Beneficial effects of cinnamon proanthocyanidins on the formation of specific advanced glycation endproducts and methylglyoxal-induced impairment on glucose consumption.
Advanced glycation endproducts (AGEs) are a group of complex and heterogeneous compounds formed from nonenzymatic reactions. The accumulation of AGEs in vivo has been implicated as a major pathogenic process in diabetic complications and other health disorders, such as atherosclerosis and Alzheimer's disease, and normal aging. In this study, we investigate the inhibitory effects of cinnamon bark proanthocyanidins, catechin, epicatechin, and procyanidin B2 on the formation of specific AGE representatives including pentosidine, N(epsilon)-(carboxymethyl)lysine (CML), and methylglyoxal (MGO) derived AGEs. These compounds displayed obvious inhibitory effects on these specific AGEs, which are largely attributed to both their antioxidant activities and carbonyl scavenging capacities. Meanwhile, in terms of their potent MGO scavenging capacities, effects of these proanthocyanidins on insulin signaling pathways interfered by MGO were evaluated in 3T3-L1 adipocytes. According to the results, proanthocyanidins exerted protective effects on glucose consumption impaired by MGO in 3T3-L1 fat cells.


Frequency domain analysis of cerebral blood flow velocity and its correlation with arterial blood pressure.
We applied frequency domain analysis to detect and quantify spontaneous fluctuations in the blood flow velocity of the middle cerebral artery (MCAFV). Instantaneous MCAFV of normal volunteers was detected using transcranial Doppler sonography. Spectral and transfer function analyses of MCAFV and arterial blood pressure (ABP) were performed by fast Fourier transform. We found the fluctuations in MCAFV, like ABP, could be diffracted into three components at specific frequency ranges, designated as high-frequency (HF, 0.15 to 0.4 Hz), low-frequency (LF, 0.04 to 0.15 Hz), and very low-frequency (VLF, 0.016 to 0.04 Hz) components. The HF and LF components of MCAFV exhibited high coherence with those of ABP, indicating great similarity of MCAFV and ABP fluctuations within the two frequency ranges. However, it was not the case for the VLF component. Transfer function analysis revealed that the ABP-MCAFV phase angle was frequency-dependent in the LF range (r = -0.79, P < 0.001) but not in the HF range. The time delay between LF fluctuations of ABP and those of MCAFV was evaluated as 2.1 seconds. We conclude that in addition to traditional B-wave equivalents, there are at least two different mechanisms for MCAFV fluctuations: the HF and LF fluctuations of MCAFV are basically secondary to those of ABP, and cerebral autoregulation may operate efficiently in LF rather than HF range. Frequency domain analysis offers an opportunity to explore the nature and underlying mechanism of dynamic regulation in cerebral circulation.


Experimental introduction of a microsporidian into a wild population of Culex pipiens fatigans Wied.
Chemical control of C. p. fatigans frequently fails because the mosquito rapidly develops resistance to insecticides. A possible alternative or complementary method is biological control, including the introduction of pathogens. The microsporidian Plistophora culicis was known to infect readily and have an adverse effect on C. p. fatigans populations in the laboratory, so an attempt was made to introduce and establish this pathogen in a wild population of the mosquito on the Pacific island of Nauru. Two years after introduction the pathogen was still present in the wild population. However, the infection rate was similar to that found in naturally occurring infections in other mosquitos and is almost certainly not high enough to affect a natural population of C. p. fatigans adversely.


Two MMP-2 promoter polymorphisms (-790T/G and -735C/T) in chronic heart failure.
Remodelling of extracellular matrix by activated matrix metalloproteinases is considered to contribute to progression of ventricle remodelling during chronic heart failure. The aim of this study was to associate two promoter polymorphisms, -790T/G and -735C/T, in the gene for matrix metalloproteinase (MMP)-2 (gelatinase A) with chronic heart failure (CHF). For this purpose, 164 patients (124 men, 40 women, median age 56 years, range 21-91 years) with CHF (functional class NYHA II-IV, ejection fraction median 25%, cardiothoracic index more than 50%) were compared with 196 control subjects without clinical signs of cardiovascular disease (131 men and 65 women, median age 56 years, range 27-84 years) in -790T/G and -735C/T MMP-2 genotype distributions and allelic frequencies. The genotypes were determined by polymerase chain reaction (PCR) with restriction analyses. A significant increase of the T allele of the -790T/G MMP-2 polymorphism (p = 0.04), as well as of the C allele of the -735C/T MMP-2 gene polymorphism, in patients with CHF was proven (p = 0.04). The heterozygote CT of the -735C/T MMP-2 polymorphism exhibits a 7 times higher odds ratio (OR) for the CHF patients with lower levels of total cholesterol (less than 5 mmol/l), especially for non-hypertensive CHF men (OR = 7.28, 95% confidence interval 1.51-35.03, p = 0.006). Determination of MMP polymorphisms in the regulatory area of the gene could help us to comprehend individual susceptibility of patients with CHF to MMP inhibitors based on known risks of MMP genotypes.


Competing risk models to estimate the excess mortality and the first recurrent-event hazards.
In medical research, one common competing risks situation is the study of different types of events, such as disease recurrence and death. We focused on that situation but considered death under two aspects: "expected death" and "excess death", the latter could be directly or indirectly associated with the disease. The excess hazard method allows estimating an excess mortality hazard using the population (expected) mortality hazard. We propose models combining the competing risks approach and the excess hazard method. These models are based on a joint modelling of each event-specific hazard, including the event-free excess death hazard. The proposed models are parsimonious, allow time-dependent hazard ratios, and facilitate comparisons between event-specific hazards and between covariate effects on different events. In a simulation study, we assessed the performance of the estimators and showed their good properties with different drop-out censoring rates and different sample sizes. We analyzed a population-based dataset on French colon cancer patients who have undergone curative surgery. Considering three competing events (local recurrence, distant metastasis, and death), we showed that the recurrence-free excess mortality hazard reached zero six months after treatment. Covariates sex, age, and cancer stage had the same effects on local recurrence and distant metastasis but a different effect on excess mortality. The proposed models consider the excess mortality within the framework of competing risks. Moreover, the joint estimation of the parameters allow (i) direct comparisons between covariate effects, and (ii) fitting models with common parameters to obtain more parsimonious models and more efficient parameter estimators.


The importance of exposure for healthy eating in childhood: a review.
Children's food preferences are strongly associated with their consumption patterns. Identifying the factors that influence preferences is therefore crucial to the development of effective interventions to improve children's diets. Perhaps the most important determinant of a child's liking for a particular food is the extent to which it is familiar. Put simply, children like what they know and they eat what they like. From the very earliest age, children's experiences with food influence both preferences and intake, and research suggests that the earlier and broader that experience, the healthier the child's diet. Laboratory studies of children's food acceptance have indicated that repeated opportunities to taste unfamiliar foods results in increased liking and consumption. In order to investigate whether these results can be replicated in real-world situations, a series of naturalistic studies testing the efficacy of exposure-based interventions have been carried out. In a school-based study large increases in liking and intake of raw red pepper were seen in 5- to 7-year olds and two further studies, in which mothers used exposure techniques to increase children's acceptance of vegetables, achieved similar results. If future large-scale interventions prove to be successful, training could be offered to health professionals or directly to parents themselves.


[Psychological contract in the light of flexible employment: The review of studies].
Changing employment relations between employees and employers due to the increasing employment flexibility have contributed to the development of a new paradigm to analyze these relations based on the concept of psychological contract. This paradigm might be particularly relevant in Poland where the employment flexibility understood as the number of workers with temporary contracts is the highest in Europe. In this paper the concept of psychological contract is presented along with the existing findings related to its range, balance and contract fulfilment vs. contract breach. The results of studies showing the differences in psychological contract of temporary and permanent workers are also presented. The majority of them indicate that psychological contracts of temporary workers are limited in their extent, less balanced and asymmetric (to workers' disadvantage), as well as more transactional in their nature than those of permanent workers. The temporary workers' well-being and attitudes towards work and their reaction to psychological contract breach largely depends on their preferences for this type of employment, on their qualifications and on a labor market situation. Med Pr 2016;67(4):529-536.


Preparation and evaluation of sustained release cross-linked chitosan microspheres containing phenobarbitone.
Chitosan microspheres containing phenobarbitone were successfully prepared by glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in light liquid paraffin containing sorbitan mono-oleate as a stabilizing agent. Uniform and spherical microspheres, with a loading efficiency up to 57.2%, could be prepared depending on the preparation conditions. The main parameters affecting the preparation and the performance of the prepared microspheres were the molecular weight and concentration of chitosan as well as the concentration of the used stabilizing agent. The incorporation of citric acid into the microspheres was found to increase the formation of a water-soluble gel when the microspheres come in contact with the dissolution medium increasing the rate of drug release. The particle size was shifted towards smaller diameters with increased concentration of sorbitan mono-oleate, up to 4.0% v/v, by use of a lower concentration of chitosan (1.0% w/v) and chitosan with low molecular weight. Rapid initial drug release (20-30% of the incorporated drug) was exhibited in all the prepared microspheres followed by slow release of the remaining amount of the drug. The release rate of the drug from the microspheres prepared from high molecular weight chitosan was slow in comparison with that prepared from medium and low molecular weight chitosan. High concentrations of sorbitan mono-oleate increased the rate of drug release.


An Ophiovirus isolated from lettuce with big-vein symptoms.
Big-vein is a widespread and damaging disease of lettuce, transmitted through soil by the chytrid fungus Olpidium brassicae, and generally supposed to be caused by Lettuce big-vein virus (LBVV; genus Varicosavirus). This virus is reported to have rigid rod-shaped particles, a divided double-stranded RNA genome, and one capsid protein of 48 kD, but has not been isolated or rigorously shown to cause the disease. We provide evidence that a totally different virus, here named Mirafiori lettuce virus (MiLV), is also very frequently associated with lettuce showing big-vein symptoms. MiLV was mechanically transmissible from lettuce to Chenopodium quinoa and to several other herbaceous test plants. The virus was partially purified, and an antiserum prepared, which did not react with LBVV particles in decoration tests. As reported for LBVV, MiLV was labile, soil-transmitted and had a single capsid protein of 48 kD, but the particles morphologically resembled those of ophioviruses, and like these, MiLV had a genome of three RNA segments approximately 8.5, 1.9 and 1.7 kb in size. MiLV preparations reacted strongly in Western blots and in ISEM with antiserum to Tulip mild mottle mosaic virus, an ophiovirus from Japan also apparently Olpidium-transmitted. They reacted weakly but clearly in Western blots with antiserum to Ranunculus white mottle virus, another ophiovirus. When lettuce seedlings were mechanically inoculated with crude or partially purified extracts from MiLV-infected test plants, many became systemically infected with MiLV and some developed big-vein symptoms. Such plants did not react in ELISA using an LBVV antiserum or an antiserum to tobacco stunt virus, and varicosavirus-like particles were never seen in them in the EM after negative staining. We conclude that MiLV is a hitherto undescribed virus assignable to the genus Ophiovirus. The cause or causes of lettuce big-vein disease and the properties of LBVV may need to be re-evaluated in light of our results.


In Vivo Assessment of Neuroinflammation in 4-Repeat Tauopathies.
Neuroinflammation has received growing interest as a therapeutic target in neurodegenerative disorders, including 4-repeat tauopathies. The aim of this cross-sectional study was to investigate 18 kDa translocator protein positron emission tomography (PET) as a biomarker for microglial activation in the 4-repeat tauopathies corticobasal degeneration and progressive supranuclear palsy. Specific binding of the 18 kDa translocator protein tracer 18 F-GE-180 was determined by serial PET during pharmacological depletion of microglia in a 4-repeat tau mouse model. The 18 kDa translocator protein PET was performed in 30 patients with corticobasal syndrome (68 ± 9 years, 16 women) and 14 patients with progressive supranuclear palsy (69 ± 9 years, 8 women), and 13 control subjects (70 ± 7 years, 7 women). Group comparisons and associations with parameters of disease progression were assessed by region-based and voxel-wise analyses. Tracer binding was significantly reduced after pharmacological depletion of microglia in 4-repeat tau mice. Elevated 18 kDa translocator protein labeling was observed in the subcortical brain areas of patients with corticobasal syndrome and progressive supranuclear palsy when compared with controls and was most pronounced in the globus pallidus internus, whereas only patients with corticobasal syndrome showed additionally elevated tracer binding in motor and supplemental motor areas. The 18 kDa translocator protein labeling was not correlated with parameters of disease progression in corticobasal syndrome and progressive supranuclear palsy but allowed sensitive detection in patients with 4-repeat tauopathies by a multiregion classifier. Our data indicate that 18 F-GE-180 PET detects microglial activation in the brain of patients with 4-repeat tauopathy, fitting to predilection sites of the phenotype. The 18 kDa translocator protein PET has a potential for monitoring neuroinflammation in 4-repeat tauopathies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


'Too many girls, too much dowry': son preference and daughter aversion in rural Tamil Nadu, India.
The southern Indian state of Tamil Nadu has experienced a dramatic decline in fertility, accompanied by a trend of increased son preference. This paper reports on findings from qualitative interviews with women in rural villages about their fertility decision-making. Specifically addressed are the reasons behind increasing son preference and the consequences of this change. Findings suggest that daughter aversion, fuelled primarily by the perceived economic burden of daughters due to the proliferation of dowry, is playing a larger role in fertility decision-making than son preference. The desire for a son is often trumped by the worry over having many daughters. Women use various means of controlling the sex of their children, which in this study appear to be primarily female infanticide. It is important to distinguish between son preference and daughter aversion and to examine repercussions of low fertility within this setting.


Hypertriglyceridemia-Related Pancreatitis In Patients With Type 2 Diabetes: Links And Risks.
Disturbances in glucose and lipid homeostasis are cardinal features of the metabolic syndrome that affect millions of people worldwide. These conditions have multi-organ impact, and while cardiovascular effects are usually the core for studies and preventive measures, other systems may also be affected, including the pancreas. Acute pancreatitis related to severe hypertriglyceridemia is an under-recognized condition that could lead to significant morbidity and mortality. Therefore, when suspected, prompt diagnosis and treatment should be initiated to cover the various aspects of this disorder. Though commonly known to be associated with excess of alcohol use, hypertriglyceridemia-related pancreatitis is particularly observed in diabetics, especially when uncontrolled. Here, we portray the possible mechanisms and clinical features that link type 2 diabetes, hypertriglyceridemia and pancreatitis, and discuss their health-related outcomes and the current and novel treatment options for this unique disease.


Acanthodian dental development and the origin of gnathostome dentitions.
Chondrichthyan dentitions are conventionally interpreted to reflect the ancestral gnathostome condition but interpretations of osteichthyan dental evolution in this light have proved unsuccessful, perhaps because chondrichthyan dentitions are equally specialized, or else evolved independently. Ischnacanthid acanthodians are stem-Chondrichthyes; as phylogenetic intermediates of osteichthyans and crown-chondrichthyans, the nature of their enigmatic dentition may inform homology and the ancestral gnathostome condition. Here we show that ischnacanthid marginal dentitions were statodont, composed of multicuspidate teeth added in distally diverging rows and through proximal superpositional replacement, while their symphyseal tooth whorls are comparable to chondrichthyan and osteichthyan counterparts. Ancestral state estimation indicates the presence of oral tubercles on the jaws of the gnathostome crown-ancestor; tooth whorls or tooth rows evolved independently in placoderms, osteichthyans, ischnacanthids, other acanthodians and crown-chondrichthyans. Crown-chondrichthyan dentitions are derived relative to the gnathostome crown-ancestor, which possessed a simple dentition and lacked a permanent dental lamina, which evolved independently in Chondrichthyes and Osteichthyes.


Efficient perceptron learning using constrained steepest descent.
An algorithm is proposed for training the single-layered perceptron. The algorithm follows successive steepest descent directions with respect to the perceptron cost function, taking care not to increase the number of misclassified patterns. The problem of finding these directions is stated as a quadratic programming task, to which a fast and effective solution is proposed. The resulting algorithm has no free parameters and therefore no heuristics are involved in its application. It is proved that the algorithm always converges in a finite number of steps. For linearly separable problems, it always finds a hyperplane that completely separates patterns belonging to different categories. Termination of the algorithm without separating all given patterns means that the presented set of patterns is indeed linearly inseparable. Thus the algorithm provides a natural criterion for linear separability. Compared to other state of the art algorithms, the proposed method exhibits substantially improved speed, as demonstrated in a number of demanding benchmark classification tasks.


Sulfurimonas xiamenensis sp. nov. and Sulfurimonas lithotrophica sp. nov., hydrogen- and sulfur-oxidizing chemolithoautotrophs within the Epsilonproteobacteria isolated from coastal sediments, and an emended description of the genus Sulfurimonas.
Strains 1-1NT and GYSZ_1T were isolated from marine sediments collected from the coast of Xiamen, PR China. Cells of the two strains were Gram-stain-negative, rod-shaped or slightly curved. Strain 1-1NT was non-motile, whereas strain GYSZ_1T was motile by means of one polar flagellum. The temperature, pH and salinity concentration ranges for growth of 1-1NT were 10-45 °C (optimum 30 °C), pH 5.5-8.0 (optimum 7.0) and 0-90 g l-1 NaCl (optimum 50 g l-1), while the growth of GYSZ_1T occurred at 4-45 °C (optimum 33 °C), pH 5.0-8.5 (optimum 6.5) and 5-90 g l-1 NaCl (optimum 20 g l-1). The two novel isolates were obligate chemolithoautotrophs capable of growth using hydrogen, thiosulfate, sulfide or elemental sulfur as the sole energy source, and nitrate, elemental sulfur or molecular oxygen as an electron acceptor. The major fatty acids of 1-1NT were C16 : 1ω7c, C16 : 0, C18 : 1ω7c and C18 : 0, while the predominant fatty acids of strain GYSZ_1T were C16 : 1ω7c, C16 : 0, C18 : 1ω7c and C14 : 0 3-OH. The DNA G+C contents of 1-1NT and GYSZ_1T were 34.5 mol% and 33.2 mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that 1-1NT and GYSZ_1T represented members of the genus Sulfurimonas, with the highest sequence similarities to Sulfurimonas crateris SN118T (97.4 %) and Sulfurimonas denitrificans DSM 1251T (94.7 %), respectively. However, 1-1NT and GYSZ_1T shared 95.5 % similarity of 16S rRNA gene sequences, representing different species of the genus Sulfurimonas. On the basis of the physiological properties and the results of phylogenetic analyses, including average nucleotide identity and in silico DNA-DNA hybridization values, strains 1-1NT and GYSZ_1T represent two novel species within the genus Sulfurimonas, for which the names Sulfurimonas xiamenensis sp. nov. and Sulfurimonas lithotrophica sp. nov. are proposed, with the type strains 1-1NT (=MCCC 1A14514T=KCTC 15851T) and GYSZ_1T (=MCCC 1A14739T=KCTC 15853T), respectively. Our results also justify an emended description of the genus Sulfurimonas.


Hospital nurses' and physicians' use of information sources during their production of discharge summaries: a cross-sectional study.
Hospital nurses' and physicians' production and exchange of accurate information between levels of care are crucial for ensuring safe and seamless care for patients in transition. We report on a study in which we explored hospital providers' use of information sources when they prepared discharge information for colleges in the community health-care sector. In this cross-sectional study, 510 nurses and 236 physicians responded through a questionnaire. Our findings show that nurses and physicians use different information sources in patient records when they produce their discharge summaries.


A gender-based score system predicts the clinical outcome of patients with early B-cell chronic lymphocytic leukemia.
To facilitate the development of a prognostic model for early B-cell chronic lymphocytic leukemia (CLL), the Gruppo Italiano Malattie EMatologiche Maligne dell'Adulto (GIMEMA) proposes its multi-institutional effort as a working model. In total, 1138 newly diagnosed Binet stage A patients managed over the last 10 years outside the setting of clinical trials according to a "wait and see" policy form the basis of the present study aimed at investigating prognostic variables affecting disease progression, a surrogate endpoint for overall survival. A 3-stage risk system, simply obtained by summing the variables that proved significant in the multivariate analysis (i.e. short lymphocyte doubling time, advanced Rai substage, high peripheral blood lymphocytosis), is proposed. Clear-cut differences in the 10 year progression-free survival (PFS) were observed among patients scoring 0 (low risk), 1 (intermediate risk), 2-3 (high risk): 67.8, 41.0 and 24.8%, respectively (P<0.0001). The results of the Medical Research Council (MRC) suggesting a better clinical outcome for females prompted us to verify such a gender-related difference within our prognostic categories. Because changes in PFS only reflected gender for patients scoring 0 (P=0.04), the following prognostic subgroups are proposed: (1) females scoring 0; (2) males scoring 0; (3) patients scoring 1-3 whatever gender (10 year PFS: 76.2, 61.4 and 37.8%; P<0.00001). Our long-term database provides an adequate patient sample to generate a generalized risk stratification model based on clinical data. The indolent clinical outcome of women with early CLL is also supported by the higher frequency of the immunoglobulin heavy-chain variable (IgVH) mutational status and lower proportion of 17p and 11q deletions found in such a patient subset in the MRC CLL4 trial.


Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein.
Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2-fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1-fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from the cocultures that had been incubated with LDL induced target endothelial cells (EC) to bind monocyte but not neutrophil-like cells. Media collected from cocultures that had been incubated with LDL-induced monocyte migration into the subendothelial space of other cocultures that had not been exposed to LDL. In contrast, media from separate cultures of EC or smooth muscle cells (SMC) containing equal number of EC or SMC compared to coculture and incubated with the same LDL did not induce monocyte migration when incubated with the target cocultures. High density lipoprotein HDL, when presented to cocultures together with LDL, reduced the increased monocyte transmigration by 91%. Virtually all of the HDL-mediated inhibition was accounted for by the HDL2 subfraction. HDL3 was essentially without effect. Apolipoprotein AI was also ineffective in preventing monocyte transmigration while phosphatidylcholine liposomes were as effective as HDL2 suggesting that lipid components of HDL2 may have been responsible for its action. Preincubating LDL with beta-carotene or with alpha-tocopherol did not reduce monocyte migration. However, pretreatment of LDL with probucol or pretreatment of the cocultures with probucol, beta-carotene, or alpha-tocopherol before the addition of LDL prevented the LDL-induced monocyte transmigration. Addition of HDL or probucol to LDL after the exposure to cocultures did not prevent the modified LDL from inducing monocyte transmigration in fresh cocultures. We conclude that cocultures of human aortic cells can modify LDL even in the presence of serum, resulting in the induction of MCP-1, and that HDL and antioxidants prevent the LDL induced monocyte transmigration.


Structural and genetic assessment of the ABCA4-associated optical gap phenotype.
To investigate the developmental stages and genetic etiology of the optical gap phenotype in recessive Stargardt disease (STGD1). Single and longitudinal data points from 15 patients, including four sibling pairs, exhibiting an optical gap phenotype on spectral-domain optical coherence tomography (SD-OCT) with confirmed disease-causing ABCA4 alleles were retrospectively analyzed. Fundus images with corresponding SD-OCT scans were collected with a confocal scanning laser ophthalmoscope. Structural phenotypes were assigned to three developmental stages according to SD-OCT. The ABCA4 gene was screened in all patients. At least two disease-causing ABCA4 variants where identified in each patient; all except one (91%) were compound heterozygous for the p.G1961E mutation. All patients exhibited structural findings on SD-OCT that grouped into three progressive developmental stages over several years. Stage 1 was characterized by mild disruptions of the ellipsoid zone (EZ) band over the fovea. Stage 2 was a progressive expansion of the EZ band loss resulting in an empty lesion devoid of photoreceptors. Stage 3 observed a structural collapse of the inner retinal layers into the optical gap space leading to involvement and atrophy of the RPE thereafter. The optical gap phenotype in STGD1 can be structurally divided into three progressive stages spanning several years. This particular phenotype also appears to be highly associated with the p.G1961E mutation of ABCA4. Taken together, it appears that a focal loss of photoreceptors sequentially precedes RPE dysfunction in the early development of ABCA4-associated optical gap lesions.


A spatial method to calculate small-scale fisheries effort in data poor scenarios.
To gauge the collateral impacts of fishing we must know where fishing boats operate and how much they fish. Although small-scale fisheries land approximately the same amount of fish for human consumption as industrial fleets globally, methods of estimating their fishing effort are comparatively poor. We present an accessible, spatial method of calculating the effort of small-scale fisheries based on two simple measures that are available, or at least easily estimated, in even the most data-poor fisheries: the number of boats and the local coastal human population. We illustrate the method using a small-scale fisheries case study from the Gulf of California, Mexico, and show that our measure of Predicted Fishing Effort (PFE), measured as the number of boats operating in a given area per day adjusted by the number of people in local coastal populations, can accurately predict fisheries landings in the Gulf. Comparing our values of PFE to commercial fishery landings throughout the Gulf also indicates that the current number of small-scale fishing boats in the Gulf is approximately double what is required to land theoretical maximum fish biomass. Our method is fishery-type independent and can be used to quantitatively evaluate the efficacy of growth in small-scale fisheries. This new method provides an important first step towards estimating the fishing effort of small-scale fleets globally.


Intervention with substance-abusing mothers: Are there rural-urban differences?
The purpose of this study was to examine rural-urban differences among substance-abusing mothers enrolled in the Parent-Child Assistance Program (PCAP) from 1998 to 2008 in Washington State. This was a longitudinal study utilizing PCAP data reports of 773 women enrolled from 1998 to 2008. Differences across urban-rural PCAP participants were examined. Rural participants were more likely to report alcohol use and binge drinking at program intake and at the 3-year program exit. In addition, throughout the program, rural women were less likely to complete outpatient substance abuse treatment compared to urban participants. Rural women also used less services during the last year including alcohol/drug support and mental health provider services. Findings are troubling when we consider that at program exit, rural participants also reported higher use of alcohol and more suicidal thoughts than those residing in urban areas. Data presented indicate there are important differences between urban and rural residing participants. Findings highlight the importance of considering the barriers that rural or remote locations might create. Identifying community-specific needs of substance abusing pregnant or parenting women in both rural and urban settings is crucial for the successful development and improvement of treatment and intervention programs for this vulnerable population of women. (Am J Addict 2014;XX:1-9).


A new species of Fejervarya Bolkay, 1915 (Anura: Dicroglossidae) from the northern Western Ghats parts of Maharashtra, India.
In the recent past the systematic position and taxonomy of genus Fejervarya, Bolkay is undergoing changes in its systematic position due to fairly good amount of phylogenetic resolution, cryptic morphological characters and lack of systematic sampling for phylogenetic studies across the range of distribution. In our sampling in the northern Western Ghats, we encountered a new lineage sister to the phylogenetic cluster which comprises the 'Rufescens complex'. This new lineage is described here as new species Fejervarya marathi sp. nov. based on distinctness in a combination of morphological characters, genetic distance and geography. The problems in morphological groupings for the Fejervarya frogs of the Western Ghats in the recent studies are discussed with the sub-clade composition based on geography in the phylogenetic tree.


The human complement regulatory factor-H-like protein 1, which represents a truncated form of factor H, displays cell-attachment activity.
Complement factor H (FH) and factor-H-like protein 1 (FHL-1) are human plasma proteins with regulatory functions in the alternative pathway of complement activation. FH and FHL-1 are organized in repetitive elements termed short consensus repeats (SCRs) and the seven SCRs of FHL-1 are identical with the N-terminal domain of the 20 SCRs of FH. The fourth SCR of both proteins (SCR 4) includes the sequence Arg-Gly-Asp (RGD), a motif that is responsible for the major adhesive activity of matrix proteins like fibronectin. A synthetic hexapeptide with the sequence ERGDAV derived from the RGD domain of FH/FHL-1 interferes with cell attachment to a fibronectin matrix. Although the identical motif is present in both FH and FHL-1, only FHL-1 acts as a matrix for cell spreading and attachment, thus the two proteins differ in function. The adhesive activity of FHL-1 is localized to the RGD-containing SCR 4 by the use of recombinant fragments. All three analysed anchorage-dependent cell lines (CCl64, C32 and MRC-5) adhere to an FHL-1 matrix. The use of synthetic peptides in competition assays, on either FHL-1-derived or fibronectin matrices, shows that the cellular receptors binding to the FH/FHL-1-derived RGD motif are related to or identical with integrin receptors which interact with fibronectin. The identification of a functional adhesive domain in the FH/FHL-1 sequence demonstrates, at least for FHL-1, a role in cell attachment and adhesion.


Plastic Surgery in the late 1920s. Three points of view.
A study of three of the books of the late 1920s--Plastic Surgery of the Head, Face and Neck, by H. L. N. Hunt; La Chirurgie Esthetique, by Madame la Dr. Noel; and The Making of a Beautiful Face, by J. Howard Crum--reveals the authors' enthusiasm for facial reconstructive surgery and their variety of approaches to the subject.


Nebkha development and sediment supply.
This study examines the role of sediment supply in controlling the formation and the spatial patterns of nebkha, numbers and sizes, present in foredunes fronting coastal dunefields of the arid northwest African and the Canary Islands coasts. Sediment supply is estimated qualitatively and quantitatively by various measures, and the number and size of nebkhas are obtained on a range of beach-dune systems. In the case of the Canary Islands, LiDAR data and orthophotos with high spatial resolution (0.25 m) are used to measure sediment supply/activity, nebkha numbers and sizes, and vegetation variables, whereas data availability is less on the African coast. Results show that sediment supply exerts a major control on nebkha development such that as sediment supply increases, the number of coastal nebkha decreases, and the size of individual plants/nebkha increases. Once sediment supply is large, nebkha can only form on the immediate backshore if space is available, and a point is reached when the sediment supply is so large that nebkha do not, or cannot form. The data presented here provide two indicators which could be applicable to other dune systems. Firstly, by estimating the number of nebkha and the vegetation cover, the degree of aeolian sedimentary activity or sediment supply might be estimated. Secondly, the type of aeolian landform present provides a qualitative indication of sediment supply and aeolian activity.


Impaired prostaglandin E(2)/prostaglandin I(2) receptor-G(s) protein interactions in isolated renal resistance arterioles of spontaneously hypertensive rats.
The protective effect of vasodilator agents linked to the cAMP pathway is less effective for buffering the vasoconstrictor effect of angiotensin II in young animals with genetic hypertension. To determine the underlying cellular mechanism, experiments were performed on freshly isolated preglomerular resistance arterioles obtained from kidneys of 7-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Specific high-affinity saturable binding of (3)H-prostaglandin (PG) E(2) revealed 1 receptor class in renal microvessels; PGE(2) receptor density was similar in SHR and WKY (106 versus 115 fmol/mg; P>0.8), as was receptor affinity (3.6 versus 3.5 nmol/L; P>0.7). Basal cAMP activity was similar in renal arterioles from SHR and WKY. A major finding was that PGE(2), PGI(2), and isoproterenol produced weaker stimulation of cAMP formation in arteriolar cells of SHR (P<0.02). In contrast, GTPgammas and forskolin stimulated cAMP generation to a similar degree in both rat strains, which suggests normal adenylate cyclase activity in hypertension-prone SHR. Immunoblots revealed the presence of 3 classes of G proteins (G(s), G(i), and G(q)) in preglomerular arterioles. The relative amounts of discernible G-protein alpha-subunits in renal resistance vessels did not differ between SHR and WKY. These results extend previous in vivo studies of abnormal renal vascular reactivity in SHR and more directly localize defective coupling of the prostaglandin and beta-adrenergic receptors to a stimulatory G protein and cAMP production in freshly isolated preglomerular arteriolar cells of young SHR. This dysfunction may be due to an abnormal interaction between prostaglandin receptors and G(s) protein that leads to inefficient coupling of initiating steps in the cAMP-protein kinase A cascade during the development of hypertension.


Oxidative Stress and NLRP3-Inflammasome Activity as Significant Drivers of Diabetic Cardiovascular Complications: Therapeutic Implications.
It is now increasingly appreciated that inflammation is not limited to the control of pathogens by the host, but rather that sterile inflammation which occurs in the absence of viral or bacterial pathogens, accompanies numerous disease states, none more so than the complications that arise as a result of hyperglycaemia. Individuals with type 1 or type 2 diabetes mellitus (T1D, T2D) are at increased risk of developing cardiac and vascular complications. Glucose and blood pressure lowering therapies have not stopped the advance of these morbidities that often lead to fatal heart attacks and/or stroke. A unifying mechanism of hyperglycemia-induced cellular damage was initially proposed to link elevated blood glucose levels with oxidative stress and the dysregulation of metabolic pathways. Pre-clinical evidence has, in most cases, supported this notion. However, therapeutic strategies to lessen oxidative stress in clinical trials has not proved efficacious, most likely due to indiscriminate targeting by antioxidants such as vitamins. Recent evidence now suggests that oxidative stress is a major driver of inflammation and vice versa, with the latest findings suggesting not only a key role for inflammatory pathways underpinning metabolic and haemodynamic dysfunction in diabetes, but furthermore that these perturbations are driven by activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. This review will address these latest findings with an aim of highlighting the interconnectivity between oxidative stress, NLRP3 activation and inflammation as it pertains to cardiac and vascular injury sustained by diabetes. Current therapeutic strategies to lessen both oxidative stress and inflammation will be emphasized. This will be placed in the context of improving the burden of these diabetic complications.


Rete Testis Invasion Is Consistent With Pathologic Stage T1 in Germ Cell Tumors.
Rete testis invasion by germ cell tumors is frequently concomitant with lymphovascular or spermatic cord invasion (LVI/SCI); independent implications for staging are uncertain. In total, 171 seminomas and 178 nonseminomatous germ cell tumors (NSGCTs; 46 had 1%-60% seminoma component) came from five institutions. Metastatic status at presentation, as a proxy for severity, was available for all; relapse data were unavailable for 152. Rete direct invasion (ReteD) and rete pagetoid spread (ReteP) were assessed. ReteP and ReteD were more frequent in seminoma than NSGCT. In seminoma, tumor size bifurcated at 3 cm or more or less than 3 cm predicted metastatic status. Tumors with ReteP or ReteD did not differ in size from those without invasions but were less than with LVI/SCI; metastatic status or relapse did not show differences. In NSGCT, ReteP/ReteD did not correlate with size, metastatic status, or relapse. Findings support retaining American Joint Committee for Cancer pathologic T1 stage designation for rete testis invasion and pT1a/pT1b substaging of seminoma.


Financial Toxicity Monitoring in a Randomized Controlled Trial of Patient-Reported Outcomes During Cancer Treatment (Alliance AFT-39).
Financial toxicity (FT) affects 20% of cancer survivors and is associated with poor clinical outcomes. No large-scale programs have been implemented to mitigate FT. We evaluated the effect of monthly FT screening as part of a larger patient-reported outcomes (PROs) digital monitoring intervention. PRO-TECT (AFT-39) is a cluster-randomized trial of patients undergoing systemic therapy for metastatic cancer. Practices were randomly assigned 1:1 to digital symptom monitoring (PRO practices) or usual care (control practices). Digital monitoring consisted of between-visit online or automated telephone patient surveys about symptoms, functioning, and FT (single-item screening question from Functional Assessment of Chronic Illness Therapy-COmprehensive Score for financial Toxicity) for up to 1 year, with automated alerts sent to practice nurses for concerning survey scores. Clinical team actions in response to alerts were not mandated. The primary outcome of this planned secondary analysis was development or worsening of financial difficulties, assessed via the European Organisation for Research and Treatment of Cancer QLQ-C30 financial difficulties measure, at any time compared with baseline. A randomly selected subset of patients and nurses were interviewed about their experiences with the intervention. One thousand one hundred ninety-one patients were enrolled (593 PRO; 598 control) at 52 US community oncology practices. Overall, 30.2% of patients treated at practices that received the FT screening intervention developed, or experienced worsening of, financial difficulties, compared with 39.0% treated at control practices (P = .004). Patients and nurses interviewed stated that FT screening identified patients for financial counseling who otherwise would be reluctant to seek, or unaware of the availability of, assistance. In this report of a secondary outcome from a randomized clinical trial, FT screening as part of routine digital patient monitoring with PROs reduced the development, or worsening, of financial difficulties among patients undergoing systemic cancer therapy.


Uterine factors and delayed implantation in macropodid marsupials.
Local factors controlling uterine functions in macropodids are reviewed and the components of uterine fluids are examined. Activation of the diapausing blastocyst and subsequent development of the expanding vesicle are associated with a changing uterine environment. Concentrations of proteins, calcium and zinc in uterine exudates alter during gestation; the changes appear to be related both to the stage of development of the conceptus and to the hormonal milieu. In addition the endometrium itself may have an active endocrine role in the control of development. Cation concentrations in uterine exudates of the quokka (Setonix brachyurus) are not clearly related to events leading to blastocyst activation.


Impact of combined mTOR and MEK inhibition in uveal melanoma is driven by tumor genotype.
Uveal melanomas possess activation of the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathways. MAPK activation occurs via somatic mutations in the heterotrimeric G protein subunits GNAQ and GNA11 for over 70% of tumors and less frequently via V600E BRAF mutations. In this report, we describe the impact of dual pathway inhibition upon uveal melanoma cell lines with the MEK inhibitor selumetinib (AZD6244/ARRY-142886) and the ATP-competitive mTOR kinase inhibitor AZD8055. While synergistic reductions in cell viability were observed with AZD8055/selumetinib in both BRAF and GNAQ mutant cell lines, apoptosis was preferentially induced in BRAF mutant cells only. In vitro apoptosis assay results were predictive of in vivo drug efficacy as tumor regressions were observed only in a BRAF mutant xenograft model, but not GNAQ mutant model. We went on to discover that GNAQ promotes relative resistance to AZD8055/selumetinib-induced apoptosis in GNAQ mutant cells. For BRAF mutant cells, both AKT and 4E-BP1 phosphorylation were modulated by the combination; however, decreasing AKT phosphorylation alone was not sufficient and decreasing 4E-BP1 phosphorylation was not required for apoptosis. Instead, cooperative mTOR complex 2 (mTORC2) and MEK inhibition resulting in downregulation of the pro-survival protein MCL-1 was found to be critical for combination-induced apoptosis. These results suggest that the clinical efficacy of combined MEK and mTOR kinase inhibition will be determined by tumor genotype, and that BRAF mutant malignancies will be particularly susceptible to this strategy.


Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus at High Risk for Foot Ulcers.
To study the prevalence of cardiac autonomic neuropathy (CAN) in patients with Type 2 diabetes mellitus at high risk for foot ulcers. We screened patients attending diabetic clinic for identifying patients at high risk for foot ulcers. Those with foot risk category 1, 2 and 3 as per criteria of Foot Care Interest Group were subjected to battery of cardiovascular autonomic reflex tests. Those with one abnormal test were termed as probable CAN and those with two abnormal tests as definite CAN. Those with postural fall in blood pressure with one other abnormal test were termed to have advanced CAN. A total of 74 patients were recruited in the study. The prevalence of abnormal cardiovascular autonomic reflex test was sustained hand grip 81%, E/I ratio 66.2%, 30:15 ratio 28.3% and orthostatic hypotension 13.5%. The prevalence of possible CAN was 31.0% (23/74) and definite CAN was 66.2% (49/74). Ten patients had advanced CAN. There was no observable difference in presence of probable or definite CAN in three risk category for foot ulcers. We found a high prevalence of CAN in subgroup of diabetic patients at increased risk for foot ulcer.


[The role of the psychiatric nurse--oppressed and oppressor].
This work aims at analysing the role of the psychiatric nurse in assisting the hospitalized mentally ill, viewing that practice not in itself, but as a social and historical one. An empirical research was done in two psychiatric hospitals in two stages: field observations and interviews with nurses. It was checked that the emphasis the role of the psychiatric nurse is not in therapeutic relationship but in administratives activities and that the relationship the members of the nursing team have with the patient is authoritarian and reproduce the authoritarism of the institutions. Thus the precepts of school that says the chief role of the nurse is the therapeutic relationship seem to have an ideological character. That makes us suggest that the teaching-learning relationships must be established on a praxis basis.


Identification of low-molecular-weight compounds inhibiting growth of corynebacteria: potential lead compounds for antibiotics.
The bacterial genus Corynebacteria contains several pathogenic species that cause diseases such as diphtheria in humans and "cheesy gland" in goats and sheep. Thus, identifying new therapeutic targets to treat Corynebacteria infections is both medically and economically important. CG2496, a functionally uncharacterized protein from Corynebacterium glutamicum, was evaluated using an NMR ligand-affinity screen. A total of 11 compounds from a library of 460 biologically active compounds were shown to selectively bind CG2496 in a highly conserved region of the protein. The best binder was identified to be methiothepin (KD =54 ± 19 µM), an FDA-approved serotonin receptor antagonist. Methiothepin was also shown to inhibit the growth of C. glutamicum, but not bacteria that lack CG2496 homologs. Our results suggest that CG2496 is a novel therapeutic target and methiothepin is a potential lead compound or structural scaffold for developing new antibiotics specifically targeting Corynebacteria.


The Heading Weight Function: A Novel LiDAR-Based Local Planner for Nonholonomic Mobile Robots.
In this paper, we present a novel method for obstacle avoidance designed for a nonholonomic mobile robot. The method relies on light detection and ranging (LiDAR) readings, which are mapped into a polar coordinate system. Obstacles are taken into consideration when they are within a predefined radius from the robot. A central part of the approach is a new Heading Weight Function (HWF), in which the beams within the aperture angle of the LiDAR are virtually weighted in order to generate the best trajectory candidate for the robot. The HWF is designed to find a solution also in the case of a local-minima situation. The function is coupled with the robot's controller in order to provide both linear and angular velocities. We tested the method both by simulations in a digital environment with a range of different static obstacles, and in a real, experimental environment including static and dynamic obstacles. The results showed that when utilizing the novel HWF, the robot was able to navigate safely toward the target while avoiding all obstacles included in the tests. Our findings thus show that it is possible for a robot to navigate safely in a populated environment using this method, and that sufficient efficiency in navigation may be obtained without basing the method on a global planner. This is particularly promising for navigation challenges occurring in unknown environments where models of the world cannot be obtained.


Field test of thermally activated persulfate for remediation of PFASs co-contaminated with chlorinated aliphatic hydrocarbons in groundwater.
The co-occurrence of per- and polyfluoroalkyl substances (PFASs) and chlorinated aliphatic hydrocarbons (CAHs) in groundwater has drawn increased attention in recent years. No studies have been conducted concerning the oxidative degradation of PFASs and/or CAHs by in situ thermally activated persulfate (TAP) in groundwater, primarily due to the difficulty in cost-effectively achieving the desired temperature in the field. In this study, the effects and mechanisms of PFASs degradation by in situ TAP at a site with PFASs and CAHs co-contaminants were investigated. The target temperature of 40.0-70.0 °C was achieved in groundwater, and persulfate was effectively distributed in the demonstration area - the combination of which ensured the degradation of PFASs and CAHs co-contaminants by in situ TAP. It was demonstrated that the reductions of perfluoroalkyl carboxylic acids (PFCAs) concentration in all monitoring wells were in the range of 43.7 %-66.0 % by in situ TAP compared to those maximum rebound values in groundwater, whereas no effective perfluoroalkane sulfonic acids (PFSAs) degradation was observed. The conversion of perfluoroalkyl acids (PFAAs) precursors was one of the main factors leading to the increase in PFCAs concentrations in groundwater during in situ TAP. CAHs were effectively degraded in most monitoring wells, and furthermore, no inhibitory effects of CAHs and Cl- on the degradation of PFASs were observed due to the presence of sufficient persulfate. Additionally, there were significant increases in SO42- concentrations and reductions of pH values in groundwater due to in situ TAP, warranting their long-term monitoring in groundwater. The integrated field and laboratory investigations demonstrated that the reductions in PFCAs and CAHs concentrations can be achieved by the oxidative degradation of in situ TAP.


Managing photons for quantum information processing.
We study distinguishing information in the context of photonic quantum interference tailored for practical implementations of quantum information processing schemes. In particular, we consider the character of single-photon states optimized for multiple-source interference experiments and for experiments relying on Bell-state measurement and arrive at specific design criteria for photons produced by parametric down-conversion. Such states can be realistically implemented with available technology. We describe a novel method for characterizing the mode structure of single photons, and demonstrate it in the context of coherent light.


Implanted electroenzymatic glucose sensors.
The advent of electrochemical sensors for intermittent sampling of blood gases and hydrogen ions in the clinic, intensive care, and surgical units has revolutionized diagnostic and critical care medical technics. The use of electrochemical sensors for continuous transcutaneous monitoring of blood gases is further enhancing the medical surveillance of patients. The more recent introduction of glucose and other electroenzymatic sensors has stimulated broad research in the development of metabolic monitoring. For the present research, the glucose sensor widely used for the rapid specific micro-analysis of whole blood and plasma is explored for possible use as an in vivo intravascular or tissue-implanted sensor. This sensor is based on the polarographic measurement of hydrogen peroxide generated by glucose oxidase (EC 126.96.36.199) held between two membranes. The first membrane allows the diffusion of glucose, ions, and many other small molecules, while the second membrane allows the diffusion of the glucose-generated hydrogen peroxide to the platinum surface, but excludes ascorbic acid, bilirubin, and uric acid. Such sensors respond rapidly and specifically when acutely implanted subcutaneously in cats and dogs. They function well as glucose-sensor-tipped venous catheters. One sensor was repeatedly used for in vitro polarograms, subcutaneous and blood glucose monitoring, over a period of ten months, with storage in the cold between uses, with the complete retention of its response characteristics.


Comparative study of physicochemical, nutritional, phytochemical, and sensory properties of bread with plantain and soy flours partly replacing wheat flour.
Plantain flour (PLF) and soy flour (SF) were used to substitute wheat flour (10% and 20% w/w) in composite bread. Physicochemical, phytochemical, and sensory properties were investigated. Partial substitution by PLF significantly increased (p < .05) starch, amylose, ascorbic acid, and potassium content in bread samples. In contrast, a significant improvement (p < .05) in protein, fat, amylopectin, and calcium content was observed with SF substitution. Composite bread with PLF and SF together lowered the hydrolysis index (HI) and glycemic index (GI) as compared with whole wheat flour. The molar phytate to minerals (iron, zinc, and calcium) ratio in all composite loaves was lower than reported critical values, except for phytate to iron. Significant differences (p < .05) were found in color, specific volume, and texture characteristics of loaves made from partial substitution with PLF and SF. Sensory evaluation revealed that bread with 10% PLF exhibited better scores for appearance and willingness to pay than the control. In contrast, SF negatively affected (p < .05) the appearance, texture, color, overall acceptance, and willingness to pay. The trade-off analysis indicated that PLF can be utilized to produce bread that meets consumers' demands, while incorporating SF as an alternative high-nutrient density bread will be beneficial to health.


Arterialized venous bicarbonate is associated with lower bone mineral density and an increased rate of bone loss in older men and women.
Higher dietary net acid loads have been associated with increased bone resorption, reduced bone mineral density (BMD), and increased fracture risk. The objective was to compare bicarbonate (HCO3) measured in arterialized venous blood samples to skeletal outcomes. Arterialized venous samples collected from participants in the Health, Aging and Body Composition (Health ABC) Study were compared to BMD and rate of bone loss. The setting was a community-based observational cohort. A total of 2287 men and women age 74 ± 3 years participated. Arterialized venous blood was obtained at the year 3 study visit and analyzed for pH and pCO2. HCO3 was determined using the Henderson-Hasselbalch equation. BMD was measured at the hip by dual-energy x-ray absorptiometry at the year 1 (baseline) and year 3 study visits. Plasma HCO3 was positively associated with BMD at both year 1 (P = .001) and year 3 (P = .001) in models adjusted for age, race, sex, clinic site, smoking, weight, and estimated glomerular filtration rate. Plasma HCO3 was inversely associated with rate of bone loss at the total hip over the 2.1 ± 0.3 (mean ± SD) years between the two bone density measurements (P < .001). Across quartiles of plasma HCO3, the rate of change in BMD over the 2.1 years ranged from a loss of 0.72%/y in the lowest quartile to a gain of 0.15%/y in the highest quartile of HCO3. Arterialized plasma HCO3 was associated positively with cross-sectional BMD and inversely with the rate of bone loss, implying that systemic acid-base status is an important determinant of skeletal health during aging. Ongoing bone loss was linearly related to arterialized HCO3, even after adjustment for age and renal function. Further research in this area may have major public health implications because reducing dietary net acid load is possible through dietary intervention or through supplementation with alkaline potassium compounds.


Improved prediction of RNA secondary structure by integrating the free energy model with restraints derived from experimental probing data.
Recently, several experimental techniques have emerged for probing RNA structures based on high-throughput sequencing. However, most secondary structure prediction tools that incorporate probing data are designed and optimized for particular types of experiments. For example, RNAstructure-Fold is optimized for SHAPE data, while SeqFold is optimized for PARS data. Here, we report a new RNA secondary structure prediction method, restrained MaxExpect (RME), which can incorporate multiple types of experimental probing data and is based on a free energy model and an MEA (maximizing expected accuracy) algorithm. We first demonstrated that RME substantially improved secondary structure prediction with perfect restraints (base pair information of known structures). Next, we collected structure-probing data from diverse experiments (e.g. SHAPE, PARS and DMS-seq) and transformed them into a unified set of pairing probabilities with a posterior probabilistic model. By using the probability scores as restraints in RME, we compared its secondary structure prediction performance with two other well-known tools, RNAstructure-Fold (based on a free energy minimization algorithm) and SeqFold (based on a sampling algorithm). For SHAPE data, RME and RNAstructure-Fold performed better than SeqFold, because they markedly altered the energy model with the experimental restraints. For high-throughput data (e.g. PARS and DMS-seq) with lower probing efficiency, the secondary structure prediction performances of the tested tools were comparable, with performance improvements for only a portion of the tested RNAs. However, when the effects of tertiary structure and protein interactions were removed, RME showed the highest prediction accuracy in the DMS-accessible regions by incorporating in vivo DMS-seq data.


Durum Wheat Stress Tolerance Induced by Endophyte Pantoea agglomerans with Genes Contributing to Plant Functions and Secondary Metabolite Arsenal.
In the arid region Bou-Saâda at the South of Algeria, durum wheat Triticum durum L. cv Waha production is severely threatened by abiotic stresses, mainly drought and salinity. Plant growth-promoting rhizobacteria (PGPR) hold promising prospects towards sustainable and environmentally-friendly agriculture. Using habitat-adapted symbiosis strategy, the PGPR Pantoea agglomerans strain Pa was recovered from wheat roots sampled in Bou-Saâda, conferred alleviation of salt stress in durum wheat plants and allowed considerable growth in this unhostile environment. Strain Pa showed growth up to 35 °C temperature, 5-10 pH range, and up to 30% polyethylene glycol (PEG), as well as 1 M salt concentration tolerance. Pa strain displayed pertinent plant growth promotion (PGP) features (direct and indirect) such as hormone auxin biosynthesis, production of 1-aminocyclopropane-1-carboxylate (ACC) deaminase, and ammonia and phosphate solubilization. PGPR features were stable over wide salt concentrations (0-400 mM). Pa strain was also able to survive in seeds, in the non-sterile and sterile wheat rhizosphere, and was shown to have an endophytic life style. Phylogenomic analysis of strain Pa indicated that Pantoea genus suffers taxonomic imprecision which blurs species delimitation and may have impacted their practical use as biofertilizers. When applied to plants, strain Pa promoted considerable growth of wheat seedlings, high chlorophyll content, lower accumulation of proline, and favored K+ accumulation in the inoculated plants when compared to Na+ in control non-inoculated plants. Metabolomic profiling of strain Pa under one strain many compounds (OSMAC) conditions revealed a wide diversity of secondary metabolites (SM) with interesting salt stress alleviation and PGP activities. All these findings strongly promote the implementation of Pantoea agglomerans strain Pa as an efficient biofertilizer in wheat plants culture in arid and salinity-impacted regions.


Comparison of berry juice concentrates and pomaces and alternative plant proteins to produce spray dried protein-polyphenol food ingredients.
Spray dried functional food ingredients were prepared by complexing alternative plant protein sources - buckwheat flour alone or blended with pea and rice proteins, with polyphenol sources - blueberry, cranberry and purple muscadine grape extracts from juice concentrates and pomaces - to create colloidal aggregate powders. When fruit pomaces (rather than juice concentrates) were used as polyphenol resources, solid recovery was significantly enhanced, especially for matrices made with pea protein, buckwheat flour or pea-buckwheat blends (over two fold for pea protein-berry pomace aggregates). Polyphenol content and DPPH radical scavenging capacity were, in general, significantly greater for pomace-derived protein-polyphenol aggregates compared to those made with juice concentrates. In particular, the particles produced with muscadine grape pomace presented the highest (p < 0.05) phenolic content (147.3-174.3 mg g-1, 19.4-20.4 mg g-1 and 16.3-21.4 mg g-1 for total phenolic content, anthocyanins and proanthocyanidins respectively), and antioxidant activity (408.9-423.3 μmol TE per g) as well as good spray drying yield (38.6-63.4%). Buckwheat flour, despite its relatively low protein content (13.7%) relative to pea and rice protein isolates (84% and 89%, respectively) still demonstrated high capacity for sorption of flavonoid phytoactive compounds from the berry fruits. These results suggest an efficient plant-based approach to produce value-added protein-polyphenol aggregates with broad utility as healthy food ingredients.


[Selection of the approach to conducting nephrectomy in donors- patients' relatives].
The comparative assessment of two types of an approach (lumbotomy and thoracolumbotomy) for the performance of nephrectomy in 99 related donors was carried out. Lumbotomy was performed in 47 donors, the complications developed in 6 (12.8%) of them, including the severe ones--in 4 (8.5%). Duration of hospital stay was in average 27.26 days. Thoracolumbotomy was performed in 52 donors, the complications developed in 14 (26.9%) of them, including a severe one--in 1 (1.9%). Duration of hospital stay of the donors was in average 16 days.


Inhibition of atrial wall stretch-induced cardiac hormone secretion by lavendustin A, a potent tyrosine kinase inhibitor.
The cellular processes linking mechanical wall stretch to atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) secretion from the heart are unclear. In the present study, a paced perfused rat heart preparation was used to study the signaling mechanisms of atrial wall stretch-induced secretion of ANP and BNP. Vehicle or drugs were infused into the perfusate for 40 min and right atrial wall stretch was superimposed for 10 min after 25-min drug infusions by elevating the level of the pulmonary artery cannula tip. Lavendustin A, a potent inhibitor of protein tyrosine kinases, at the concentrations of 0.5 and 1.3 microM decreased atrial wall stretch-induced ANP secretion (53% and 68%, respectively, P < 0.001) in the perfused rat heart preparation, whereas no difference in the hemodynamic variables (heart rate, contractile force and perfusion pressure) were noted between groups. Lavendustin A also completely abolished the wall stretch-induced secretion of BNP. Several other protein kinase inhibitors including staurosporine (protein kinase C inhibitor), ML-9 (myosin light chain kinase inhibitor), KN-62 (Ca2+/calmodulin-dependent protein kinase II inhibitor) and H-89 (protein kinase A inhibitor) had no significant effect on atrial wall stretch-stimulated ANP secretion. In a separate series of experiments, in which the right atria were stretched for 2 h, administration of lavendustin A (1 microM) but not staurosporine (30 nM) significantly decreased sustained wall stretch-induced ANP secretion. Okadaic acid, a potent protein phosphatase A2 (PPA2) and PP1 inhibitor, at the concentration of 100 nM had no effect on basal ANP secretion but significantly accelerated the ANP secretory response to atrial wall stretch (P < 0.05). In conclusion, the findings that inhibitors of protein tyrosine kinase and protein phosphatase selectively modulated atrial wall stretch-induced ANP secretion suggest a new mechanism involving endogenous protein tyrosine activity in the regulation of natriuretic peptide exocytosis from cardiac myocytes.


"Preterm birth risk, me?" Women risk perception about premature delivery - a qualitative analysis.
Risk perception is based on collective indicators, but it is influenced by the individual's self-perception of his health-disease process. This study aims to investigate the risk perception of pregnant women who were identified as high-risk for premature birth and to seek strategies for better management of such cases. This is a cross-sectional study where women who had completed their participation in P5 trial were contacted and invited to answer a structured questionnaire with open questions. Data were collected by telephone and analyzed using thematic analysis. The analysis categories were defined, and all the answers were reviewed, categorized, grouped, and a descriptive summary was prepared. Two hundred eight Brazilian women have participated. Three categories were identified: (1) Risk perception mediated by health professionals; (2) Self-perception of risk through personal experiences and relationships; (3) Perception of treatment success. After receiving an explanation from a health professional about short cervix and premature birth, women understood the risk of premature delivery, recognizing the importance of early diagnosis to prevent premature birth. Unsuccessful previous experiences in prior pregnancies influenced women's risk perception. Patients believed in the success of the treatment performed, placing their hopes on the treatment even without research guarantees about benefits. Pregnant women's risk perception regarding prematurity is based partly on personal and family experiences but mainly on information given by health professionals. The risk perception about preterm birth may contribute to healthy pregnancy, guiding necessary interventions and preventing adverse outcomes. Prevention studies on prematurity should thus focus on neonatal outcomes.


Plasminogen II accumulates five times faster than plasminogen I at the site of a balloon de-endothelializing injury in vivo to the rabbit aorta: comparison with other hemostatic proteins.
In the rabbit blood stream, plasminogen circulates as two glycoforms, plasminogen I (PLG-I) and plasminogen II (PLG-II), in a molar ratio of 1:2.2. To compare their relative behaviors toward a site of vascular injury, radiolabeled samples of PLG-I and PLG-II were coinjected intravenously into NZW rabbits before inducing a de-endothelializing (balloon catheter) injury to the thoracic aorta. At various times (5 to 60 minutes) after injury, each rabbit was anesthetized and exsanguinated, the aorta was excised, and the radioactivity per centimeters squared of aortic intima-media (IM) was measured relative to that of blood at exsanguination. The uptake of iodine 125-labeled PLG-I and iodine 131-labeled PLG-II showed that the IM was essentially saturated by both glycoforms by 30 to 40 minutes after injury. Extrapolation of the flux rates to 1 minute after injury indicated that the uptake of PLG-II (2.4 pmol/min/cm2) exceeded PLG-I (0.5 pmol/min/cm2) almost five-fold. This result is consistent with an earlier report (Metabolism 1994;43:1430-7) that PLG-II is released by the liver and catabolized in vivo approximately five times faster than PLG-I. By molar comparison, the flux of total plasminogen (ie, PLG-I plus PLG-II) into the injured aorta wall in vivo was 2.4 times greater than that for prothrombin. Assuming both zymogens are converted to their respective proteases within the wound site, then approximately 2 to 3 molecules of plasmin are released for each molecule of thrombin in vivo. The possible significance of this plasmin:thrombin ratio is discussed in respect to the turnover of fibrin(ogen) within the site of vascular injury.


Health courts: an alternative to traditional tort law.
The current adversarial tort-based system of adjudicating malpractice claims is flawed. Alternate methods of compensation for birth injuries related to oxygen deprivation or mechanical injury are being utilized in Virginia and Florida. Although utilization of both of these schemes is limited, and they are not without problems in application, both have been successful in reducing the number of malpractice claims in the tort system and in reducing malpractice premiums. While the Florida and Virginia programs are primarily focused on compensation, other models outside the US focus include compensation as well as enhanced dispute resolution and potential for clinical practice change through peer review. Experts in the fields of law and public policy in the United States have evaluated a variety of approaches and have proposed models for administrative health courts that would provide both compensation and dispute resolution for medical and nursing malpractice claims. These alternative models are based on transparency and disclosure, with just compensation for injuries, and opportunities for improvements in patient safety.


Myosin V: Chemomechanical-coupling ratchet with load-induced mechanical slip.
A chemomechanical-network model for myosin V is presented on the basis of both the nucleotide-dependent binding affinity of the head to an actin filament (AF) and asymmetries and similarity relations among the chemical transitions due to an intramolecular strain of the leading and trailing heads. The model allows for branched chemomechanical cycles and takes into account not only two different force-generating mechanical transitions between states wherein the leading head is strongly bound and the trailing head is weakly bound to the AF but also load-induced mechanical-slip transitions between states in which both heads are strongly bound. The latter is supported by the fact that ATP-independent high-speed backward stepping has been observed for myosin V, although such motility has never been for kinesin. The network model appears as follows: (1) the high chemomechanical-coupling ratio between forward step and ATP hydrolysis is achieved even at low ATP concentrations by the dual mechanical transitions; (2) the forward stepping at high ATP concentrations is explained by the front head-gating mechanism wherein the power stroke is triggered by the inorganic-phosphate (Pi) release from the leading head; (3) the ATP-binding or hydrolyzed ADP.Pi-binding leading head produces a stable binding to the AF, especially against backward loading.


Fibrous dysplasia of the femoral neck. Treatment by cortical bone-grafting.
Fibrous dysplasia of the femoral neck is difficult to treat. In a series of fifteen young patients, ten had a monostotic lesion and five, the polyostotic form of the disease. Twelve patients were first seen with a fatigue fracture. Grafts of cortical bone were used. The objectives of relief of pain, union of the fracture, and prevention of deformity were achieved in all fifteen patients. Two patients required a repeat procedure. None of the patients had important deformity of the femoral neck, and none needed an osteotomy.


A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF.
Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome. The phenotype includes developmental defects, bone marrow failure, and cell cycle abnormalities. At least eight complementation groups (A-H) exist, and although three of the corresponding complementation group genes have been cloned, they lack recognizable motifs, and their functions are unknown. We have isolated a binding partner for the Fanconi anemia group C protein (FANCC) by yeast two-hybrid screening. We show that the novel gene, FAZF, encodes a 486 amino acid protein containing a conserved amino terminal BTB/POZ protein interaction domain and three C-terminal Krüppel-like zinc fingers. FAZF is homologous to the promyelocytic leukemia zinc finger (PLZF) protein, which has been shown to act as a transcriptional repressor by recruitment of nuclear corepressors (N-CoR, Sin3, and HDAC1 complex). Consistent with a role in FA, BTB/POZ-containing proteins have been implicated in oncogenesis, limb morphogenesis, hematopoiesis, and proliferation. We show that FAZF is a transcriptional repressor that is able to bind to the same DNA target sequences as PLZF. Our data suggest that the FAZF/FANCC interaction maps to a region of FANCC deleted in FA patients with a severe disease phenotype. We also show that FAZF and wild-type FANCC can colocalize in nuclear foci, whereas a patient-derived mutant FANCC that is compromised for nuclear localization cannot. These results suggest that the function of FANCC may be linked to a transcriptional repression pathway involved in chromatin remodeling.


Outcomes associated with peripherally inserted central catheters in hospitalised children: a retrospective 7-year single-centre experience.
The use of peripherally inserted central catheters (PICCs) are an integral part of caring for hospitalised children. We sought to estimate the incidence of and identify the risk factors for complications associated with PICCs in an advanced registered nurse practitioners (ARNP)-driven programme. Retrospective cohort study. Single-centre, large quaternary children's hospital. Hospitalised children who had PICC inserted from 1 January 2010 to 31 December 2016. None. A total of 2558 PICCs were placed during the study period. Mean age at PICC insertion was 8.7 years, mean dwell time was 17.7 days. The majority of PICCs (97.8%) were placed by ARNP. Most were placed in a single attempt (79.6%). Mean PICC residual external length outside was 2.1±2.7 cm. The rate of central line-associated bloodstream infection (CLABSI), thrombosis and significant bleeding were 1.9%, 1% and 0.2%, respectively. The CLABSI rate in infants and early childhood was higher than those aged ≥5 years (2.8%, 3.1%, respectively vs 1.3%). In a multivariate analysis after adjustment of confounding effects of race and gender, infants (OR= 2.24, CI=1.14 to 4.39, p=0.02) and early childhood cohort (OR=2.37, CI=1.12 to 5.01, p=0.02) were associated with significantly higher odds of developing CLABSI compared with ≥5 years old. In the early childhood cohort, PICCs with longer residual external catheter length (OR=1.30, 95% CI=1.07 to 1.57, p=0.008) and those placed in the operating room (OR=5.49, 95% CI=1.03 to 29.19, p=0.04), were associated with significantly greater risk of developing CLABSI. The majority of PICCs were successfully placed by ARNPs on the first attempt and had a low incidence of complications. Infants required more attempts for successful PICC placement than older children. The presence of residual external catheter length and placement in the operating room were independent predictors of CLABSI in younger children.


iSCAN: An RT-LAMP-coupled CRISPR-Cas12 module for rapid, sensitive detection of SARS-CoV-2.
The COVID-19 pandemic caused by SARS-CoV-2 affects all aspects of human life. Detection platforms that are efficient, rapid, accurate, specific, sensitive, and user friendly are urgently needed to manage and control the spread of SARS-CoV-2. RT-qPCR based methods are the gold standard for SARS-CoV-2 detection. However, these methods require trained personnel, sophisticated infrastructure, and a long turnaround time, thereby limiting their usefulness. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP), a one-step nucleic acid amplification method conducted at a single temperature, has been used for colorimetric virus detection. CRISPR-Cas12 and CRISPR-Cas13 systems, which possess collateral activity against ssDNA and RNA, respectively, have also been harnessed for virus detection. Here, we built an efficient, rapid, specific, sensitive, user-friendly SARS-CoV-2 detection module that combines the robust virus amplification of RT-LAMP with the specific detection ability of SARS-CoV-2 by CRISPR-Cas12. Furthermore, we combined the RT-LAMP-CRISPR-Cas12 module with lateral flow cells to enable highly efficient point-of-care SARS-CoV-2 detection. Our iSCAN SARS-CoV-2 detection module, which exhibits the critical features of a robust molecular diagnostic device, should facilitate the effective management and control of COVID-19.


Summertime sun protection used by adults for their children.
Because an estimated 50% to 80% of the skin's lifetime sun damage is thought to occur in childhood and adolescence, it is during these critical periods that intense, intermittent sun exposure causing burning increases melanoma risk. A 1997 telephone survey of 503 households evaluated parental attitudes about their child having a tan, and ease of practicing sun protection, sun protection methods used, and sunburning on 5 successive summer weekends. In a random sample of 1 child from each household, 13% of children sunburned during the past week or weekend, and 9% of their parents experienced a sunburn during the past weekend. Children's sunburn was significantly associated with sunburn in the adult respondent, increasing age of the child, having fair skin, being white, and using sunscreens. Duration and peak hours of sun exposure were associated for children and parents. Sunscreen with a sun protection factor of at least 15 was the predominant form of sun protection used. Sunscreen use in children was significantly associated with longer duration of sun exposure, sunny weather conditions, younger age, fair skin, a history of sunburns before this study, a family history of skin cancer, and a higher family income. Feeling that a tan appeared healthy was associated with male gender of the adult and increasing age of the child. Complimenting the child on the appearance of a tan was associated with male gender of the adult, older children, children with skin type reported as olive or dark, and lower educational levels. Although there has been a promising initial effort to alert parents to the need to protect their children from sunburns, many view a tan as healthy and do not effectively implement sun protection behaviors for their children, which results in sunburns. Sun protection that prevents sunburning could be achieved by more children seeking shade, wearing protective clothing, limiting exposure during peak hours, and effectively using sunscreen.


Validity of caries detection on occlusal surfaces and treatment decisions based on results from multiple caries-detection methods.
The aim of this in vitro study was to evaluate whether having results available from multiple detection methods influences dentist's treatment decisions for incipient caries lesions on occlusal surfaces. The occlusal surface of 96 extracted permanent molars without frank cavitation was examined by three examiners initially by visual examination alone, following which they chose one of three treatment options: (i) no treatment, (ii) preventive or non-invasive treatment (sealants), and (iii) invasive treatment. Four weeks later the examiners again selected one of the three treatment options for the surfaces, but this time were able to refer to the results from additional caries-detection methods [bitewing radiographs, electric conductance measurement (ECM), quantitative light fluorescence (QLF), and DIAGNOdent] that had been performed in the interim time. Stereomicroscopy was used to evaluate sensitivity, specificity, accuracy, and area under the Receiver Operating Characteristic (ROC) curve (AUC) for the detection methods at the D1 diagnostic threshold. Slight improvement was obtained in the percentage of sites correctly diagnosed, and in the AUC, when referring to the results obtained from all detection methods compared with visual examination alone. However, a drastic effect on the selection of treatment options was observed by having results available from multiple methods, with the choice of invasive treatment increasing substantially. In conclusion, having data available from multiple methods did not improve the accuracy of examiners in detecting early occlusal caries lesions, but it had a great influence on the number of surfaces indicated for operative treatment. The potential decrease in overall specificity while using multiple methods of detection may be of concern in populations with a low prevalence of occlusal caries lesions.


[China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage Ⅳ non-small cell lung cancer (version 2023)].
The incidence and mortality of lung cancer rank first among malignant tumors in China. Among them, non-small cell lung cancer (NSCLC) is the most important pathological type, accounting for 80%-85% of lung cancer patients, including adenocarcinoma, squamous cell carcinoma and other pathological subtypes. In recent years, with the discovery of epidermal growth factor receptor (EGFR) gene and the successful development of tyrosine kinase inhibitors (TKIs), the treatment efficacy of stage Ⅳ NSCLC patients with EGFR gene sensitive mutation has been greatly improved. As of August 23, 2023, the first generation EGFR-TKIs, gefitinib, icotinib, and erlotinib; the second generation EGFR-TKIs, afatinib and dacomitinib; and the third generation EGFR-TKIs, osimertinib, almonertinib, furmonertinib and befotertinib were all approved for marketing by China National Medical Products Administration (NMPA). In addition, multiple domestic third-generation EGFR-TKIs are undergoing clinical trials, such as rezivertinib (BPI-7711), limertinib (ASK120067), and oritinib (SH-1028). Meanwhile, mobocertinib and sunvozertinib, which targets EGFR 20ins mutations, were also approved by NMPA. With the increasing variety of EGFR-TKIs approved for marketing subsequently, it brings confusion to clinicians when choosing specific medications, and there is an urgent need to develop relevant treatment guidelines. Hence, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists convened experts to integrate the research results of various EGFR-TKIs, and proposed the "China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage Ⅳ non-small cell lung cancer (version 2023)", to provide reference for better clinical practice.


The impact of the Dental Practicality Index on treatment planning.
Aim To compare the treatment planning decisions made by undergraduate and postgraduate dental students before and after training on the use of the Dental Practicality Index (DPI).Methodology One hundred and eight undergraduate and postgraduate dental students were randomly assigned to test (DPI) or control groups. The baseline knowledge was assessed in the first session; both groups were shown 15 clinical scenarios and asked to assign one of four treatment plan options (no treatment, simple treatment, complex treatment or extract). The most appropriate treatment plan had been agreed by a consensus panel of experienced dentists. The test group was then trained on the use of the DPI. In the second session, both groups were shown the same clinical scenarios again in a different order and asked to assign one of the four treatment plan options. Both groups completed the confidence questionnaire.Results Training with the DPI improved the test (DPI) group mean scores from 9.1 in the first session to 10.3 out of 15 in the second session, which was a statistically significant difference (p = 0.005) when compared to the control group mean scores of 8.9 in the first session to 9.2 out of 15 in the second session. The mean confidence score of the students was 6.5 out of 10. There was no correlation between self-reported confidence scores of the students and the treatment planning result scores.Conclusions The DPI aids in the systematic assessment and appropriate treatment planning of dental restorative problems by dental students.


Cerebral haemodynamics and depression in the elderly.
Evidence from epidemiological and neuroimaging studies suggests that cerebrovascular disease is associated with depressive disorders in the elderly, but the extent to which it contributes to the pathogenesis of late life depression is unclear. To investigate the relation between cerebral haemodynamics and depression in a population based study, using transcranial Doppler ultrasonography. Cerebral blood flow velocity and CO2 induced vasomotor reactivity in the middle cerebral artery were measured in 2093 men and women who participated in the Rotterdam study. All subjects were screened for depressive symptoms using the Center of Epidemiological Studies Depression scale, and those with a score of 16 or over had a psychiatric work up. In a semistructured interview, diagnoses of depressive disorders according to the DSM-IV and subthreshold depressive disorder were established. Analyses of covariance controlled for age, sex, stroke, cognitive score, and cardiovascular risk factors were used to compare means of haemodynamic variables. Subjects with depressive symptoms had reduced blood flow velocities (mean difference, -2.9 cm/s; 95% confidence interval (CI), -5.0 to -0.8; p = 0.008) and lower vasomotor reactivity (mean difference -0.5%/kPa; 95% CI, -1.0 to -0.05; p = 0.03). Blood flow velocity was reduced most in subjects suffering from a DSM-IV depressive disorder (mean difference, -4.9 cm/s; 95% CI, -8.5 to -1.4; p = 0.006). The overall reduction in vasomotor reactivity was accounted for by subjects with subthreshold depressive disorder. Depression in late life is associated with cerebral haemodynamic changes that can be assessed by transcranial Doppler ultrasonography. The observed reduction in cerebral blood flow velocity could be a result of reduced demand in more seriously depressed cases with a DSM-IV disorder, whereas reduced CO2 induced cerebral vasomotor reactivity is a possible causal factor for subthreshold depressive disorder.


Structural stigma and all-cause mortality among sexual minorities: Differences by sexual behavior?
Using updated data from the General Social Survey/National Death Index (GSS/NDI) study, we examined whether the relationship between structural stigma-measured by aggregating 4 items assessing prejudice towards homosexuality to the community level-and all-cause mortality is present among gay men/lesbian women. Our hypothesis is based on emerging evidence that indicators of structural stigma specific to homosexuality, such as those used in the GSS/NDI, uniquely predict health outcomes among this group. Because the GSS/NDI lacked an identity-based measure of sexual orientation, we tested our hypothesis by employing a strategy that has a relatively high degree of sensitivity and specificity for ascertaining individuals most likely to identify as gay or lesbian: restricting analyses to individuals who reported same-sex sexual partners in the past year. We compared this approach against an alternative strategy, which has weaker specificity for identifying gay men/lesbian women: restricting analyses to individuals who reported any lifetime same-sex sexual behaviors. After controlling for 6 individual-level factors and fixed effects of survey year, structural stigma was associated with mortality among individuals who reported past-year same-sex sexual partners (HR = 1.95, 95% CI: 1.14, 3.31). Further, there was a dose-response relationship with mortality in this group, such that those residing in communities in the highest quartile of structural stigma had the greatest mortality risk, controlling for these same factors (HR = 2.12, 95% CI: 1.03, 4.38). In sensitivity analyses, the effect size for structural stigma ranged from 1.54 to 2.30, indicating a consistent, but small-to-moderate, effect. In contrast, no association between structural stigma and mortality was observed among respondents who reported lifetime same-sex sexual partners, nor among those reporting only opposite-sex sexual partners. This analysis therefore delimits potential boundary conditions of the association between structural stigma related to same-sex sexuality and all-cause mortality, highlighting the conditions under which this association is (and is not) observed.


[Control of the energizing of liver mitochondria at the adenine nucleotide carrier level under hypotonic conditions].
The effects of ADP, carboxyatractyloside (CAT) and the local anaesthetic nupercaine on the energy-dependent Ca2+ uptake by rat liver mitochondria oxidizing succinate in the presence of oligomycin were compared, using incubation media of 320 mosM and 120 mosM tonicities. In hypotonic media the mitochondrial Ca2+ capacity was increased by 50%, and the mitochondria were more stable to the damaging effects of Ca + Pi. In the presence of ADP the Ca2+ capacities of mitochondria increased both in normotonic and hypotonic media; however, the absolute amounts of calcium consumed were levelled off. CAT abolished the effect of ADP on the mitochondrial Ca2+ uptake and equalized the Ca2+ capacities of rat liver mitochondria in the both media. The local anaesthetic nupercaine also increased the Ca2+ capacity of mitochondria. The effects of nupercaine and ADP were additive. CAT abolished the effect of ADP but not that of nupercaine. Measurements of the intramitochondrial contents of adenine nucleotides showed that in 120 mosM media there was a significant increase in the intramitochondrial content of ATP and the total pool of adenine nucleotides. It was concluded that in hypotonic media the mitochondrial adenine nucleotide carrier exists predominantly in the m-conformation thus facilitating the energization of mitochondria.


Use of Established Guidelines When Reporting on Interprofessional Team-Based Learning in Health Professions Student Education: A Systematic Review.
Team-based learning (TBL) has gained popularity across the health professions, including in interprofessional contexts. The authors conducted this systematic review to summarize the published evidence regarding the extent, design, and practice of interprofessional TBL within health professions (including medical) degree programs to inform interprofessional education (IPE) educators and curricula designers. In June 2020, the authors searched PubMed Central, CINAHL, Web of Science, and ERIC for original research articles describing TBL programs with student representation from multiple health professions degree programs that were published between January 2010 and June 2020. Included articles underwent data extraction for study characteristics (e.g., country of origin, topics covered, class descriptors) and the 7 core design elements of TBL: team formation, readiness assurance, immediate feedback, sequencing of in-class problem solving, the 4 Ss (significant problem, same problem, specific choice, and simultaneous reporting), incentive structure, and peer review. Twelve articles were included. Significant variability was noted in the application and reporting of the 7 core design elements of TBL, which highlighted challenges to the implementation of interprofessional TBL. Although the structured format of TBL provides a suitable pedagogy for IPE, this review identified challenges associated with the effective integration of IPE into TBL, including: the unequal distribution of students to teams as a result of there being multiple disciplines from different programs; varied levels of student experience with the pedagogy of TBL; a lack of resources required for large groups of students; timetabling requirements for multiple disciplines from different programs; inability to provide more than 1 TBL session; design of patient cases that suit multiple disciplines; alignment of topics within the curricula of multiple disciplines, programs, and universities; inequities in grading for different students within the same TBL program; and limited opportunity for peer review.


Metal exposure and biological responses in resident and transplanted blue mussels (Mytilus edulis) from the Scheldt estuary.
The Western Scheldt river and estuary is known to be highly polluted as it receives industrial, agricultural and domestic effluents from one of the most populated and industrialised zones in Europe. Aquatic organisms are exposed to pollutants, specifically metals that are present in different environmental phases, e.g. dissolved, suspended material or sediment phases. The objective of this study was to study the relationship that exists between environmental metal levels, the degree of metal uptake by aquatic organisms with the concomitant biological responses. For this purpose the bivalve mollusk, Mytilus edulis, was selected as bioaccumulation indicator organism. Environmental (water and sediment) and mussel samples were collected during the late winter (March 2000) from sampling sites in the Scheldt estuary. Sites were selected to represent a salinity gradient from the mouth of the estuary to the furthest distribution area of mussels upstream in the system. Together with standard water quality parameters (e.g. salinity, dissolved oxygen, dissolved organic carbon, etc.) concentrations of twelve metals were analysed in the water (dissolved and suspended matter) and sediments. Levels of these metals were also measured in the soft tissue of M. edulis, together with concomitant biomarker responses in resident mussel populations at each site. The biomarkers that were included in this study were condition index, scope for growth, survival in air, cell membrane stability, DNA damage, and metallothioneins. Data were subjected to multivariate statistical analysis. The physico-chemical parameters and metals in the environmental samples clustered the sites to reflect the distribution based on the salinity gradient. Bioaccumulation results revealed increased metal uptake along a pollution gradient with the highest metal bioaccumulation occurring at the upstream most sites and therefore closest to the in the industrial activities. However, the biomarker responses clustered the sites in a manner that reflected the influence of combination of internal exposure (bioaccumulation) and external exposure (physico-chemical conditions). These differences in biomarker responses clearly demonstrated were attributed to abiotic factors other than metal pollution alone e.g. localized short-term increases in increased suspended sediment concentrations and decreased dissolved oxygen concentrations.