[Hybrid 3D visualization and virtual endoscopy in cochlear implants].
The aim of this study was to demonstrate on a complex anatomical structure the possibilities and the advantages of a superimposition of a color-coded surface and volume rendering (hybrid rendering) method with the possibility of the performance of a virtual endoscopy. In 6 patients with cochlear implants a high-resolution spiral computed tomography of the petrous bone was performed. The cochlear implants, the middle and inner ear structures were visualized using a color-coded surface rendering method, either shaded or as a grid. The petrous bone was visualized using a transparent volume rendering method. The hybrid 3D visualization uses the advantages of both the color-coded 3D surface and volume rendering method. In comparison to the axial source images, the hybrid 3D visualization thus facilitates a clearer representation and better assessment of the complex topographical relationship without loss of diagnostic information. The virtual endoscopy facilitates an intraluminal visualization and inspection of all color-coded 3D surface- and volume rendered structures. The hybrid rendering and virtual endoscopy make the morphological assessment of cochlear implants easier by the simultaneous visualization of the surrounding structures and thereby support the diagnostic imaging methods. This image processing method can be used pre-operatively for the individual planning, simulation, training and further development of surgical procedures and interventions and post-operatively for the control of the position and further developments of implants.


Spatial distribution and determinants of barriers of health care access among female youths in Ethiopia, a mixed effect and spatial analysis.
Access to healthcare services is a fundamental human right for every citizen, and it is the responsibility of the nation to guarantee that these services are acceptable, easily accessible, and timely. Barriers to accessing health services may have a detrimental effect on an individual's physical, and mental health, and overall quality of life. However, access to health care services is a common problem in developing countries. Therefore, this study aimed to investigate spatial distribution and determinants of barriers to healthcare access among female youths in Ethiopia. Secondary data analysis was conducted based on the Demographic and Health Surveys data conducted in Ethiopia. A total weighted sample of 6143 female youths aged 15-24 years old was included in this study. A mixed-effect analysis was employed to identify factors contributing to barriers to healthcare access among youths in Ethiopia. Adjusted Odds Ratio with 95% CI was used to declare the strength and significance of the association. The concentration index was used to assess wealth-related inequalities, while spatial analysis was used to explore the spatial distribution and significant windows of barriers to healthcare access. This study revealed that the magnitude of barriers to healthcare access among female youth was 61.3% with 95%CI (60.1 to 62.5) to at least one or more of the four reasons. Age 15-19 years old (AOR = 0.80, 95%CI 0.68 to 0.95), no formal education (AOR = 2.26, CI 1.61, 3.18), primary education (AOR = 2.21, CI 1.66, 2.95), marital status (AOR = 1.43, 95% CI 1.21, 1.70), poor household wealth (AOR = 1.63, 95% CI 1.31, 2.05), no Media exposure (AOR = 1.67, 95%CI 1.41-1.98), reside in rural areas (AOR = 1.63, 95%CI 1.05 to 2.54), and low community media exposure (AOR = 1.45, 95%CI 1.01-2.08) were significantly associated with barriers of health care service. Barriers to healthcare access were significantly and disproportionately concentrated in poor households. A non-random Barrier to healthcare access was observed in Ethiopia. Among the 9 regions, primary clusters were identified in only 4 regions (North Ormiya, Benishangul Gumuz, Gambella, and South Nation Nationality and Peoples regions. A significant proportion of female youths faced barriers to health care access Age, educational status, marital status, rural residency, low economic status, and media exposure were factors associated with barriers to health care access. Therefore, program planners and decision-makers should work on improving the country's economy to a higher economic level to improve the wealth status of the population, promote media exposure, and increase access to education.


Identification of mammosomatotrophs in the turkey hen pituitary: increased abundance during hyperprolactinemia.
We have previously reported that the hyperprolactinemia in incubating turkey hens is associated with recruitment of lactotrophs in the pituitary gland. In this study we have used double immunofluorescence and in situ hybridization histochemistry to 1) identify mammosomatotrophs in the anterior pituitary gland of egg-laying turkey hens and incubating hens, and 2) verify PRL gene expression within mammosomatotrophs by colocalizing PRL messenger RNA in GH-immunoreactive (ir) cells. The pituitaries of laying and incubating turkey hens were collected, and the midsagittal sections were dual labeled for either PRL and GH or PRL messenger RNA and GH. The plasma PRL concentrations were higher in incubating hens (231 +/- 10.6 ng/ml) than in laying hens (43 +/- 7.4 ng/ml; P < 0.01). In the midsagittal pituitary sections, mammosomatotrophs were predominantly found scattered in the caudal lobe of the anterior pituitary gland, in the ventral half of the cephalic lobe, and at the junction of cephalic and caudal lobes. In incubating hens, the proportion of mammosomatotrophs was 7.4 +/- 1.52% (mean +/- SEM) of the total number of GH-ir and/or PRL-ir cells counted, which was significantly higher (P < 0.05) than that found in laying hens (0.6 +/- 0.23%). Furthermore, PRL gene expression was observed in many GH-ir cells in the incubating hen pituitary gland. These data suggest that 1) mammosomatotrophs are present in the turkey pituitary gland, and 2) there is an increased abundance of mammosomatotrophs in the incubating turkey hen that may contribute to hyperprolactinemia.


Accurate, predictable, repeatable micro-assembly technology for polymer, microfluidic modules.
A method for the design, construction, and assembly of modular, polymer-based, microfluidic devices using simple micro-assembly technology was demonstrated to build an integrated fluidic system consisting of vertically stacked modules for carrying out multi-step molecular assays. As an example of the utility of the modular system, point mutation detection using the ligase detection reaction (LDR) following amplification by the polymerase chain reaction (PCR) was carried out. Fluid interconnects and standoffs ensured that temperatures in the vertically stacked reactors were within ± 0.2 C° at the center of the temperature zones and ± 1.1 C° overall. The vertical spacing between modules was confirmed using finite element models (ANSYS, Inc., Canonsburg, PA) to simulate the steady-state temperature distribution for the assembly. Passive alignment structures, including a hemispherical pin-in-hole, a hemispherical pin-in-slot, and a plate-plate lap joint, were developed using screw theory to enable accurate exactly constrained assembly of the microfluidic reactors, cover sheets, and fluid interconnects to facilitate the modular approach. The mean mismatch between the centers of adjacent through holes was 64 ± 7.7 μm, significantly reducing the dead volume necessary to accommodate manufacturing variation. The microfluidic components were easily assembled by hand and the assembly of several different configurations of microfluidic modules for executing the assay was evaluated. Temperatures were measured in the desired range in each reactor. The biochemical performance was comparable to that obtained with benchtop instruments, but took less than 45 min to execute, half the time.


Dysfunctional elimination syndrome: is it related to urinary tract infection or vesicoureteral reflux diagnosed early in life?
It has been suggested that urinary tract infections (UTIs) early in life predispose to dysfunctional elimination syndrome (DES). This study evaluated the relationship between early UTI, vesicoureteral reflux (VUR), and DES by comparing two cohorts of school-aged children. The UTI cohort (n = 123) included children previously enrolled in a prospective treatment trial conducted between 1992 and 1997. All were diagnosed with a febrile UTI before 2 years of age. The comparison cohort (n = 125) included children who were evaluated for fever in the emergency department between 1992 and 1997, whose urine culture was negative. Dysfunctional elimination symptoms were compared in the two cohorts by having families complete a revised version of the Dysfunctional Voiding Scoring System. Completed questionnaires were received from 248 children. There were no significant differences in selected demographic or clinical characteristics between the two cohorts. DES was present in 22% and 21% of children with and without a history of early UTI, respectively. Among children with UTIs, 18% of those with VUR and 25% of those without VUR had DES. Dysfunctional elimination is common in a general pediatric population. Neither UTI nor VUR diagnosed before 2 years of age was associated with DES in school-aged children.


Exploring barriers and promoters of CRC screening use among agricultural operators: a pilot study of an application of concept mapping.
The purpose of the study was to identify barriers and facilitators of colorectal cancer (CRC) screening use among agricultural operators in Nebraska, US. The concept mapping approach was used to engage participants and enhance the generation of ideas and opinions regarding CRC screening. Two focus groups (seven women and seven men) were conducted. Among women, the cost domain was most agreed upon as important, followed by experiencing symptoms, awareness, and family. Among men, the important concepts related to CRC screening were family and friend support, feeling too young to get CRC, family or personal history of CRC, and lack of awareness of the need to be screened. Some gender differences regarding barriers were observed, such as women were more concerned about the cost of screening while men were far more concerned about the embarrassment associated with CRC screening. These findings will be crucial to developing educational materials to increase knowledge of risk factors for CRC and of CRC screening in the agricultural population.


Prediction of Microdroplet Breakup Regime in Asymmetric T-Junction Microchannels.
Splitting droplets is becoming a major functional component in increasing number of droplet microfluidic applications, and there is an increasing interest in splitting droplets into two daughter droplets with different volumes. However, designing an asymmetric droplet splitter and predicting how a droplet splits in such designs is not trivial. In this study, numerical simulations were conducted to study droplet breakup in asymmetric T-junctions of square cross-sections having different pressure gradient ratios (i.e. T-junctions with outlet branches of different lengths). The goal of the simulation is to identify the conditions where a parent droplet breaks or does not break into two smaller droplets of different sizes (so called critical condition) and to identify the important fluid and microchannel parameters in this process. Four modes of droplet breakup (primary-, transition-, bubble-, and non-breakups) are identified and an empirical correlation is introduced that can predict the breakup/non-breakup of the droplet based on the parent droplet size and the capillary number. The simulation results are then compared with experimental data to verify its accuracy and the effect of fluids properties on the proposed correlation are studied. Two major asymmetric breakup mechanisms are determined, namely "breakup with permanent obstruction" and "unstable breakup". The numerical results show that the splitting ratio for the asymmetric breakup mechanisms depends on flow conditions and dwell time of the droplet at the junction prior to splitting. Finally, the results from two-dimensional and three-dimensional simulations were compared. It is shown that two-dimensional simulation may not accurately predict the breakup behavior for asymmetric droplet breakup and viscosity ration has a greater effect on the prediction critical condition.


Cardiopulmonary resuscitation in small animal medicine: an update.
In December 2005, the American Heart Association published new guidelines for cardiopulmonary cerebral resuscitation (CPCR) in humans for the 1st time in 5 years. Many of the recommendations are based on research conducted in animal species and may be applicable to small animal veterinary patients. One important change that may impact how CPCR is performed in veterinary medicine is the recommendation to avoid administration of excessive ventilatory rates because this maneuver severely decreases myocardial and cerebral perfusion, decreasing the chance of survival. The new guidelines also emphasize the importance of providing well-executed, continuous, uninterrupted chest compressions. Interruption of chest compressions should be avoided and, if necessary, should be minimized to <10 seconds. During defibrillation, immediate resumption of chest compressions for 2 minutes after a single shock, before reassessment of the rhythm by ECG, is recommended. This recommendation replaces previous recommendations for the delivery of 3 defibrillatory shocks in rapid succession. Allowing permissive hypothermia postresuscitation has been found to be beneficial and may increase success rate. Medications utilized in cardiopulmonary resuscitation, including amiodarone, atropine, epinephrine, lidocaine, and vasopressin, along with the indications, effects, routes of administration, and dosages, are discussed. The application of the new guidelines to veterinary medicine as well as a review of cardiopulmonary resuscitation in small animals is provided.


Association of cardiovascular risk using non-linear heart rate variability measures with the framingham risk score in a rural population.
Cardiovascular risk can be calculated using the Framingham cardiovascular disease (CVD) risk score and provides a risk stratification from mild to very high CVD risk percentage over 10 years. This equation represents a complex interaction between age, gender, cholesterol status, blood pressure, diabetes status, and smoking. Heart rate variability (HRV) is a measure of how the autonomic nervous system (ANS) modulates the heart rate. HRV measures are sensitive to age, gender, disease status such as diabetes and hypertension and processes leading to atherosclerosis. We investigated whether HRV measures are a suitable, simple, noninvasive alternative to differentiate between the four main Framingham associated CVD risk categories. In this study we applied the tone-entropy (T-E) algorithm and complex correlation measure (CCM) for analysis of HRV obtained from 20 min. ECG recordings and correlated the HRV score with the stratification results using the Framingham risk equation. Both entropy and CCM had significant analysis of variance (ANOVA) results [F (172, 3) = 9.51; <0.0001]. Bonferroni post hoc analysis indicated a significant difference between mild, high and very high cardiac risk groups applying tone-entropy (p < 0.01). CCM detected a difference in temporal dynamics of the RR intervals between the mild and very high CVD risk groups (p < 0.01). Our results indicate a good agreement between the T-E and CCM algorithm and the Framingham CVD risk score, suggesting that this algorithm may be of use for initial screening of cardiovascular risk as it is noninvasive, economical and easy to use in clinical practice.


Quantitative Assessment of the Effects of Trypsin Digestion Methods on Affinity Purification-Mass Spectrometry-based Protein-Protein Interaction Analysis.
Affinity purification-mass spectrometry (AP-MS) has become the method of choice for discovering protein-protein interactions (PPIs) under native conditions. The success of AP-MS depends on the efficiency of trypsin digestion and the recovery of the tryptic peptides for MS analysis. Several different protocols have been used for trypsin digestion of protein complexes in AP-MS studies, but no systematic studies have been conducted on the impact of trypsin digestion conditions on the identification of PPIs. Here, we used NFκB/RelA and Bromodomain-containing protein 4 (BRD4) as baits and test five distinct trypsin digestion methods (two using "on-beads," three using "elution-digestion" protocols). Although the performance of the trypsin digestion protocols change slightly depending on the different baits, antibodies and cell lines used, we found that elution-digestion methods consistently outperformed on-beads digestion methods. The high-abundance interactors can be identified universally by all five methods, but the identification of low-abundance RelA interactors is significantly affected by the choice of trypsin digestion method. We also found that different digestion protocols influence the selected reaction monitoring (SRM)-MS quantification of PPIs, suggesting that optimization of trypsin digestion conditions may be required for robust targeted analysis of PPIs.


Learning Compressible 360 ° Video Isomers.
Standard video encoders developed for conventional narrow field-of-view video are widely applied to 360° video as well, with reasonable results. However, while this approach commits arbitrarily to a projection of the spherical frames, we observe that some orientations of a 360° video, once projected, are more compressible than others. We introduce an approach to predict the sphere rotation that will yield the maximal compression rate. Given video clips in their original encoding, a convolutional neural network learns the association between a clip's visual content and its compressibility at different rotations of a cubemap projection. Given a novel video, our learning-based approach efficiently infers the most compressible direction in one shot, without repeated rendering and compression of the source video. We validate our idea on thousands of video clips and multiple popular video codecs. The results show that this untapped dimension of 360° compression has substantial potential-"good" rotations are typically 8-18 percent more compressible than bad ones, and our learning approach can predict them reliably 78 percent of the time.


Orenia salinaria sp. nov., a fermentative bacterium isolated from anaerobic sediments of Mediterranean salterns.
A diverse range of fermentative bacteria have been isolated from the commercial salterns of Salin-de-Giraud (Camargue, France). One of these isolates, strain SG 3902T, has many of the morphological and physiological characteristics of the genus Orenia, as was confirmed by a phylogenetic study based on 16S rRNA gene sequencing. The closest species is Orenia marismortui, with a similarity of only 95.1%. However, strain SG 3902T, unlike O. marismortui, does not ferment mannose, glycogen or starch. The G + C contents of the DNA also differ significantly, being 29.6 mol% for O. marismortui and 33.7 mol% for strain SG 3902T. On the basis of these physiological and genetic differences, it is proposed that strain SG 3902T should be considered as a representative of a new species belonging to the genus Orenia, under the name Orenia salinaria sp. nov. The type strain is SG 3902T (= ATCC 700911).


Expression of the muscle atrophy factor muscle atrophy F-box is suppressed by testosterone.
The ubiquitin ligase muscle atrophy F-box (MAFbx; also called atrogin-1) is thought to play important roles in muscle loss. Conversely, testosterone reduces atrophy from glucocorticoids or denervation associated with repression of MAFbx. To characterize mechanisms of such repression, the effects of testosterone on MAFbx expression in C2C12 cells were tested. Testosterone reduced MAFbx mRNA levels as well as expression of a reporter gene under the control of 3.1 kb of the human MAFbx promoter. Repression required the androgen receptor (AR) as well as sequences within the first 208 bases upstream of the first codon of the MAFbx gene. This sequence is downstream of known forkhead transcription factor binding sites and testosterone did not alter Forkhead box O 3A phosphorylation. The AR associated with sequences conferring repression in a manner that was stimulated by testosterone and was independent of DNA binding. In gel shift studies, octamer binding transcription factor (Oct)-1 bound two predicted Oct-1 sites within these sequences. Deletion of Oct-1 sites from reporter genes prevented repression by testosterone. Gene knockdown of Oct-1 blocked repression of MAFbx reporter gene activity by testosterone and binding of AR to sequences conferring repression. In conclusion, testosterone represses MAFbx expression via interactions of the AR with Oct-1 that are associated with sequences within the 5' untranslated region of the MAFbx promotor located just upstream of the first codon. This action of testosterone may contribute to beneficial actions of testosterone on muscle.


Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.
Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease, but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined. We aimed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol. 2838 patients aged 40-75 years in 132 centres in the UK and Ireland were randomised to placebo (n=1410) or atorvastatin 10 mg daily (n=1428). Study entrants had no documented previous history of cardiovascular disease, an LDL-cholesterol concentration of 4.14 mmol/L or lower, a fasting triglyceride amount of 6.78 mmol/L or less, and at least one of the following: retinopathy, albuminuria, current smoking, or hypertension. The primary endpoint was time to first occurrence of the following: acute coronary heart disease events, coronary revascularisation, or stroke. Analysis was by intention to treat. The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met. Median duration of follow-up was 3.9 years (IQR 3.0-4.7). 127 patients allocated placebo (2.46 per 100 person-years at risk) and 83 allocated atorvastatin (1.54 per 100 person-years at risk) had at least one major cardiovascular event (rate reduction 37% [95% CI -52 to -17], p=0.001). Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years. Assessed separately, acute coronary heart disease events were reduced by 36% (-55 to -9), coronary revascularisations by 31% (-59 to 16), and rate of stroke by 48% (-69 to -11). Atorvastatin reduced the death rate by 27% (-48 to 1, p=0.059). No excess of adverse events was noted in the atorvastatin group. Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events, including stroke, in patients with type 2 diabetes without high LDL-cholesterol. No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins. The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld.


Molecular determinants of Ca2+ potentiation of diltiazem block and Ca2+-dependent inactivation in the pore region of cav1.2.
Diltiazem block of Cav1.2 is frequency-dependent and potentiated by Ca2+. We examined the molecular determinants of these characteristics using mutations that affect Ca2+ interactions with Cav1.2. Mutant and wild-type (WT) Cav1.2 channels were transiently expressed in tsA 201 cells with beta1b and alpha2delta subunits. The four conserved glutamates that compose the Ca2+ selectivity filter in Cav1.2 were mutated to Gln (E363Q, E709Q, E1118Q, E1419Q), and each single mutant was assayed for block by diltiazem using whole-cell voltage-clamp recordings in either 10 mM Ba2+ or 10 mM Ca2+. In Ba2+, none of the mutations affected the potency of diltiazem block of closed channels (0.05 Hz stimulation). However, frequency-dependent block (1Hz stimulation) was eliminated in the mutant E1419Q (domain IV), which recovered more rapidly than WT channels from inactivated channel block. Potentiation of diltiazem block of closed Cav1.2 channels in Ca2+ was abolished in the E1118Q, F1117G (domain III), and E1419Q mutants. Frequency-dependent block in Ca2+ was reduced compared with WT Cav1.2 in the F1117G, E1118Q, and E1419Q mutants. The C-terminal tail IQ domain mutation I1627A, which disrupts Ca2+ dependent inactivation, enhanced diltiazem block of closed channels in Ba2+. We conclude that, in Ba2+, E1419 slows recovery from diltiazem block of depolarized Cav1.2 channels, but in Ca2+, E1118, E1419, and F1117 form a Ca2+ binding site that mediates the potentiation of diltiazem block of both closed and inactivated Cav1.2 channels. Furthermore, Ca2+-dependent inactivation, which is impaired in E709Q, E1118Q, E1419Q, and I1627A, is not required for Ca2+ potentiation of diltiazem block.


The negative health spillover effects of universal primary education policy: Ethnographic evidence from Uganda.
Scholars of global health have embraced universal education as a structural intervention to prevent HIV. Yet the costs of school, including fees and other ancillary costs, create an economic burden for students and their families, indicating both the challenge of realising the potential of education for preventing HIV and the ways in which the desire for education may produce vulnerabilities to HIV for those struggling to afford it. To explore this paradox, this article draws from collaborative, team-based ethnographic research conducted from June to August 2019 in the Rakai district of Uganda. Respondents reported that education is the most significant cost burden faced by Ugandan families, sometimes amounting to as much as 66% of yearly household budgets per student. Respondents further understood paying for children's schooling as both a legal requirement and a valued social goal, and they pointed to men's labour migrations to high HIV-prevalence communities and women's participation in sex work as strategies to achieve that. Building from regional evidence showing young East African women participate in transactional, intergenerational sex to secure school fees for themselves, our findings point to the negative health spillover effects of Uganda's universal schooling policies for the whole family.


Evaluating determinants of environmental risk perception for risk management in contaminated sites.
Understanding the differences in the risk judgments of residents of industrial communities potentially provides insights into how to develop appropriate risk communication strategies. This study aimed to explore citizens' fundamental understanding of risk-related judgments and to identify the factors contributing to perceived risks. An exploratory model was created to investigate the public's risk judgments. In this model, the relationship between laypeople's perceived risks and the factors related to the physical nature of risks (such as perceived probability of environmental contamination, probability of receiving impacts, and severity of catastrophic consequences) were examined by means of multiple regression analysis. Psychological factors, such as the ability to control the risks, concerns, experiences, and perceived benefits of industrial development were also included in the analysis. The Maptaphut industrial area in Rayong Province, Thailand was selected as a case study. A survey of 181 residents of communities experiencing different levels of hazardous gas contamination revealed rational risk judgments by inhabitants of high-risk and moderate-risk communities, based on their perceived probability of contamination, probability of receiving impacts, and perceived catastrophic consequences. However, risks assessed by people in low-risk communities could not be rationally explained and were influenced by their collective experiences.


Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2.
Human progesterone receptors (PR) are phosphorylated by cyclin-dependent protein kinase 2 (CDK2) at multiple sites, including Ser400. Herein, we have addressed the significance of phosphorylation of this residue. PR phospho-Ser400-specific antibodies revealed regulated phosphorylation of Ser400 in response to progestins and mitogens, and this correlated with increased CDK2 levels and activity. Expression of cyclin E elevated CDK2 activity and downregulated PR independently of ligand. Similarly, overexpression of activated mutant CDK2 increased PR transcriptional activity in the absence and presence of progestin. Mutation of PR Ser400 to alanine (S400A) blocked CDK2-induced PR activity in the absence, but not in the presence, of progestin. PR was unresponsive to activated CDK2 in breast cancer cells with elevated p27, and RNA interference knock-down of p27 partially restored CDK2-induced ligand-independent PR activation. Similarly, in p27(-/-) mouse embryonic fibroblasts, elevated CDK2 activity increased wild-type (wt) but not S400A PR transcriptional activity in the absence of progestin. CDK2 induced nuclear localization of unliganded wt but not S400A PR; liganded S400A PR exhibited delayed nuclear accumulation. These studies demonstrate that CDK2 regulates PR in the absence of progestins via phosphorylation of Ser400, thus revealing a novel mechanism for upregulated PR transcriptional activity in human breast cancer cells expressing altered cell cycle regulatory molecules.


Orexin-A infusion in the locus ceruleus triggers norepinephrine (NE) release and NE-induced long-term potentiation in the dentate gyrus.
The orexins (ORX-A/ORX-B) are neuroactive peptides known to have roles in feeding and sleep. Evidence of dense, excitatory projections of ORX-A neurons to the noradrenergic pontine nucleus, the locus ceruleus (LC), suggests ORX-A also participates in attention and memory. Activation of LC neurons by glutamate produces a beta-adrenergic receptor-mediated long-term potentiation (LTP) of the perforant path-evoked potential in the dentate gyrus, a target structure of the LC that has been implicated in memory. We asked whether ORX-A also activates norepinephrine (NE)-induced LTP by initiating NE release in the hippocampus. Here, we show that ORX-A infusion (0.25-25 fmol) into the LC produces a robust, beta-adrenergic receptor-dependent, long-lasting potentiation of the perforant path-evoked dentate gyrus population spike in the anesthetized rat. Pharmacological inactivation of the LC with an alpha2-adrenergic receptor agonist, before ORX-A infusion, prevents this potentiation. Analysis of NE concentrations in the hippocampus after ORX-A infusion into the LC reveals a transient, but robust, increase in NE release. Thus, this study demonstrates that the dense orexinergic projection to the LC promotes the induction of NE-LTP in the dentate gyrus. ORX-A modulation of LC activity may provide important support for the cognitive processes of attention and memory.


ID1, inhibitor of differentiation/DNA binding, is an effector of the p53-dependent DNA damage response pathway.
ID1, inhibitor of differentiation/DNA binding, plays an important role in cell proliferation, differentiation, and tumorigenesis. It has been shown that ID1 is de-regulated in multiple cancers and up-regulation of ID1 is correlated with high grades and poor prognosis of human cancers. In contrast, the p53 tumor suppressor was found to be mutated or inactivated in most human cancers and loss of p53 results in early onset of multiple cancers. Although the biological functions of the ID1 oncogene and the p53 tumor suppressor have been intensively investigated, little is known about the upstream regulators of ID1 and the cross-talk between ID1 and p53. Here, we showed that ID1 is down-regulated in cells treated with various DNA damage agents in a p53-dependent manner. Interestingly, we found that DEC1, which was recently identified as a p53 target and mediates p53-dependent cell cycle arrest and senescence, is capable of inhibiting ID1 expression. Conversely, we found that knockdown of DEC1 attenuates DNA damage-induced ID1 repression. In addition, we identified several potential DEC1 responsive elements in the proximal promoter region of the ID1 gene. Moreover, we showed that overexpression of ID1 or ID1', an isoform of ID1, promotes cell proliferation potentially through inhibition of p21 expression. Finally, we found that the extent of DNA damage-induced premature senescence was substantially decreased by overexpression of ID1 or ID1'. Taken together, our study suggests that p53 trans-repressional activity can be mediated by its own target DEC1 and ID1 is an effector of the p53-dependent DNA damage response pathway.


Seroepidemiological study of relationships between Epstein-Barr virus and rheumatoid arthritis.
To elucidate the relationship between Epstein-Barr virus (EBV) and rheumatoid arthritis (RA), we measured antibodies to RA-associated nuclear antigen (anti-RANA) and three other EBV-related antigens in the sera of RA patients and controls. Our study groups consisted of 89 patients with definite or classical RA, mean age 56, male/female ratio 47:42; and 53 normal and osteoarthritis controls, mean age 51, male/female ratio 25:28. In addition to anti-RANA, we measured antibodies to viral capsid antigen (anti-VCA), early antigen (anti-EA) and EBV-associated nuclear antigen (anti-EBNA). Anti-RANA was detected in 71% of RA patients but in only 6% of controls. Elevated anti-VCA titers (greater than 1:160) were more common in RA patients than controls, 31% compared with 15%. The geometric mean titer of anti-VCA was significantly higher iun the RA group, 133 compared with 58. Anti-EA was present in 53% of RA patients but only 19% of controls. Anti-EA in elevated titers (greater than 1:20) was present in 26% of RA patients but only 7% of controls. Characterization of the anti-EA antibodies revealed that the RA patients reacted primarily with the diffuse component, whereas the majority of the controls reacted with the restricted component of the EA complex. In contrast, the frequencies, distributions, and geometric mean titers of anti-EBNA were not significantly different between the two groups. Correlative analysis of these antibodies showed highly significant relationships between anti-VCA and anti-EA, and anti-RANA and anti-EBNA in the RA group. These data are compatible with the interpretation that RA patients have either more active EBV infections than controls or an altered regulation of their immune response to this infectious agent.


Dual-Drug Containing Core-Shell Nanoparticles for Lung Cancer Therapy.
Late-stage diagnosis of lung cancer occurs ~95% of the time due to late manifestation of its symptoms, necessitating rigorous treatment following diagnosis. Existing treatment methods are limited by lack of specificity, systemic toxicity, temporary remission, and radio-resistance in lung cancer cells. In this research, we have developed a folate receptor-targeting multifunctional dual drug-loaded nanoparticle (MDNP) containing a poly(N-isopropylacrylamide)-carboxymethyl chitosan shell and poly lactic-co-glycolic acid (PLGA) core for enhancing localized chemo-radiotherapy to effectively treat lung cancers. The formulation provided controlled releases of the encapsulated therapeutic compounds, NU7441 - a potent radiosensitizer, and gemcitabine - an FDA approved chemotherapeutic drug for lung cancer chemo-radiotherapy. The MDNPs showed biphasic NU7441 release and pH-dependent release of gemcitabine. These nanoparticles also demonstrated good stability, excellent hemocompatibility, outstanding in vitro cytocompatibility with alveolar Type I cells, and dose-dependent caveolae-mediated in vitro uptake by lung cancer cells. In addition, they could be encapsulated with superparamagnetic iron oxide (SPIO) nanoparticles and visualized by MRI in vivo. Preliminary in vivo results demonstrated the low toxicity of these particles and their use in chemo-radiotherapy to effectively reduce lung tumors. These results indicate that MDNPs can potentially be used as nano-vehicles to provide simultaneous chemotherapy and radiation sensitization for lung cancer treatment.


Targeting the coronavirus SARS-CoV-2: computational insights into the mechanism of action of the protease inhibitors lopinavir, ritonavir and nelfinavir.
Coronavirus SARS-CoV-2 is a recently discovered single-stranded RNA betacoronavirus, responsible for a severe respiratory disease known as coronavirus disease 2019, which is rapidly spreading. Chinese health authorities, as a response to the lack of an effective therapeutic strategy, started to investigate the use of lopinavir and ritonavir, previously optimized for the treatment and prevention of HIV/AIDS viral infection. Despite the clinical use of these two drugs, no information regarding their possible mechanism of action at the molecular level is still known for SARS-CoV-2. Very recently, the crystallographic structure of the SARS-CoV-2 main protease (Mpro), also known as C30 Endopeptidase, was published. Starting from this essential structural information, in the present work we have exploited supervised molecular dynamics, an emerging computational technique that allows investigating at an atomic level the recognition process of a ligand from its unbound to the final bound state. In this research, we provided molecular insight on the whole recognition pathway of Lopinavir, Ritonavir, and Nelfinavir, three potential C30 Endopeptidase inhibitors, with the last one taken into consideration due to the promising in-vitro activity shown against the structurally related SARS-CoV protease.


Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber.
Epidemiology associates whole-grain (WG) consumption with several health benefits. Mounting evidence suggests that WG wheat polyphenols play a role in mechanisms underlying health benefits. The objective was to assess circulating concentration, excretion, and the physiologic role of WG wheat polyphenols in subjects with suboptimal dietary and lifestyle behaviors. A placebo-controlled, parallel-group randomized trial with 80 healthy overweight/obese subjects with low intake of fruit and vegetables and sedentary lifestyle was performed. Participants replaced precise portions of refined wheat (RW) with a fixed amount of selected WG wheat or RW products for 8 wk. At baseline and every 4 wk, blood, urine, feces, and anthropometric and body composition measures were collected. Profiles of phenolic acids in biological samples, plasma markers of metabolic disease and inflammation, and fecal microbiota composition were assessed. WG consumption for 4-8 wk determined a 4-fold increase in serum dihydroferulic acid (DHFA) and a 2-fold increase in fecal ferulic acid (FA) compared with RW consumption (no changes). Similarly, urinary FA at 8 wk doubled the baseline concentration only in WG subjects. Concomitant reduction in plasma tumor necrosis factor-α (TNF-α) after 8 wk and increased interleukin (IL)-10 only after 4 wk with WG compared with RW (P = 0.04) were observed. No significant change in plasma metabolic disease markers over the study period was observed, but a trend toward lower plasma plasminogen activator inhibitor 1 with higher excretion of FA and DHFA in the WG group was found. Fecal FA was associated with baseline low Bifidobacteriales and Bacteroidetes abundances, whereas after WG consumption, it correlated with increased Bacteroidetes and Firmicutes but reduced Clostridium. TNF-α reduction correlated with increased Bacteroides and Lactobacillus. No effect of dietary interventions on anthropometric measurements and body composition was found. WG wheat consumption significantly increased excreted FA and circulating DHFA. Bacterial communities influenced fecal FA and were modified by WG wheat consumption. This trial was registered at clinicaltrials.gov as NCT01293175.


Efficacy and tolerability of olmesartan medoxomil in patients with mild to moderate essential hypertension: the OLMEBEST Study.
Achieving target BP is important to control the increased cardiovascular risk associated with uncontrolled hypertension. However, failure to respond to therapy is common with all classes of antihypertensive agents. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) possess many of the positive features of angiotensin-converting enzyme inhibitors, with fewer adverse effects. However, many patients fail to respond adequately to low-dose monotherapy. This study examined whether olmesartan medoxomil dose titration and olmesartan medoxomil/hydrochlorothiazide combination therapy were therapeutically equivalent in patients with mild to moderate essential hypertension who had shown an inadequate response to low-dose olmesartan medoxomil monotherapy. This was a prospective, parallel group, partially randomised, double-blind study set in 463 centres in nine European countries. 2306 male and female adult patients aged 18-75 years with mild to moderate essential hypertension (sitting diastolic BP [DBP] > or =90mm Hg and <110mm Hg) were enrolled. All enrolled patients received open-label olmesartan medoxomil 20mg once daily for 8 weeks. At the end of this period, patients whose BP had not normalised (sitting DBP > or =90mm Hg) were randomised to receive olmesartan medoxomil monotherapy (40mg once daily, n = 302) or olmesartan medoxomil (20mg once daily)/hydrochlorothiazide (12.5mg once daily) combination therapy (n = 325) for 4 weeks. The main outcome measure was change in mean sitting DBP during randomised treatment. After 8 weeks of open-label treatment with olmesartan medoxomil 20 mg/day, 76% of patients showed a DBP response (sitting DBP <90mm Hg or reduction of > or =10mm Hg). During the randomised phase of the study, both treatments were associated with further improvements in sitting SBP/DBP: a reduction of 5.3/5.1mm Hg with olmesartan medoxomil 40 mg/day, and a reduction of 10.8/7.9mm Hg with olmesartan medoxomil/hydrochlorothiazide combination therapy. Final mean BPs of 145.3/90.9mm Hg (olmesartan medoxomil 40 mg/day) and 140.7/88.7mm Hg (olmesartan medoxomil 20mg + hydrochlorothiazide) were achieved, compared with a mean BP of 160.8/100.5mm Hg at baseline. The two treatments were not therapeutically equivalent. Sitting DBP showed a response and was normalised (<90mm Hg) in 62% and 47% of olmesartan medoxomil monotherapy patients, respectively. In the combination therapy group, these endpoints were achieved by 71% (response) and 59% (normalisation) of patients. Treatment with olmesartan medoxomil 40 mg/day was associated with a lower frequency of adverse events than olmesartan medoxomil/hydrochlorothiazide combination therapy (21.5% vs 28.3%, respectively). For patients who did not achieve adequate BP control after initial treatment with olmesartan medoxomil 20 mg/day, olmesartan medoxomil dose titration (to 40 mg/day) or addition of hydrochlorothiazide (12.5 mg/day) elicited a sitting DBP response in the majority of patients who had failed to respond to low-dose monotherapy, and normalisation of sitting DBP in approximately 50% of patients. Both these strategies represent effective and well tolerated treatment options in patients who show an inadequate response to low-dose monotherapy with olmesartan medoxomil.


Quality Measures in Pre-Analytical Phase of Tissue Processing: Understanding Its Value in Histopathology.
Quality monitoring in histopathology unit is categorized into three phases, pre-analytical, analytical and post-analytical, to cover various steps in the entire test cycle. Review of literature on quality evaluation studies pertaining to histopathology revealed that earlier reports were mainly focused on analytical aspects with limited studies on assessment of pre-analytical phase. Pre-analytical phase encompasses several processing steps and handling of specimen/sample by multiple individuals, thus allowing enough scope for errors. Due to its critical nature and limited studies in the past to assess quality in pre-analytical phase, it deserves more attention. This study was undertaken to analyse and assess the quality parameters in pre-analytical phase in a histopathology laboratory. This was a retrospective study done on pre-analytical parameters in histopathology laboratory of a tertiary care centre on 18,626 tissue specimens received in 34 months. Registers and records were checked for efficiency and errors for pre-analytical quality variables: specimen identification, specimen in appropriate fixatives, lost specimens, daily internal quality control performance on staining, performance in inter-laboratory quality assessment program {External quality assurance program (EQAS)} and evaluation of internal non-conformities (NC) for other errors. The study revealed incorrect specimen labelling in 0.04%, 0.01% and 0.01% in 2007, 2008 and 2009 respectively. About 0.04%, 0.07% and 0.18% specimens were not sent in fixatives in 2007, 2008 and 2009 respectively. There was no incidence of specimen lost. A total of 113 non-conformities were identified out of which 92.9% belonged to the pre-analytical phase. The predominant NC (any deviation from normal standard which may generate an error and result in compromising with quality standards) identified was wrong labelling of slides. Performance in EQAS for pre-analytical phase was satisfactory in 6 of 9 cycles. A low incidence of errors in pre-analytical phase implies that a satisfactory level of quality standards was being practiced with still scope for improvement.


New antibiotics for Gram-negative pneumonia.
Pneumonia is frequently encountered in clinical practice, and Gram-negative bacilli constitute a significant proportion of its aetiology, especially when it is acquired in a hospital setting. With the alarming global rise in multidrug resistance in Gram-negative bacilli, antibiotic therapy for treating patients with pneumonia is challenging and must be guided by in vitro susceptibility results. In this review, we provide an overview of antibiotics newly approved for the treatment of pneumonia caused by Gram-negative bacilli. Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam have potent activity against some of the carbapenem-resistant Enterobacterales, especially Klebsiella pneumoniae carbapenemase producers. Several novel antibiotics have potent activity against multidrug-resistant Pseudomonas aeruginosa, such as ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relabactam and cefiderocol. Cefiderocol may also play an important role in the management of pneumonia caused by Acinetobacter baumannii, along with plazomicin and eravacycline.


Chiropractic Manipulation Causing Anterior-Posterior Compression Type Pelvic Ring Injury: A Case Report.
We present a case of an anteroposterior compression (APC) type pelvic ring injury that occurred after chiropractic manipulation in a patient with a history of quadriplegia. Emergent surgical stabilization was undertaken, and he had an excellent outcome with no complications at 3.5-year follow-up. APC type pelvic ring injuries usually occur to high-energy mechanisms. We describe a case of a patient with quadriplegia and osteopenia that suffered a pelvic ring injury because of a unique mechanism. Practitioners performing pelvic manipulation should be aware of this type of injury in at-risk patients.


Deep Learning Approaches for Detecting COVID-19 From Chest X-Ray Images: A Survey.
Chest X-ray (CXR) imaging is a standard and crucial examination method used for suspected cases of coronavirus disease (COVID-19). In profoundly affected or limited resource areas, CXR imaging is preferable owing to its availability, low cost, and rapid results. However, given the rapidly spreading nature of COVID-19, such tests could limit the efficiency of pandemic control and prevention. In response to this issue, artificial intelligence methods such as deep learning are promising options for automatic diagnosis because they have achieved state-of-the-art performance in the analysis of visual information and a wide range of medical images. This paper reviews and critically assesses the preprint and published reports between March and May 2020 for the diagnosis of COVID-19 via CXR images using convolutional neural networks and other deep learning architectures. Despite the encouraging results, there is an urgent need for public, comprehensive, and diverse datasets. Further investigations in terms of explainable and justifiable decisions are also required for more robust, transparent, and accurate predictions.


Charge transport, interfacial interactions and synergistic mechanisms in BiNbO4/MWO4 (M = Zn and Cd) heterostructures for hydrogen production: insights from a DFT+U study.
In the 21st century, the growing demand of global energy is one of the key challenges. The photocatalytic generation of hydrogen has attracted extensive attention to discuss the increasing global demand for sustainable and clean energy. However, hydrogen evolution reactions normally use the economically expensive rare noble metals and the processes remain a challenge. Herein, low-cost BiNbO4/MWO4(010) heterostructures are studied for the first time to check their suitability towards photocatalytic hydrogen production. A theoretical study with the aid of density functional theory (DFT) is used to investigate the synergistic effect, ionisation energy, electron affinities, charge transfer, electronic properties and the underlying mechanism for hydrogen generation of BiNbO4/MWO4(010) heterostructures. The experimental band gaps of bulk ZnWO4, CdWO4 and BiNbO4 are well reproduced using the DFT+U method. The calculated band edge position shows a type-II staggered band alignment and the charge transfer between BiNbO4 and MWO4 monolayers results in a large interfacial built-in potential, which will favour the separation of charge carriers in the heterostructures. The effective mass of the photoinduced holes is higher compared to the electrons, making the heterostructures useful in hydrogen production. The relatively low ionisation energy and electron affinity for the heterostructures compared to the monolayers make them ideal for photocatalysis applications due to their small energy barrier for the injection of electrons and creation of holes. The BiNbO4/MWO4(010) heterostructures are more suitable for photocatalytic hydrogen production due to their strong reducing power relative to the H+/H2O potential. This study sheds light on the less known BiNbO4/ZnWO4(010) heterostructures and the fully explored electronic and optical properties will pave way for future photocatalytic water splitting applications.


Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein.
Prion protein (PrP) is a required factor for susceptibility to transmissible spongiform encephalopathy or prion diseases. In transgenic mice, expression of prion protein (PrP) from another species often confers susceptibility to prion disease from that donor species. For example, expression of deer or elk PrP in transgenic mice has induced susceptibility to chronic wasting disease (CWD), the prion disease of cervids. In the current experiments, transgenic mice expressing two naturally occurring allelic variants of deer PrP with either glycine (G) or serine (S) at residue 96 were found to differ in susceptibility to CWD infection. G96 mice were highly susceptible to infection, and disease appeared starting as early as 160 days postinfection. In contrast, S96 mice showed no evidence of disease or generation of disease-associated protease-resistant PrP (PrPres) over a 600-day period. At the time of clinical disease, G96 mice showed typical vacuolar pathology and deposition of PrPres in many brain regions, and in some individuals, extensive neuronal loss and apoptosis were noted in the hippocampus and cerebellum. Extraneural accumulation of PrPres was also noted in spleen and intestinal tissue of clinically ill G96 mice. These results demonstrate the importance of deer PrP polymorphisms in susceptibility to CWD infection. Furthermore, this deer PrP transgenic model is the first to demonstrate extraneural accumulation of PrPres in spleen and intestinal tissue and thus may prove useful in studies of CWD pathogenesis and transmission by oral or other natural routes of infection.


Elemental Sulfur and Organic Matter Amendment Drive Alkaline pH Neutralization and Mineral Weathering in Iron Ore Tailings Through Inducing Sulfur Oxidizing Bacteria.
Mineral weathering and alkaline pH neutralization are prerequisites to the ecoengineering of alkaline Fe-ore tailings into soil-like growth media (i.e., Technosols). These processes can be accelerated by the growth and physiological functions of tolerant sulfur oxidizing bacteria (SOB) in tailings. The present study characterized an indigenous SOB community enriched in the tailings, in response to the addition of elemental sulfur (S0) and organic matter (OM), as well as resultant S0oxidation, pH neutralization, and mineral weathering in a glasshouse experiment. The addition of S0 was found to have stimulated the growth of indigenous SOB, such as acidophilic Alicyclobacillaceae, Bacillaceae, and Hydrogenophilaceae in tailings. The OM amendment favored the growth of heterotrophic/mixotrophic SOB (e.g., class Alphaproteobacteria and Gammaproteobacteria). The resultant S0 oxidation neutralized the alkaline pH and enhanced the weathering of biotite-like minerals and formation of secondary minerals, such as ferrihydrite- and jarosite-like minerals. The improved physicochemical properties and secondary mineral formation facilitated organo-mineral associations that are critical to soil aggregate formation. From these findings, co-amendments of S0 and plant biomass (OM) can be applied to enhance the abundance of the indigenous SOB community in tailings and accelerate mineral weathering and geochemical changes for eco-engineered soil formation, as a sustainable option for rehabilitation of Fe ore tailings.


Nannochloropsis algae pyrolysis with ceria-based catalysts for production of high-quality bio-oils.
Pyrolysis of Nannochloropsis was carried out in a fixed-bed reactor with newly prepared ceria based catalysts. The effects of pyrolysis parameters such as temperature and catalysts on product yields were investigated. The amount of bio-char, bio-oil and gas products, as well as the compositions of the resulting bio-oils was determined. The results showed that both temperature and catalyst had significant effects on conversion of Nannochloropsis into solid, liquid and gas products. The highest bio-oil yield (23.28 wt%) and deoxygenation effect was obtained in the presence of Ni-Ce/Al2O3 as catalyst at 500°C. Ni-Ce/Al2O3 was able to retain 59% of the alga starting energy in the bio-oil, compared to only 41% in absence of catalyst. Lower content of acids and oxygen in the bio-oil, higher aliphatics (62%), combined with HHV show promise for production of high-quality bio-oil from Nannochloropsis via Ni-Ce/Al2O3 catalytic pyrolysis.


Visceral adipose tissue and cardiometabolic risk factors in young Hispanic and non-Hispanic girls.
Risk factors for cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular disease) can begin developing in childhood. Elevated body mass index (BMI) is associated with greater likelihood of developing such diseases; however, this relationship varies by race and ethnicity. Notably, Hispanics tend to have high rates of obesity and are disproportionately affected by type 2 diabetes. We aimed to determine if visceral adiposes tissue (VAT) is associated with cardiometabolic risk factors (i.e., triglycerides, cholesterol, insulin resistance, C-reactive protein, and blood pressure), independent of BMI percentile, in a sample of primarily Hispanic adolescent girls. A total of 337 girls (73% Hispanic) took part in the cross-sectional study. Hispanic girls generally had greater BMI percentile, VAT, and cardiometabolic risk factors compared to non-Hispanic girls. Multiple linear regression was used to assess the relationships between Dual-energy X-ray Absorptiometry (DXA)-derived VAT and cardiometabolic outcomes, controlling for BMI percentile (<85th percentile or ≥85th percentile), age, ethnicity (Hispanic/non-Hispanic), and Tanner stage. Significant interactions between VAT and BMI percentile were identified for almost all cardiometabolic outcomes. Upon stratification, the association between VAT and cardiometabolic outcomes was strongest in girls ≥85th BMI percentile, as compared to girls <85th percentile. However, VAT was only significantly associated with higher triglycerides (girls ≥85th percentile) and higher insulin resistance (both BMI percentiles) after stratification. VAT was associated with increased triglycerides and insulin resistance in girls with overweight or obesity. These findings warrant further investigation between VAT and cardiometabolic health in Hispanic adolescents who tend to accumulate more adipose tissue during adolescence.


First display of Haloalkane Dehalogenase LinB on the Surface of Bacillus subtilis Spore.
LinB, as a Haloalkane dehalogenase, has good catalytic activity for many highly toxic and recalcitrant compounds, and can realize the elimination of chemical weapons HD in a green non-toxic mode. In order to display Haloalkane dehalogenase LinB on the surface of Bacillus subtilis spore. We have constituted the B. subtilis spore surface display system of halogenated alkanes dehalogenase LinB by gene recombination. Data revealed that LinB can display on spore surface successfully. The hydrolyzing HD analogue 2-chloroethyl ethylsulfide (2-CEES) activity of displayed LinB spores was 4.30±0.09 U/mL, and its specific activity was 0.78±0.03U/mg. Meanwhile, LinB spores showed a stronger stress resistance activity on 2-CEES than free LinB. This study obtained B. subtilis spores of LinB (phingobium japonicum UT26) with enzyme activity that was not reported before. Spore surface display technology uses resistance spore as the carrier to guarantee LinB activity, enhances its stability, and reduces the production cost, thus expanding the range of its application.


Effects of the Erika oil spill on the common starfish Asterias rubens, evaluated by field and laboratory studies.
Impacts of the Erika oil spill on the common starfish Asterias rubens were investigated in the field and using laboratory experiments based on contamination via food at different stages of the starfish reproductive cycle. Two months after the shipwreck, levels of hydrocarbons characteristic of Erika fuel were significantly higher in pyloric ceca and body wall of A. rubens from a contaminated site, compared with control animals from an unpolluted reference area. Concomitant immunological responses and detoxification enzyme activity (CYP1A) were enhanced in the impacted starfish, suggesting rapid biotransformation processes. This was confirmed by laboratory experiments which showed a fast PAH uptake during the 10 first days of contamination and the start of biotransformation processes from the third day. Our study confirms benzo(a)pyrene hydroxylase activity (BPH) in A. rubens and demonstrates the influence of CYP1A in the conversion of insoluble PAHs into soluble derivatives in this species for the first time. The rapidity of decontamination could explain why starfish growth, level of motile activity, reproductive investment, energy storage, and larval development were not significantly affected by these contaminants.


Reasons for complementary therapies and characteristics of users among HIV-infected people.
The aim of this study was to analyse in a large sample of HIV-infected subjects the expectations toward complementary therapies (CT) and the characteristics of users. Self-administered anonymous questionnaires were distributed in seven European countries among HIV-infected subjects consecutively attending the offices of AIDS organizations. Among 632 ever CT users, nutritional supplements (124 subjects) and psycho-physiological approaches (116 subjects) were the most frequent CT used: 61.4% used CT to improve energy. Half the CT users wanted to prevent or alleviate the highly active antiretroviral therapy (HAART) side effects. General malaise and neuropathy were the most common HAART side effects, where CT users found improvement (62.0% and 54.7%, respectively). Acupuncture improved neuropathy in a high proportion of subjects (87.5%); whereas for others CT were considered less effective (range 20.0-36.4%). The most common expectations from CT were to improve energy and to prevent or alleviate the HAART side effects. This suggests that HIV-infected people expect not so much specific help as general support from CT.


[Drugs induced osteopathies].
Drug induced bone diseases concerns : induced osteoporosis, induced osteomalacia (by loss of calcium, phosphate or vitamin D) and induced sarcopenia. Some of these drugs are well known, such as anti-hormones, corticotherapy (which could induce all of osteoporosis, osteomalacia and sarcopenia). In the present article, we will focus on 3 others less known but frequently used drugs : iron replacement, proton pump inhibitors therapy, and serotonin reuptake inhibitor antidepressants treatment. For each of them we will discuss the pathophysiological mechanism leading to bone fragility as well as the recommendations of prevention / management to be proposed in case of absolute necessity of the treatment.


The identification of N6-methyladenosine-related miRNAs predictive of hepatocellular carcinoma prognosis and immunotherapy efficacy.
Hepatocellular carcinoma (HCC) has a high degree of malignancy and poor prognosis. N6-methyladenosine (m6A) modifications and microRNAs (miRNAs) play pivotal roles in tumorigenesis and development. However, the role of m6A-related miRNAs in HCC has not been clarified yet. This study aimed to identify the role of m6A-miRNAs in HCC prognosis through bioinformatics analysis. The clinicopathological information and RNA sequencing data of 369 HCC tumor tissues and 49 tumor-adjacent tissues were downloaded from the TCGA database. A total of 23 m6A regulators were extracted to evaluated the m6A-related miRNAs using Pearson's correlation analysis. Then, we selected prognosis-related m6A-miRNAs using a univariate Cox regression model and used the consensus cluster analysis to explore the characteristics of the m6A-miRNAs. The coefficient of the least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct a prognostic risk score model. The receiver operated characteristic (ROC) analysis was applied to evaluate the prognostic value of the signature. The biological functions of targeted genes were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Then, to validate the potential predictive value for prognosis, the miRNA expression profiles from the GSE76903 and GSE6857 were used. Single sample Gene Set Enrichment Analysis (ssGSEA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were applied to assess the immune microenvironment of HCC. Additionally, a meta-analysis was used to verify the prognostic value of the m6A-microRNAs. RT-PCR was applied to validated the expression of miRNAs in HCC tissues. Cell viability, transwell assay and RNA m6A dot blot assays of HCC cells was applied to access the function of miR-17-5p. The expression of 48 m6A-related miRNAs was identified and 17 prognostic m6A-miRNAs was discovered. The expression profile of those 17 miRNAs was divided into three clusters, and these clusters were associated with the tumor microenvironment (TME) and prognosis. The nine m6A-related miRNA signature was associated with the prognosis of HCC, the AUC of the ROC was 0.771(TCGA dataset), 0.788(GSE76903) and 0.646(GSE6857). The TME and the expression of immune checkpoint molecules were associated with the risk score. The meta-analysis also validated the prognostic value of the m6A-related miRNAs (miR182-5p (HR:1.58, 95%CI:1.04-2.40) and miR-17-5p (HR:1.58, 95%CI: 1.04-2.40)). The expression of miR-17-5p was upregulated in HCC tissues and miR-17-5p showed an oncogenic role in HCC cells. The clinical innovation is the use of m6A-miRNAs as biomarkers for predicting prognosis regarding immunotherapy response in HCC patients.


Factors associated with health-related quality of life among patients with implantable cardioverter defibrillator: identification of foci for nursing intervention.
To explore factors associated with health-related quality of life of patients with implantable cardioverter defibrillators. Substantial evidence indicates that implantable cardioverter defibrillator is proven to increase survival rate by terminating life-threatening arrhythmia. However, this device can negatively affect health-related quality of life. Little is known about factors associated with health-related quality of life of patients with implantable cardioverter defibrillators, particularly in Asian population. A transversal descriptive design was used. Data were collected from a convenience sample of 139 adult patients with implantable cardioverter defibrillators from 4 January-30 April 2012 using the structured questionnaires administered by the researcher and medical record reviews. The Short Form-36 Health Survey version 2 was used to measure health-related quality of life. A total of 139 Chinese patients, including 107 (77·0%) males with a mean age of 63·0 (14·6) years, were selected. The physical component summary was relatively lower, whereas the mental component summary was relatively higher than that of the general Hong Kong Chinese population. Multivariable regression analysis revealed gender, self-care dependence, educational level, atrial fibrillation, diabetes mellitus, anxiety and depression significantly associated with physical or mental quality of life. Depression was a common factor affecting physical and mental quality of life. Self-care dependence, atrial fibrillation, diabetes mellitus, depression and anxiety could be improved. Our findings expand existing knowledge on identifying at-risk patients for having lower quality of life, thus allowing development of appropriate interventions targeting risk factors for improving health-related quality of life of patients with implantable cardioverter defibrillator.


Assessment of the haemodynamic response to exercise by means of electrical impedance cardiography: method, validation and clinical applications.
Over the past three decades, the technique of electrical impedance cardiography (EIC) has developed into a valid and reliable instrument for the assessment of stroke volume. Recent developments have made EIC suitable for routine use during exercise testing, too. However, standardization of electrode positioning, stroke volume calculation, and data processing is lacking. In our opinion the most reliable options are, respectively, a modified semicircular electrode array, the Kubicek equation including a haematocrit-based resistivity value, and computerized signal averaging. Although EIC derived stroke volume calculation is based on several debated assumptions, numerous validation studies have shown good accuracy and reproducibility, also during exercise. Addition of EIC measurements during standard clinical exercise testing might be of benefit in occupational medicine, cardiology and pulmonary medicine. Although in the latter setting no validation studies have been performed, major methodological problems are not expected.


A thin multifunctional coating on a separator improves the cyclability and safety of lithium sulfur batteries.
Lithium-sulfur batteries are one of the most promising next-generation batteries due to their high theoretical specific capacity, but are impeded by the low utilization of insulating sulfur, unstable morphology of the lithium metal anode, and transport of soluble polysulfides. Here, by coating a layer of nano titanium dioxide and carbon black onto a commercial polypropylene separator, we demonstrate a new composite separator that can confine the polysulfides on the cathode side, forming a catholyte chamber, and at the same time block the dendritic lithium on the anode side. Lithium-sulfur batteries using this separator show a high initial capacity of 1206 mA h g-1 and a low capacity decay rate of 0.1% per cycle at 0.5C. Analyses reveal the electrocatalytic effect and the excellent dendrite-blocking capability of the ∼7 µm thick coating.


Resting-state fMRI analysis in apathetic Alzheimer's disease.
Diagnosis of comorbid psychiatric conditions are a significant determinant for the prognosis of neurodegenerative diseases. Apathy, which is a behavioral executive dysfunction, frequently accompanies Alzheimer's disease (AD) and leads to higher daily functional loss. We assume that frontal lobe hypofunction in apathetic AD patients are more apparent than the AD patients without apathy. This study aims to address the neuroanatomical correlates of apathy in the early stage of AD using task-free functional magnetic resonance imaging (MRI). Patients (n=20) were recruited from the Neurology and Psychiatry Departments of İstanbul University, İstanbul School of Medicine whose first referrals were 6- to 12-month history of progressive cognitive decline. Patients with clinical dementia rating 0.5 and 1 were included in the study. The patient group was divided into two subgroups as apathetic and non-apathetic AD according to their psychiatric examination and assessment scores. A healthy control group was also included (n=10). All subjects underwent structural and functional MRI. The resting-state condition was recorded eyes open for 5 minutes. The difference between the three groups came up in the pregenual anterior cingulate cortex (pgACC) at the trend level (P = 0.056). Apathetic AD group showed the most constricted activation area at pgACC. The region in and around anterior default mode network (pgACC) seems to mediate motivation to initiate behavior, and this function appears to weaken as the apathy becomes more severe in AD.


Slow versus traditional strength training in obese female participants: preliminary results.
The aim of this study was to provide comparative data on a slow versus a traditional supervised resistance training in an obese female population. Forty obese female patients admitted to our rehabilitation hospital were assigned randomly to a slow training group (ST group; mean age: 47.44 years, mean BMI: 38.53 kg/m) and a traditional training group (TT group; mean age: 54.34 years, mean BMI: 39.37 kg/m). The ST protocol included five repetitions for five consecutive bouts on the leg press and extension machine. The duration of each repetition (concentric+eccentric phases) was 6 s for leg press and 5 s for leg extension. The initial load was 50% of the one repetition maximum and then gradually reduced by 20% for each bout. The TT protocol included six consecutive repetitions for five bouts on the leg press and leg extension with 80% of the one repetition maximum load. Both groups performed 10 sessions. All of the patients were assessed by a visual analogue scale for pain, a Borg scale for subjective fatigue, and an isokinetic strength test. Statistically significant strength improvements were observed in both groups. In ST group statistically significant improvements in visual analogue scale scores for knee pain were found at post, larger than that observed in TT group. Subjectively perceived fatigue on the Borg scale decreased more at post in ST group in comparison with TT group. Our preliminary data suggest that ST may represent a preferential strengthening method in obese patients as it can lead to significant strength gains with a relatively lower loading effect on the knee, and hence reduced perception of pain.


PDGFRβ Activation Induced the Bovine Embryonic Genome Activation via Enhanced NFYA Nuclear Localization.
Embryonic genome activation (EGA) is a critical step during embryonic development. Several transcription factors have been identified that play major roles in initiating EGA; however, this gradual and complex mechanism still needs to be explored. In this study, we investigated the role of nuclear transcription factor Y subunit A (NFYA) in bovine EGA and bovine embryonic development and its relationship with the platelet-derived growth factor receptor-β (PDGFRβ) by using a potent selective activator (PDGF-BB) and inhibitor (CP-673451) of PDGF receptors. Activation and inhibition of PDGFRβ using PDGF-BB and CP-673451 revealed that NFYA expression is significantly (p < 0.05) affected by the PDGFRβ. In addition, PDGFRβ mRNA expression was significantly increased (p < 0.05) in the activator group and significantly decreased (p < 0.05) in the inhibitor group when compared with PDGFRα. Downregulation of NFYA following PDGFRβ inhibition was associated with the expression of critical EGA-related genes, bovine embryo development rate, and implantation potential. Moreover, ROS and mitochondrial apoptosis levels and expression of pluripotency-related markers necessary for inner cell mass development were also significantly (p < 0.05) affected by the downregulation of NFYA while interrupting trophoblast cell (CDX2) differentiation. In conclusion, the PDGFRβ-NFYA axis is critical for bovine embryonic genome activation and embryonic development.


HIV-associated cognitive impairment before and after the advent of combination therapy.
The objective of this study was to describe the occurrence of HIV dementia and neuropsychological testing abnormalities in a new cohort of HIV-seropositive individuals at high risk for HIV dementia and to compare these results to a cohort before the advent of highly active antiretroviral therapy (HAART). HAART has been associated with improvements in cognitive performance in some HIV-infected patients. However, it is uncertain whether HAART has changed the frequency of specific neurocognitive abnormalities. Baseline data from 272 HIV-seropositive subjects in the Dana cohort recruited from January, 1994, to December, 1995, and 251 HIV-seropositive subjects in the Northeastern AIDS Dementia Consortium (NEAD) cohort recruited from April, 1998, to August, 1999, were compared. Participants in both cohorts received nearly identical assessments. After adjusting for differences in age, education, gender, race, and CD4 count between the two cohorts, there were no differences in the occurrence of HIV dementia or abnormalities either 1 SD or 2 SDs below established norms for any of the neuropsychological tests. Even though HAART has reduced the incidence of HIV dementia, HIV-associated cognitive impairment continues to be a major clinical problem among individuals with advanced infection.


A mutation in a CD44 variant of inflammatory cells enhances the mitogenic interaction of FGF with its receptor.
Synovial fluid cells from joints of rheumatoid arthritis (RA) patients express a novel variant of CD44 (designated CD44vRA), encoding an extra trinucleotide (CAG) transcribed from intronic sequences flanking a variant exon. The CD44vRA mutant was detected in 23 out of 30 RA patients. CD44-negative Namalwa cells transfected with CD44vRA cDNA or with CD44v3-v10 (CD44vRA wild type) cDNA bound FGF-2 to an equal extent via their associated heparan sulfate chains. However, Namalwa cells, immobilizing FGF-2 via their cell surface CD44vRA, bound substantially more soluble FGF receptor-1 (FGFR-1) than did Namalwa cells immobilizing the same amount of FGF-2 via their cell surface CD44v3-v10. The former cells stimulated the proliferation of BaF-32 cells, bearing FGFR-1, more efficiently than did the latter cells. Finally, isolated primary synovial fluid cells from RA patients expressing CD44vRA bound more soluble FGFR-1 to their cell surface-associated FGF-2 than did corresponding synovial cells expressing CD44v3-v10 or synovial cells from osteoarthritis patients. The binding of soluble FGFR-1 to RA synovial cells could be specifically reduced by their preincubation with Ab's against the v3 exon product of CD44. Hence, FGF-2 attached to the heparan sulfate moiety expressed by the novel CD44 variant of RA synovium cells exhibits an augmented ability to stimulate FGFR-1-mediated activities. A similar mechanism may foster the destructive inflammatory cascade not only in RA, but also in other autoimmune diseases.


Scattering of light by a system of anisotropic particles.
The cross-spectral density function of the scattered field that is produced by scattering of a coherent plane light wave incident on a collection of different types of anisotropic particles is derived. We show the phenomena of interference of the fields scattered by each of the particles in the system. Numerical results indicate that the information about the shape, the distance, and the relative orientation of the particles may be obtained from far-zone measurements of the scattered field.


Traumatic-Induced Coagulopathy as a Systems Failure: A New Window into Hemostasis.
Traumatic-induced coagulopathy (TIC) is often associated with significant bleeding, transfusion requirements, inflammation, morbidity, and mortality. This review considers TIC as a systems failure, not as a single-event manifestation of trauma. After briefly reviewing the meaning of TIC and the bewildering array of fibrinolysis phenotypes, we will discuss the role of platelets and fibrinogen in coagulopathy. Next, we will review the different TIC hypotheses and drill down to a single mechanistic domain comprising (1) thrombin's differential binding to thrombomodulin, (2) the expression of annexin II-S100A10 complex, and (3) the functional integrity of the endothelial glycocalyx. This triad forms the basis of the "switch" hypothesis of TIC. We will next address the potential limitations of current practice in treating a coagulation or fibrinolytic defect, and the next defect, and so on down the line, which often leads to what U.S. surgeon William C. Shoemaker considered "an uncoordinated and sometimes contradictory therapeutic outcome." The treat-as-you-go approach using sequential, single-target treatments appears to be a by-product of decades of highly reductionist thinking and research. Lastly, we will present a unified systems hypothesis of TIC involving three pillars of physiology: the central nervous system (CNS)-cardiovascular system, the endothelial glycocalyx, and mitochondrial integrity. If CNS control of ventriculoarterial coupling is maintained close to unity following trauma, we hypothesize that the endothelium will be protected, mitochondrial energetics will be maintained, and TIC (and inflammation) will be minimized. The Systems Hypothesis of Trauma (SHOT) also helps to answer why certain groups of severely bleeding trauma patients are still dying despite receiving the best care. Currently, no drug therapy exists that targets the whole system.


The effects of quinine on the calcium and magnesium content of the sarcoplasmic reticulum and the temperature-dependence of quinine contractures.
A significant decrease in the Ca2+ and increase in the Mg2+ content of the terminal cisternae (TC) of the sarcoplasmic reticulum (SR) during quinine contraction was demonstrated by electron probe analysis of rapidly frozen frog muscles. The extent of Ca2+ release (71% of total) from the TC and the absence of an increase in total cell Ca2+ support the conclusion that quinine contractures are caused by passive efflux of Ca2+ from the SR when the latter is uncompensated due to inhibition of the SR Ca2+ pump by quinine. A rapid warming contraction (RWC) was observed, in the presence of quinine, when the temperature of intact and skinned muscles was increased from about 5 degrees C to 18-23 degrees C. The duration of the latency of quinine contracture, in intact muscle bundles, was approximately 31 s at 3 degrees C and 2 s at 23 degrees C. The results suggest a significant temperature sensitivity of the passive Ca2+ channels of the SR membrane, although an effect of temperature on the lipid partition coefficient of quinine into the SR has not been ruled out.


Injection of Anabolic Steroids in Men Who Had Sex with Men in Madrid and Barcelona: Prevalence Correlates and Role as a Risk Factor for Transmitted Infections.
This study describes the prevalence of anabolic-androgenic steroid (AAS) injection, their main correlates, and the prevalence of specific AAS injection risk behaviours among men who have sex with men (MSM), an area insufficiently addressed in scientific research. Participants were HIV-negative MSM attending four HIV/STI diagnosis services: two clinics and two community programmes in Madrid and Barcelona. Participants answered an online self-administered questionnaire. Crude and adjusted lifetime prevalence and prevalence ratios (PRs) were calculated by different factors and using Poisson regression models with robust variance. Of the 3510 participants, 6.1% (95% CI: 5.3-6.9) had injected AAS before and 3.5% (95% CI: 2.9-4.2) had done so in the last 12 months. In the multivariate analysis, AAS injection was independently associated with being over 40 years old (aPR = 3.6; 95% CI: 2.0-6.5) and being born in Latin America (aPR = 2.5; 95% CI:1.9-3.4), and was less strongly associated (aPRs of around two) with having been recruited into STI clinics, having ever been paid for sex before, injected drugs, used drugs for sex, having been diagnosed with an STI before, and having been diagnosed with HIV at the recruitment consultation. Only three participants, 1.4%, of those who had injected AAS before had shared AAS or equipment for preparation or injecting before. Conclusions: In contrast to drugs, AAS injecting behaviours do not play a relevant, direct role in the transmission of blood-borne infections among MSM. However, AAS injectors have a higher prevalence of sexual risk behaviours. These findings should be confirmed using new studies that employ other sampling procedures.


Analysis of Flow Dynamics and Outcomes of Cerebral Aneurysms Treated with Intrasaccular Flow-Diverting Devices.
Intrasaccular flow diversion offers a promising treatment option for complex bifurcation aneurysms. The purpose of this study was to compare the flow conditions between successfully occluded and incompletely occluded aneurysms treated with intrasaccular devices. The hemodynamics in 18 completely occluded aneurysms after treatment with intrasaccular devices was compared against 18 that were incompletely occluded at follow-up. Hemodynamic and geometric parameters were obtained from computational fluid dynamics models constructed from 3D angiographies. Models of the intrasaccular devices were created and interactively deployed within the vascular models using posttreatment angiography images for guidance. Hemodynamic and geometric variables were compared using the Mann-Whitney test and univariate logistic regression analysis. Incomplete occlusion was associated with large posttreatment mean aneurysm inflows (P = .02) and small reductions in the mean inflow rate (P = .01) and inflow concentration index (P = .03). Incompletely occluded aneurysms were larger (P = .002) and had wider necks (P = .004) than completely occluded aneurysms and tended to have more complex flow patterns, though this trend was not significant after adjusting for multiple testing. The outcome of cerebral aneurysm treatment with intrasaccular flow diverters is associated with flow conditions created immediately after device implantation. Flow conditions unfavorable for immediate and complete occlusion seem to be created by improper positioning or orientation of the device. Complete occlusion is more difficult to achieve in larger aneurysms, aneurysms with wider necks, and aneurysms with stronger and more complex flows.


Integrated light-sheet illumination using metallic slit microlenses.
Light sheet microscopy (LSM) - also known as selective plane illumination microscopy (SPIM) - enables high-speed, volumetric imaging by illuminating a two-dimensional cross-section of a specimen. Typically, this light sheet is created by table-top optics, which limits the ability to miniaturize the overall SPIM system. Replacing this table-top illumination system with miniature, integrated devices would reduce the cost and footprint of SPIM systems. One important element for a miniature SPIM system is a flat, easily manufactured lens that can form a light sheet. Here we investigate planar metallic lenses as the beam shaping element of an integrated SPIM illuminator. Based on finite difference time domain (FDTD) simulations, we find that diffraction from a single slit can create planar illumination with a higher light throughput than zone plate or plasmonic lenses. Metallic slit microlenses also show broadband operation across the entire visible range and are nearly polarization insensitive. Furthermore, compared to meta-lenses based on sub-wavelength-scale diffractive elements, metallic slit lenses have micron-scale features compatible with low-cost photolithographic manufacturing. These features allow us to create inexpensive integrated devices that generate light-sheet illumination comparable to tabletop microscopy systems. Further miniaturization of this type of integrated SPIM illuminators will open new avenues for flat, implantable photonic devices for in vivo biological imaging.


Electron microscopic heteroduplex mapping identifies regions of the engrailed locus that are conserved between Drosophila melanogaster and Drosophila virilis.
Physical localization of mutations in the engrailed (en) gene suggested that at least 70 kilobases (kb) of genomic sequences contribute to the normal function of this gene. Molecular characterization has suggested that en function is encoded in a small, 4.5-kb primary transcript. To identify functional regions within the 70 kb of the en locus of D. melanogaster, we identified sequences conserved in the D. virilis genome (estimated divergence time, 60 million years). Based on homology to D. melanogaster, we isolated en DNA from a D. virilis genomic library. Electron microscopic heteroduplex analysis indicated that in 70 kb there is 20 kb of conserved DNA in 33 different regions dispersed throughout the en locus, including two which encode parts of the major embryonic transcript. The conserved regions are in the same linear order and are spaced by similar lengths of nonconserved sequences in the D. virilis and D. melanogaster DNAs. What functional constraints have enforced conservation of sequences throughout the entire 70 kb and protected the region from divergence of size and arrangement? Our working hypothesis is that sequences necessary for the complex spatial and temporal pattern of en expression are dispersed throughout the 70-kb en locus and that selection for proper regulation restricts evolutionary divergence.


Occurrence of Aedes aegypti (L.) and Culex quinquefasciatus Say (Diptera, Culicidae) in houses of different constructions in Phnom Penh, Kampuchea.
The relation between the number of mosquito specimens of the most abundant species Aedes aegypti (L.) and Culex quinquefasciatus Say and the construction of houses which they inhabited was studied. The effect of the building materials and of the height at which the floor was situated above the ground were assessed in five and four localities, respectively. It was found that in the localities having the character of a town the mosquitoes were most abundant in houses constructed from corrugated plate and in those the floor of which was situated 2-3.5 m above the ground. In the locality of a village character, the mosquitoes were most numerous in brick houses with the floors at the ground level.


Sensing of molecules using quantum dynamics.
We design sensors where information is transferred between the sensing event and the actuator via quantum relaxation processes, through distances of a few nanometers. We thus explore the possibility of sensing using intrinsically quantum mechanical phenomena that are also at play in photobiology, bioenergetics, and information processing. Specifically, we analyze schemes for sensing based on charge transfer and polarization (electronic relaxation) processes. These devices can have surprising properties. Their sensitivity can increase with increasing separation between the sites of sensing (the receptor) and the actuator (often a solid-state substrate). This counterintuitive response and other quantum features give these devices favorable characteristics, such as enhanced sensitivity and selectivity. Using coherent phenomena at the core of molecular sensing presents technical challenges but also suggests appealing schemes for molecular sensing and information transfer in supramolecular structures.


Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.
To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) oncogene. After 7.3 years of follow-up of the Netherlands Cohort Study (n = 120,852), adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed, based on 401 colon and 130 rectal cancer patients. Total, saturated and monounsaturated fat were not associated with the risk of colon or rectal cancer, or different molecular subgroups. There was also no association between polyunsaturated fat and the risk of overall or subgroups of rectal cancer. Linoleic acid, the most abundant polyunsaturated fatty acid in the diet, was associated with increased risk of colon tumors with only a KRAS mutation and no additional truncating APC mutation or lack of MLH1 expression (RR = 1.41, 95% CI 1.18-1.69 for one standard deviation (i.e., 7.5 g/day) increase in intake, p-trend over the quartiles of intake <0.001). Linoleic acid intake was not associated with risk of colon tumors without any of the gene defects, or with tumors harboring aberrations in either MLH1 or APC. Linoleic acid intake is associated with colon tumors with an aberrant KRAS gene, but an intact APC gene and MLH1 expression, suggesting a unique etiology of tumors with specific genetic aberrations.


Predictors of medication self-management skill in a low-literacy population.
Patients' ability to manage medications is critical to chronic disease control. Also known as medication management capacity (MMC), it includes the ability to correctly identify medications and describe how they should be taken. To evaluate the effects of low literacy, medication regimen complexity, and sociodemographic characteristics on MMC. Cross-sectional analysis of enrollment data from participants in a randomized trial. Patients with coronary heart disease in an inner-city clinic. Medication management capacity was measured with the Drug Regimen Unassisted Grading Scale (DRUGS), which scores subjects' ability to identify, open, describe the dose, and describe the timing of their medications. DRUGS overall and component scores were compared by literacy, Mini Mental State Exam score, regimen complexity (number of prescription medications), and sociodemographic characteristics. Most of the 152 participants were elderly (mean age 65.4 years), women (54.6%), and African American (94.1%). Approximately half (50.7%) had inadequate literacy skills, and 28.9% had marginal skills. In univariate analysis, MMC was significantly associated with literacy (P<.001), and this effect was driven by the ability to identify medications. In multivariable models, patients with inadequate literacy skills had 10 to 18 times the odds of being unable to identify all of their medications, compared with those with adequate literacy skills (P<.05). Adults with inadequate literacy skills have less ability to identify their medications. Techniques are needed to better educate low-literacy patients about their medications, as a potential strategy to enhance adherence.


[3H]rauwolscine (alpha-yohimbine): a specific antagonist radioligand for brain alpha 2-adrenergic receptors.
[3H]Rauwolscine, a specific and potent alpha 2-antagonist radioligand, was used to characterize alpha 2-receptor binding in bovine cerebral cortex. [3H]Rauwolscine binding was reversible, stereospecific, and saturable. Association, dissociation, and saturation studies revealed one site interactions (k -1/k+1 = 1.2 nM, KD = 2.5 nM, Bmax = 160 fmol/mg protein) and competition studies indicated that [3H]rauwolscine labeled the alpha 2-receptor. Agonists inhibited [3H]rauwolscine binding in a shallow, GTP-sensitive manner. These results suggest that [3H]rauwolscine specifically labels both the high and low affinity states of the alpha 2-receptor in brain membranes.


Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice.
1. Using a rabbit cerebellar slice preparation, we stimulated a classical conditioning procedure by stimulating parallel fiber inputs to Purkinje cells with the use of a brief, high-frequency train of eight constant-current pulses 80 ms before climbing fiber inputs to the same Purkinje cell were stimulated with the use of a brief, lower frequency train of three constant-current pulses. In all experiments, we assessed the effects of stimulation by measuring the peak amplitude of Purkinje cell excitatory postsynaptic potentials (EPSPs) to single parallel fiber test pulses. 2. Intradendritically recorded Purkinje cell EPSPs underwent a long-term (> 20 min) reduction in peak amplitude (30%) after paired stimulation of the parallel and climbing fibers but not after unpaired or parallel fiber alone stimulation. We call this phenomenon pairing-specific long-term depression (PSD). 3. Facilitation of the peak amplitude of a second EPSP elicited by a parallel fiber train occurred both before and after paired stimulation suggesting that the locus of depression was not presynaptic. Depression of the peak amplitude of a depolarizing response to focal application of glutamate following pairings of parallel and climbing fiber stimulation added support to a suggested postsynaptic locus of the PSD effect. 4. The application of aniracetam potentiated EPSP peak amplitude by 40%, but these values returned to baseline as a result of pairings. With the removal of aniracetam from the bath 20 min after pairings, normal levels of pairing-specific EPSP depression were observed, indicating that the effect did not result from direct desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptors. 5. Incubation of slices in the protein kinase inhibitor H-7 potentiated EPSP peak amplitudes slightly (9%), but peak amplitudes returned to baseline levels after pairings. The net reduction in EPSP peak amplitude of < 10% after pairings suggested that H-7 partially blocked PSD and that, in turn, PSD involved protein kinases. 6. The means of induction and the specificity of those means suggest that the phenomenology of PSD is fundamentally different from that of long-term depression. PSD only occurs with pairings of trains of parallel fiber and climbing fiber stimulation; it occurs without the need for bicuculline; and it can overcome the blocking effects of aniracetam. 7. Nevertheless, the involvement of protein kinases and the potential role of calcium suggest that the mechanisms involved in the induction of PSD and long-term depression have a number of features in common. 8. Because of the pairing-specific nature of the long-term synaptic depression observed in these experiments, PSD provides a mechanism that may contribute to the role of the cerebellar cortex in classical conditioning.


Changes in attachment representations for young people in long-term therapeutic foster care.
This article reports on a 1-year follow-up study exploring changes in attachment security of children placed in long-term therapeutic foster care over three data collection time points. A group of eight children (age 14 to 17) were assessed over a period of 1 year using a modified version of the Separation Anxiety Test (SAT). Interviews were also conducted to explore the young people's and the carers' experiences of the placements and their personal perspectives of changes. The findings indicated some positive changes in the young people's attachment security over time, for example, a reduction in extreme reactions and a trust that adults could understand their feelings (PAE - parental accurate empathy). However, despite this PAE, the young people did not expect adults to enact this by offering them support, and this lack of expectation persisted over the 1-year period. Specific differences in relation to placement success were suggested in that young people for whom their placements broke down indicated more initial fearful and aggressive representations of adults. Overall, young people emphasised positive aspects of their placements as including being treated as adults, listened to and made to feel safe.