Pivalophenone imine as a benzonitrile surrogate for directed C-H bond functionalization.
Pivalophenone N-H imine has been found to serve as a prominent substrate for directed C-H alkylation and arylation reactions with alkyl bromides and aryl chlorides, respectively, under cobalt-N-heterocyclic carbene (NHC) catalysis. Unlike the case of the parent pivalophenone imine, the increased steric bulk of the resulting ortho-substituted pivalophenone imines allows them to undergo clean imine-to-nitrile conversion under peroxide photolysis or aerobic copper catalysis conditions. Overall, these two-step transformations offer convenient synthetic methods for ortho-functionalized benzonitriles.


The global burden of trachomatous visual impairment: II. Assessing burden.
This paper builds on results of a previous paper on the prevalence of trachomatous visual impairment as the foundation for assessing the global burden of trachomatous blindness and low vision: approximately 2.9 million cases of trachomatous blindness and 3.8 million low visioned corresponding to a global prevalence of trachomatous visual impairment equal to 1.3/1,000 in 1990 was estimated. For each visually impaired person, the years of life lost due to premature mortality and the years lived in a handicapped state are added to yield a single measure of disease burden called handicap adjusted life years (HALYs). Age, gender and visual acuity group specific HALYs are multiplied by the prevalence of trachomatous visual impairment to yield an estimate of the global burden of trachoma visual impairment equal to 80 million HALYs. Analysis of the distribution of the global burden by age, gender, visual acuity and region provide direction for trachoma research and programme priorities. Sensitivity analysis reveals that the burden estimates of trachomatous visual impairment may vary from as low as 15 million to as high as 500 million HALYs. Given this degree of variability, burden comparisons with other blinding and non-blinding conditions for the purposes of identifying health sector priorities may be misleading.


Feeding response and dynamic of intoxication and detoxification in two populations of the flat oyster Ostrea chilensis exposed to paralytic shellfish toxins (PST).
Juvenile oysters (Ostrea chilensis) from two populations (Quempillén estuary and Pullinque bay) were exposed to a toxic diet containing paralytic shellfish toxins (PST), produced by Alexandrium catenella, followed by a detoxification period. Feeding behaviour, toxin profile, dynamics of intoxication/detoxification, and survival were evaluated over the entire experimental period. Both populations reduced their feeding rates during the 30-day exposure to the toxic diet. This negative effect was reversible when the diet was switched to the non-toxic one. Oysters from the estuary accumulated PST more rapidly than the population from the bay, suggesting their increased ability to cope with more adverse conditions. Both populations showed low detoxification capacity. Survival was significantly higher in oysters from the estuary, compared to those from the bay. Due to the increasing frequency and intensity of A. catenella blooms in southern Chile, it is necessary to better understand the responses of O. chilensis in different environments. This is important not only because of the ecological and commercial relevance of the bivalve, but also in consideration of expected climate change scenarios, where the new environmental conditions could favour the frequency and intensity of harmful algal bloom events.


Insights from Experiences on Antiplatelet Drugs in Stroke Prevention: A Review.
Reduction of hazard risk of cerebral ischemic event (stroke, transient ischemic attack (TIA)) represents the hard point to be achieved from primary or secondary preventive strategy in the best clinical practice. However, results from clinical trials, recommendations, guidelines, systematic review, expert opinions, and meta-analysis debated on the optimal pharmacotherapy to achieve the objective. Aspirin and a number of antiplatelet agents, alone or in combination, have been considered from large trials focused on stroke prevention. The present review summarizes, discusses results from trials, and focuses on the benefits or disadvantages originating from antiplatelet drugs. Sections of the review were organized to show both benefits or consequences from antiplatelet pharmacotherapy. Conclusively, this review provides a potential synopsis on the most appropriate therapeutic approach for stroke prevention in clinical practice.


Vitamin K antagonists versus low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism.
People with venous thromboembolism (VTE) generally are treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin (LMWH), followed by three months of vitamin K antagonists (VKAs). Treatment with VKAs requires regular laboratory measurements and carries risk of bleeding; some patients have contraindications to such treatment. Treatment with LMWH has been proposed to minimise the risk of bleeding complications. This is the second update of a review first published in 2001. The purpose of this review was to evaluate the efficacy and safety of long term treatment (three months) with LMWH versus long term treatment (three months) with VKAs for symptomatic VTE. For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (last searched November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), The Cochrane Vascular Information Specialistalso searched clinical trials registries for ongoing studies. Randomised controlled trials comparing LMWH versus VKA for long treatment (three months) of symptomatic VTE. Two review authors independently evaluated trials for inclusion and methodological quality. Review authors independently extracted data and assessed risk of bias. We resolved disagreements by discussion and performed meta-analysis using fixed-effect models with Peto odds ratios (Peto ORs) and 95% confidence intervals (CIs). Outcomes of interest were recurrent VTE, major bleeding, and mortality. We used GRADE to assess the overall quality of evidence supporting these outcomes. Sixteen trials, with a combined total of 3299 participants fulfilled our inclusion criteria. According to GRADE, the quality of evidence was moderate for recurrent VTE, low for major bleeding, and moderate for mortality. We downgraded the quality of the evidence for imprecision (recurrent VTE, mortality) and for risk of bias and inconsistency (major bleeding).We found no clear differences in recurrent VTE between LMWH and VKA (Peto OR 0.83, 95% confidence interval (CI) 0.60 to 1.15; P = 0.27; 3299 participants; 16 studies; moderate-quality evidence). We found less bleeding with LMWH than with VKA (Peto OR 0.51, 95% CI 0.32 to 0.80; P = 0.004; 3299 participants; 16 studies; low-quality evidence). However, when comparing only high-quality studies for bleeding, we observed no clear differences between LMWH and VKA (Peto OR 0.62, 95% CI 0.36 to 1.07; P = 0.08; 1872 participants; seven studies). We found no clear differences between LMWH and VKA in terms of mortality (Peto OR 1.08, 95% CI 0.75 to 1.56; P = 0.68; 3299 participants; 16 studies; moderate-quality evidence). Moderate-quality evidence shows no clear differences between LMWH and VKA in preventing symptomatic VTE and death after an episode of symptomatic DVT. Low-quality evidence suggests fewer cases of major bleeding with LMWH than with VKA. However, comparison of only high-quality studies for bleeding shows no clear differences between LMWH and VKA. LMWH may represent an alternative for some patients, for example, those residing in geographically inaccessible areas, those who are unable or reluctant to visit the thrombosis service regularly, and those with contraindications to VKA.


The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis.
The identification of personalized germline markers with biologic relevance for the prediction of cutaneous melanoma prognosis is highly demanded but to date, it has been largely unsuccessful. As melanoma progression is controlled by host immunity, here we present a novel approach interrogating immunoregulatory pathways using the genome-wide maps of expression quantitative trait loci (eQTL) to reveal biologically relevant germline variants modulating cutaneous melanoma outcomes. Using whole genome eQTL data from a healthy population, we identified 385 variants significantly impacting the expression of 268 immune-relevant genes. The 40 most significant eQTLs were tested in a prospective cohort of 1,221 patients with cutaneous melanoma for their association with overall (OS) and recurrence-free survival using Cox regression models. We identified highly significant associations with better melanoma OS for rs6673928, impacting IL19 expression (HR, 0.56; 95% CI, 0.41-0.77; P = 0.0002) and rs6695772, controlling the expression of BATF3 (HR, 1.64; 95% CI, 1.19-2.24; P = 0.0019). Both associations map in the previously suspected melanoma prognostic locus at 1q32. Furthermore, we show that their combined effect on melanoma OS is substantially enhanced reaching the level of clinical applicability (HR, 1.92; 95% CI, 1.43-2.60; P = 2.38e-5). Our unique approach of interrogating lymphocyte-specific eQTLs reveals novel and biologically relevant immunomodulatory eQTL predictors of cutaneous melanoma prognosis that are independent of current histopathologic markers. The significantly enhanced combined effect of identified eQTLs suggests the personalized utilization of both SNPs in a clinical setting, strongly indicating the promise of the proposed design for the discovery of prognostic or risk germline markers in other cancers. Clin Cancer Res; 22(13); 3268-80. ©2016 AACR.


End-of-life care for old people: a review of the literature.
The aim of this study was to make an inventory of various aspects of end-of-life care of the old people. An additional aim was to illuminate gaps in existing knowledge. A systematic literature review focusing on intervention studies was carried out. Three concepts were of special interest: end-of-life care, palliative care, and terminal care. The result encompassed 29 studies, and the articles were grouped together under 4 headings: education and support for close relatives, education and support for staff, education and support for patients, and articles dealing with care planning. The result highlights the need for further research regarding end-of-life care in geographical and cultural settings that differ from those in the USA, needs of old people (ie, 80+), preferences concerning end-of-life care, and the effect of adjusted and generalizable palliative care models.


What kind of animal is the "Three Rs"?
Fifty years after the publication of The Principles of Humane Experimental Technique by Russell and Burch, this paper explores the contemporary role of the Three Rs. This is illustrated by reference to a recent social scientific study, which involved a total of 50 in-depth interviews with scientists who use animals and with other stakeholders in the debate. The data analysis shows how the Three Rs are conceptualised in at least three ways: firstly, as an ethical animal, either as a shorthand for a moral imperative, or as a route to managing an ethical dilemma; secondly, as a scientific animal, internal to the scientific method; and finally, as a political animal, with some stakeholders referring to the Three Rs as a way to promote consensus in a controversial domain. Pushing the metaphor a little further, the paper concludes that the Three Rs concept has become a kind of hybrid animal.


Gender and the relationship between marital status and first onset of mood, anxiety and substance use disorders.
Prior research on whether marriage is equally beneficial to the mental health of men and women is inconsistent due to methodological variation. This study addresses some prior methodological limitations and investigates gender differences in the association of first marriage and being previously married, with subsequent first onset of a range of mental disorders. Cross-sectional household surveys in 15 countries from the WHO World Mental Health survey initiative (n=34493), with structured diagnostic assessment of mental disorders using the Composite International Diagnostic Interview 3.0. Discrete-time survival analyses assessed the interaction of gender and marital status in the association with first onset of mood, anxiety and substance use disorders. Marriage (versus never married) was associated with reduced risk of first onset of most mental disorders in both genders; but for substance use disorders this reduced risk was stronger among women, and for depression and panic disorder it was confined to men. Being previously married (versus stably married) was associated with increased risk of all disorders in both genders; but for substance use disorders, this increased risk was stronger among women and for depression it was stronger among men. Marriage was associated with reduced risk of the first onset of most mental disorders in both men and women but there were gender differences in the associations between marital status and onset of depressive and substance use disorders. These differences may be related to gender differences in the experience of multiple role demands within marriage, especially those concerning parenting.


The development of an economic threshold for Nasonovia ribisnigri (Hemiptera: Aphididae) on lettuce in central Spain.
This study reports economic thresholds for the lettuce aphid Nasonovia ribisnigri (Mosley), based exclusively on cosmetic damage, that is, presence or absence of aphids at harvest time. Field trials were conducted in La Poveda Experimental Farm, Madrid (Spain) during autumn (2004 and 2005) and spring (2005 and 2006). Plants were arranged in plots and just before the formation of lettuce hearts they were infested with different densities of N. ribisnigri. Two days later, half of each plot was treated with tau-fluvalinate (Klartan24AF) and the other half remained as an untreated control. Economic thresholds were obtained from nonlinear regressions calculated between the percentage of commercial plants at the end of the crop cycle for both, treated and untreated semiplots, and the different initial densities of N. ribisnigri per plant. Two criteria were used to consider a commercial lettuce plant: a conservative estimate (0 aphids/plant) and a lax one (< 5 aphids/plant). Thus, an economic threshold was established for each season and criterium. The economic thresholds that were obtained with the most and least conservative criteria were in spring 0.06 and 0.12 aphids per plant, and in autumn 0.07 and 0.13 aphids per plant, respectively. These results show that to avoid cosmetic damage, insecticide sprays are required when a very low aphid density is detected in lettuce seedlings soon after transplant.


What is love? The materiality of care in Ghanaian transnational families.
In the West, economics and intimacy are assumed to occupy separate – even antithetical – domains. In Ghanaian family life, however, affection is understood to be expressed through the distribution of material resources across generations and a person's life cycle. Such an understanding of love means that migrant parents who leave their children behind in Ghana can continue to be good parents by sending remittances, and, in fact, may be considered better parents than caregivers who stay and are poorer. This construction of love also means that children tend to attach themselves to more financially secure caregivers over those with fewer economic opportunities — to men in favour of women, to those abroad over those in Ghana. It is precisely because love is signalled through material exchanges that children long to be with parental migrants far away who support them and feel abandoned by those parents who do not. The intertwining of economic and emotional ties in Ghanaian transnational families has significant implications for policy, as discussed in the conclusion.


Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction.
Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). The pup retrieval test and maternal observations were conducted during lactation to quantify maternal care. In the pup retrieval test, dams that were concurrently experiencing CR (i.e., from the lactation and lifelong groups) displayed shorter latencies to retrieve all pups than the control and preconception groups and the lactation group constructed better nests than all groups. Adult offspring were tested in three tests of anxiety: the elevated plus maze, open field, and emergence test. No differences were observed in the elevated plus maze; however, in the open field preconception animals made fewer entries and spent more time in the central zone than controls. In addition, preconception offspring exhibited longer latencies to full body emergence, spent less time fully emerged, and spent more time engaged in risk assessment behaviours than all other groups. Offspring from the preconception group were also on average 11% heavier than control rats throughout life and displayed 37% higher serum leptin concentrations than controls. A potential role for leptin in the anxiogenic effect of preconception CR is discussed.


Direct Observation and Control of Surface Termination in Perovskite Oxide Heterostructures.
Interfacial behavior of quantum materials leads to emergent phenomena such as quantum phase transitions and metastable functional phases. Probes for in situ and real time surface-sensitive characterization are critical for control during epitaxial synthesis of heterostructures. Termination switching in complex oxides has been studied using a variety of probes, often ex situ; however, direct in situ observation of this phenomena during growth is rare. To address this, we establish in situ and real time Auger electron spectroscopy for pulsed laser deposition with reflection high energy electron diffraction, providing structural and compositional surface information during film deposition. Using this capability, we show the direct observation and control of surface termination in heterostructures of SrTiO3 and SrRuO3. Density-functional-theory calculations capture the energetics and stability of the observed structures, elucidating their electronic behavior. This work demonstrates an exciting approach to monitor and control the composition of materials at the atomic scale for control over emergent phenomena and potential applications.


Attitudes and practices of physicians regarding hypertension and smoking: The Stanford Five City Project.
A survey was sent to 318 physicians in Monterey County, California, to assess their attitudes and practices regarding hypertension and cigarette smoking. After three mailings, 62% returned completed questionnaires. Eight percent of the respondents were smokers, 5% were women, and 34% were in primary care specialties. Older physicians and primary care specialists were less aggressive in their treatment of high blood pressure, but none of the assessed attitudes was significantly associated with treatment practice. Only half of the sample advised all patients to quit smoking. Physicians who doubted the effectiveness of their anti-smoking advice or who did not know what to say to smoking patients were less likely to provide advice. Most physicians felt that their smoking patients lacked sufficient motivation to quit. Programs to encourage physicians to increase smoking cessation activities should address these attitudes.


Looking Through Paintings by Combining Hyper-Spectral Imaging and Pulse-Compression Thermography.
The use of different spectral bands in the inspection of artworks is highly recommended to identify the maximum number of defects/anomalies (i.e., the targets), whose presence ought to be known before any possible restoration action. Although an artwork cannot be considered as a composite material in which the zero-defect theory is usually followed by scientists, it is possible to state that the preservation of a multi-layered structure fabricated by the artist's hands is based on a methodological analysis, where the use of non-destructive testing methods is highly desirable. In this paper, the infrared thermography and hyperspectral imaging methods were applied to identify both fabricated and non-fabricated targets in a canvas painting mocking up the famous character "Venus" by Botticelli. The pulse-compression thermography technique was used to retrieve info about the inner structure of the sample and low power light-emitting diode (LED) chips, whose emission was modulated via a pseudo-noise sequence, were exploited as the heat source for minimizing the heat radiated on the sample surface. Hyper-spectral imaging was employed to detect surface and subsurface features such as pentimenti and facial contours. The results demonstrate how the application of statistical algorithms (i.e., principal component and independent component analyses) maximized the number of targets retrieved during the post-acquisition steps for both the employed techniques. Finally, the best results obtained by both techniques and post-processing methods were fused together, resulting in a clear targets map, in which both the surface, subsurface and deeper information are all shown at a glance.


Allergenic proteins of natural rubber latex.
As the living cytoplasm of laticiferous cells, Hevea brasiliensis latex is a rich blend of organic substances that include a mélange of proteins. A small number of these proteins have given rise to the problem of latex allergy. The salient characteristics of H. brasiliensis latex allergens that are recognized by the International Union of Immunological Societies (IUIS) are reviewed. These are the proteins associated with the rubber particles, the cytosolic C-serum proteins and the B-serum proteins that originate mainly from the lutoids. Procedures for the isolation and purification of latex allergens are discussed, from latex collection in the field to various preparative approaches adopted in the laboratory. As interest in recombinant latex allergens increases, there is a need to validate recombinant proteins to ascertain equivalence with their native counterparts when used in immunological studies, diagnostics, and immunotherapy.


The malleability of spatial skills: a meta-analysis of training studies.
Having good spatial skills strongly predicts achievement and attainment in science, technology, engineering, and mathematics fields (e.g., Shea, Lubinski, & Benbow, 2001; Wai, Lubinski, & Benbow, 2009). Improving spatial skills is therefore of both theoretical and practical importance. To determine whether and to what extent training and experience can improve these skills, we meta-analyzed 217 research studies investigating the magnitude, moderators, durability, and generalizability of training on spatial skills. After eliminating outliers, the average effect size (Hedges's g) for training relative to control was 0.47 (SE = 0.04). Training effects were stable and were not affected by delays between training and posttesting. Training also transferred to other spatial tasks that were not directly trained. We analyzed the effects of several moderators, including the presence and type of control groups, sex, age, and type of training. Additionally, we included a theoretically motivated typology of spatial skills that emphasizes 2 dimensions: intrinsic versus extrinsic and static versus dynamic (Newcombe & Shipley, in press). Finally, we consider the potential educational and policy implications of directly training spatial skills. Considered together, the results suggest that spatially enriched education could pay substantial dividends in increasing participation in mathematics, science, and engineering.


GC/MS detection of central nervous tissue as specified BSE risk material in meat products and meat and bone meals: thermal stability of markers in comparison with immunochemistry and RT-PCR.
Methods for the detection of central nervous tissue (CNT) are urgently needed in food control as a means for controlling strict adherence to both food labeling and banning of specified BSE risk material. Here, we report data on heat stability of the CNT markers neuron-specific enolase (NSE) in western blotting, glial fibrillary acidic protein (GFAP) in an enzyme linked immunoassay, mRNA(GFAP) in a real-time PCR assay, and several fatty acids (C22:6, C24:0-OH, C24:1ω9/ω7, C24:1ω9-OH/ω7-OH, and C24:0) in gas chromatography mass spectrometry (GC/MS). The sample matrix, a standard material of emulsion-type sausage with varied contents of CNT (brain), was heat-treated in three studies: (1) routine meat technological heat treatment with low (85 °C, 30 min), medium (115 °C, 30 min), and high (133 °C, 30 min, 3 bar) heating of 72 anonymous samples from a blind trial; (2) heat treatment under experimental conditions (100, 110, …, 200 °C, 45 min); and (3) fractionized heating of central nervous system (up to three times) under moderate routine technological conditions (85, 100, and 115 °C, 30 min). The markers of the immunochemical methods showed a low GFAP or very low NSE temperature stability at medium and high temperature conditions. The real-time PCR assay gave inconsistent, non-quantitative results, which indicated an uncontrollable matrix effect. The relevant GC/MS markers (C24:0-OH, C24:1ω9/ω7, and C24:1ω9-OH/ω7-OH) proved to be extremely stable. Neither meat and bone meal conditions (133 °C) nor experimental heating (up to and above 140 °C) showed any reduction of GC/MS CNT quantification. On the contrary, a slight but significant increase was noted over a certain temperature range (120-140 °C) for most fatty acids, possibly due to an improved extractability of the fatty acids. We conclude that a quantitative approach is highly unreliable when using immunochemical methods; moreover, these methods might be basically prone to false-negative results depending on heat treatment and matrix composition. Therefore, antibodies with higher affinity to heat-treated CNT marker epitopes are needed. Relevant amounts of CNT (≥0.5%) in low- and medium-heated products would still be reliably detectable by the GFAP ELISA, which justifies its use as a screening method in official food control. The results obtained by the real-time PCR assay were contradictory to recently published data, indicating a need for further protocol optimization and collaborative trials. Up to date, the analytical approach using GC/MS is the only valid procedure as pertaining to heat stability and quantitative analysis; consequently, it should be recommended as the reference procedure in official food control for CNT detection in heat-treated meat products.


Nifedipine inhibits the progression of an experimentally induced cerebral aneurysm in rats with associated down-regulation of NF-kappa B transcriptional activity.
Cerebral aneurysm (CA) causes a life-threatening subarachnoid hemorrhage. However, no effective medical treatment to prevent the growth of CA is available. Nifedipine, a widely used calcium antagonist, was shown to improve endothelial function in various cardiovascular diseases. We examined whether nifedipine has a protective effect on CA progression. CAs were experimentally induced in Sprague-Dawley rats followed by intraperitoneal injection of either 10mg/kg of nifedipine per day or vehicle. The size and media thickness of CAs were measured one month after aneurysm induction. NF-kappa B (NF-kappaB) activity in aneurysmal walls was assessed by immunohistochemistry for activated NF-kappaB p65 subunit and electrophoretic mobility shift assay (EMSA). Expression of monocyte chomoattractant protein-1 (MCP-1) and matrix metalloproteinase (MMP) -2 in aneurysmal walls was examined by RT-PCR and immunohistochemistry. To examine whether nifedipine has a suppressive effect on preexisting CAs, nifedipine administration started at one month after aneurysm induction and pathological changes were assessed at two months after aneurysm induction. Aneurysm size was smaller and the media was thicker in the nifedipine-treated group even though blood pressure was not different between groups. Nifedipine inhibited DNA binding of NF-kappaB in aneurysmal walls. As regards MCP-1 expression and macrophage, which is the main inflammatory cell in the aneurysmal walls, infiltration into aneurysmal walls was decreased by nifedipine. Immunohistochemistry and gelatin zymography showed that the expression and activity of MMP-2 was also reduced by nifedipine. Furthermore, nifedipine significantly prevented the enlargement and degeneration of aneurysmal walls of preexisting CAs. Nifedipine may be useful as a medical drug for patients with CAs.


Fine mapping of the latency-related gene of herpes simplex virus type 1: alternative splicing produces distinct latency-related RNAs containing open reading frames.
The latency-related (LR) gene of herpes simplex virus type 1 (HSV-1) is transcriptionally active during HSV-1 latency, producing at least two LR-RNAs. The LR gene partially overlaps the immediate-early gene ICP0 and is transcribed in the opposite direction from ICP0, producing LR-RNAs that are complementary (antisense) to ICP0 mRNA. The LR gene is thought to be involved in HSV-1 latency. We report here the fine mapping and partial sequence analysis of this HSV-1 LR gene. 32P-labeled genomic DNA restriction fragments and synthetic oligonucleotides were used as probes for in situ hybridizations and Northern (RNA) blot hybridizations of RNA from trigeminal ganglia of rabbits latently infected with HSV-1. The two most abundant LR-RNAs appeared to share their 5' and 3' ends and to be produced by alternative splicing. These LR-RNAs were approximately 2 and 1.3 to 1.5 kilobases in length and were designated LR-RNA 1 and LR-RNA 2, respectively. Their 5' ends started approximately 1,210 nucleotides downstream from the 3' end of the ICP0 mRNA. Their 3' ends overlapped ICP0 by nearly 1,000 nucleotides. LR-RNA 1 appeared to have at least one intron removed, while LR-RNA 2 appeared to have at least two introns removed. The LR-RNAs contained two potential long open reading frames, suggesting the possibility that one or more of the LR-RNAs may be a functional mRNA.


Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating CaMKII-CREB signaling.
Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally to disrupt the interaction between PSD-95 and NR2B and detected by coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced thermal hyperalgesia and mechanical allodynia, and upregulated pain-related proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD-95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD-95, CaMKII, and CREB in the spinal cord. The present study indicates that dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB signaling and relieves pain.


Recent trends in breast cancer mortality among white and black US women.
Time trends in breast cancer mortality were analyzed from 1970 to 1992 among White and Black US women aged 25 and over. Mortality data from the National Center for Health Statistics were summarized within three periods 1970 to 1979, 1980 to 1988, and 1989 to 1992. The annual change was calculated as the average yearly percentage of change based on the logistic model. For White women of all ages, breast cancer mortality decreased by 1.6% (95% confidence interval = -2.0%, -1.1%) per year on average during 1989 to 1992, in contrast to the flat mortality rates observed during the 1970s and a 0.5% average annual increase during 1980 to 1988. The decline was observed for White women under age 60, among whom breast cancer mortality had been decreasing, and for White women aged 60 to 79, among whom breast cancer mortality had been increasing, but it was not observed among Black women. The long-awaited decline in US breast cancer mortality has finally appeared, although only among White women. The possible contributions are changes in inherent risk of disease, changes in treatment effectiveness, and increased use of screening mammography.


Frailty in relation to the accumulation of deficits.
This review article summarizes how frailty can be considered in relation to deficit accumulation. Recalling that frailty is an age-associated, nonspecific vulnerability, we consider symptoms, signs, diseases, and disabilities as deficits, which are combined in a frailty index. An individual's frailty index score reflects the proportion of potential deficits present in that person, and indicates the likelihood that frailty is present. Although based on a simple count, the frailty index shows several interesting properties, including a characteristic rate of accumulation, a submaximal limit, and characteristic changes with age in its distribution. The frailty index, as a state variable, is able to quantitatively summarize vulnerability. Future studies include the application of network analyses and stochastic analytical techniques to the evaluation of the frailty index and the description of other state variables in relation to frailty.


[Morphological characteristics of bone tissue regeneration process in young and old animals].
The paper describes the results of the morphological study of the bone tissue repair process in young and old animals on the model of bone skeleton damage. The defect of the cortical bone was reached by means of bringing in a teflon fistula to make a tunnel surrounded by bone tissue, providing condition for studying the character of bone marrow elements migration to the created hollow space. Repair processes in the bone tissue of old animals were found to elapse much slower than in young ones. However, administration of embryonic cartilaginous and bone tissue extracts into the area of bone defect in old animals facilitated the process of bone tissue repair. The obtained results may serve as a prerequisite for the development of methods for optimization of rehabilitation in old and senile patients with fractures of cortical bones.


Five different types of putative GnRH receptor gene are expressed in the brain of masu salmon (Oncorhynchus masou).
Recent studies have shown that there are multiple genes encoding gonadotropin-releasing hormone receptor (GnRH-R) in single species. In salmonids, however, only a single gene has been identified in the rainbow trout. We therefore isolated partial cDNAs from the brain and the pituitary of masu salmon Oncorhynchus masou by reverse transcription-polymerase chain reaction and 5'-rapid amplification of cDNA ends, using primers corresponding to conserved transmembrane domains (TMs). Five different partial cDNAs were isolated from an individual and termed as msGnRH-R1, R2, R3, R4 and R5. They are divided into two groups, msGnRH-R1, R2, R3 and msGnRH-R4, R5. Two groups share 59-71% nucleotide sequence identities. Phylogenetic analysis showed that the former group is closely related to the goldfish GnRH-R GfA, and the latter to GfB. All five msGnRH-R genes were expressed in the brain and msGnRH-R1, R3 and R5 were expressed in the pituitary. In addition, we found mRNA for msGnRH-R1 in the kidney and ovary, and R2 in the ovary, whereas msGnRH-R5 gene was widely expressed in the muscle, heart, kidney and testis. Differences in the expression of msGnRH-R genes between maturing and spawning fish were observed in the brain and pituitary, except for the constantly expressed msGnRH-R5. A splicing variant of msGnRH-R1 mRNA that is capable of generating a truncated GnRH-R that consists of 5TMs was also expressed in the brain, pituitary and kidney. These results indicate that five different types of putative GnRH-R gene are present and expressed in the brain of masu salmon.


Reversal of two-kidney one clip renovascular hypertension in the rat.
Attempted correction of two-kidney, one clip Goldblatt hypertension in the rat was carried out by three techniques; removal of the constricting clip, removal of the ischemic kidney, and converting enzyme blockade by oral captopril. Since duration of hypertension is said to be a critical factor, groups of rats were studied after short term (less than 6 weeks from clipping) and chronic (greater than 4 months) hypertension. Blood pressure, sodium balance, and plasma renin concentration (PRC) were followed before and after these correcting procedures. In a control group of animals, removal of a loose renal artery clip did not influence blood pressure and only caused trivial postoperative retention of sodium. Unclipping, however, normalized blood pressure in both short-term and chronic hypertension. After a major postoperative fall, blood pressure returned to somewhat elevated levels after nephrectomy in animals with chronic (but not short-term) hypertension. Sodium balance became markedly positive with the fall in blood pressure of operated hypertensive animals and was significantly correlated with the fall in blood pressure of operated hypertensive animals and was significantly correlated with the fall in blood pressure in these four groups at 7 days (r = 0.43). Captopril also produced a fall in blood pressure at 24 hours, with a positive sodium balance, although the relationship between blood pressure fall and sodium balance did not reach statistical significance (r = 0.30). The PRC was elevated in all hypertensive groups, although individual values overlapped with values from normal rats and nonhypertensive rats with a loose renal artery clip. The PRC fell to normal or subnormal values after either operative procedure and stabilized for at least 2 months independently of whether blood pressure fell or not. It is concluded that neither sodium retention nor renin hypersecretion maintains blood pressure in this model. Also, the rapidity of the blood pressure fall is not consistent with a role for vascular hypertrophy. The greater efficacy of unclipping suggests that the revascularized kidney after this procedure exerts a vasodepressor function independent of sodium excretion or the renin-angiotensin system.


Self-Assembly of Ultralong Aligned Dipeptide Single Crystals.
Oriented arrangement of single crystals plays a key role in improving the performance of their functional devices. Herein we describe a method for the exceptionally fast fabrication (mm/min) of ultralong aligned dipeptide single crystals (several centimeters). It combines an induced nucleation step with a continuous withdrawal of substrate, leading to specific evaporation/composition conditions at a three-phase contact line, which makes the growth process controllable. These aligned dipeptide fibers possess a uniform cross section with active optical waveguiding properties that can be used as waveguiding materials. The approach provides guidance for the controlled arrangement of organic single crystals, a family of materials with considerable potential applications in large-scale functional devices.


Comparison of positron emission tomography with [(18)F]FDG and [(68)Ga]DOTATOC in recurrent differentiated thyroid cancer: preliminary data.
The aim of this study was to retrospectively analyse the value of positron emission tomography (PET) with a radiolabelled somatostatin analogue, [(68)Ga]DOTATOC, in recurrent radioiodine positive and negative differentiated thyroid cancer (DTC) compared to [(18)F]FDG PET. Seventeen patients with known or suspected recurrent DTC were enrolled in this study. All patients underwent PET with [(68)Ga]DOTATOC and [(18)F]FDG under TSH suppressive therapy and whole-body scintigraphy (WBS) after administration of [(131)I] following TSH stimulation. The total number of tumour lesions was defined as the sum of the lesions detected by at least one of these three imaging techniques. Pathologic findings were confirmed histopathologically or by follow-up and conventional radiological imaging. Both PET tracers consistently detected metastases in 12 patients. In two cases, only [(131)I] WBS and computed tomography revealed metastatic disease; in the remaining three patients with an increased thyroglobulin no correlate could be found. From a total of 104 tumour lesions, [(18)F]FDG PET showed only slightly higher detection rate than [(68)Ga]DOTATOC PET in radioiodine positive patients (28/31 versus 25/31), whereas significant differences were seen in the group with negative [(131)I] WBS (70/73 versus 26/73, P<0.01). Three out of 104 lesions were only visible using [(68)Ga]DOTATOC PET. [(68)Ga]DOTATOC and [(18)F]FDG PET showed comparable diagnostic performance in recurrent, radioiodine positive DTC. Due to much higher lesion detection rates, [(18)F]FDG PET should be preferred to [(68)Ga]DOTATOC PET in the work-up of radioiodine negative DTC relapse. These preliminary results have to be confirmed by more extensive data in further studies.


Oral health-related quality of life among rural-dwelling indigenous Australians.
There is limited information on the impact of poor oral health on Indigenous Australian quality of life. This study aimed to determine the prevalence, extent and severity of, and to calculate risk indicators for, poor oral health-related quality of life among a convenience sample of rural-dwelling Indigenous Australians. Participants (n = 468) completed a questionnaire that included socio-demographic, lifestyle, dental service utilization, dental self-care and oral health-related quality of life (OHIP-14) factors. The prevalence of having experienced one or more of OHIP-14 items 'fairly often' or 'very often' was 34.8%. The extent of OHIP-14 scores was 1.88, while the severity was 15.0. Risk indicators for having experienced one or more of OHIP-14 items 'fairly often' or 'very often' included problem-based dental attendance, avoiding dental care because of cost, difficulty paying a $100 dental bill and non-ownership of a toothbrush. An additional risk indicator for OHIP-14 extent was healthcare card ownership, while additional indicators for OHIP-14 severity were healthcare card ownership and having had 5+ teeth extracted. Risk indicators for poor oral health-related quality of life among this marginalized population included socio-economic factors, dentate status factors, dental service utilization patterns, financial factors and dental self-care factors.


Codon preference optimization increases heterologous PEDF expression.
Pigment epithelium-derived factor (PEDF) is widely known for its neurotrophic and antiangiogenic functions. Efficacy studies of PEDF in animal models are limited because of poor heterologous protein yields. Here, we redesigned the human PEDF gene to preferentially match codon frequencies of E coli without altering the amino acid sequence. Following de novo synthesis, codon optimized PEDF (coPEDF) and the wtPEDF genes were cloned into pET32a containing a 5' thioredoxin sequence (Trx) and the recombinant Trx-coPEDF or Trx-wtPEDF fusion constructs expressed in native and two tRNA augmented E coli hosts - BL21-CodonPlus(DE3)-RIL and BL21-CodonPlus(DE3)-RP, carrying extra copies of tRNAarg,ile,leu and tRNAarg,pro genes, respectively. Trx-PEDF fusion proteins were isolated using Ni-NTA metal affinity chromatography and PEDF purified after cleavage with factor Xα. Protein purity and identity were confirmed by western blot, MALDI-TOF, and UV/CD spectral analyses. Expression of the synthetic gene was ∼3.4 fold greater (212.7 mg/g; 62.1 mg/g wet cells) and purified yields ∼4 fold greater (41.1 mg/g; 11.3 mg/g wet cell) than wtPEDF in the native host. A small increase in expression of both genes was observed in hosts supplemented with rare tRNA genes compared to the native host but expression of coPEDF was ∼3 fold greater than wtPEDF in both native and codon-bias-adjusted E coli strains. ΔGs at -3 to +50 of the Trx site of both fusion genes were -3.9 kcal/mol. Functionally, coPEDF was equally as effective as wtPEDF in reducing oxidative stress, promoting neurite outgrowth, and blocking endothelial tube formation. These findings suggest that while rare tRNA augmentation and mRNA folding energies can significantly contribute to increased protein expression, preferred codon usage, in this case, is advantageous to translational efficiency of biologically active PEDF in E coli. This strategy will undoubtedly fast forward studies to validate therapeutic utility of PEDF in vivo.


Pneumothorax during anesthesia with changes in ECG.
A patient known to suffer from CNSLD was to undergo cervical lymph node dissection for gingival carcinoma. Pneumothorax developed immediately after introduction of anesthesia. In addition to the usual physical diagnostic signs, an abrupt decrease in amplitude of the QRS- complex and T -waves was observed in the ECG on the scope, the sensitivity of which remained unchanged. The ECG changes disappeared after abolition of the pneumothorax.


EEG abnormalities and long term seizure outcome in high functioning autism.
Electroencephalographic abnormalities may occur in autistic spectrum disorders (ASD) even in the absence of clinical seizures. These abnormalities may vary from nonspecific changes to epileptiform abnormalities and are more common compared to the overall population. The level of intelligence is a significant risk factor for epilepsy in ASD. However, the relation between the functionality of the individuals with autism and the electroencephalographic (EEG) abnormalities, and the clinical significance of these abnormalities still remain relatively unclear. In this study we investigated the presence of EEG abnormalities in sixteen children diagnosed with high-functioning ASD. EEG recording was performed for at least 2 h and included at least 90 min of sleep activity. While none of the patients had clinical seizures, 5 patients (31.3%) were detected to have EEG abnormalities. Four of these were epileptiform (25%), and one patient developed seizure during follow-up. Our results support the fact that EEG abnormalities are observed at a higher rate also in ASD with a better functionality. The potential impact of EEG abnormalities on cognition and behavior, and the risk of epilepsy should be considered during long-term follow-up of these patients.


Concurrent serotyping and genotyping of pneumococci by use of PCR and electrospray ionization mass spectrometry.
A pneumococcal serotyping/genotyping system (PSGS) was developed based upon targeted PCR, followed by electrospray ionization mass spectrometry and amplicon base composition analysis. Eight multiplex PCRs, 32 targeting serotype-determining capsular biosynthetic loci, and 8 targeting multilocus sequence typing (MLST) loci were employed for each of 229 highly diverse Streptococcus pneumoniae isolates. The most powerful aspect of the PSGS system was the identification of capsular serotypes accounting for the majority of invasive and carried pneumococcal strains. Altogether, 45 different serotypes or serogroups were correctly predicted among the 196 resolvable isolates, with only 2 unexpected negative results. All 33 isolates that represented 23 serotypes not included in the PSGS yielded negative serotyping results. A genotyping database was constructed using the base compositions of 65- to 100-bp sections of MLST alleles compiled within http://www.mlst.net. From this database, one or more MLST sequence types (STs) that comprised a PSGS genotype were identified. The end result of more PSGS genotypes (163) than conventional STs actually tested (155) was primarily due to amplification failures of 1 to 3 targets. In many instances, the PSGS genotype could provide resolution of single- and double-locus variants. This molecular serotyping/genotyping scheme is well suited to rapid characterization of large sets of pneumococcal isolates.


Rapid solid phase isolation of 20 specific tRNAs from Escherichia coli.
A solid phase procedure has been developed for the rapid isolation of all 20 species of tRNA from Escherichia coli. The overall yields for a single preparation cycle ranged from 62 to 96%, the average being 80%. The values for the amino acid acceptor activities of the tRNA species equaled those reported in the literature for highly purified tRNAs. Starting from crude tRNA, a given tRNA species can easily be isolated in less than 2 h. One milliliter of the resin, which is reusable, is sufficient for the isolation of 200 mg of a specific tRNA. The procedure requires a bifunctional reagent, one moiety of which (--SO2Cl) reacts with the amino acid on the aminoacylated tRNA, the other, with the --SH group on the resin. Thus, only the desired tRNA species is bound to the resin; any of the other tRNAs in the filtrate can be isolated in another cycle. Raising the pH results in deacylation and release from the resin of the desired tRNA species. For tRNA Cys, it is necessary to block the --SH of cysteine prior to reaction with the bifunctional reagent. Side reactions involving the bifunctional reagent. Side reactions involving the bifunctional reagent and tRNA are either easily reversible or negligible (less than 0.01%).


Rifapentine: its role in the treatment of tuberculosis.
To review the pharmacokinetics, efficacy, adverse effects, and cost of the newest antitubercular drug, rifapentine. A MEDLINE search using key terms such as rifapentine, rifampin, isoniazid, Mycobacterium tuberculosis, and pyrazinamide was conducted for the time period 1966-November 1998. Animal data were used for basic information and human studies were selected for inclusion if they were randomized, controlled studies assessing efficacy, or if they were single- or multiple-dose studies assessing the pharmacokinetics of rifapentine. Background articles on the pathophysiology of tuberculosis and cost of care and noncontrolled studies assessing drug interactions were also included. Compared with an oral solution, the relative bioavailability of rifapentine is 70% following oral admninistration of tablets. Food increased bioavailability by 55%. Rifapentine accumulated significantly in human macrophages and its elimination half-life was longer than that of rifampin. Comparative studies of rifapentine and rifampin in humans during intensive- and continuation-phase treatment of tuberculosis suggest that at currently accepted doses, rifapentine was slightly less effective than rifampin. The most significant drug interaction with rifapentine involves indinavir: the maximum concentration and AUC of indinavir are reduced by 55% and 70%, respectively, when rifapentine is coadministered with indinavir. Adverse events of rifapentine may occur less frequently at the currently recommended 600-mg dose as compared with rifampin; however, the difference was not statistically significant. If only drug costs were evaluated during the six-month treatment of tuberculosis, rifapentine is more expensive than rifampin. Rifapentine can be administered twice weekly during the intensive phase of tuberculosis treatment and then once weekly during the continuation phase of treatment. This may improve patient adherence over some other treatments and possibly reduce costs of treatment by preventing development of resistant tubercular strains due to nonadherence. Rifapentine is well tolerated, with most patients experiencing adverse effects at a similar rate as rifampin. Rifapentine induces cytochrome P450 somewhat less than rifampin, although few drug interaction studies have been done with rifapentine. Its efficacy at the currently approved dosage of 600 mg may be slightly lower than that of rifampin. Studies are needed to determine if equal or greater efficacy can be achieved with higher doses of rifapentine. Rifampin is less expensive than rifapentine. Further pharmacoeconomic studies are needed to evaluate costs of relapse and failure in patients receiving these agents.


American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults.
Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings. Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.


Catalyst-particle configurations: From nanowires to carbon nanotubes.
Surface-energy minimization is used to study capillary effects that determine the stable configurations of (liquid or solid) particles atop tubes or wires. The results give allowable ranges for the volume (V_{c}) of the particles as a function of the inner and outer radii of the tubes, R_{I} and R_{o}, respectively. When R_{I}/R_{o}=0, the object is a nanowire. When R_{I}/R_{o}=1, it is a single-wall carbon nanotube. When 0<R_{I}/R_{o}<1, it can be thought of as a multiwall carbon nanotube. Moreover, the transition paths among different configurations are studied. These results suggest possible mechanisms for the reshaping of the "pear-like" catalyst particles in carbon nanotubes that oscillate across local energy-maximum points with respect to the position of the lower interface in the inner wall.


Risk of infections during interferon-based treatment in patients with chronic hepatitis C virus infection and advanced hepatic fibrosis.
Pegylated interferon-based treatment is still the backbone of current hepatitis C therapy and is associated with bone marrow suppression and an increased risk of infections. The aim of this retrospective cohort study was to assess the risk of infections during interferon-based treatment among patients with chronic hepatitis C virus (HCV) infection and advanced hepatic fibrosis and its relation to treatment-induced neutropenia. This cohort study included all consecutive patients with chronic HCV infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak 4-6) who started treatment between 1990 and 2003 in five large hepatology units in Europe and Canada. Neutrophil counts between 500-749/μL and below 500/μL were considered as moderate and severe neutropenia, respectively. This study included 723 interferon-based treatments, administered to 490 patients. In total, 113 infections were reported during 88 (12%) treatments, of which 24 (21%) were considered severe. Only one patient was found to have moderate neutropenia and three patients were found to have severe neutropenia at the visit before the infection. Three hundred and twelve (99.7%) visits with moderate neutropenia and 44 (93.6%) visits with severe neutropenia were not followed by an infection. Multivariable analysis showed that cirrhosis (odds ratio [OR] 2.85, 95% confidence interval [CI] 1.38-5.90, P=0.005) and severe neutropenia at the previous visit (OR 5.42, 95% CI 1.34-22.0, P=0.018) were associated with the occurrence of infection, while moderate neutropenia was not. Among a subgroup of patients treated with pegylated interferon, severe neutropenia was not significantly associated (OR 1.63, 95% CI 0.19-14.2, P=0.660). In this large cohort of patients with bridging fibrosis and cirrhosis, infections during interferon-based therapy were generally mild. Severe interferon-induced neutropenia rarely occurred, but was associated with on-treatment infection. Moderate neutropenia was not associated with infection, suggesting that current dose reduction guidelines might be too strict.


Acupuncture Treatment is Associated with a Decreased Risk of Dementia in Patients with Depression: A Propensity Score-Matched Cohort Study.
Depression is one of the most disabling disorders, which causes long-term complications such as neurodegenerative disorder and cerebrovascular disease. Some patients with depression seek acupuncture treatment. We aimed to investigate the association between acupuncture treatment and the risk of dementia in patients with depression from the perspective of real-world evidence. Patients over 18 years old and newly diagnosed with depression between 1997 and 2010 were selected from the Taiwanese National Health Insurance Research Database and followed up until the end of 2013. Propensity score was used to match equal numbers of patients 1:1 (N = 16,609 per group) into acupuncture and non-acupuncture cohorts based on characteristics including sex, age, baseline comorbidity and drug use. The outcome measurement was the comparison of dementia incidence in the two cohorts. Compared with the non-acupuncture cohort, patients who received acupuncture treatment had a decreased risk of dementia (adjusted hazard ratio (aHR) = 0.54; 95% confidence interval (CI) = 0.50-0.58, P < 0.001) after adjustment for age, sex, comorbidities and drug use. Compared with depression patients who did not receive acupuncture, the aHR of vascular dementia and Alzheimer's disease incidences for patients who had acupuncture therapy was 0.59 (95% CI 0.48-0.71) and 0.51 (95% CI 0.39-0.67), respectively. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (Log rank test, p < 0.001). The present study from real-world data revealed that acupuncture reduced the risk of dementia in depression patients, which supports healthcare decisions in clinical practice.


A new species of the rare genus Rutaraphes Jałoszyński from Japan (Coleoptera, Staphylinidae, Scydmaeninae).
To date, the stenichnine genus Rutaraphes Jałoszyński includes only two species: R. shikokuensis Jałoszyński (Japan) and R. taiwanicus Jałoszyński (Taiwan), both known from a single holotype male. Consequently, Rutaraphes can be placed among the rarest Palaearctic genera of Scydmaeninae. Three males of this remarkable genus were found recently during a museum survey, all collected in a flight intercept trap in Central Honshū, Japan. They represent a new species, described herein as Rutaraphes honshuensis sp. n., morphologically close to R. shikokuensis.


Effects of microplastics mixed with natural particles on Daphnia magna populations.
The toxicity of microplastics on Daphnia magna as a key model for freshwater zooplankton is well described. While several studies predict population-level effects based on short-term, individual-level responses, only very few have validated these predictions experimentally. Thus, we exposed D. magna populations to irregular polystyrene microplastics and diatomite as natural particle (both ≤63 μm) over 50 days. We used mixtures of both particle types at fixed particle concentrations (50,000 particles mL-1) and recorded the effects on overall population size and structure, the size of the individual animals, and resting egg production. Particle exposure adversely affected the population size and structure and induced resting egg production. The terminal population size was 28-42 % lower in exposed compared to control populations. Interestingly, mixtures containing diatomite induced stronger effects than microplastics alone, highlighting that natural particles are not per se less toxic than microplastics. Our results demonstrate that an exposure to synthetic and natural particles has negative population-level effects on zooplankton. Understanding the mixture toxicity of microplastics and natural particles is important given that aquatic organisms will experience exposure to both. Just as for chemical pollutants, better knowledge of such joint effects is essential to fully understand the environmental impacts of complex particle mixtures. ENVIRONMENTAL IMPLICATIONS: While microplastics are commonly considered hazardous based on individual-level effects, there is a dearth of information on how they affect populations. Since the latter is key for understanding the environmental impacts of microplastics, we investigated how particle exposures affect the population size and structure of Daphnia magna. In addition, we used mixtures of microplastics and natural particles because neither occurs alone in nature and joint effects can be expected in an environmentally realistic scenario. We show that such mixtures adversely affect daphnid populations and highlight that population-level and mixture-toxicity designs are one important step towards more environmental realism in microplastics research.


Contribution of the radiological assessment in the compensation of occupational shoulder tendinopathy.
Musculoskeletal disorders (MSDs) currently represent the first occupational health problem. Tendinopathy of the shoulder is the most common occupational diseas. It is responsible for variable aftereffects arriving until the articular steepness. To determine the influence of clinical and radiological investigations in setting the rate of permanent partial disability related to occupational shoulder tendinopathies. This is a retrospective study of 63 patients followed for tendinopathy of the shoulder. The files were collected from the regional commission of attribution of the rates of permanent partial incapacity of the victims of the occupational accidents and diseases. For each patient we collected the social and occupational data, the result of the clinical examination and the radiological investigations as well as the attributed PPD rate (partial permanent disability). The data analysis allowed to determine the variation of the PPD according to the articular mobility and according to the severity of the hurts revealed by the radiological investigations. The average age of our patients was of 45 years with a feminine predominance (sex ratio 6.87). The patients were mainly workers of confections (51%). The imaging objectified a tendinopathy without tear in 23 cases (36,5 We showed that the rate of PPD increased in a proportional way according to the severity of the limitation of the mobility expressed in degrees lost of abduction or of extension as well as according to the gravity of the hurts revealed by the radiological investigations. we were able to attribute for every type of radiological lesion and according to the limitation of the mobility an interval of rather specific PPD, this allows directing the experts in the compensation of occupational shoulder tendinopathy victims.


Assessing Changes in Parent Sensitivity in Telehealth and Hybrid Implementation of Attachment and Biobehavioral Catch-Up During the COVID-19 Pandemic.
During the COVID-19 pandemic, home visiting services for families with young children pivoted to continue providing services virtually. One such service was Attachment and Biobehavioral Catch-up (ABC), a brief prevention/intervention program targeting increased parental sensitivity. 70 families participated in a sensitivity assessment before and after receiving ABC. Forty-three families received the program fully through telehealth, and 27 families received the program through an in-person/telehealth hybrid format. Parent sensitivity was assessed pre- and post-intervention, and results suggested that when ABC was delivered through a telehealth or hybrid format, parents showed increased following the lead and decreased intrusiveness from pre- to post-intervention, with moderate effect sizes. Ongoing supervision in the model, weekly fidelity maintenance checks, and the flexibility of families and parent coaches likely contributed to the maintenance of significant change in parental sensitivity from pre- to post-intervention during the move from face-to-face home visiting to the provision of virtual services.


Aphasia rehabilitation in Australia: Current practices, challenges and future directions.
This study reports on current aphasia rehabilitation practices of speech-language pathologists in Australia. A 30-item web-based survey targeted approaches to aphasia rehabilitation, education, discharge, follow-up practices, counselling, interventions to improve communication access, community aphasia support services, and challenges to practice. One hundred and eighty-eight surveys were completed representing ~33% of the potential target population, with 58.5% urban and 41.5% rural participants across all states and territories. Respondents reported embracing a wide variety of approaches to aphasia rehabilitation; however, significant challenges in providing aphasia management in acute and residential care were identified. Low levels of knowledge and confidence were reported for both culturally and linguistically diverse clients and discourse approaches. Group and intensive services were under-utilized and clinicians reported inflexible funding models as major barriers to implementation. Few clinicians work directly in the community to improve communicative access for people with aphasia. Despite the chronic nature of aphasia, follow-up practices are limited and client re-entry to services is restricted. Counselling is a high frequency practice in aphasia rehabilitation, but clinicians report being under-prepared for the role. Respondents repeatedly cited lack of resources (time, space, materials) as a major challenge to effective service provision. Collective advocacy is required to achieve system level changes.


Biocompatibility assessment of haemodialysis membrane materials by proteomic investigations.
The exposure of blood to an artificial surface such as the haemodialysis membrane results in the nearly instantaneous deposition of a layer of plasma proteins. The composition of the protein layer profoundly influences all subsequent events, and to a large extent determines the biocompatibility of the biomaterial. In the present study, we examine the protein adsorption capacity and coagulation profiles of the polysulfone-based helixone material in comparison to cellulose triacetate. A differential profiling investigation using shotgun proteomics data-independent analysis was applied to eluates obtained with each membrane after a dialysis session, in order to assess the function of desorbed proteins. Functional classification and network analysis performed using bioinformatics tools shed light on the involvement of adsorbed proteins into important molecular processes, such as lipid transport and metabolism, cell growth differentiation and communication, and the coagulation cascade. The collected evidence was further validated by targeted mass spectrometry using selected reaction monitoring on proteotypic transitions of key protein effectors, confirming the different panels of adsorbed protein on each membrane. The coagulation profile during haemodialysis of patients under polysulfone-based helixone filter cartridges was also assessed showing a slightly higher platelet activation profile after the dialysis session. The overall collected evidence highlights a modulation of the coagulation biological pathway during haemodialysis, which is largely influenced by the biomaterial used.


Evaluation of Cognitive and Physical Function Among Older Adults by Their Physical Activity: A Cross-Sectional Kasama Study, Japan.
The amyloid-β1-42 (Aβ42) level is a biomarker that is widely used to evaluate individual cognitive dysfunction early in neurodegenerative diseases, as well as differentiate between normal cognitive function, mild cognitive impairment, Alzheimer's disease, and vascular cognitive impairment. Our cross-sectional study evaluated the association between daily exercise and physical and cognitive function and Aβ42 levels among a subsample of 325 older adults from the Kasama Study. Participants (age: 74.5 [range 65-90] years) were classified into three exercise groups: the dual-task (DEG, n = 128), single-task (SEG, n = 122), and non-exercise (NEG, n = 75) groups. The main outcomes were the plasma Aβ42 levels and the scores of the five cognitive (5-COG) tests and five cognition-related physical function (5-PHYS) tests. The Aβ42 levels and 5-COG and 5-PHYS scores were higher in the SEG and DEG than in the NEG. The Aβ42 levels were higher in the DEG than in the NEG (p = 0.008). Physical activities such as regular exercise may benefit older adults, improving their cognitive and physical function.


Printed droplet microfluidics for on demand dispensing of picoliter droplets and cells.
Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay.


Tracking UNC-45 chaperone-myosin interaction with a titin mechanical reporter.
Myosins are molecular motors that convert chemical energy into mechanical work. Allosterically coupling ATP-binding, hydrolysis, and binding/dissociation to actin filaments requires precise and coordinated structural changes that are achieved by the structurally complex myosin motor domain. UNC-45, a member of the UNC-45/Cro1/She4p family of proteins, acts as a chaperone for myosin and is essential for proper folding and assembly of myosin into muscle thick filaments in vivo. The molecular mechanisms by which UNC-45 interacts with myosin to promote proper folding of the myosin head domain are not known. We have devised a novel approach, to our knowledge, to analyze the interaction of UNC-45 with the myosin motor domain at the single molecule level using atomic force microscopy. By chemically coupling a titin I27 polyprotein to the motor domain of myosin, we introduced a mechanical reporter. In addition, the polyprotein provided a specific attachment point and an unambiguous mechanical fingerprint, facilitating our atomic force microscopy measurements. This approach enabled us to study UNC-45-motor domain interactions. After mechanical unfolding, the motor domain interfered with refolding of the otherwise robust I27 modules, presumably by recruiting them into a misfolded state. In the presence of UNC-45, I27 folding was restored. Our single molecule approach enables the study of UNC-45 chaperone interactions with myosin and their consequences for motor domain folding and misfolding in mechanistic detail.


Human Monoclonal Antibodies Potently Neutralize Zika Virus and Select for Escape Mutations on the Lateral Ridge of the Envelope Protein.
The mosquito-borne Zika virus (ZIKV) has been causing epidemic outbreaks on a global scale. Virus infection can result in severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we characterized monoclonal antibodies isolated from a patient with an active Zika virus infection that potently neutralized virus infection in Vero cells at the nanogram-per-milliliter range. In addition, these antibodies enhanced internalization of virions into human leukemia K562 cells in vitro, indicating their possible ability to cause antibody-dependent enhancement of disease. Escape variants of the ZIKV MR766 strain to a potently neutralizing antibody, AC10, exhibited an amino acid substitution at residue S368 in the lateral ridge region of the envelope protein. Analysis of publicly availably ZIKV sequences revealed the S368 site to be conserved among the vast majority (97.6%) of circulating strains. We validated the importance of this residue by engineering a recombinant virus with an S368R point mutation that was unable to be fully neutralized by AC10. Four out of the 12 monoclonal antibodies tested were also unable to neutralize the virus with the S368R mutation, suggesting this region to be an important immunogenic epitope during human infection. Last, a time-of-addition infection assay further validated the escape variant and showed that all monoclonal antibodies inhibited virus binding to the cell surface. Thus, the present study demonstrates that the lateral ridge region of the envelope protein is likely an immunodominant, neutralizing epitope.IMPORTANCE Zika virus (ZIKV) is a global health threat causing severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we analyzed the human monoclonal antibody response to acute ZIKV infection and found that neutralizing antibodies could not elicit Fc-mediated immune effector functions but could potentiate antibody-dependent enhancement of disease. We further identified critical epitopes involved with neutralization by generating and characterizing escape variants by whole-genome sequencing. We demonstrate that the lateral ridge region, particularly the S368 amino acid site, is critical for neutralization by domain III-specific antibodies.


Endogenous opioid regulation of gonadotropin-releasing hormone release from the human fetal hypothalamus in vitro.
Endogenous opioid regulation of GnRH release from the human fetal (21-23 weeks gestation) mediobasal hypothalamus was investigated in an in vitro perifusion system. Pulse injection of an opiate receptor antagonist, naloxone, reproducibly elicited an acute increase in GnRH release within 30 min. Constant infusion of naloxone (60 min) induced a sustained increase in GnRH release, which was promptly inhibited by a pulse of beta-endorphin administered halfway during the naloxone infusion. These studies unequivocally demonstrate that endogenous opiates exert an inhibitory effect on GnRH release from the human fetal mediobasal hypothalamus in vitro.


Probiotic Supplementation for Promotion of Growth in Children: A Systematic Review and Meta-Analysis.
Probiotics are commonly prescribed to promote a healthy gut microbiome in children. Our objective was to investigate the effects of probiotic supplementation on growth outcomes in children 0-59 months of age. We conducted a systematic review and meta-analysis which included randomized controlled trials (RCTs) that administered probiotics to children aged 0-59 months, with growth outcomes as a result. We completed a random-effects meta-analysis and calculated a pooled standardized mean difference (SMD) or relative risk (RR) and reported with a 95% confidence interval (CI). We included 79 RCTs, 54 from high-income countries (HIC), and 25 from low- and middle-income countries (LMIC). LMIC data showed that probiotics may have a small effect on weight (SMD: 0.26, 95% CI: 0.11-0.42, grade-certainty = low) and height (SMD 0.16, 95% CI: 0.06-0.25, grade-certainty = moderate). HIC data did not show any clinically meaningful effect on weight (SMD: 0.01, 95% CI: -0.04-0.05, grade-certainty = moderate), or height (SMD: -0.01, 95% CI: -0.06-0.04, grade-certainty = moderate). There was no evidence that probiotics affected the risk of adverse events. We conclude that in otherwise healthy children aged 0-59 months, probiotics may have a small but heterogenous effect on weight and height in LMIC but not in children from HIC.


Quantification and characterization of microplastics in blue mussels (Mytilus edulis): protocol setup and preliminary data on the contamination of the French Atlantic coast.
Microplastics (MPs) constitute a main environmental issue due to their threat to marine organisms and so far to humans. The lack of a fast standard protocol in MP isolation and identification from living organisms bring to challenge for the science. In this paper, an optimized protocol using potassium hydroxide 10% (KOH 10%; m/v) for digestion of mussel soft tissues (Mytilus edulis) and multi-steps of sedimentation has been developed. Efficiency higher than 99.9% of organic and mineral matter elimination was shown by application on mussels sampled on the French Atlantic coast. The identification of MPs was performed by FTIR microscopy straight on the filter and the whole analysis can be compatible with a routine goal. Fourteen MPs of four different chemical natures were found and identified in 5 pools of 3 sampled mussels. Their size ranged from 30 to 200 μm. Further investigations are now needed to evaluate the potential risk of such particles within this marine bivalve species and other filter feeders.


The effect of directive tutor guidance on students' conceptual understanding of statistics in problem-based learning.
Education is aimed at students reaching conceptual understanding of the subject matter, because this leads to better performance and application of knowledge. Conceptual understanding depends on coherent and error-free knowledge structures. The construction of such knowledge structures can only be accomplished through active learning and when new knowledge can be integrated into prior knowledge. The intervention in this study was directed at both the activation of students as well as the integration of knowledge. Undergraduate university students from an introductory statistics course, in an authentic problem-based learning (PBL) environment, were randomly assigned to conditions and measurement time points. In the PBL tutorial meetings, half of the tutors guided the discussions of the students in a traditional way. The other half guided the discussions more actively by asking directive and activating questions. To gauge conceptual understanding, the students answered open-ended questions asking them to explain and relate important statistical concepts. Results of the quantitative analysis show that providing directive tutor guidance improved understanding. Qualitative data of students' misconceptions seem to support this finding. Long-term retention of the subject matter seemed to be inadequate.


Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats.
Brain injury after focal cerebral ischemia, the most common cause of stroke, develops from a series of pathological processes, including excitotoxicity, inflammation, and apoptosis. While NMDA receptors have been implicated in excitotoxicity, attempts to prevent ischemic brain damage by blocking NMDA receptors have been disappointing. Disruption of neuroprotective pathways may be another avenue responsible for ischemic damage, and thus preservation of neuronal survival may be important for prevention of ischemic brain injury. Here, we report that suppression of proteolytic degradation of transient receptor potential canonical 6 (TRPC6) prevented ischemic neuronal cell death in a rat model of stroke. The TRPC6 protein level in neurons was greatly reduced in ischemia via NMDA receptor-dependent calpain proteolysis of the N-terminal domain of TRPC6 at Lys¹⁶. This downregulation was specific for TRPC6 and preceded neuronal death. In a rat model of ischemia, activating TRPC6 prevented neuronal death, while blocking TRPC6 increased sensitivity to ischemia. A fusion peptide derived from the calpain cleavage site in TRPC6 inhibited degradation of TRPC6, reduced infarct size, and improved behavioral performance measures via the cAMP response element-binding protein (CREB) signaling pathway. Thus, TRPC6 proteolysis contributed to ischemic neuronal cell death, and suppression of its degradation preserved neuronal survival and prevented ischemic brain damage.


Fractionating the role of executive control in control over worry: a preliminary investigation.
Uncontrollable anxious thought characterizes a number of emotional disorders. Little is known, however, about the cognitive mechanisms that underlie the ability to control these thoughts. The present study investigated the extent to which two well-characterized executive control processes--working memory and inhibition--are engaged when an individual attempts to control worry. Participants completed a concurrent assessment of these processes while attempting to control personally-relevant worried and neutral thoughts. To examine the specificity of these effects to attempts to control worry, versus a residual "depletion" effect of having previously engaged in worry, a subset of participants completed the assessment without instructions to control their worried or neutral thoughts. Attempts to control worry engaged working memory and inhibition to a greater extent than did attempts to control neutral thought. This increased engagement was not explained solely by anxious affect, nor was it significantly associated with trait worry. Engagement did not differ by group, suggesting that executive control depletion by worry cannot be dismissed as an alternative explanation of these findings. These results highlight working memory and inhibition as potentially valuable constructs for deepening our understanding of the nature and treatment of worry and its control.


Survival prognosis and surgical management of ischemic mitral regurgitation.
Ischemic mitral regurgitation (IMR) has an adverse prognosis, but survival characteristics and management are controversial. This study reviewed a 20-year series of IMR patients managed with multiple approaches to assess and refine surgical strategies. Patients having surgery for primary coronary disease from 1986 to 2006 were divided into group 1 (no IMR; bypass grafting only; n = 16,209), group 2a (IMR; bypass only; n = 3,181), group 2b (IMR; mitral repair; n = 416), and group 2c (IMR; mitral replacement; n = 106). Cox proportional hazards modeling adjusted for baseline differences, and therapeutic adequacy was quantified by area under each survival curve expressed as a percentage of group 1. Group 2 patients were older than group 1 patients and had worse baseline characteristics. Group 2a had less severe MR and group 2b had the most comorbidity. Assuming group 1 provided the best adjusted outcome at a given baseline risk, group 2a achieved 97.7%, 2b achieved 93.7%, and 2c achieved 79.1% of potential survival (hazard ratio 1.1, 1.4, and 1.6, respectively; p < 0.003). Most of the survival difference was perioperative. Worse baseline risk is a major factor reducing long-term survival in IMR. Current algorithms in which mild to moderate IMR is managed with bypass only (group 2a) generally produced good late results. In patients with moderate and severe IMR, repair achieved 93.7% of full survival potential; valve replacement was less satisfactory, primarily owing to higher operative mortality. Future therapeutic refinement, emphasizing reparative procedures and better perioperative care, could enhance the surgical prognosis of IMR.


Mental health carers' experiences of an Australian Carer Peer Support program: Tailoring supports to carers' needs.
Carer Peer Support Workers (CPSWs) are people who have lived experience as carers/family members of persons with a mental illness, and are employed to provide support to other carers/family members. This qualitative study aimed to explore carers' experiences within a community-based CPSW pilot program in an Australian mental health service. Semi-structured phone interviews were conducted with 20 carer participants in 2015, 5-10 months following their last contact with the service. Thematic analysis uncovered that carers were generally positive about the CPSW's emotional support, practical support, shared lived experience and mutual understanding, and the "ripple effect" the support had on service users. Some carers, on the other hand, felt that the support was unnecessary; either because they believed that it did not have a lasting effect, the focus should have been on the service user, or that they had previously received enough support. Nevertheless, the study highlighted how mental health services could best utilise and benefit from CPSWs. Moreover, to be most useful, the nature of the carer peer support work should be tailored to the specific needs of the carers; which may vary according to their culture, years of caring experience, and previous experiences with mental health services.


Acid rock drainage in Nevado Pastoruri glacier area (Huascarán National Park, Perú): hydrochemical and mineralogical characterization and associated environmental implications.
The generation of acid rock drainage (ARD) was observed in an area of Nevado Pastoruri as a result of the oxidative dissolution of pyrite-rich lutites and sandstones. These ARDs are generated as abundant pyrite becomes exposed to atmospheric conditions as a result of glacier retreat. The proglacial zone contains lagoons, springs, streams and wetlands, scant vegetation, and intense fluvioglacial erosion. This work reports a comprehensive identification and the results of sampling of the lagoons and springs belonging to the microbasin, which is the headwaters of the Pachacoto River, as well as mapping results based on the hydrochemical data obtained in our study. The physical properties and water chemistry of 12 springs and 22 lagoons from the proglacial zone are also presented. Water springs are far from being chemically uniform, with pH and EC values ranging between 2.55-6.42 and 23-1110 μS/cm respectively, which suggests a strong geologic control on water chemistry. Fe-SO4-2 concentrations confirm the intense process of pyrite oxidative dissolution. Many of the lagoons are affected by ARD, with low pH (~ 3), and high EC (256-1092 μS/cm) values when compared with unaffected lagoons (EC between 7 and 59 μS/cm), indicating a high degree of mineralization. The affected lagoons show higher concentrations of SO42- and SiO2, and elements as Fe, Al, Mg, Mn, Zn, Co, and Ni, which are related to the alteration of pyrite and the dissolution of aluminosilicate minerals. Schwertmannite-goethite appears to be the most important mineral phases controlling the Fe solubility at a pH of 2-3.5. Moreover, they act as a sorbent of trace elements (As, Sb, V, Pb, Zn, Cr), which is an efficient mechanism of natural attenuation. Despite of this, the water flowing out from the basin is acid (pH 3.1) and contains significant concentrations of Fe (0.98 mg/L) and Al (3.76 mg/L) that confer mineral acidity to water. The Pachacoto River located 5.5 km downstream from this point showed a strong natural attenuation, with a pH of 6.9 and low concentration of metals. This mitigating process is possible due to (i) the formation of precipitates that retain toxic elements and (ii) the mixing with natural waters that promote dilution, which favor the increase of pH until circumneutral conditions.


Physical mapping and expression of hybrid plasmids carrying chromosomal beta-lactamase genes of Escherichia coli K-12.
Hybrid plasmids carrying the ampC gene of Escherichia coli K-12 that codes for the chromosomal beta-lactamase were physically studied. The ampC gene was mapped to a deoxyribonucleic acid segment encompassing 1,370 base pairs. The mapping was facilitated by the isolation of a plasmid carrying an insertion of the transposable element gamma delta (gamma delta) close to ampC. The ampA1 mutation, which increases the expression of ampC by a factor of about 20, was localized to a 370-base pair segment of the 1,370-base pair deoxyribonucleic acid segment that contains the ampC gene. Using a minicell protein labeling system, it was seen that plasmids carrying either ampA+, ampC, or ampA1 and ampC coded for a 36,000-dalton protein which comigrated with purified chromosomal beta-lactamase. In cells carrying plasmids that bore the ampA1 allele, the production of this protein was greater. In addition, a protein with a slightly higher molecular weight (38,000) was expressed by both ampA+ ampC and ampA1 ampC plasmids in this protein labeling system. This protein might represent a precursor form of chromosomal beta-lactamasee. From E. coli K-12 strains carrying the ampA1 allele, second-step mutants were isolated that hyperproduced chromosomal beta-lactamase. By reciprocal recombination, plasmid derivatives were isolated that carried these mutations. Two second-step regulatory mutations mapped within the same 370-base pair region as ampA1. This piece of deoxyribonucleic acid therefore contains ampA, a control sequence region for ampC.


The timing and causality of ecological shifts on Caribbean reefs.
Caribbean reefs have experienced unprecedented changes in the past four decades. Of great concern is the perceived widespread shift from coral to macroalgal dominance and the question of whether it represents a new, stable equilibrium for coral-reef communities. The primary causes of the shift-grazing pressure (top-down), nutrient loading (bottom-up) or direct coral mortality (side-in)-still remain somewhat controversial in the coral-reef literature. We have attempted to tease out the relative importance of each of these causes. Four insights emerge from our analysis of an early regional dataset of information on the benthic composition of Caribbean reefs spanning the years 1977-2001. First, although three-quarters of reef sites have experienced coral declines concomitant with macroalgal increases, fewer than 10% of the more than 200 sites studied were dominated by macroalgae in 2001, by even the most conservative definition of dominance. Using relative dominance as the threshold, a total of 49 coral-to-macroalgae shifts were detected. This total represents ~35% of all sites that were dominated by coral at the start of their monitoring periods. Four shifts (8.2%) occurred because of coral loss with no change in macroalgal cover, 15 (30.6%) occurred because of macroalgal gain without coral loss, and 30 (61.2%) occurred owing to concomitant coral decline and macroalgal increase. Second, the timing of shifts at the regional scale is most consistent with the side-in model of reef degradation, which invokes coral mortality as a precursor to macroalgal takeover, because more shifts occurred after regional coral-mortality events than expected by chance. Third, instantaneous observations taken at the start and end of the time-series for individual sites showed these reefs existed along a continuum of coral and macroalgal cover. The continuous, broadly negative relationship between coral and macroalgal cover suggests that in some cases coral-to-macroalgae phase shifts may be reversed by removing sources of perturbation or restoring critical components such as the herbivorous sea urchin Diadema antillarum to the system. The five instances in which macroalgal dominance was reversed corroborate the conclusion that macroalgal dominance is not a stable, alternative community state as has been commonly assumed. Fourth, the fact that the loss in regional coral cover and concomitant changes to the benthic community are related to punctuated, discrete events with known causes (i.e. coral disease and bleaching), lends credence to the hypothesis that coral reefs of the Caribbean have been under assault from climate-change-related maladies since the 1970s.


The Effect of Light Exposure at Night (LAN) on Carcinogenesis via Decreased Nocturnal Melatonin Synthesis.
In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that can influence the activity of the clock's genes and be involved in the inhibition of cancer development. On the other hand, in the literature, some papers highlight that artificial light exposure at night (LAN)-induced circadian disruptions promote cancer. In the present review, we summarize the potential mechanisms by which LAN-evoked disruption of the nocturnal increase in melatonin synthesis counteracts its preventive action on human cancer development and progression. In detail, we discuss: (i) the Warburg effect related to tumor metabolism modification; (ii) genomic instability associated with L1 activity; and (iii) regulation of immunity, including regulatory T cell (Treg) regulation and activity. A better understanding of these processes could significantly contribute to new treatment and prevention strategies against hormone-related cancer types.


High-intensity focused ultrasound therapy for prostate cancer.
Recent advances in high-intensity focused ultrasound, which was developed in the 1940s as a viable thermal tissue ablation approach, have increased its popularity. High-intensity focused ultrasound is currently utilized the most in Europe and Japan, but has not yet been approved by the Food and Drug Administration, USA, for this indication. The purpose of the present report is to review the scientific foundation of high-intensity focused ultrasound technology and the clinical outcomes achieved with commercially available devices. Recently published articles were reviewed to evaluate the current status of high-intensity focused ultrasound as a primary or salvage treatment option for localized prostate cancer. Improvements in the clinical outcome as a result of technical, imaging and technological advancements are described herein. A wide range of treatment options for organ-confined prostate cancer is available. However, high-intensity focused ultrasound is an attractive choice for men willing to choose less invasive options, although establishing the efficacy of high-intensity focused ultrasound requires longer follow-up periods. Technological advances, together with cultural and economic factors, have caused a dramatic shift from traditional open, radical prostatectomy to minimally invasive techniques. High-intensity focused ultrasound is likely to play a significant role in the future of oncology practice.


What Do New Findings About Social Interaction in Autistic Adults Mean for Neurodevelopmental Research?
Deficit-based accounts of social and communication abilities continue to dominate autism research. However, emerging findings suggest that this view may be overly simplistic and discount the two-way nature of interaction. Here we discuss the reconceptualization of social cognition to consider such difficulties as examples of bidirectional, multifaceted misattunement between autistic and nonautistic individuals. Aligned with progressive theoretical frameworks, emerging empirical research indicates that mismatches in communication styles can contribute to autistic social difficulties and the important role that nonautistic difficulties play. We highlight two areas of future research with the aim of providing empirical support for the views that the autistic community has proposed over the past 2 decades. We discuss the impact of such a paradigm shift on a number of levels, including how bridging the gap between different interaction styles can reduce stigma and increase understanding. Adopting such a framework will provide radical opportunities for transformative societal changes and education around inclusion.


[Obstructive apnea during sleep: clinical and polygraphic evaluation of 150 cases].
Obstructive sleep apnea is one of the most common causes of excessive daytime sleepiness. In our sample, clinical evaluation generally suggested this diagnosis by daytime sleepiness (90.6%) and loud snoring (92.0%). Respiratory pauses and inspiratory gasps were frequently reported (12.6%). The age of presentation was after the fourth decade in 87.2%. Polysomnography was characterized by numerous obstructive or mixed apneas, with mean apnea index 37.1; frequent arousals following the apneas; reduction or abscence of stages 3 and 4; reduction of sleep efficiency; hypoxemia and EEG arrhythmias during the respiratory pauses. Tracheostomy was performed in 45 cases, uveopalatopharyngoplasty in 43 and both surgeries in 5, as treatment of choice.