of almost 100% whilst keeping divergence at the end station very low (<0.1 mrad). The legacy of LhARA will be the demonstration of technologies that could drive a step-change in the provision of proton and light ion therapy (i.e. a laser source coupled to a Gabor lens capture and a fixed-field accelerator), and a system capable of delivering a comprehensive set of experimental data that can be used to enhance the clinical application of proton and light ion therapy.


Association of circulating high-sensitivity C-reactive protein with late recurrence after ischemic stroke.
We investigated the association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and stroke recurrence events in a cohort of patients with acute ischemic stroke (IS). We prospectively studied 286 patients with acute IS who were admitted within 24 h after the onset of symptoms. Serum levels of hs-CRP, and National Institutes of Health stroke scale (NIHSS) were measured at admission. The primary endpoint was stroke recurrence 1 year after stroke onset. We used logistic regression models to assess the relationship between hs-CRP levels and the risk of recurrent stroke. In multivariable models, hs-CRP levels were associated with an increased risk of an NIHSS greater than 6 [odds ratio=1.17; 95% confidence interval (CI)=1.05-1.48; P=0.021]. Among the participants, stroke recurrence was found in 48 (16.8%) cases. In multivariate analyses, the third and fourth quartiles of hs-CRP were significantly associated with stroke recurrence during the observation period compared with the first quartile group (P<0.01). In addition, the hs-CRP level in the highest quartile was associated with a higher risk of stroke recurrence (odds ratio=2.75; 95% CI=1.62-3.92; P=0.006). Hs-CRP (area under the curve=0.71; 95% CI=0.64-0.79) improved the ability of the NIHSS score to diagnose stroke recurrence (area under the curve of the combined model 0.78; 95% CI=0.73-0.84; P<0.01). Serum levels of hs-CRP at admission predicted the future stroke recurrence in patients with IS.


[Nagashima-type palmoplantar keratoderma: A little-known palmoplantar keratoderma in Europe].
Herein we present a case of palmoplantar keratoderma (PPK) in a young adopted girl of Chinese origin living in France. The patient, aged six years, had presented transgressive PPK since birth, as well as erythema progressing in congestive inflammatory episodes, palmoplantar hyperhidrosis and progressive characteristics (moderate hyperkeratosis in areas of rubbing other than the palms and soles, namely the elbows and knees). Histopathological examination of a skin biopsy revealed a thick epidermis with lengthening and thickening of crests. The epithelium displayed a thick granular layer. Electron microscopy showed hyperorthokeratosis with hypergranulosis and loss of lamellar structure of the keratinosomes, as well as cleavage between corneocytes. Molecular studies showed the presence of two composite heterozygous mutations of the SERPINB7 gene, enabling a diagnosis of Nagashima-type PPK (NPPK) to be made. NPPK is an autosomal recessive disease caused by a mutation in the SERPINB7, a member of the superfamily of serine protease inhibitors. It was described by Nagashima in 1977 with molecular characterisation by Kubo following in 2013. It is the most widespread form of PPK in Asia (with a prevalence of 1.2/10,000 in Japan and 3.1/10,000 in China). It is distinguished from the other PPKs in terms of transgressive soft hyperkeratosis, inflammatory episodes and hyperhidrosis, as well as by its non-progressive nature. In the present case, while the clinical presentation was characteristic, diagnosis was only made thanks to sequencing of a panel of over 50 genes responsible for PPK. The disease is effectively little-known in Europe. This study highlights the increasing importance of diagnostic investigation methods involving the use of gene panels.


Neurodegeneration: An early event of diabetic retinopathy.
Diabetic retinopathy (DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia. However, retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination. In other words, retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR. Elevated levels of glutamate and the overexpression of the renin- angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina. Among neuroprotective factors, pigment epithelial derived factor, somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review. Nevertheless, it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye. New strategies, based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors, are currently being tested in experimental models and in clinical pilot studies. Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.


Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Elderly Patients with Metastatic Breast Cancer: A Meta-Analysis.
Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an approved treatment for metastatic breast cancer (MBC). However, there is an ongoing debate about the efficacy and safety of nab-paclitaxel in elderly patients. We conducted a meta-analysis to evaluate nab-paclitaxel efficacy and adverse events in MBC patients 65 years and older, compared with MBC patients younger than 65 years (control group). We performed a literature search using PubMed, the Cochrane Library, and EMBASE, from their inception to 30 September 2019. The relevant studies compared overall response rates (ORRs) and incidence of adverse events; four studies comprising 1204 patients were identified and included. ORRs were similar in patients older than 65 years and controls (odds ratio (OR) 0.71, 95% confidence interval (CI) 0.42-1.21). On subgroup analysis, both first-line therapy (OR 2.54, 95% CI 1.92-3.36) and lower Eastern Cooperative Oncology Group (ECOG) performance status (OR 0.20, 95% CI 0.06-0.69) were associated with a higher ORR. Adverse events including neutropenia, sensory neuropathy, diarrhea, and nausea were comparable between the groups. In conclusion, nab-paclitaxel showed comparable efficacy and safety in older and younger patients with MBC. Nab-paclitaxel can be a first-line treatment option for MBC patients 65 years and older.


Reduced variation among northern deer tick populations at an autosomal microsatellite locus.
To determine whether genes flow freely between populations of the Ixodes ricinus-like ticks of eastern North America, and to determine whether the abundant northerly populations of these vectors of Lyme disease and other zoonotic infections may have arisen recently from a small cohort of ancestral founders, we characterized the nuclear IR27 microsatellite alleles in ticks sampled from the geographic extremes of their ranges. These microsatellite alleles differentiated populations located in the southeastern, northcentral and northeastern United States, respectively. Although evident heterozygous genotypes are about as frequent as would be expected in randomly mating populations, particular microsatellite alleles and diploid genotypes occur more frequently in certain populations than in others. Ticks from the Northeast and upper Midwest are markedly more related to each other than to ticks from the Southeast. Patterns of diversity present in this nuclear microsatellite marker correspond to those evident at a mitochondrial locus and indicate that the deer ticks of the Northeast and upper Midwest are genetically isolated from those in the Southeast. The Ixodes ricinus-like ticks that impose a public health burden in the northeastern and northcentral United States originated recently in a common founder population.


Safety of 2-Octyl Cyanoacrylate in Spreader Grafting.
Cyanoacrylate adhesives can make the placement of spreader grafts in open septorhinoplasty technically easier, but its use is off-label beneath the skin. There is a theoretical risk of toxicity from cyanoacrylate breakdown products, but this risk has not been thoroughly studied in rhinoplasty. The objective was to evaluate the effects of subcutaneous cyanoacrylate use during spreader graft placement in rhinoplasty in a retrospective review of open septorhinoplasties in which 2-octyl cyanoacrylate was used to aid placement of spreader grafts. The review was carried out in a tertiary care military academic medical center. A total of 140 adults underwent open septorhinoplasty between September 2013 and May 2016 with spreader graft placement. The authors excluded patients in whom 2-octyl cyanoacrylate was not used to aid graft placement and those who did not follow up postoperatively in our clinic. 108 (85 males and 23 females) patients were included in the final analysis. Nine (8.3%) patients had inflammatory reactions possibly attributable to 2-octyl cyanoacrylate toxicity. The overall rate of postoperative inflammation possibly attributable to 2-octyl cyanoacrylate was 17% among females and 5.9% among males, and this difference was not statistically significant (p = 0.07). However, the rate of postoperative inflammation attributable to 2-octyl cyanoacrylate that required an intervention (incision and drainage or antibiotics) was 2.7% overall, 13% among women and 0% among men, and this difference was significant based on chi-square testing (p < 0.001). Further, revision cases were significantly more likely to develop abnormal postoperative inflammation than initial cases (p = 0.02). Herein, the authors present the largest series of patients in whom 2-octyl cyanoacrylate was used to assist placement of cartilage spreader grafts during open septorhinoplasty. While 2-octyl cyanoacrylate is an effective adjunct to facilitate graft placement, they recommend against its use, as the risk of postoperative inflammation is significant.


Sentence Repetition as a Clinical Marker of Developmental Language Disorder: Evidence From Arabic.
Research on the typical and impaired grammatical acquisition of Arabic is limited. This study systematically examined the morphosyntactic abilities of Arabic-speaking children with and without developmental language disorder (DLD) using a novel sentence repetition task. The usefulness of the task as an indicator of DLD in Arabic was determined. A LITMUS (Language Impairment Testing in Multilingual Settings) sentence repetition task was developed in Palestinian Arabic (LITMUS-SR-PA-72) and administered to 30 children with DLD (M = 61.50 months, SD = 11.27) and 60 age-matched typically developing (TD) children (M = 63.85 months, SD = 10.16). The task targeted grammatical structures known to be problematic for Arabic-speaking children with DLD (language specific) and children with DLD across languages (language independent). Responses were scored using binary, error, and structural scoring methods. Children with DLD scored below TD children on the LITMUS-SR-PA-72, in general, and in the repetition of language-specific and language-independent structures. The frequency of morphosyntactic errors was higher in the DLD group relative to the TD group. Despite the large similarity of the type of morphosyntactic errors between the two groups, some atypical errors were exclusively produced by the DLD group. The three scoring methods showed good diagnostic power in the discrimination between children with DLD and children without DLD. Sentence repetition was an area of difficulty for Palestinian Arabic-speaking children with DLD. The DLD group demonstrated difficulties with language-specific and language-independent structures, particularly complex sentences with noncanonical word order. Most grammatical errors made by the DLD group resembled those of the TD group and were mostly omissions or substitutions of grammatical affixes or omissions of function words. SR appears to hold promise as a good indicator for the presence or absence of DLD in Arabic. Further validation of these findings using population-based studies is warranted. Supplemental Material https://doi.org/10.23641/asha.16968043.


Three-dimensional CT angiography in the detection and characterization of intracranial berry aneurysms.
To assess the accuracy of three-dimensional CT angiography (CTA) in the detection and characterization of intracranial aneurysms and to help determine its role as a screening test for aneurysms in the asymptomatic population and as an adjunct to angiography in subarachnoid hemorrhages and in the follow-up of untreated aneurysms. In a blinded, prospective study, the 3-D CTA studies in 80 patients with symptomatic aneurysms were analyzed for the presence and morphology of aneurysms. Angiography or surgery acted as the control. Ninety-four aneurysms were found in 63 patients. Negative findings at angiography were noted in 17. Sensitivity and specificity of 3-D CTA for all aneurysms, all patients, and aneurysms 5 mm or smaller were 90.4% and 50%, 98.4% and 82.4%, and 78.8% and 51.9%, respectively. Three-dimensional CTA may have a role in noninvasive screening for asymptomatic aneurysms in the general population, but caution is advocated when data obtained from symptomatic patients are extrapolated to the asymptomatic population who harbor smaller aneurysms. Also, 3-D CTA may be useful as an adjunct to angiography in the characterization of berry aneurysms and in the follow-up of untreated aneurysms.


Ambient temperature and preeclampsia: A historical cohort study.
Previous studies found inconsistent associations between ambient temperature during pregnancy and the risk of preeclampsia. If such associations are causal, they may impact the future burden of preeclampsia in the context of climate change. We used a historical cohort of 129,009 pregnancies (5074 preeclampsia cases) from southern Israel that was merged with temperature assessments from a hybrid satellite-based exposure model. Distributed-lag and cause-specific hazard models were employed to study time to all preeclampsia cases, followed by stratification according to early (≤34 weeks) and late (>34 weeks) onset disease and identify critical exposure periods. We found a positive association between temperature and preeclampsia during gestation, which was stronger in the 3rd trimester. For example, during week 33, compared to the reference temperature of 22.4 °C, the cause-specific hazard ratio (HRCS) of preeclampsia was 1.01 (95% confidence interval (CI): 1.01-1.02) when exposed to 30 °C, 1.05 (95%CI: 1.03-1.08) at 35 °C, and 1.07 (95%CI: 1.04-1.10) at 37 °C. The associations existed with both early- and late-onset preeclampsia; however, the associations with the early-onset disease were somewhat stronger, limited to the first weeks of pregnancy and the third trimester, and with larger confidence intervals. The HRCS for early preeclampsia onset, when exposed to 37 °C compared to 22.4 °C during week 33, was 1.12 (95%CI: 0.96-1.30), and for late-onset preeclampsia, the HRCS was 1.09 (95%CI: 1.05-1.13). To conclude, exposure to high temperatures at the beginning and, particularly, the end of gestation is associated with an increased risk of preeclampsia in southern Israel.


Continuous recovery and enhanced yields of volatile fatty acids from a continually-fed 100 L food waste bioreactor by filtration and electrodialysis.
A novel method to recover VFAs from a continually-fed 100 L food waste bioreactor was developed using industrially applicable methods. The in-situ recovery of VFAs increased production rates from 4 to 35 mgvfa gvs-1 day-1 by alleviating end-product inhibition and arresting methanogenesis, and electrodialysis was able to concentrate the recovered VFAs to 4000 mg L-1. There remains considerable scope to increase the production rates and concentrations further, and the VFAs were recovered in a form that made them suitable for use as platform chemicals with minimal refining. This is the first time that continuous VFA recovery from real-world food waste has been reported at this scale with continual feeding, and represents a promising means through which to produce sustainable platform chemicals. Furthermore the production of VFAs arrests methane production in bioreactors, which is a low value product around which there is a growing concern about fugitive emissions contributing to climate change.


A beef herd model for simulating feed intake, animal performance, and manure excretion in farm systems.
A beef herd submodel was created for integration with other farm components to form a whole-farm model capable of simulating a wide range of beef production systems. This herd submodel determined the best available feed or feed mix to meet the fiber, energy, and protein requirements for each of up to six animal groups on the farm. The groups comprised any combination of cows, nursing calves, young heifers, yearling heifers, stockers, and finishing cattle. Protein, energy, and mineral requirements were determined for each group using the Cornell Net Carbohydrate and Protein System, Level 1. Diets were formulated to meet these requirements with available feeds, and the resulting feed intake, growth, and manure DM and nutrient (N, P, and K) excretions were predicted. Required feed characteristics included CP, ruminally degradable protein, acid detergent insoluble protein, NDF, P, and K concentrations. Feed intake was predicted by considering energy intake, potentially limited by fill, and exceeding a minimum roughage requirement. Fill and roughage limits were functions of feed NDF concentrations adjusted to consider particle size distribution and the relative rate of ruminal digestibility or the physical effectiveness of the fiber. The herd submodel was verified to predict feed intakes, nutrient requirements, diets, and manure excretions similar to those recommended or measured for beef animals. Incorporation of the beef herd submodel with other farm components, including crop growth (alfalfa, grass, corn, small grain, and soybean), harvest, storage, feeding, grazing, and manure handling, provided the Integrated Farm System Model. This comprehensive farm-simulation model is a useful research and teaching tool for evaluating and comparing the long-term performance, economics, and environmental impact of beef, dairy, and crop production systems.


Superdrainage of the ileocolic vein to the internal jugular vein interposed by an inferior mesenteric vein graft in replacing the esophagus with the right hemicolon.
The fear of serious complications, such as a necrotic conduit caused by an impaired blood circulation can arise when replacing the esophagus with an intestinal conduit. The aim of this paper is to present effective superdrainage of an intestinal conduit using an inferior mesenteric vein (IMV) interposition graft. In 2008, we performed superdrainage of the ileocolic vein to the internal jugular vein interposed by an IMV graft in replacing the esophagus with the right hemicolon for advanced thoracic esophageal cancer in three patients with a synchronous gastric cancer or a previous gastrectomy. No leakage at the enteric anastomoses occurred. Neither ischemic lesions in these intestinal conduits nor complications caused by harvesting an IMV graft were observed. Superdrainage of the ileocolic vein to the internal jugular vein interposed by an IMV graft effectively improves the blood circulation in intestinal conduits brought up to the neck as an esophageal replacement.


[Role of the change in social position in readjustment of the motivational-purposeful sphere of oncologic patients].
A psychological analysis of 125 patients with breast cancer showed that cancer, creating a crisis situation for a woman, leads to changes in a life position transforming her motivational sphere. At the diagnostic stage when the position of despondency is predominant, the major motivation is the desire to survive. At the preoperative stage the desire to preserve health and to survive is prevailing. Postoperatively the motive to preserve health becomes prevalent. At the same time it acquires a new sense of social survival. At longterm stages of treatment this motive of social survival becomes predominant. Psychocorrective work with cancer patients should be based on the principle of active mediation of motivational formation of the person. Proceeding from the principle of "involvement" of the person into meaningful activity, it is necessary to consider the process of psychological rehabilitation as a process of transformation of the objective position of the person, which is determined by a definite social role.


RTL-P: a sensitive approach for detecting sites of 2'-O-methylation in RNA molecules.
2'-O-methylation is present within various cellular RNAs and is essential to RNA biogenesis and functionality. Several methods have been developed for the identification and localization of 2'-O-methylated sites in RNAs; however, the detection of RNA modifications, especially in low-abundance RNAs and small non-coding RNAs with a 2'-O-methylation at the 3'-end, remains a difficult task. Here, we introduce a new method to detect 2'-O-methylated sites in diverse RNA species, referred to as RTL-P [Reverse Transcription at Low deoxy-ribonucleoside triphosphate (dNTP) concentrations followed by polymerase chain reaction (PCR)] that demonstrates precise mapping and superior sensitivity compared with previous techniques. The main procedures of RTL-P include a site-specific primer extension by reverse transcriptase at a low dNTP concentration and a semi-quantitative PCR amplification step. No radiolabeled or fluorescent primers are required. By designing specific RT primers, we used RTL-P to detect both previously identified and novel 2'-O-methylated sites in human and yeast ribosomal RNAs (rRNAs), as well as mouse piwi-interacting RNAs (piRNAs). These results demonstrate the powerful application of RTL-P for the systematic analysis of fully or partially methylated residues in diverse RNA species, including low-abundance RNAs or small non-coding RNAs such as piRNAs and microRNAs (miRNAs).


New psychoactive substances in Eurasia: a qualitative study of people who use drugs and harm reduction services in six countries.
This study examines the use of new psychoactive substances (NPS) and the harm reduction response in six Eurasian countries: Belarus, Moldova, Serbia, Kazakhstan, Kyrgyzstan, and Georgia. The aim is to identify current patterns of NPS use and related harms in each country through recording the perspectives and lived experience of people who use drugs and people who provide harm reduction services in order to inform the harm reduction response. The study involved desk-based research and semi-structured interviews/focus groups with 124 people who use drugs and 55 health and harm reduction service providers across the six countries. People who use drugs in all countries were aware of NPS, primarily synthetic cathinones and synthetic cannabinoids. NPS users generally reflected two groups: those with no prior history of illicit drug use (typically younger people) and those who used NPS on an occasional or regular basis due to the lack of availability of their preferred drug (primarily opiates). In many cases, these respondents reported they would not use NPS if traditional opiates were available. Common factors for choosing NPS included cost and accessibility. Respondents in most countries described NPS markets that use the DarkNet and social media for communication, secretive methods of payment and hidden collection points. A recurring theme was the role of punitive drug policies in driving NPS use and related harms. Respondents in all countries agreed that current harm reduction services were important but needed to be enhanced and expanded in the context of NPS. The study identified patterns and drivers of NPS use, risk behaviours and drug-related harms. It identified gaps in the current harm reduction response, particularly the needs of non-injectors and overdose response, as well as the harmful effects of punitive drug policies. These findings may inform and improve current harm reduction services to meet the needs of people who use NPS.


Role of transforming growth factor beta in breast carcinogenesis.
Transforming growth factor (TGF) beta is a pre-eminent negative growth regulator that has antiproliferative effects on a range of epithelial cells. This ability has evoked interest in this growth factor as a tumour suppressor with potential clinical significance. In the early stages of breast carcinogenesis, a growth-inhibitory response to TGFbeta is maintained, which depends on an intact TGFbeta signalling pathway. Tumour development and progression of cells along a neoplastic continuum is accompanied by loss of this growth-inhibitory response to TGFbeta, which might instead promote tumour growth indirectly through a combination of permissive effects on stromal tissue, angiogenesis, and the immune system. This review discusses the complexity of functional pleiotropy and the continually changing roles of TGFbeta as a tumour evolves, along with competing therapeutic strategies. The boosting of local endogenous amounts of TGFbeta in conjunction with enhancement of cellular responsiveness might be appropriate in early malignant disease, and anti-TGFbeta approaches could yield a therapeutic gain in metastatic states.


Calibration of the Leg Muscle Responses Elicited by Predictable Perturbations of Stance and the Effect of Vision.
Motor adaptation due to task practice implies a gradual shift from deliberate control of behavior to automatic processing, which is less resource- and effort-demanding. This is true both for deliberate aiming movements and for more stereotyped movements such as locomotion and equilibrium maintenance. Balance control under persisting critical conditions would require large conscious and motor effort in the absence of gradual modification of the behavior. We defined time-course of kinematic and muscle features of the process of adaptation to repeated, predictable perturbations of balance eliciting both reflex and anticipatory responses. Fifty-nine sinusoidal (10 cm, 0.6 Hz) platform displacement cycles were administered to 10 subjects eyes-closed (EC) and eyes-open (EO). Head and Center of Mass (CoM) position, ankle angle and Tibialis Anterior (TA) and Soleus (Sol) EMG were assessed. EMG bursts were classified as reflex or anticipatory based on the relationship between burst amplitude and ankle angular velocity. Muscle activity decreased over time, to a much larger extent for TA than Sol. The attenuation was larger for the reflex than the anticipatory responses. Regardless of muscle activity attenuation, latency of muscle bursts and peak-to-peak CoM displacement did not change across perturbation cycles. Vision more than doubled speed and the amount of EMG adaptation particularly for TA activity, rapidly enhanced body segment coordination, and crucially reduced head displacement. The findings give new insight on the mode of amplitude- and time-modulation of motor output during adaptation in a balancing task, advocate a protocol for assessing flexibility of balance strategies, and provide a reference for addressing balance problems in patients with movement disorders.


Informed clinical management: decision support systems and physicians.
In addition to providing value today, information systems should pave the way for greater systems' value tomorrow. An organization that begins now to transform its administrative decision support system into a clinically oriented decision support system has taken one significant step in the direction of the future.


The use of temporary atrial wire electrodes to record atrial electrograms in patients who had cardiac surgery.
The use of temporary atrial electrodes after surgery provides the medical staff with a valuable diagnostic tool in patients who have undergone open heart surgery. Recording a unipolar or bipolar atrial EG is a simple procedure that can be performed at bedside with an ECG machine. The bipolar recording lead has specific advantages over a unipolar recording lead. The use of a bipolar recording lead simplifies the identification of the P wave during rapid tachycardias and atrioventricular dissociation. The use of unipolar and bipolar atrial EGs recorded simultaneously and sequentially can be used to identify atrial rhythm and ascertain the atrioventricular relationship. Nurses need to integrate unipolar and bipolar EGs as part of their baseline assessment.


Tech.Sight. Antibody design by man and nature.
Catalytic antibodies have emerged as being without peer as rationally designed biocatalysts. They have been shown to catalyze an ever-increasing array of chemical reactions with both high substrate specificity and selectivity. Probing the immune repertoire, via an expanding number of techniques, has lead to the production of proteins that can catalyze chemistry that is both difficult to perform using existing chemical methods and that is not catalyzed by endogenous enzymes. Remarkably, recent evidence has pointed to a hitherto unknown catalytic function of all antibodies that seems to be intrinsic to their immunoglobulin structure, the conversion of 1O2* into H2O2. This new catalytic potential of antibodies points to a new 'chemical arm' of the immune system and reveals that the evolution of catalytic antibodies significantly predates their rational design.


In-plane thermal diffusivity measurement of thin plates by the transient fin method.
The transient fin method has mainly been used for the measurement of in-plane thermal diffusivity of rather highly diffusive materials available under the form of thin plates. This paper presents an extension of the method to low diffusivity materials such as plastics. A new analytical model is used in the real space, avoiding to make a Laplace transform of experimental temperatures recordings that may be inaccurate. Experiments carried on two materials under gas pressure varying from 10-2 mbar to 1 bar show the great influence of heat conduction in the air surrounding the sample, leading to estimation errors that can reach 30% at atmospheric pressure. The experimental results also show that accurate measurements can be achieved if the pressure is lower than 10-2 mbar.


Masking of tones and speech by Schroeder-phase harmonic complexes in normally hearing and hearing-impaired listeners.
Tone detection and sentence recognition were measured for normally hearing and hearing-impaired listeners using maskers consisting of harmonic series with components summed in positive or negative Schroeder phase. Each task was carried out with the signal set at 60, 70, or 80 dB SPL. For listeners with normal hearing, positive Schroeder-phase complexes masked tones and sentences less than negative Schroeder-phase maskers. In the two experimental tasks, to achieve the same amount of masking, positive Schroeder-phase complexes had to be set as much as 12-15 dB higher than negative Schroeder-phase complexes. Large phase effects were observed on both tasks at all three test levels. The two maskers were more nearly equal in effectiveness in the presence of cochlear damage. The findings support an interpretation that involves differences in the shape of the basilar-membrane waveform generated by each masker and active cochlear processing which enhances the internal signal-to-masker ratio for signals presented in the positive Schroeder masker. This spectral enhancement appears to require nonlinear active gain that is characteristic of normal auditory processing at moderate presentation levels. The results of the sentence recognition task suggest that group differences observed in tone detection transfer fairly directly to speech perception under masking.


Effect of high-pressure-jet processing on the physiochemical properties of low-fat ice cream mix.
The objective of this study was to use high-pressure-jet (HPJ) processing to produce functional properties in a low-fat (4.5% fat) ice cream mix similar to those seen when emulsifiers are used. Ice cream mix or serum (nonfat portion of the ice cream mix) were subjected to 200 or 400 MPa HPJ processing and compared with a non-HPJ-treated control. A similar non-HPJ-treated formulation but containing polysorbate 80 (0.075% wt/wt) was also used as a control. The mix samples were characterized in terms of their particle size, density, flow properties, stability, crystallization kinetics, and fat-protein interactions. The sample from the mix subjected to 400 MPa HPJ processing (HPJ-M-400) had increased consistency coefficient (5°C; 228 ± 102.7 mPa·s) and particle size (D[4,3]; 16.0 ± 2.5 μm) compared with the non-HPJ-treated control sample, with viscosity and particle size (volume-moment mean diameter, D[4,3]) values of 7.5 ± 0.4 mPa·s and 0.50 ± 0.1 μm, respectively. These differences were attributed to an increase in casein-fat interactions and casein-casein interactions caused by the 400 MPa HPJ treatment, which were observed using confocal scanning laser microscopy and inferred from an increase in protein and fat concentrations in the sediment after ultracentrifugation. Interestingly, the density of HPJ-M-400 was also lower (0.79 ± 0.17 g/mL) than that of the control (1.04 ± 0.00 g/mL) because bubbles were trapped within these complexes. The large casein-fat complexes formed in the HPJ-M-400 sample also appeared to act as steric barriers that slowed ice crystal growth during quiescent freezing. The alterations in physiochemical properties and apparent ice crystal growth induced by the 400 MPa treatment of low-fat ice cream mix have many potential applications, including clean-label confections.


What are the factors that contribute to road accidents? An assessment of law enforcement views, ordinary drivers' opinions, and road accident records.
What are the main contributing factors to road accidents? Factors such as inexperience, lack of skill, and risk-taking behaviors have been associated with the collisions of young drivers. In contrast, visual, cognitive, and mobility impairment have been associated with the collisions of older drivers. We investigated the main causes of road accidents by drawing on multiple sources: expert views of police officers, lay views of the driving public, and official road accident records. In Studies 1 and 2, police officers and the public were asked about the typical causes of road traffic collisions using hypothetical accident scenarios. In Study 3, we investigated whether the views of police officers and the public about accident causation influence their recall accuracy for factors reported to contribute to hypothetical road accidents. The results show that both expert views of police officers and lay views of the driving public closely approximated the typical factors associated with the collisions of young and older drivers, as determined from official accident records. The results also reveal potential underreporting of factors in existing accident records, identifying possible inadequacies in law enforcement practices for investigating driver distraction, drug and alcohol impairment, and uncorrected or defective eyesight. Our investigation also highlights a need for accident report forms to be continuously reviewed and updated to ensure that contributing factor lists reflect the full range of factors that contribute to road accidents. Finally, the views held by police officers and the public on accident causation influenced their memory recall of factors involved in hypothetical scenarios. These findings indicate that delay in completing accident report forms should be minimised, possibly by use of mobile reporting devices at the accident scene.


Regulation of survival signals from the insulin-like growth factor-I receptor.
Suppression of apoptosis by survival factors is important for the maintenance of normal tissue homoeostasis and the response to infection or injury. Survival factors such as insulin-like growth factor-I (IGF-I) initiate a signalling cascade that starts by tyrosine phosphorylation of substrates leading to the activation of serine kinases that modulate the activity of members of the Bcl-2 family, which regulates the apoptotic machinery in most cells. Tumour cells often have enhanced survival mechanisms due either to up-regulation of the IGF-I receptor and its ligands or to loss of function of a phosphatase (PTEN) that regulates part of this survival pathway. The C-terminus of the IGF-I receptor appears to be a regulatory domain for the anti-apoptotic activity of this receptor, and certain residues within the C-terminus are essential for this regulatory activity. Knowledge of the proteins and pathways, which interact with these C-terminal domains, should lead us to ways of modulating IGF-I-mediated survival in tumours.


Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.
High-throughput screening for inhibitors of the human metalloprotease, methionine aminopeptidase-2 (MetAP2), identified a potent class of 3-anilino-5-benzylthio-1,2,4-triazole compounds. Efficient array and interative synthesis of triazoles led to rapid SAR development around the aniline, benzylthio, and triazole moeities. Evaluation of these analogs in a human MetAP2 enzyme assay led to the identification of several inhibitors with potencies in the 50-100 picomolar range. The deleterious effects on inhibitor potency by methylation of the anilino-triazole nitrogens, as well as the X-ray crystal structure of triazole 102 bound in the active site of MetAP2, confirm the key interactions between the triazole nitrogens, the active site cobalt atoms, and the His-231 side-chain. The structure has also provided a rationale for interpreting SAR within the triazole series. Key aniline (2-isopropylphenyl) and sulfur substituents (furanylmethyl) identified in the SAR studies led to the identification of potent inhibitors (103 and 104) of endothelial cell proliferation. Triazoles 103 and 104 also exhibited dose-dependent activity in an aortic ring tissue model of angiogenesis highlighting the potential utility of MetAP2 inhibitors as anticancer agents.


Individual differences in behavioral and subjective responses to alcohol.
The reinforcing properties and subjective effects of alcohol were assessed in 29 normal volunteers using a seven-session choice procedure. On the first four sessions, subjects sampled an alcohol (0.5 g/kg) and a placebo beverage twice each. On three subsequent choice sessions, subjects chose the drink they preferred. The number of times they chose alcohol was the measure of its reinforcing properties. On all sessions subjects completed mood questionnaires before and several times after consuming the beverage. Other dependent measures during the experiment included a cognitive performance task, drug liking and identification questionnaires, and breathalyzer alcohol determinations. Demographic and personality data also were obtained. Approximately one-third of the subjects chose the alcohol-containing beverage on all three choice sessions, one-third alternated in their choices of alcohol and placebo, and one-third consistently chose the placebo. When the subjective effects of alcohol (determined during sampling sessions) were compared across the three choice groups, qualitative differences in response to alcohol were observed. For example, alcohol increased elation and vigor scores in the consistent choosers of alcohol, whereas it decreased scores on these measures in the consistent placebo choosers. Consistent alcohol choosers did not differ from placebo choosers in gender or age but they reported more marijuana use and slightly more alcohol use outside the laboratory. They also scored higher on certain measures of arousal and depression, on the Sensation Seeking Scale and on the Psychopathic State Inventory. The results are discussed in terms of individual differences in vulnerability to excessive use of alcohol.


The transformation of health care for patients: Information and communication technology, digiceuticals, and digitally enabled care.
The way patients access care and interact with health care systems is rapidly changing through the use of information and communication technology (ICT). Health care is being transformed through digital innovations, such as wearable technology, remote monitoring, patient portals, mobile applications (apps), and new service models such as telemedicine and virtual visits. Through a review of the current literature, this article presents the use of digitally enabled tools and ICT, including electronic health records, telehealth, remote patient monitoring, and mobile health apps. These effective and innovative digitally enabled tools have expanded options for patients interested in actively engaging in their own health. Information and communication technology can improve health outcomes, enhance the patient experience, and curtail costs. Providers must stay fluent with ICT options to best collaborate with patients. Although providers recognize that patient-centered care can improve effectiveness and efficiency, many have been slow to incorporate digital therapeutics, or "digiceuticals," into practice.


In ovo CpG DNA delivery increases innate and adaptive immune cells in respiratory, gastrointestinal and immune systems post-hatch correlating with lower infectious laryngotracheitis virus infection.
Cytosine-guanosine deoxynucleotides (CpG) DNA can be delivered in ovo at embryo day (ED)18 for the stimulation of toll-like receptor (TLR)21 signaling pathway that ultimately protects chickens against a number of bacterial and viral infections. There is a dearth of information understanding the mechanisms of protection induced by in ovo delivered CpG DNA. The objective of this study was to determine the immune cell changes post-hatch following in ovo delivery of the TLR21 ligand, CpG DNA. In order to quantify changes of percentage of KUL01+, IgM+ B, cluster of differentiation (CD)4+ and CD8α+ cells, trachea, lung, duodenum, large intestine, spleen and bursa of Fabricius were collected on day 1 post-hatch. We found increased recruitments of KUL01+ cells, in organs of these body systems post-hatch following in ovo delivery of CpG DNA. Although IgM+ B cells, CD4+ and CD8α+ cells were increased in lungs and immune system organs, these cells were not quantifiable from the trachea, duodenum and large intestine immediately following the hatch. Furthermore, when CpG DNA is delivered in ovo and subsequently infected with infectious laryngotracheitis virus (ILTV) post-hatch on day 1, CpG DNA reduces morbidity and mortality resulting from ILTV infection. This study provides insights into the mechanisms of host responses elicited following in ovo delivery of CpG DNA in avian species.


Current practice of continence advisors in managing faecal incontinence in the United Kingdom: results of an online survey.
To investigate the current practice of continence advisors in the United Kingdom. Continence advisors were contacted by email or letter to participate in a survey. The survey contained 27 questions which addressed the practice of each continence advisor, their knowledge of continence management and the adequacy of their training. Two hundred and twenty-six out of a total of 448 continence advisors (50.4%), responded. One hundred and seventy (76.9%) advisors treated both faecal and urinary incontinence, 51 (23.1%) treated urinary incontinence. Thirty-six advisors (16.1%) were lone workers and 130 (58.6%) had more than 10 years' experience. The majority of the advisors (75.6%) performed a digital rectal examination as part of their assessment. Regarding the management of faecal incontinence, 148 prescribed suppositories, 127 offered enemas and 147 advised on rectal irrigation. Most of the advisors taught pelvic floor exercises (n = 207) and urge resistance techniques (n = 188). One hundred and fifty-nine (87.4%) prescribed the Peristeen Coloplast® anal plug and 78 (47.6%) prescribed the Renew® anal insert. Eighty-nine advisors (42.6%) felt they had not been adequately trained to provide a bowel continence service. The majority of continence advisors in the UK manage faecal incontinence. They are able to initiate a broad range of conservative treatment options; however, almost half of the advisors who answered the survey felt inadequately trained and may be better supported by further training.


[Features of respiratory diseases in ecologically unfavorable region].
Examination of 400 workers in Bratsk aluminium plant proved respiratory diseases formation to be influenced by both occupational factors and various toxic chemicals that are released into atmosphere by other industrial polluters. Structure of respiratory diseases is represented mainly by diffuse pneumoconiosis caused by toxic and dust factors. Prophylaxis of those diseases should be aimed not only to better work conditions, but also to specify measures improving regional ecologic situation.


A model of higher accuracy for the individual haplotyping problem based on weighted SNP fragments and genotype with errors.
In genetic studies of complex diseases, haplotypes provide more information than genotypes. However, haplotyping is much more difficult than genotyping using biological techniques. Therefore effective computational techniques have been in demand. The individual haplotyping problem is the computational problem of inducing a pair of haplotypes from an individual's aligned SNP fragments. Based on various optimal criteria and including different extra information, many models for the problem have been proposed. Higher accuracy of the models has been an important issue in the study of haplotype reconstruction. The current article proposes a highly accurate model for the single individual haplotyping problem based on weighted fragments and genotypes with errors. The model is proved to be NP-hard even with gapless fragments. Based on the characteristics of Single Nucleotide Polymorphism (SNP) fragments, a parameterized algorithm of time complexity O(nk(2)2(k(2)) + m log m + mk(1)) is developed, where m is the number of fragments, n is the number of SNP sites, k(1) is the maximum number of SNP sites that a fragment covers (no more than n and usually smaller than 10) and k(2) is the maximum number of the fragments covering a SNP site (usually no more than 19). Extensive experiments show that this model is more accurate in haplotype reconstruction than other models. The program of the parameterized algorithm can be obtained by sending an email to the corresponding author.


Infrared and ab initio studies on 1,2,4,5-tetrafluorobenzene clusters with methanol and 2,2,2-trifluoroethanol: presence and absence of an aromatic C-H...O hydrogen bond.
The (1:1) clusters of 1,2,4,5-tetrafluorobenzene (TFB) with methanol and with 2,2,2-trifluoroethanol (TFE) were studied both experimentally and computationally. Through use of fluorescence-detected infrared spectroscopy, the (1:1) clusters were identified in supersonic jets. Intermolecular interactions in the clusters were characterized by the spectral shifts of the aromatic C-H stretching modes in the TFB moiety owing to the cluster formation. The molecular structures, stabilization energies, and vibrational frequencies of the clusters were computed at the MP2/6-31+G level. Both computational and experimental data indicate that an aromatic C-H...O hydrogen bond is present in the TFB-methanol cluster, while it is absent in the TFB-TFE cluster.


Technology update: computer-assisted video instruction in hospitals.
Interactive videodisks are state-of-the-art technology, and their potential is rapidly beginning to be recognized in the health care industry. A recent survey of 169 health institutions found that 79% planned the purchase of videodisks within the next year, and 72% planned to develop a videodisk program. As the role of the medical records practitioner increasingly includes acting as a hospitalwide information manager, CAVI provides the medical records professional a unique opportunity to both provide effective training within the department and hospital and be the leader in bringing the advantages of CAVI to the institution.


Campylobacter jejuni Infections: update on emerging issues and trends.
Infection with Campylobacter jejuni is one of the most common causes of gastroenteritis worldwide; it occurs more frequently than do infections caused by Salmonella species, Shigella species, or Escherichia coli O157:H7. In developed countries, the incidence of Campylobacter jejuni infections peaks during infancy and again during early adulthood. Most infections are acquired by the consumption and handling of poultry. A typical case is characterized by diarrhea, fever, and abdominal cramps. Obtaining cultures of the organism from stool samples remains the best way to diagnose this infection. An alarming recent trend is the rapid emergence of antimicrobial agent--resistant Campylobacter strains all over the world. Use of antibiotics in animals used for food has accelerated this trend. It is fortunate that complications of C. jejuni infections are rare, and most patients do not require antibiotics. Guillain-Barré syndrome is now recognized as a post-infectious complication of C. jejuni infection, but its incidence is <1 per 1000 infections. Careful food preparation and cooking practices may prevent some Campylobacter infections.


A combination of evolutionary trace method, molecular surface accessibility and hydrophobicity analysis to design a high hydrophobicity laccase.
Laccases are industrially attractive enzymes and their applications have expanded to the field of bioremediation. The challenge of today's biotechnology in enzymatic studies is to design enzymes that not only have a higher activity but are also more stable and could fit well with the condition requirements. Laccases are known to oxidize non-natural substrates like polycyclic aromatic hydrocarbons (PAHs). We suppose by increasing the hydrophobicity of laccase, it would increase the chance of the enzyme to meet the hydrophobic substrates in a contamination site, therefore increasing the bioremediation efficacy of PAHs from environment. In this attempt, the applications of evolutionary trace (ET), molecular surface accessibility and hydrophobicity analysis on laccase sequences and laccase's crystal structure (1KYA) are described for optimal design of an enzyme with higher hydrophobicity. Our analysis revealed that Q23A, Q45I, N141A, Q237V, N262L, N301V, N331A, Q360L and Q482A could be promising exchanges to be tested in mutagenesis experiments.


Chronic aspiration in children.
Chronic aspiration in children can cause life-threatening pulmonary consequences as well as multiple hospital stays and costly nursing requirements. Causes of aspiration vary widely and must be accurately assessed for treatment to be optimal. This disorder can be successfully controlled with a number of medical and surgical interventions. Rarely, children with severe neurologic disorders will continue to aspirate saliva despite treatment with voice-conserving measures. In cases of life-threatening aspiration, laryngotracheal separation can be lifesaving.


Ketamine induces rapid and sustained antidepressant-like effects in chronic pain induced depression: Role of MAPK signaling pathway.
Chronic pain produces psychologic distress, which often leads to mood disorders such as depression. Co-existing chronic pain and depression pose a serious socio-economic burden and result in disability affecting millions of individuals, which urges the development of treatment strategies targeting this comorbidity. Ketamine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, is shown to be efficient in treating both pain and depression-related symptoms. However, the molecular characteristics of its role in chronic pain-induced depression remain largely unexplored. Hence, we studied the behavioral and molecular effects of a single systemic administration of ketamine (15 mg/kg, i.p.) on mechanical hypersensitivity and depressive-like consequences of chronic neuropathic pain. We showed that ketamine transiently alleviated mechanical hypersensitivity (lasting <24 h), while its antidepressant effect was observed even 72 h after administration. In addition, ketamine normalized the upregulated expression of the mitogen activated protein kinase (MAPK) phosphatase 1 (MKP-1) and the downregulated phosphorylation of extracellular signal-regulated kinase (pERK) in the anterior cingulate cortex (ACC) of mice displaying neuropathic pain-induced depressive-like behaviors. This effect of ketamine on the MKP-1 was first detected 30 min after the ketamine administration and persisted until up to 72 h. Altogether, these findings provide insight into the behavioral and molecular changes associated with single ketamine administration in the comorbidity of chronic pain and depression.


Localization of beta-defensin genes in non human primates.
Defensins are a family of host defence peptides that play an important role in the innate immunity of mammalian and avian species. In humans, four beta-defensins have been isolated so far, corresponding to the products of the genes DEFB1 (h-BD1, GenBank accession number NM_005218); DEFB4 (h-Bd2, NM_004942.2), DEFB103 (h-BD3, NM_018661); and DEFB104 (hBD4, NM_080389) mapping on chromosome 8p23.22. We have localized beta-defensin genes on metaphasic chromosomes of great apes and several non-human primate species to determine their physical mapping. Using fluorescent in situ hybridization and BAC probes containing the four beta-defensin genes, we have mapped the homologous regions to the beta-defensin genes on chromosome 8p23-p.22 in non-human primates, while no signals were detected on prosimians chromosomes.


Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro.
This study examined the effects of intermittent hydrostatic pressure (IHP) and transforming growth factor-beta 3 on chondrogenesis of adult human mesenchymal stem cells (hMSCs) in vitro. Chondrogenic gene expression was determined by quantifying mRNA signal levels for SOX9, a transcription factor critical for cartilage development and the cartilage matrix proteins, aggrecan and type II collagen. Extracellular matrix production was determined by weight and histology. IHP was applied to hMSCs in pellet culture at a level of 10 MPa and a frequency of 1 Hz for 4 h per day for periods of 3, 7, and 14 days. hMSCs responded to addition of TGF-beta 3 (10 ng/mL) with a greater than 10-fold increase (p < 0.01) in mRNA levels for each, SOX9, type II collagen, and aggrecan during a 14-day culture period. Applying IHP in the presence of TGF-beta 3 further increased the mRNA levels for these proteins by 1.9-, 3.3-, and 1.6-fold, respectively, by day 14. Chondrogenic mRNA levels were increased with just exposure to IHP. Extracellular matrix deposition of type II collagen and aggrecan increased in the pellets as a function of treatment conditions and time of culture. This study demonstrated adjunctive effects of IHP on TGF-beta 3-induced chondrogenesis and suggests that mechanical loading can facilitate articular cartilage tissue engineering.


Iron and copper as virulence modulators in human fungal pathogens.
Fungal pathogens have evolved sophisticated machinery to precisely balance the fine line between acquiring essential metals and defending against metal toxicity. Iron and copper are essential metals for many processes in both fungal pathogens and their mammalian hosts, but reduce viability when present in excess. However, during infection, the host uses these two metals differently. Fe has a long-standing history of influencing virulence in pathogenic fungi, mostly in regards to Fe acquisition. Numerous studies demonstrate the requirement of the Fe acquisition pathway of Candida, Cryptococcus and Aspergillus for successful systemic infection. Fe is not free in the host, but is associated with Fe-binding proteins, leading fungi to develop mechanisms to interact with and to acquire Fe from these Fe-bound proteins. Cu is also essential for cell growth and development. Essential Cu-binding proteins include Fe transporters, superoxide dismutase (SOD) and cytochrome c oxidase. Although Cu acquisition plays critical roles in fungal survival in the host, recent work has revealed that Cu detoxification is extremely important. Here, we review fungal responses to altered metal conditions presented by the host, contrast the roles of Fe and Cu during infection, and outline the critical roles of fungal metal homeostasis machinery at the host-pathogen axis.


[Alleviating effects of hydrogen on hyperhomocysteinemia and fatty liver induced by high-methionine diet].
Objective: To investigate the alleviating effect of hydrogen (H2) on homocysteine (Hcy) levels and non alcoholic fatty liver in rats with hyperhomocysteinemia (HHcy). Methods: After one week of adaptive feeding, Wistar rats were randomly divided into three groups: the general diet group (CHOW), the high methionine group (HMD), and the high methionine plus hydrogen rich water group (HMD+HRW), with 8 rats in each group. The CHOW group was fed with AIN-93G feed, while the HMD and HMD+HRW groups were fed with AIN-93G+2% methionine feed to construct an HHcy model. The HMD+HRW group was also gavaged with hydrogen rich water (3 ml/animal, twice a day, with a hydrogen concentration of 0.8 mmol/L), and body weight data were recorded. After 6 weeks of feeding, the plasma and liver samples were processed and collected. The plasma homocysteine (Hcy) and lipid contents of each group were measured, and the histological morphology of the liver was observed. The activities of key enzymes in the Hcy metabolism pathway and mRNA expression were detected in the liver. Results: Compared with the CHOW group rats, the Hcy level in the blood of HMD rats was significantly increased significantly (P<0.05). Pathological tissue sections showed liver enlargement, injury, and fatty liver in the rats; Compared with the HMD group rats, the HMD+HRW group rats showed a significant decrease in Hcy in the blood, reduced liver damage, and increased Hcy metabolism key enzyme activity and mRNA expression in the liver, with statistical differences (P<0.05). Conclusion: Hydrogen has a significant improvement effect on liver injury induced by HMD diet in HHcy rats, possibly by enhancing the three metabolic pathways of Hcy to reduce excessive Hcy in the body, thereby improving liver metabolic function and symptoms of non-alcoholic fatty liver disease.


Improving the physical health of patients with schizophrenia: therapeutic nihilism or realism?
Schizophrenia is associated with a raised mortality due to both an increase in suicide and factors related to poor physical health. The increased rates of gastrointestinal, respiratory and cardiovascular disease in this population are likely to be due to high rates of smoking and obesity accompanied by a poor diet, lack of exercise and the side effects of medication. The evidence suggests that such risk factors in the schizophrenic population are largely ignored by the medical profession. Research to date has failed to address the health needs of this vulnerable population. Systematic research, with the aim of assessing the potential benefits of health improvement measures, should be a matter of priority.


Reconstitution of bile acid transport in the rat hepatoma McArdle RH-7777 cell line.
The liver recovers bile acids from the portal circulation primarily via an active process that is dependent on sodium ions. Hepatocytes lose the ability to transport bile acids in culture, and, in liver-derived permanent cell lines, this ability is severely reduced or absent. To study the importance of bile acids in regulating liver-specific functions (e.g., cellular bile acid and cholesterol metabolism), we have re-established active bile acid transport in cultured cells. The complementary DNA (cDNA) encoding the rat sodium/taurocholate cotransporting polypeptide (ntcp) was placed under the control of a cytomegalovirus promoter and transfected into the rat hepatoma cell line, McArdle RH-7777. Transfected cells were screened for the ability to take up [3H]-taurocholate. Clones that displayed the ability to take up taurocholate were expanded (designated McNtcp) and further characterized. The apparent Michaelis constant (Km) for taurocholate uptake was similar among the different clones. The observed maximum velocity (Vmax), however, differed and was positively correlated with the abundance of recombinant ntcp messenger RNA (mRNA). The highest level of taurocholate uptake activity observed in McNtcp cells was comparable with that of freshly isolated hepatocytes. Efflux of accumulated taurocholate from McNtcp cells proceeded in a manner similar to primary hepatocytes, indicating that McArdle RH-7777 cells have retained the ability to secrete bile acids. Moreover, taurocholate uptake in McNtcp cells was inhibited by other bile acid species. Based on the observed kinetic parameters, the reconstituted McArdle RH-7777 cells mimic the ability of primary hepatocytes to transport bile acids.


Simulation training for pelvic examination: A systematic review.
Pelvic examination including vaginal digital examination and speculum inspection are crucial medical skills that are challenging to teach for both professors and students, because of its intimate nature. Consequently, education has shifted from a traditional approach to a simulation-enhanced education. This literature review summarizes the level of evidence for these not-so-new training modalities. For this systematic review, the Pudmed database have been consulted using the following keywords: (Pelvic examination OR Vaginal examination) AND simulation. Eligible studies had to be published in French or English within the past 20 years and investigate simulation training for pelvic examination in the field of gynecology and obstetrics. For each paper, the following outcomes were analyzed: Competence, confidence and communication, and were classified according to the Kirkpatrick hierarchy. About competence, in initial training, one meta-analysis (9 studies of which 4 randomized studies) about pelvic examination teaching on procedural simulators have shown a significant benefit of simulation. One meta-analysis and one systematic review also demonstrated that Gynecological Teaching Associates (GTAs) teaching, who exist in Northern America and Scandinavian countries, was better that pelvic task trainers in terms of technical competence, and comfort. For the vaginal examination of women in labor, two randomized trials also showed a positive impact of pelvic task trainer on students' accuracy. Simulation-enhanced education of pelvic examination brings a significant benefit in comparison to a classic education without simulation in terms of competence, confidence and communication. GTAs have the best impact on competence and communication, but they do not exist currently in France. Hybrid simulation (a patient actor combined with a pelvic task trainer) could be a solution to teach both technical skills and communication.


A MRI and polarized gases compatible respirator and gas administrator for the study of the small animal lung: volume measurement and control.
We have developed over the past years an experimental magnetic resonance imaging (MRI) and polarized gases compatible mechanical respirator for the study of the small experimental animal. The respirator has been successfully used for experiments both in the MRI setting for polarized (3)He, (19)F, and proton imaging as well as for functional measurements of the lungs. The new main pneumatic valve with the two integrated sensors for simultaneous lung pressure and volume measurements and the proportional valve to set the tidal volume of the respiration are described. It is shown how the device measures and controls the tidal volume of the lungs.


Testing relationship recognition in wild jackdaws (Corvus monedula).
According to the social intelligence hypothesis, understanding the challenges faced by social animals is key to understanding the evolution of cognition. In structured social groups, recognising the relationships of others is often important for predicting the outcomes of interactions. Third-party relationship recognition has been widely investigated in primates, but studies of other species are limited. Furthermore, few studies test for third-party relationship recognition in the wild, where cognitive abilities are deployed in response to natural socio-ecological pressures. Here, we used playback experiments to investigate whether wild jackdaws (Corvus monedula) track changes in their own relationships and the relationships of others. Females were presented with 'infidelity simulations': playbacks of their male partner copulating with a neighbouring female, and their male neighbour copulating with another female, against a congruent control. Our results showed substantial inter-individual variation in responses, but females did not respond more strongly to infidelity playbacks, indicating that jackdaws may not attend and/or respond to relationship information in this experimental context. Our results highlight the need for further study of relationship recognition and other cognitive traits that facilitate group-living in the wild, particularly in non-primates and in a wider range of social systems.


Molecular analysis of Ac transposition and DNA replication.
Molecular events associated with transposition of the mobile element Activator (Ac) from the P locus of maize have been examined in daughter lineages of twinned sectors. Genetic and molecular analyses indicate that the donor Ac has excised from only one of the two daughter chromosomes in these lineages. Cloning and sequence analyses of target sites on daughter chromosomes indicate that Ac insertion can occur either before or after the completion of DNA replication. Transpositions from a replicated donor site to both unreplicated and replicated target sites imply that most transpositions of Ac occur during or shortly after the S phase of the cell cycle.


The association of consumption of fruits/vegetables with decreased risk of glaucoma among older African-American women in the study of osteoporotic fractures.
To explore the association between consumption of fruits and vegetables and the presence of glaucoma in older African-American women. Cross-sectional study. Disc photographs and suprathreshold visual fields were obtained from the 662 African-American participants in the Study of Osteoporotic Fractures. Masked, trained readers graded all discs, and 2 glaucoma specialists reviewed photographs and visual fields. The Block Food Frequency Questionnaire assessed food consumption. Relationships between selected fruit/vegetable/nutrient consumption and glaucoma were evaluated using logistic regression models after adjusting for potential confounders. After excluding women missing Food Frequency Questionnaire and disc data, 584 African-American women (88.2% of total African-American cohort) were included. Glaucoma was diagnosed in at least 1 eye in 77 subjects (13%). Women who ate 3 or more servings/day of fruits/fruit juices were 79% (odds ratio [OR] = 0.21; 95% confidence interval [CI]: 0.08-0.60) less likely to have glaucoma than women who ate less than 1 serving/day. Women who consumed more than 2 servings/week of fresh oranges (OR = 0.18; 95% CI: 0.06-0.51) and peaches (OR = 0.30; 95% CI: 0.13-0.67) had a decreased odds of glaucoma compared to those consuming less than 1 serving/week. For vegetables, >1 serving/week compared to ≤1 serving/month of collard greens/kale decreased the odds of glaucoma by 57% (OR = 0.43; 95% CI: 0.21-0.85). There was a protective trend against glaucoma in those consuming more fruit/fruit juices (P = .023), fresh oranges (P = .002), fresh peaches (P = .002), and collard greens/kale (P = .014). Higher consumption of carrots (P = .061) and spinach (P = .094) also showed some associations. Individual nutrient intake from food sources found protective trends with higher intakes of vitamin A (P = .011), vitamin C (P = .018), and α-carotene (P = .021), and close to statistically significant trends with β-carotene (P = .052), folate (P = .056), and lutein/zeaxanthin (P = .077). Higher intake of certain fruits and vegetables high in vitamins A and C and carotenoids may be associated with a decreased likelihood of glaucoma in older African-American women. Randomized controlled trials are needed to determine whether the intake of specific nutrients changes the risk of glaucoma.


Uncovering the critical soil moisture thresholds of plant water stress for European ecosystems.
Understanding the critical soil moisture (SM) threshold (θcrit ) of plant water stress and land surface energy partitioning is a basis to evaluate drought impacts and improve models for predicting future ecosystem condition and climate. Quantifying the θcrit across biomes and climates is challenging because observations of surface energy fluxes and SM remain sparse. Here, we used the latest database of eddy covariance measurements to estimate θcrit across Europe by evaluating evaporative fraction (EF)-SM relationships and investigating the covariance between vapor pressure deficit (VPD) and gross primary production (GPP) during SM dry-down periods. We found that the θcrit and soil matric potential threshold in Europe are 16.5% and -0.7 MPa, respectively. Surface energy partitioning characteristics varied among different vegetation types; EF in savannas had the highest sensitivities to SM in water-limited stage, and the lowest in forests. The sign of the covariance between daily VPD and GPP consistently changed from positive to negative during dry-down across all sites when EF shifted from relatively high to low values. This sign of the covariance changed after longer period of SM decline in forests than in grasslands and savannas. Estimated θcrit from the VPD-GPP covariance method match well with the EF-SM method, showing this covariance method can be used to detect the θcrit . We further found that soil texture dominates the spatial variability of θcrit while shortwave radiation and VPD are the major drivers in determining the spatial pattern of EF sensitivities. Our results highlight for the first time that the sign change of the covariance between daily VPD and GPP can be used as an indicator of how ecosystems transition from energy to SM limitation. We also characterized the corresponding θcrit and its drivers across diverse ecosystems in Europe, an essential variable to improve the representation of water stress in land surface models.


Intrinsic antiviral immunity drives neurodegeneration in Alzheimer disease.
β-Amyloid aggregates found in brain plaques are viewed as triggers of cytotoxicity and neuroinflammation in Alzheimer disease (AD). However, the main β-amyloid (Aβ) species and what imbues the aggregates with such toxic potential are still not yet understood. In this issue of the JCI, Roy et al. show that Aβ complexed with nucleic acids triggers an antiviral type I interferon response in neuroglia, resulting in complement-mediated synapse elimination in AD models. These findings identify a putative endogenous immune signaling axis that drives neurodegeneration in AD and has strong implications for the development of precise therapeutic strategies.


Neutrophil-to-lymphocyte ratio predicts early mortality in females with metastatic triple-negative breast cancer.
The aim of this study was to determine the utility of the neutrophil-to-lymphocyte ratio (NLR) as a biomarker for predicting early-mortality (<2 years) among females with metastatic triple-negative breast cancer (mTNBC). We reviewed 118 medical records of females with mTNBC. The cut-off value for the NLR (<2.5 and ≥2.5) was determined with receiver operating characteristic curves (area under the curve: 0.73; 95% CI: 0.62-0.85). Survival curves were estimated using the Kaplan-Meier method and compared with the Log-rank test. Multivariate Cox regression was used to identify the risk of mortality at two years. Moreover, we performed sensitivity analyses with different cut-off values and a subgroup analysis in females that only received chemotherapy. The median follow-up was 24 months. Females with NLR ≥2.5 had a poor overall survival compared to females with NLR <2.5 (6% vs. 28%, p<0.001) at two years. This outcome remained when we stratified for females that only received chemotherapy (8% vs. 36%, p = 0.001). Multivariate analyses identified NLR ≥2.5 as a poor prognostic risk factor for mortality in the entire population (HR: 2.12, 95% CI: 1.32-3.39) and among females that received chemotherapy (HR: 2.68, 95% CI: 1.46-4.92). The NLR is an accessible and reliable biomarker that predicts early mortality among females with mTNBC. Our results suggest that females with high NLR values have poor prognosis despite receiving standard chemotherapy. Health providers should evaluate the possibility to enroll these patients in novel immunotherapy trials.


Determination and comparison of chemical characteristics of Arbutus unedo L. and Arbutus andrachnae L. (family Ericaceae) fruits.
The fruits and leaves of Arbutus species are well known in folk medicine as antiseptics, diuretics, and laxatives in many parts of Turkey. Some chemical properties including pH, soluble solid content, titratable acidity, protein, moisture, ash, ascorbic acid, fructose, glucose, sucrose, total phenols, total antioxidant activity, and minerals were determined in fully matured Arbutus unedo L. and Arbutus andrachnae L. fruits collected from different sites of Canakkale, Turkey in 2006 and 2007. Total soluble solids, titratable acidity, protein, moisture, and ash content of A. unedo and A. andrachnae berries were on average 16.0% and 14.0%, 0.4% and 0.6%, 2.38% and 3.77%, 47.21% and 38.21%, and 2.82% and 4.35%, respectively. The mean values of ascorbic acid were 270.50 mg/100 g for A. unedo and 140.30 mg/100 g for A. andrachnae, which suggested that Arbutus berries contain high amounts of vitamin C. In the strawberry tree fruits, fructose and glucose were determined to be the major sugars. The analysis showed that fructose and glucose occurred in concentrations of 24.09% and 19.09%, respectively. However, ripe A. andrachnae fruits contained small amounts of fructose (4.12%), glucose (2.73%), and sucrose (0.16%) detectable by high-performance liquid chromatography analysis. The general order of abundance of the minerals was K > Ca > P > Mg > Na in whole fruit of the strawberry tree. The chemical composition of Arbutus fruits indicates that the fruits are good sources of minerals and ascorbic acid and that they are high in phenolics and antioxidant capacity and low in soluble sugars, especially A. andrachnae. The data should be useful for research purposes and for compiling local food composition tables. In view of its chemical composition, the use of Arbutus fruits in some food products may be suggested.


Macrocytosis as a consequence of alcohol abuse among patients in general practice.
Macrocytosis, a common finding in patients without anemia or other hematologic abnormalities, is often ignored. The purpose of this prospective study was to investigate 300 consecutive, adult health-center patients with a mean cell volume (MCV) value greater than or equal to 100 fl. The incidence of macrocytosis was 2.4%. Of the 177 male and 123 female patients, only 14 (4.7%) were anemic; 80.2% of the men (89.3% of those under 60 years) and 34.1% of the women were alcohol abusers, representing the largest diagnostic group. The highest MCV value found in alcoholics without folate or vitamin B12 deficiency was 120 fl. The most useful laboratory test for identifying alcohol abuse among macrocytic patients was the measurement of serum gamma-glutamyltransferase. Of the several morphologic abnormalities in the marrow the only specific finding were vacuoles in the granulocyte or erythrocyte precursors. No underlying cause was found for macrocytosis in 6.8% of the men and 35.8% of the women. Even when it is not associated with anemia, macrocytosis should not be ignored. It may be the only indicator of a disease which often, particularly in young and middle-aged men, is alcohol abuse.


[Emergent drugs (III): hallucinogenic plants and mushrooms].
An increase in the consumption of vegetable substances with a hallucinogenic effect has been observed. Some of these substances are associated with ancestral religious ceremonies, while many of them are legal or are partially regulated. Salvia divinorum is a powerful kappa receptor agonist, with dissociative and hallucinogenic properties, which start quickly and have a short duration. Kratom (Mytragyna speciosa) has mitragynine as its principal alkaloid, with stimulating effects at low doses (coke-like effect), and sedative effects (opiate-like effect) at high doses. Several deaths from its consumption have been detected. The consumption of hallucinogenic mushrooms appears in cyclic form, although there has been increase in their online offer. They are consumed in search of their hallucinogenic effects, above all those belonging to the family of psilocybes, which contain tryptamines with a hallucinogenic effect similar to LSD. Peyote (Lophophora psilocybes), a cactus rich in mescaline (trimetoxifeniletilamina), produces hallucinations of the five senses, and forms part of the religious culture of the North American Indians. Daturas, which are ubiquitous, produce anticholinergic symptoms and effects on the central nervous system (delirium, hallucinations, etc.), due to their high atropine and scopolamine content. Other substances used for their hallucinogenic effects include the drink known as ayahuasca, and seeds for preparing infusions like Ololiuqui, Morning Glory (Ipomoea violacea), Hawaian Baby Woodrose (Argyreia nervosa), Syrian Rue (Peganum harmala) and Iboga Rootbark (Tabernanthe iboga).


Use, access, and equity in health care services in São Paulo, Brazil.
The study analyzed how socioeconomic factors are associated with seeking, access, use, and quality of health care services in São Paulo, Brazil. Data were obtained from two household health surveys in São Paulo. We used logistic regression to analyze associations between socioeconomic factors and seeking, access, use, and quality of health care services. Access to health care services was high among those who sought it (94.91% in 2003 and 94.98% in 2008). The proportion of access to and use of health care services did not change significantly from 2003 to 2008. Use of services in the public sector was more frequent in lower socioeconomic groups. There were some socioeconomic differences in seeking health care and resolution of health problems. The study showed almost universal access to health care services, but the results suggest problems in quality of services and differences in quality experienced by lower socioeconomic groups, who mostly use the Brazilian Unified National Health System (SUS).


Walking strategies in subjects with congenital or early onset strabismus.
In congenital strabismus, sensory adaptations occur hampering the correct development of normal binocular vision. The aim of this study is to investigate if patients with congenital or early onset exotropic or esotropic strabismus adopt different walking strategies with respect to healthy subjects. Our hypothesis is that the abnormal binocular cooperation, occurring in patients with exotropic or esotropic strabismus, could influence neurosensorial adaptation of the gait pattern. Twenty-five patients were enrolled: 19 with esotropic (ESO) and 6 with exotropic strabismus (EXO). All patients underwent an ophthalmological and orthoptic evaluation. Biomechanical data were collected using a stereophotogrammetric system and a force platform. Twenty-seven age-matched healthy subjects (HS) were used as controls. The comparison between patients with ESO and patients with EXO strabismus showed that the maximal power at the knee and at the ankle was lower in EXO group (p < 0.01 and p < 0.05, respectively). The step width was statistically different between ESO and EXO groups (p < 0.01), lower in patients with ESO and higher in patients with EXO strabismus when compared with HS (though not statistically significant). The deviation angle values showed a relationship with the step width (at the near fixation p < 0.05) and with the maximal power at the knee and at the ankle (at the far fixation for the knee p < 0.001 and for the ankle p < 0.05; at the near fixation for the knee p < 0.05): in the patients with EXO the increased angle deviation is related to larger step width and to lower power at the knee and at the ankle. In the patients with ESO strabismus this relationship is less robust. Patients with EXO and ESO strabismus adopt different strategies to compensate their walking difficulties, and these strategies are likely due to an expanded binocular visual field in patients with EXO and to a reduced visual field in patients with ESO strabismus.


Global burden of influenza as a cause of cardiopulmonary morbidity and mortality.
Severe acute respiratory infections, including influenza, are a leading cause of cardiopulmonary morbidity and mortality worldwide. Until recently, the epidemiology of influenza was limited to resource-rich countries. Emerging epidemiological reports characterizing the 2009 H1N1 pandemic, however, suggest that influenza exerts an even greater toll in low-income, resource-constrained environments where it is the cause of 5% to 27% of all severe acute respiratory infections. The increased burden of disease in this setting is multifactorial and likely is the result of higher rates of comorbidities such as human immunodeficiency virus, decreased access to health care, including vaccinations and antiviral medications, and limited healthcare infrastructure, including oxygen therapy or critical care support. Improved global epidemiology of influenza is desperately needed to guide allocation of life-saving resources, including vaccines, antiviral medications, and direct the improvement of basic health care to mitigate the impact of influenza infection on the most vulnerable populations.


Outcomes of Endodontic Therapy Comparing Conventional Sodium Hypochlorite Irrigation with Passive Ultrasonic Irrigation Using Sodium Hypochlorite and Ethylenediaminetetraacetate. A Retrospective Analysis.
The aim of the present study was to investigate the clinical outcomes of two different standardized endodontic irrigation protocols. It was assumed that the additional use of ethylenediaminetetraacetate (EDTA) and passive ultrasonic irrigation (PUI) would result in an increased rate of absence of symptoms and remission based on the periapical index (PAI) compared to passive irrigation using only sodium hypochlorite (NaOCl). Data and radiographs from 199 teeth retrieved from the institutional endodontic database were analyzed retrospectively. In 106 teeth irrigation was performed using only NaOCl (protocol 1). Ninety-three teeth were irrigated using NaOCl and EDTA (protocol 2). Chlorhexidine (CHX) was additionally used in revision treatments in both groups. All irrigants in group 2 were activated by PUI. Mean follow-up periods were: protocol 1 = 9.2 ± 4.4 and protocol 2 = 6.6 ± 2.5 months (p < 0.0001 (chi-square test). The frequencies of the PAImasterpoint and PAIfollow-up scores did not differ significantly between teeth, which received either protocol 1 or 2 (p = 0.555 and 0.138). Statistical analysis revealed no significant association between treatment success (absence of clinical symptoms and PAIfollow-up = I or PAImasterpoint > PAIfollow-up > I) and the applied protocol (success rates: protocol 1 = 72.6% vs. protocol 2 = 82.8%; p = 0.203). Furthermore, the frequency of extractions did not differ significantly between the two protocols (p = 0.102). No association was found between follow-up time and treatment success (p = 0.888). The hypothesis was not confirmed. Even though the obtained success rate was higher after supplementing the irrigation protocol with EDTA and PUI, no significance was recorded. Hence, protocol 2 was not superior to protocol 1 regarding therapy success, at least within the limited follow-up period. It may be cautiously concluded that sufficient mechanical debridement combined with passive NaOCl irrigation results in comparably high success rates compared to EDTA and PUI.


Pharmacokinetics of chronic fluoride ingestion in growing pigs.
The present study was undertaken to estimate bio-availability and biological half-life of fluoride and accumulation of fluoride in bone in the domestic pig. Eight animals receiving 2 mg F-/kg b.w. per day from age 8 to 14 months were compared with eight controls. Plasma fluoride concentrations just prior to the daily oral dose were measured at regular intervals. After 112 days post-dose, plasma fluoride levels were measured over a 48-hour period following the daily oral dose or a single intravenous dose. Mean bio-availability factor for the oral dose was 0.3 (range 0.2-0.4), and mean biological half-life was 59 days (range 49-72). Bone fluoride content calculated from the pharmacokinetic parameters derived from plasma data was similar to the content of fluoride measured in the bone at slaughter. The study showed that accumulation of fluoride in bone influences plasma fluoride levels during chronic administration of fluoride to growing pigs. The long biological half-life found showed that it was not possible to achieve steady-state plasma levels within the six-month experimental period used. This means that, for dose-response studies of dental fluorosis in this animal, it is not possible to achieve steady-state plasma concentrations as a basis for correlations to the degrees of pathological change observed in the teeth.


Tubule-forming capacity of the movement proteins of alfalfa mosaic virus and brome mosaic virus.
The structural phenotype of the movement proteins (MPs) of two representatives of the Bromoviridae, alfalfa mosaic virus (AMV) and brome mosaic virus (BMV), was studied in protoplasts. Immunofluorescence microscopy showed that the MPs of these viruses, for which there has been no evidence of a tubule-guided mechanism, assemble into long tubular structures at the surface of the infected protoplast. Electron microscopy and immunogold analysis confirmed the presence of both MP and virus particles in the tubules induced by AMV and BMV. The significance of the tubule-forming properties of these viral MPs is discussed.


Prolene monofilament suture in Boston Keratoprosthesis surgery.
Toxic reaction to nylon following uncomplicated cataract surgery and vitrectomy has been documented in the literature. We report the case of an aniridic patient with a known adverse reaction to nylon in whom Prolene suture was used in Boston Keratoprosthesis type 1 (KPro) surgery. During follow-up the cornea was checked for signs of inflammation and toxic reaction; at last follow-up (18 months) the patient showed no signs of complications due to Prolene. Our study suggests that Prolene suture may be used as an alternative to nylon in Boston KPro surgery in patients with a history of nylon toxicity.


Genetic immunization: a new era in vaccines and immune therapeutics.
DNA inoculation represents a novel approach to vaccine and immune therapeutic development. The direct injection of gene expression cassettes into a living host transforms a number of cells into factories for production of the introduced gene products. Expression of these delivered genes has important immunological consequences and may result in the specific immune activation of the host against the novel expressed antigens. The recent demonstration by laboratories that these immune responses are protective in some infectious disease experimental models as well as cancers is viewed with cautious optimism. Further, the relatively short development times, ease of large-scale production, low development, manufacturing, and distribution costs all combine with immunological effectiveness to suggest that this technology will dramatically influence the production of a new generation of experimental vaccines and immune therapies. It is hoped that DNA inoculation will ultimately lead to new vaccines that are immunologically effective and economically accessible to all nations.


Dependence on Size of Supported Rh Nanoclusters in the Dehydrogenation of Methanol-d4 Obstructed by CO.
The size effect on the activity of a catalyst has been a focal issue since ideal catalysts were pursued, whereas that on the degradation of a catalyst, by reaction intermediates such as CO, is little discussed. We demonstrate that the dehydrogenation of methanol-d4 on supported Rh nanoclusters precovered with CO (Rh-CO clusters) was obstructed, indicated by a decreased production of CO and D2; the obstructive effect exhibits a remarkable dependence on the cluster size, with a minimum at a cluster diameter near 1.4 nm. The decreased production arose from a decreased reaction probability controlled by the increased activation energy for each dehydrogenation step (including formation of methoxy-d3), adsorption energies of CO, and repulsion from the CO array on the Rh-CO surface. The effects of these factors in deactivating the clusters varied separately with the cluster size. Consequently, the size effect on the CO poisoning should be taken into account in engineering the cluster size to optimize the catalytic performance.


Segmentation of the thoracic aorta in noncontrast cardiac CT images.
Studies have shown that aortic calcification is associated with cardiovascular disease. In this study, a method for localization, centerline extraction, and segmentation of the thoracic aorta in noncontrast cardiac-computed tomography (CT) images, toward the detection of aortic calcification, is presented. The localization of the right coronary artery ostium slice is formulated as a regression problem whose input variables are obtained from simple intensity features computed from a pyramid representation of the slice. The localization, centerline extraction, and segmentation of the aorta are formulated as optimal path detection problems. Dynamic programming is applied in the Hough space for localizing key center points in the aorta which guide the centerline tracing using a fast marching-based minimal path extraction framework. The input volume is then resampled into a stack of 2-D cross-sectional planes orthogonal to the obtained centerline. Dynamic programming is again applied for the segmentation of the aorta in each slice of the resampled volume. The obtained segmentation is finally mapped back to its original volume space. The performance of the proposed method was assessed on cardiac noncontrast CT scans and promising results were obtained.


Building towards Precision Oncology for Pancreatic Cancer: Real-World Challenges and Opportunities.
The advent of next-generation sequencing (NGS) has provided unprecedented insight into the molecular complexity of pancreatic ductal adenocarcinoma (PDAC). This has led to the emergence of biomarker-driven treatment paradigms that challenge empiric treatment approaches. However, the growth of sequencing technologies is outpacing the development of the infrastructure required to implement precision oncology as routine clinical practice. Addressing these logistical barriers is imperative to maximize the clinical impact of molecular profiling initiatives. In this review, we examine the evolution of precision oncology in PDAC, spanning from germline testing for cancer susceptibility genes to multi-omic tumor profiling. Furthermore, we highlight real-world challenges to delivering precision oncology for PDAC, and propose strategies to improve the generation, interpretation, and clinical translation of molecular profiling data.


The effects of low pH on the properties of protochlorophyllide oxidoreductase and the organization of prolamellar bodies of maize (Zea mays).
Prolamellar bodies (PLB) contain two photochemically active forms of the enzyme protochlorophyllide oxidoreductase POR-PChlide640 and POR-PChlide650 (the spectral forms of POR-Chlide complexes with absorption maxima at the indicated wavelengths). Resuspension of maize PLB in media with a pH below 6.8 leads to a rapid conversion of POR-PChlide650 to POR-PChlide640 and a dramatic re-organization of the PLB membrane system. In the absence of excess NADPH, the absorption maximum of the POR complex undergoes a further shift to about 635 nm. This latter shift is reversible on the re-addition of NADPH with a half-saturation value of about 0.25 mm NADPH for POR-PChlide640 reformation. The disappearance of POR-PChlide650 and the reorganization of the PLB, however, are irreversible. Restoration of low-pH treated PLB to pH 7.5 leads to a further breakdown down of the PLB membrane and no reformation of POR-PChlide650. Related spectral changes are seen in PLB aged at room temperature at pH 7.5 in NADPH-free assay medium. The reformation of POR-PChlide650 in this system is readily reversible on re-addition of NADPH with a half-saturation value about 1.0 microm. Comparison of the two sets of changes suggest a close link between the stability of the POR-PChlide650, membrane organization and NADPH binding. The low-pH driven spectral changes seen in maize PLB are shown to be accelerated by adenosine AMP, ADP and ATP. The significance of this is discussed in terms of current suggestions of the possible involvement of phosphorylation (or adenylation) in changes in the aggregational state of the POR complex.


Spectrin isoforms in the mammalian retina.
Spectrin is a major component of the mammalian neuronal cytoskeleton. In the CNS, three isoforms of brain spectrin are known to exist: a cellular and dendritic isoform, (240/235E), related to neurons and glia; a cellular and axonal isoform, (240/235), related to neurons; and an isoform specific for astrocytes, (240/235A). In the present study, brain spectrins (240/235E) and (240/235) were localized within the mouse retina and optic nerve. Immunoblot analyses of proteins isolated from mouse retinas utilizing polyclonal antibodies to either brain spectrin (240/235) or brain spectrin (240/235E) revealed that these spectrins are present in the retina and that the two isoforms are the same molecular weights as those found in the brain. Immunocytochemical studies revealed that spectrin (240/235E) was localized in cell bodies of the inner nuclear, outer nuclear, and ganglion cell layers, and processes arborizing within the inner and outer plexiform layers. Spectrin (240/235) was distributed diffusely within the retina, lightly staining neurons in both the inner nuclear and outer nuclear layers, and the ganglion cell layer. In contrast to the situation found in the brain, spectrin (240/235) was but one of the axonal forms in the retina. We found that spectrin (240/235E) was also present in the axon-rich fiber layer and in the optic nerve and was often associated with fibrous elements. Spectrin (240/235) was also detected in the nerve fiber layer and optic nerve, but this isoform was not localized to fibers.(ABSTRACT TRUNCATED AT 250 WORDS)