[Lung tuberculosis in HIV positive patients. Clinico-radiologic correlations].
We investigated the radiologic features of pulmonary tuberculosis in HIV+ patients. 24 cases of pulmonary tuberculosis in HIV+ patients were studied (17 men and 7 women, average age: 38 years). The study includes 19 drug addicts, 3 homosexuals, 1 polytransfused subject and 1 patient not belonging to the categories considered at risk). Three subgroups were identified by the CD4/mm3 cell count (< 200, 200-500, > 500). In our 24 patients, we identified 37 radiologic manifestations (in 13 cases associated in the same patient), with 6 cases of bilateral pulmonary and 9 atypical localizations. In detail: 10 consolidations, 7 productive (miliary) cavitations, 8 mediastinal lymphadenitis, 3 extrapulmonary forms and 4 cases with no chest X-ray alterations. There is a major frequency of consolidations and cavitations in the patients with CD4 > 200 and a major frequency of productive forms, lymphadenitis and extrapulmonary localizations in the subjects with CD4 < 200. We observed no cases of tuberculosis in patients with CD4 > 500. The medical therapy is usually more effective in the more immunocompetent subjects and, anyway, in the exudative forms, improving in 35% of cases, than in the productive and disseminated forms improving in 6% of cases only. Only the severely immunodeficient HIV+ patients (CD4 < 500) are affected with tuberculosis. There exists a significant rate of parenchymal consolidations and tisiogenic forms in subjects with CD4 > 200 and a high rate of miliary forms, lymphadenitis and extrapulmonary localizations in patients with low cell count (< 200). The medical therapy is more effective in the more immunocompetent subjects and, anyway, in the exudative forms, than in the productive and disseminated forms. Finally, atypical localization of pulmonary tuberculosis are frequent in HIV patients.


Sustainable governance of scarce metals: the case of lithium.
Minerals and metals are finite resources, and recent evidence suggests that for many, primary production is becoming more difficult and more expensive. Yet these resources are fundamentally important for society--they support many critical services like infrastructure, telecommunications and energy generation. A continued reliance on minerals and metals as service providers in modern society requires dedicated and concerted governance in relation to production, use, reuse and recycling. Lithium provides a good example to explore possible sustainable governance strategies. Lithium is a geochemically scarce metal (being found in a wide range of natural systems, but in low concentrations that are difficult to extract), yet recent studies suggest increasing future demand, particularly to supply the lithium in lithium-ion batteries, which are used in a wide variety of modern personal and commercial technologies. This paper explores interventions for sustainable governance and handling of lithium for two different supply and demand contexts: Australia as a net lithium producer and Switzerland as a net lithium consumer. It focuses particularly on possible nation-specific issues for sustainable governance in these two countries' contexts, and links these to the global lithium supply chain and demand scenarios. The article concludes that innovative business models, like 'servicizing' the lithium value chain, would hold sustainable governance advantages for both producer and consumer countries.


Review of enoxaparin and its clinical applications in venous and arterial thromboembolism.
Venous and arterial thromboembolic disorders are common medical conditions that are associated with considerable morbidity and mortality. Unfractionated heparin (UFH) and its derivatives, the low molecular weight heparins (LMWHs), are the anticoagulants of choice when a rapid anticoagulant effect is required. LMWHs have several advantages over UFH, including a longer plasma half-life and higher bioavailability; a predictable dose response, which enables once- or twice-daily dosing; and a more convenient route of administration (subcutaneous instead of intravenous), which enables patients to self-inject in an out-patient setting. Enoxaparin is a LMWH prepared by alkaline hydrolysis of the benzylin ester of UFH. The efficacy of enoxaparin in the management of venous and arterial thromboembolism has been shown in a wide range of patient groups using doses ranging from fixed doses of 20 - 60 mg o.d. and 0.75 - 1.5 mg/kg b.i.d. Other doses, such as 80 mg/day for pregnant women with combined thrombophilic defects, have also been studied. The use of subcutaneous enoxaparin as an effective and safe home treatment for patients with acute proximal deep vein thrombosis (DVT) has been demonstrated. The benefits of preventing venous thromboembolic events with enoxaparin include reducing the costs associated with investigating the symptoms of DVT, acute treatment and hospitalisation, and potentially the development of post-thrombotic syndrome, while improving quality of life and so making the treatment cost effective. In contrast to other LMWHs, enoxaparin has been shown to provide better outcomes than UFH in the treatment of unstable angina and non-ST-segment elevation myocardial infarction, without increasing major bleeding. Adverse events with enoxaparin are infrequent; the most common events are minor bleeding complications. It should be noted that different doses or indications are approved in each country.


Fluorescence photoswitching of a diarylethene-perylenebisimide dyad based on intramolecular electron transfer.
A fluorescent photochromic molecule, which is composed of a photochromic diarylethene (DE) and a fluorescent perylenebisimide (PBI), was synthesized and its fluorescence photoswitching was studied. The fluorescence quantum yield of the open-ring isomer is constant irrespective of solvent polarity, while that of the closed-ring isomer decreases with an increase in the dielectric constant of solvents. Femtosecond time-resolved transient and fluorescence lifetime measurements revealed that the fluorescence quenching of the closed-ring isomer is attributed to the intramolecular electron transfer from the PBI chromophore to the DE unit.


Total glucosides of paeony (TGP) inhibits the production of inflammatory cytokines in oral lichen planus by suppressing the NF-κB signaling pathway.
Total glucosides of paeony (TGP) is a bioactive compound extracted from paeony roots and has been widely used to ameliorate inflammation in several autoimmune and inflammatory diseases. However, the anti-inflammatory effect of TGP on oral lichen planus (OLP), a chronic inflammatory oral condition characterized by T-cell infiltration and abnormal epithelial keratinization cycle remains unclear. In this study, we found that TLR4 was highly expressed and activation of the NF-κB signaling pathway was obviously observed in the OLP tissues. Moreover, there was significant higher mRNA expression of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in OLP keratinocytes than normal oral epithelial keratinocytes. With the help of the cell culture model by stimulating the keratinocyte HaCaT cells with lipopolysaccharides (LPS), we mimicked the local inflammatory environment of OLP. And we further confirmed that TGP could inhibit LPS-induced production of IL-6 and TNF-α in HaCaT cells via a dose-dependent manner. TGP treatment decreased the phosphorylation of IκBα and NF-κB p65 proteins, thus leading to less nuclear translocation of NF-κB p65 in HaCaT cells. Therefore, our data suggested that TGP may be a new potential candidate for the therapy of OLP.


Exploratory Graph Analysis of the Multidimensional Schizotypy Scale.
The present study examined the dimensional structure underlying the Multidimensional Schizotypy Scale (MSS) and its brief version (MSS-B). We used Exploratory Graph Analysis (EGA) to evaluate their dimensional structure in two large, independent samples (n = 6265 and n = 1000). We then used Confirmatory Factor Analysis (CFA) to compare the fit of the theoretical dimensions with the EGA dimensions. For the MSS, EGA identified four dimensions: positive schizotypy, two dimensions of negative schizotypy (affective and social anhedonia), and disorganized schizotypy. For the MSS-B, EGA identified three dimensions, which corresponded to the theorized positive, negative, and disorganized dimensions. Based on the MSS's EGA dimensions, we also estimated a four-factor model for the MSS-B. The CFA comparison found that the four-factor model fit significantly better than the theoretical three-factor model for both the MSS and MSS-B, providing support for the theoretical model and offering a more nuanced interpretation of the negative schizotypy factor. In addition, EGA also revealed that the positive and negative schizotypy dimensions of the MSS and MSS-B might be mediated by the disorganized dimension. Our findings offer new implications for future research on the MSS and MSS-B dimensions that may provide differential associations with interview and questionnaire measures.


Generic inequivalence between two brands of chloramphenicol capsule.
Generic inequivalence between two brands of chloramphenicol capsules has been investigated. Both brands complied with official standards for drug content and capsule disintegration time, and exhibited similar anti-bacterial activity when tested in vitro. A slow dissolution rate was observed with one brand which could be related to a formulation defect which might explain reported therapeutic inefficacy.


[Various features of the favorable dynamics of obsessive fears with onset in childhood].
Peculiarities of the formation of the syndrome of obsessive fears originating in childhood and showing a favourable outcome are considered. Thirty-eight subjects (aged 17-24 years) taken off the psychiatric registry in connection with recovery were examined. A comparative analysis of 2 groups of patients with different clinical manifestations and age at the disease onset allowed the identification of conditions contributing to a favourable time course of obsessive fears. The author outlines the optimum therapeutic measures compensating neurotic disorders in children and adolescents with obsessive fears.


Buying Happiness in an Unequal World: Rank of Income More Strongly Predicts Well-Being in More Unequal Countries.
Does income rank matter more for well-being in more unequal countries? Using more than 160,000 observations from 24 countries worldwide, we replicate previous studies and show that the ranked position of an individual's income strongly predicts life evaluation and positive daily emotional experiences, whereas absolute and reference income generally have weak or no effects. Furthermore, we find the association between income rank and an individual's well-being to be significantly larger in countries where income inequality, represented by the share of taxable income held by the top 1% of income earners, is high. These results are robust to using an alternative measure of income inequality and different reference group specifications. Our findings suggest that people in more unequal societies place greater weight on the pursuit of higher income ranks, which may contribute to enduring income inequality in places where greater well-being can be bought from moving up the income ladder.


Do brief motivational interventions increase motivation for change in drinking among college students? A two-step meta-analysis of individual participant data.
Brief motivational interventions (BMIs) are one of the most effective individually focused alcohol intervention strategies for college students. Despite the central theoretical role of motivation for change in BMIs, it is unclear whether BMIs increase motivation to change drinking behavior. We conducted a two-step meta-analysis of individual participant data (IPD) to examine whether BMIs increase motivation for change. N = 5903;59% women, 72% White) from Project INTEGRATE. The BMIs included individually delivered motivational interviewing with personalized feedback (MI + PF), stand-alone personalized feedback (PF), and group-based motivational interviewing (GMI). We included 15 trials of BMI (N = 5903;59% women, 72% White) from Project INTEGRATE. The BMIs included individually-delivered motivational interviewing with personalized feedback (MI + PF), stand-alone personalized feedback (PF), and group-based motivational interviewing (GMI). Different measures and responses used in the original trials were harmonized. Effect size estimates were derived from a model that adjusted for baseline motivation and demographic variables for each trial (step 1) and subsequently combined in a random-effects meta-analysis (step 2). The overall intervention effect of BMIs on motivation for change was not statistically significant (standard mean difference [SMD]: 0.026, 95% CI: [-0.001, 0.053], p = 0.06, k = 19 comparisons). Of the three subtypes of BMIs, GMI, which tended to provide motivation-targeted content, had a statistically significant intervention effect on motivation, compared with controls (SMD: 0.055, 95% CI: [0.007, 0.103], p = 0.025, k = 5). By contrast, there was no evidence that MI + PF (SMD = 0.04, 95% CI: [-0.02, 0.10], k = 6, p = 0.20) nor PF increased motivation (SMD = 0.005, 95% CI: [-0.028, 0.039], k = 8, p = 0.75), compared with controls. Post hoc meta-regression analysis suggested that motivation sharply decreased each month within the first 3 months postintervention (b = -0.050, z = -2.80, p = 0.005 for k = 14). Although BMIs provide motivational content and normative feedback and are assumed to motivate behavior change, the results do not wholly support the hypothesis that BMIs improve motivation for change. Changing motivation is difficult to assess during and following interventions, but it is still a theoretically important clinical endpoint. Further, the evidence cautiously suggests that changing motivation may be achievable, especially if motivation-targeted content components are provided.


Effects of a sulfated exopolysaccharide produced by Altermonas infernus on bone biology.
The growth and differentiation of bone cells is controlled by various factors, which can be modulated by heparan sulfates. Here, we investigated the effects of an oversulfated exopolysaccharide (OS-EPS) on the bone. We compared the effect of this compound with that of a native EPS. Long-term administration of OS-EPS causes cancellous bone loss in mice due, in part, to an increase in the number of osteoclasts lining the trabecular bone surface. No significant difference in cancellous bone volume was found between EPS-treated mice and age-matched control mice, underlying the importance of sulfation in trabecular bone loss. However, the mechanism sustaining this osteoporosis was unclear. To clarify OS-EPS activities, we investigated the effect of OS-EPS on osteogenesis. Our results demonstrated that OS-EPS inhibited osteoclastogenesis in two cell models. Using the surface plasmon resonance technique, we revealed that OS-EPS can form a hetero-molecular complex OS-EPS/receptor activator of NF-κB ligand (RANKL)/RANK and that RANK had a higher affinity for RANKL pre-incubated with OS-EPS than for RANKL alone, which would be in favor of an increase in bone resorption. However, in vitro, OS-EPS inhibited the early steps of osteoclast precursor adhesion and therefore inhibited the cell fusion step. In addition, we showed that OS-EPS reduced proliferation and accelerated osteoblastic differentiation, leading to strong inhibition of mineralized nodule formation, which would be in favor of an increase in bone resorption. Taken together, these data show different levels of bone resorption regulation by EPSs, most of them leading to proresorptive effects.


Phytochemical screening, antioxidant activity, total phenolic and total flavonoid contents of seven local varieties of Rosa indica L.
Rosa indica symbol of godness and beauty known for various healing power, has astringent, sedative, anti-inflammatory and antidepressant qualities. Standard methods were used for qualitative detection of phyto-compounds, and quantitative detection of antioxidants was done using DPPH radical scavenging assay, total phenolics and total flavonoids content were expressed in mg GAE/g dry weight and mg QE/g dry weight. Results revealed phyto-compounds presence in all varieties under study however maximum % inhibition was observed by R. indica var pink perfume (94 ± 0.6) with IC50 value 0.3376 ± 0.01 mg/mL. Highest phenolic and flavonoid content was observed in the leaves extract of R. indica var cardinal red, i.e. 3.3553 ± 0.11 (ethanol) mg of Gallic acid equivalents (GAE)/g dry weight and 3.736 ± 0.001(ethanol) mg of quercetin equivalents (QE)/g dry weight, respectively, at conc. 0.125 mg/mL. Our finding provides evidence that all varieties of rose contain medicinally important bioactive compounds and justifies their use for treatment of different diseases.


Vascularized metatarsophalangeal joint transfer for radial hypoplasia.
The relatively new concept and technique of microvascular joint transplantation for the correction of the congenitally deformed wrist is presented with a series of 24 operated radial club hands. The results from the 19 upper extremities with a mean follow-up of 11 years show that the new technique will not diminish the longitudinal growth of the ulna. The ulna length in the series is now 15.4 cm in mean and will develop further and presumably better than that reported in the previous long-term studies after centralization. The superiority in wrist active mobility compared with those of some previous long-term studies is reported with total active motion of 83 degrees in mean. The radial deviation deformity has become increased by 12 degrees in mean in the long-term follow-up compared with the results reported previously by the same author in the series of the first nine patients in 1998. The balance in the growth between the supporting metatarsal joint and the distal ulna has remained satisfactory, and the resting radial deviation angle is 28 degrees in mean (range, 0 to 45 degrees) in the cases with successful joint transfer. A subluxation tendency in six of the transplanted joints is a new finding, and its prevention needs careful attention during the reconstruction. With respect to timing, the joint alignment and transplantation procedure is best performed between the ages of 2.5 and 4 years according to the current experience of the author. A pollicization is usually added after the wrist alignment procedure. This technique will give the child a period of ~10 years without any new need for surgical treatment, and usually no splinting is needed during that period. However, an additional corrective osteotomy may be needed at early puberty depending on the growth properties of the joint graft and original ulna and because of ulnar bowing. The reported technique with preoperative and postoperative measures takes a period of about one-half year, and the whole procedure is considered quite demanding as far as an adequate preoperative soft tissue distraction and the microvascular joint transplantation are concerned. It is recommended that the treatment be performed in dedicated microsurgical centers with adequate pediatric tissue transfer experience.


Beta-endorphin and met-enkephalin stimulate human peripheral blood mononuclear cell chemotaxis.
The neuropeptides beta-endorphin and met-enkephalin are potent analgesics and have a broad spectrum of biologic activities including the recently described alterations of lymphocyte proliferation and antibody production. The current study demonstrates that beta-endorphin and met-enkephalin stimulate human mononuclear cell chemotaxis, as measured by the in vitro leading front assay for migration. The response to both beta-endorphin and met-enkephalin was bimodal, with peak activities occurring at 10(-12) M and 10(-8) M. The distance migrated in response to optimal concentrations of beta-endorphin or met-enkephalin was approximately 80% of that obtained with 10(-8) M formyl-methionyl-leucyl-phenylalanine (f-MLP) and was blocked by prior incubation with 10(-8) M naloxone. Removal of glass adherent cells resulted in a loss of the response to beta-endorphin. Quantitation of the number of cells responding to beta-endorphin showed that only about 50% as many cells responded to beta-endorphin as compared with f-MLP. Human neutrophils showed some migration in response to beta-endorphin and met-enkephalin, although the average optimal migration was less than 30% of that observed with 10(-8) M f-MLP. Studies of the in vivo infusion of beta-endorphin into the cerebral ventricle of the rat resulted in the immigration of macrophage-like cells and are consistent with the in vitro evidence for a chemotactic effect of beta-endorphin.


Epitopes of the cholera family of enterotoxins.
Hybridoma-derived monoclonal antibodies were raised to enterotoxins of the cholera family and to chimeric B-subunit proteins in which individual amino acid residues of a heat-labile, cholera-related enterotoxin from an Escherichia coli strain of porcine origin (P-LT) were substituted with corresponding residues from such an enterotoxin from an E. coli strain of human origin (H-LT). Single amino acid substitutions were found to have profound effects on the physicochemical behavior of the proteins and on their immunologic reactivity. With the use of enzyme-linked immunosorption assays (ELISAs) with and without the GM1 ganglioside receptor for these toxins, several distinct epitopes in GM1-binding domains were identified by different monoclonal antibodies. Polyclonal rabbit antisera to synthetic peptides of the cholera enterotoxin B subunit were cross-reactive to various degrees with the proteins in our library, which include two different cholera enterotoxins, two H-LTs, P-LT, and four chimeric proteins. Some of these reactions were blocked by GM1 ganglioside but not by the oligosaccharide of GM1, a finding suggesting that the peptides generated antibodies to epitopes near, but not in, a GM1-binding domain. A hypothetical evolutionary tree based on the reported amino acid sequences of the various enterotoxins is constructed. As additional enterotoxins are described, it will be interesting to determine if and where they fit in this scheme.


IL-2Rβγ signalling in lymphocytes promotes systemic inflammation and reduces plasma cholesterol in atherosclerotic mice.
The relationship between inflammation and lipid metabolism is complex and bidirectional. Lymphocyte-driven inflammation has been shown to modulate both atherosclerotic plaque development and cholesterol levels, but the mechanisms are incompletely understood. The cardiometabolic effects of IL-2Rβγ signalling in atherosclerotic Apoe-/- mice were investigated by treatment with an agonistic IL-2Rβγ-targeting IL-2/anti-IL-2 complex or a monoclonal anti-CD122 (IL-2Rβ) blocking antibody. Administration of IL-2Rβγ agonistic IL-2/anti-IL-2 complexes to Apoe-/- mice augmented opposing arms of the adaptive immune system. Expansion of effector/memory T cells and increased levels of circulating pro-inflammatory cytokines were observed along with elevated levels of regulatory T cells and IL-10. Notably, IL-2/anti-IL-2 treatment did not affect plaque size but decreased levels of plasma cholesterol. The cholesterol lowering effect of IL-2Rβγ agonism was not affected by anti-CD8 or anti-NK1.1 depleting antibody treatment but was contingent on the presence of adaptive immunity. Expression of multiple liver X receptor (LXR)-related genes, including Pltp and Srebp1c in the liver, was decreased by IL-2/anti-IL-2 treatment. Although IL-2Rβγ agonism lowered cholesterol levels, blocking IL-2Rβγ signalling using an anti-CD122 monoclonal antibody did not impact cholesterol levels or plaque burden in Apoe-/- mice. Elevated IL-2Rβγ signalling results in activation of both inflammatory and regulatory lymphocytes with a net zero effect on atherosclerosis and decreased plasma cholesterol levels. Changes in cholesterol levels were associated with reductions in hepatic LXR-related gene expression. Further studies are needed to investigate the clinical significance of IL-2 mediated modulation of hepatic LXR signalling in inflammatory disorders.


Adaptive filter model of the cerebellum.
The Marr-Albus model of the cerebellum has been reformulated with linear system analysis. This adaptive linear filter model of the cerebellum performs a filtering action of a phase lead-lag compensator with learning capability, and will give an account for the phenomena which have been termed "cerebellar compensation". It is postulated that a Golgi cell may act as a phase lag element; for example, as a leaky integrator with time constant about several seconds. Under this assumption, a mossy fiber - granule cell - Golgi cell input network functions as a phase lead-lag compensator. Output signals from Golgi-granule cell systems, namely, parallel fiber signals, are gathered together through variable synaptic connections to form a Purkinje cell output. From a general theory of adaptive linear filters, learning principles for these modifiable connections are derived. By these learning principles, a Purkinje cell output converges to the "desired response" to minimize the mean square error of the performance. In a more general sense, a Purkinje cell acquires a filtering function on the basis of multiple pairs of input signals and corresponding desired output signals. The mode of convergence of the output signal is described when the input signal is sinusoidal.


[68Ga]FAPI-PET/CT for radiation therapy planning in biliary tract, pancreatic ductal adeno-, and adenoidcystic carcinomas.
Biliary-tract-carcinomas (BTC), pancreatic-ductal-adenocarcinomas (PDAC) and adenoidcystic-carcinomas (AC) have in common that they are traditionally treated with large clinical-target-volumes (CTV). The aim of this study is to examine the impact of pretreatment-[68Ga]FAPI-PET/CT on target-volume-definition and posttreatment-[68Ga]FAPI-PET/CT-response-assessment for BTC-, PDAC- and AC-patients referred to radiation-therapy. All consecutive BTC-, PDAC-, and AC-patients who received pretreatment-[68Ga]FAPI-PET/CT±[18F]FDG-PET/CT were included from 01.01.2020 to 01.03.2022. MTV and SUVmax were separately generated based on [68Ga]FAPI- and [18F]FDG-PET/CT-images. A [68Ga]FAPI- and [18F]FDG-based-CTV was defined. Treatment-plans were compared. Treatment-response was reassessed by a second [68Ga]FAPI-PET/CT and [18F]FDG-PET/CT after treatment-completion. Intermodality comparison of lesion-to-background-ratios [SUVmax_lesion/SUVmean_background] for individual timepoints t1 and t2 revealed significant higher values for [68Ga]FAPI compared to [18F]FDG (t1, p = 0.008; t2, p = 0.005). Intermodality comparison of radiation-therapy-plans showed that [68Ga]FAPI-based planning resulted in D100% = 97.2% and V95% = 98.8% for the [18F]FDG-MTV. [18F]FDG-based-planning resulted in D100% = 35.9% and V95% = 78.1% for [68Ga]FAPI-MTV. [18F]FDG-based-planning resulted only in 2 patients in V95% > 95% for [68Ga]FAPI-MTV, and in 1 patient in D100% > 97% for [68Ga]FAPI-MTV. GTV-coverage in terms of V95% was 76.4% by [18F]FDG-based-planning and 99.5% by [68Ga]FAPI-based-planning. Pretreatment [68Ga]FAPI-PET/CT enhances radiation-treatment-planning in this particular group of patients. While perilesional and tumoral follow-up [18F]FDG-uptake behaved uniformly, perilesional and tumoral reaction may differ in follow-up [68Ga]FAPI-imaging. Complementary [68Ga]FAPI- and [18F]FDG-imaging enhance treatment-response-assessment.


Spectrally pure heralded single photons by spontaneous four-wave mixing in a fiber: reducing impact of dispersion fluctuations.
We model the spectral quantum-mechanical purity of heralded single photons from a photon-pair source based on nondegenerate spontaneous four-wave mixing taking the impact of distributed dispersion fluctuations into account. The considered photon-pair-generation scheme utilizes pump-pulse walk-off to produce pure heralded photons and phase matching is achieved through the dispersion properties of distinct spatial modes in a few-mode silica step-index fiber. We show that fiber-core-radius fluctuations in general severely impact the single-photon purity. Furthermore, by optimizing the fiber design we show that generation of single photons with very high spectral purity is feasible even in the presence of large core-radius fluctuations. At the same time, contamination from spontaneous Raman scattering is greatly mitigated by separating the single-photon frequency by more than 32 THz from the pump frequency.


Variation in rates of uptake of preventive options by Canadian women carrying the BRCA1 or BRCA2 genetic mutation.
Women with a BRCA1 or BRCA2 genetic mutation have several options for cancer prevention, including prophylactic surgery, chemoprevention and screening. In this study we report on preventive practices used by women with and without breast cancer and examine differences in their selection of preventive practices according to geographic area in Canada. Canadian women with a BRCA1 or BRCA2 mutation were followed after genetic testing and questioned about their preventive practices. Women reported on uptake of prophylactic mastectomy, prophylactic oophorectomy, tamoxifen or raloxifene usage and screening practices. We analyzed the uptake of each preventive option and completed a subanalysis according to the geographic area in Canada where genetic testing was provided. The study included 672 women. Follow-up questionnaires were completed after a mean of 4.0 years (range 1.6-9.1 years). Of the 342 women without breast cancer, 72 (21%) had had a prophylactic bilateral mastectomy. Three hundred and sixty-three women (54%) had had a bilateral prophylactic oophorectomy. Seventeen (6%) of the 270 women without breast cancer who had not had a prophylactic mastectomy took tamoxifen, and 12 (4%) reported taking raloxifene. Of the 342 women without breast cancer, 157 (46%) had not undertaken any cancer prevention option (mastectomy, oophorectomy or treatment with tamoxifen or raloxifene). Sixty-five (39%) of the 167 women from Ontario, 19 (34%) of the 56 women from Western Canada and 73 (62%) of the 119 women from Quebec had not undertaken any preventive procedure. Significant differences in the uptake of preventive options by women with a BRCA1 or BRCA2 mutation were observed across 3 regions of Canada. Future research is needed to explain why these differences exist.


Toward a psychology of humiliation in asymmetric conflict.
Humiliation is often cited in attempts to understand the origins of asymmetric conflicts, especially conflicts involving terrorism. This article reviews common usage, expert opinion, and experiences in interpersonal and intergroup conflicts to suggest a construct definition of humiliation as a combination of anger and shame. Following appraisal theory, this definition distinguishes between the situational appraisals associated with humiliation (insult and injury; failure to retaliate) and the emotional experience of humiliation (in which the combination of anger and shame may be more synergism than summation). Research on humiliation has barely begun and focuses on interpersonal relations; a crucial issue is whether interpersonal humiliation is the same experience as the intergroup humiliation salient in accounts of terrorism and terrorists. Also important is the prediction that the targets of terrorist attack will experience humiliation if the terrorists are unknown or unreachable; thus failure to retaliate may humiliate the strong as well as the weak in asymmetric conflict. Better understanding of humiliation may be useful for understanding both terrorist violence and government reactions to this violence. (PsycINFO Database Record


Evidence of anhedonia and differential reward processing in prefrontal cortex among post-withdrawal patients with prescription opiate dependence.
Anhedonia is an important but understudied element of a neuroadaptive model underlying vulnerability to relapse in opioid dependence. Previous research using fMRI has shown reduced activation to pleasant stimuli in rostral prefrontal cortex among heroin-dependent patients in early recovery. This study evaluated the presence of anhedonia among recently withdrawn prescription opiate dependent patients (PODP) in residential treatment compared to control subjects. Anhedonia was assessed using self-report, affect-modulated startle response (AMSR), and a cue reactivity task during which participant's rostral prefrontal cortex (RPFC) and ventrolateral prefrontal cortex (VLPFC) was monitored with functional near infrared spectroscopy (fNIRS). The cue reactivity task included three distinct categories of natural reward stimuli: highly palatable food, positive social situations, and intimate (non-erotic) interactions. PODP reported greater anhedonia on self-report (Snaith-Hamilton Pleasure Scale), and showed reduced hedonic response to positive stimuli in the AMSR task relative to controls. PODP also exhibited reduced neural activation in bilateral RPFC and left VLPFC in response to food images and reduced left VLPFC in response to images depicting positive social situations relative to controls. No differences were found for emotionally intimate stimuli. When patients were divided into groups based on the Snaith-Hamilton criteria for the presence or absence of anhedonia, patients endorsing anhedonia showed reduced neural responses to images depicting positive social stimuli and food relative to patients who did not endorse anhedonia. Activations were in areas of RPFC that support the retrieval of episodic memories. The results suggest the presence of anhedonia in a subsample of PODP.


Mitochondrial Processing Peptidases-Structure, Function and the Role in Human Diseases.
Mitochondrial proteins are encoded by both nuclear and mitochondrial DNA. While some of the essential subunits of the oxidative phosphorylation (OXPHOS) complexes responsible for cellular ATP production are synthesized directly in the mitochondria, most mitochondrial proteins are first translated in the cytosol and then imported into the organelle using a sophisticated transport system. These proteins are directed mainly by targeting presequences at their N-termini. These presequences need to be cleaved to allow the proper folding and assembly of the pre-proteins into functional protein complexes. In the mitochondria, the presequences are removed by several processing peptidases, including the mitochondrial processing peptidase (MPP), the inner membrane processing peptidase (IMP), the inter-membrane processing peptidase (MIP), and the mitochondrial rhomboid protease (Pcp1/PARL). Their proper functioning is essential for mitochondrial homeostasis as the disruption of any of them is lethal in yeast and severely impacts the lifespan and survival in humans. In this review, we focus on characterizing the structure, function, and substrate specificities of mitochondrial processing peptidases, as well as the connection of their malfunctions to severe human diseases.


Bio-based hyperbranched poly(ester amide)-MWCNT nanocomposites: multimodalities at the biointerface.
There has been a growing interest in the use of nanomaterials featuring potent biocompatibility and biodegradability together with the added facet of antibacterial activity, particularly against drug-resistant bacterial species. Addressing these three features at the biointerface, we report the fabrication of multimodal bio-based hyperbranched poly(ester amide) (HBPEA)-microwave functionalized multiwalled carbon nanotube (f-MWCNT) nanocomposites by incorporation of various weight percentages (1, 2.5, and 5 wt%) of the f-MWCNTs into HBPEA by using an ex situ polymerization technique. Fourier transform infrared spectroscopy confirmed the structural changes upon interaction of the f-MWCNTs with HBPEA. The formation of thermosetting nanocomposites resulted in an acceptable improvement of the desired properties including their mechanical properties (∼170%), instrumental for providing mechanical integrity in cultured cells. The nanocomposite films were found to be biocompatible substrates for the in vitro adhesion and proliferation of peripheral blood mononuclear cells (PBMC) with enhanced cell viability correlating with the increase of the f-MWCNT content. The antibacterial results, monitored by a CFU count and the protein concentration, demonstrated that the prepared nanocomposites were more toxic towards Gram positive bacteria and Mycobacterium smegmatis than the Gram negative ones. The damage of bacterial cells upon interaction with the nanocomposites was validated by UV-visible spectroscopy and a SEM study. The antibacterial and biocompatibility studies suggested that these microporous nanocomposite films (3D interconnected porous structures with pore diameters of 5-105 μm and a porosity of 39.90%) possess concurrent long-term lethal activity against the bacterial cells and biocompatibility with PBMC. Thus, the prepared nanocomposites may find potential bio-medical applications, particularly as antimicrobial dressing materials for infected burn wounds.


Impact evaluation of iron & iodine fortified salt.
As a novel approach to tackle the problems of iron deficiency anaemia and iodine deficiency disorders (IDDs), which often coexist, the National Institute of Nutrition has developed iron and iodine fortified common salt (double fortified salt-DFS) as a public health measure. This salt has undergone a battery of laboratory and field tests to evaluate its feasibility for use in a national programme. The DFS is designed to provide 1 mg of iron and 15 micrograms of iodine per gram of common salt. This was made possible by the inclusion of a polyphosphate stabilizer, sodium hexametaphosphate (SHMP) at 1 per cent level. The stability of iron and iodine was found to be good up to 6 months. However, the stability of iodine depended upon the quality of the salt used for fortification. The biological effects of long-term consumption of DFS were evaluated in experimental rats and in field trials. Both iron and iodine from the salt were found to be biologically available in regenerating haemoglobin and in increasing excretion of iodine in urine. When this salt was tested in tribal villages endemic for goitre and iron deficiency anaemia, the bioresponse was good with regard to the iodine status but was not uniform in all segments with regard to iron, probably due to confounding variables. In a study carried out in residential school children where such variables did not exist, DFS was found to have significant impact on haemoglobin status in anaemic children and improved their urinary iodine excretion. The consumption of DFS for 2 yr did not have any adverse effects in school children as well as in the tribal population. Parameters related to calcium homeostasis were not altered in children receiving DFS. Histopathological examination of tissues and radiological examination of bone did not reveal any abnormality in DFS fed rats. Similarly serum and urinary parameters related to calcium and phosphorus were not altered in DFS fed rats. Therefore, DFS is presented as a feasible and effective strategy to control the double deficiency of iron and iodine in our community.


Threatened Neotropical seasonally dry tropical forest: evidence of biodiversity loss in sap-sucking herbivores over 75 years.
Tropical forests cover 7% of the earth's surface and hold 50% of known terrestrial arthropod species. Alarming insect declines resulting from human activities have recently been documented in temperate and tropical ecosystems worldwide, but reliable data from tropical forests remain sparse. The sap-sucking tribe Athysanini is one herbivore group sensitive to anthropogenic perturbation and the largest within the diverse insect family Cicadellidae distributed in America's tropical forests. To measure the possible effects of deforestation and related activities on leafhopper biodiversity, a survey of 143 historic collecting localities was conducted to determine whether species documented in the Mexican dry tropical forests during the 1920s to 1940s were still present. Biostatistical diversity analysis was performed to compare historical to recent data on species occurrences. A data matrix of 577 geographical records was analysed. In total, 374 Athysanini data records were included representing 115 species of 41 genera. Historically, species richness and diversity were higher than found in the recent survey, despite greater collecting effort in the latter. A strong trend in species decline was observed (-53%) over 75 years in this endangered seasonally dry ecosystem. Species completeness was dissimilar between historic and present data. Endemic taxa were significantly less important and represented in the 1920s-1940s species records. All localities surveyed in the dry tropical forest are disturbed and reduced by modern anthropogenic processes. Mexico harbours highly endemic leafhopper taxa with a large proportion of these inhabiting the dry forest. These findings provide important data for conservation decision making and modelling of distribution patterns of this threatened seasonally dry tropical ecosystem.


Outcome of rhinoplasty in patients undergoing autospreader flaps without notable dorsal hump reduction: A clinical trial.
Reconstruction of the nasal midvault is an important component of successful rhinoplasty outcomes. Use of the autospreader flap is a beneficial technique for preserving the middle vault. In the present study, we evaluated the esthetic and functional outcomes of this technique in patients without notable dorsal hump reduction. A nonrandomized clinical trial was performed from December 2017 to April 2018 with a minimum follow-up time of 6 months. From among patients seeking rhinoplasty, 38 were eligible for inclusion in the study. The autospreader flap was used to recreate the middle vault in patients undergoing open rhinoplasty, with up to 2 mm bony and cartilaginous dorsal hump removal. Preoperative and postoperative standard photographs were obtained. Assessment of patients was based on Rhinoplasty Outcome Evaluation (ROE) and Nasal Obstruction Symptom Evaluation Scale (NOSE) scores. Objective assessment included quantitative analysis of anthropometric angles, mean dorsal width, nasal length, and projection which was performed on standard pre- and postoperative photos. Overall, the patients had statistically significant improvement in their postoperative NOSE scores (9 vs. 6.92, p = 0.0001). The majority of patients were satisfied with the postoperative appearance of their noses. The mean nasal dorsal width (NDW) decreased postoperatively (43% vs. 36%). No difference was found between the mean height of the nose and projection pre- and postoperatively. There was a significant postoperative increase in the nasolabial angle and reduction in nasal length. The autospreader flap is an effective technique for preservation and restoration of the middle vault and dorsal esthetic line in cases of less than 2 mm dorsal hump reduction. Nasal function can be improved while achieving good cosmetic outcomes.


[Oxidative phosphorylation of Krebs cycle substrates in experimental treatment of enterocolitis with cytochrome c].
After administration of exogenous cytochrome c into rats with enterocolitis, caused by salmonellae, tissue respiration and oxidative phosphorylation in presence of succinic, alpha-ketoglutaric, pyruvic and oxaloacetic acids were increased in the liver tissue. Treatment with cytochrome c produced a positive effect on the general state of an organism, led to disappearance of macroscopic alterations in mucosa of small intestine. The data obtained suggest that cytochrome c possesses the positive therapeutic effects in enterocolitis caused by salmonellae.


Persistent postpartum urinary retention in contemporary obstetric practice. Definition, prevalence and clinical implications.
To prospectively evaluate the prevalence, presumed etiologies and clinical implications of persistent postpartum urinary retention in modern obstetric practice. The study population comprised 8,402 consecutive, unselected parturients delivered in a university-affiliated maternity hospital over a one-year period. If a woman was unable to void spontaneously until the third postpartum day despite intermittent use of a Foley catheter, a diagnosis of persistent postpartum urinary retention was established. Patients were treated by insertion of a Foley catheter for up to two weeks and subsequently by a suprapubic catheter. Obstetric data were collected from the hospital records. Four patients (0.05% of the study population), aged 29-37 years, developed persistent postpartum urinary retention. Risk factors included vaginal delivery after cesarean section, prolonged second stage of labor, epidural analgesia, and delayed diagnosis and intervention. Urodynamic evaluation, performed on two patients one month after removal of the suprapubic catheter, revealed genuine stress incontinence in one and detrusor instability in another. None had had any lower urinary tract symptoms before pregnancy and delivery. Persistent postpartum urinary retention in contemporary obstetric practice is rare but may be associated with long-term bladder dysfunction. Early diagnosis and intervention are required to prevent irreversible bladder damage.


Isolation and amino acid sequence of a short-chain neurotoxin from an Australian elapid snake, Pseudechis australis.
A short-chain neurotoxin Pseudechis australis a (toxin Pa a) was isolated from the venom of an Australian elapid snake Pseudechis australis (king brown snake) by sequential chromatography on CM-cellulose, Sephadex G-50 and CM-cellulose columns. Toxin Pa a has an LD50 (intravenous) value of 76 micrograms/kg body wt. in mice and consists of 62 amino acid residues. The amino acid sequence of Pa a shows considerable homology with those of short-chain neurotoxins of elapid snakes, especially of true sea snakes.


Inhibition of muscle cell relaxation by somatostatin: tissue-specific, cAMP-dependent, pertussis toxin-sensitive.
The direct action of somatostatin on smooth muscle was examined in muscle cells isolated from the stomach and intestine of human and guinea pig. Somatostatin inhibited relaxation in gastric but not intestinal muscle cells of the two species, and its mechanism of action was explored in more detail in gastric muscle cells of the guinea pig. Somatostatin inhibited relaxation induced by vasoactive intestinal peptide (VIP, 83 +/- 7%, P less than 0.001) and isoproterenol (85 +/- 5%, P less than 0.001), as well as the concomitant increase in adenosine 3',5'-cyclic monophosphate (cAMP) production [81 +/- 25% inhibition with VIP (P less than 0.02) and 68 +/- 12% inhibition with isoproterenol (P less than 0.01)]. Inhibition of relaxation and cAMP production was abolished by pretreatment of the cells with pertussis toxin. Relaxation induced by the permeant derivative of cAMP, N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate, by sodium nitroprusside, which acts by increasing levels of guanosine 3',5'-cyclic monophosphate, or by ATP, which acts by opening of K+ channels, was not affected by somatostatin. The fact that inhibition by somatostatin and its reversal by pertussis toxin was confined to agonists that stimulate an increase in the levels of cAMP implied that somatostatin acts by inhibiting the generation and not the action of cAMP. It is concluded that somatostatin receptors on gastric muscle cells mediate inhibition via a GTP-binding, pertussis-sensitive regulatory protein, Gi, coupled to adenylate cyclase.


Cs2InAgCl6: A New Lead-Free Halide Double Perovskite with Direct Band Gap.
A2BB'X6 halide double perovskites based on bismuth and silver have recently been proposed as potential environmentally friendly alternatives to lead-based hybrid halide perovskites. In particular, Cs2BiAgX6 (X = Cl, Br) have been synthesized and found to exhibit band gaps in the visible range. However, the band gaps of these compounds are indirect, which is not ideal for applications in thin film photovoltaics. Here, we propose a new class of halide double perovskites, where the B3+ and B+ cations are In3+ and Ag+, respectively. Our first-principles calculations indicate that the hypothetical compounds Cs2InAgX6 (X = Cl, Br, I) should exhibit direct band gaps between the visible (I) and the ultraviolet (Cl). Based on these predictions, we attempt to synthesize Cs2InAgCl6 and Cs2InAgBr6, and we succeed to form the hitherto unknown double perovskite Cs2InAgCl6. X-ray diffraction yields a double perovskite structure with space group Fm3̅m. The measured band gap is 3.3 eV, and the compound is found to be photosensitive and turns reversibly from white to orange under ultraviolet illumination. We also perform an empirical analysis of the stability of Cs2InAgX6 and their mixed halides based on Goldschmidt's rules, and we find that it should also be possible to form Cs2InAg(Cl1-xBrx)6 for x < 1. The synthesis of mixed halides will open the way to the development of lead-free double perovskites with direct and tunable band gaps.


The prognostic ease and difficulty of invasive breast carcinoma.
Breast carcinoma (BC) has been extensively profiled by high-throughput technologies for over a decade, and broadly speaking, these studies can be grouped into those that seek to identify patient subtypes (studies of heterogeneity) or those that seek to identify gene signatures with prognostic or predictive capacity. The sheer number of reported signatures has led to speculation that everything is prognostic in BC. Here, we show that this ubiquity is an apparition caused by a poor understanding of the interrelatedness between subtype and the molecular determinants of prognosis. Our approach constructively shows how to avoid confounding due to a patient's subtype, clinicopathological profile, or treatment profile. The approach identifies patients who are predicted to have good outcome at time of diagnosis by all available clinical and molecular markers but who experience a distant metastasis within 5 years. These inherently difficult patients (~7% of BC) are prioritized for investigations of intratumoral heterogeneity.


Predicting optimal electrical stimulation for repetitive human muscle activation.
Functional electrical stimulation is the use of electrical currents to activate paralyzed muscles to produce functional movements. Muscle force output must meet or exceed the external load to maintain a posture or produce movements. A mathematical force-fatigue modeling system that predicts muscle force responses during repetitive electrical stimulation has been developed in our laboratory to help identify stimulation patterns that optimize force output for individual subjects. This study tests how well this model predicts the number of contractions that can be maintained above a required force level (successful contractions) during repetitive activation of a muscle. Healthy human quadriceps muscles were tested isometrically on 12 subjects. Data were first collected and used to parameterize the model. Next, the model was used to predict the number of successful contractions that were produced by trains with frequencies ranging from 5 to 100 Hz while the pulse durations and amplitudes were held constant. Finally, three clinically relevant stimulation frequencies were selected and tested to verify the model's predictions. Under these conditions, the model accurately predicted the number of successful contractions for clinically relevant stimulation frequencies. Furthermore, the model appears to have the potential to identify the stimulation frequency that maximizes muscle force output and minimizes fatigue for each subject.


Effect of Olea oleaster and Juniperus procera leaves extracts on thioacetamide induced hepatic cirrhosis in male albino mice.
The effect of Olea oleaster and Juniperus procera leaves extracts and their combination on thioacetamide (TAA)-induced hepatic cirrhosis were investigated in male albino mice. One hundred sixty mice were used in this study and were randomly distributed into eight groups of 20 each. Mice of group 1 served as controls. Mice of group 2 were treated with TAA. Mice of group 3 were exposed to TAA and supplemented with O. oleaster leaves extracts. Mice of group 4 were treated with TAA and supplemented with J. procera leaves extracts. Mice of group 5 were subjected to TAA and supplemented with O. oleaster and J. procera leaves extracts. Mice of groups 6, 7 and 8 were supplemented with O. oleaster, J. procera, and O. oleaster and J. procera leaves extracts respectively. Administration of TAA for six and twelve weeks resulted in a decline in body weight gain and increased the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Histopathological evaluations of hepatic sections from mice treated with TAA showed severe alterations including increase of fibrogenesis processes with structural damage. Treatment of mice with these extracts showed a pronounced attenuation in TAA induced hepatic cirrhosis associated with physiological and histopathological alterations. Finally, this study suggests that the supplementation of these extracts may act as antioxidant agents and could be an excellent adjuvant support in the therapy of hepatic cirrhosis.


Validity of the multidimensional fatigue symptom inventory-short form in an African-American community-based sample.
This study examined the psychometric properties of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) in a community-based sample of African-Americans. A sample of 340 African-Americans (116 men, 224 women) ranging in age from 18-81 years were recruited from the community (e.g., churches, health fairs, and beauty salons). Participants completed a brief demographic survey, the MFSI-SF and the Positive and Negative Affect Schedule. The structural validity of the MFSI-SF for a community-based sample of African-Americans was not supported. The five dimensions of fatigue (General, Emotional, Physical, Mental, Vigor) found for Whites in prior research were not found for African-Americans in this study. Instead, fatigue, while multidimensional for African-Americans, was best represented by a unique four-four profile in which general and emotional fatigue are collapsed into a single dimension and physical fatigue, mental fatigue, and vigor are relatively distinct. Hence, in the absence of modifications, the MFSI-SF cannot be considered to be structurally invariant across ethnic groups. A modified four-factor version of the MFSI-SF exhibited excellent internal consistency reliability and evidence supports its convergent validity. Using the modified four-factor version, gender, and age were not meaningfully associated with MFSI-SF scores. Future research should further examine whether modifications to the MFSI-SF would, as the findings suggest, improve its validity as a measure of multidimensional fatigue in African-Americans.


Tunneling transverse to a magnetic field and its occurrence in correlated 2D electron systems.
We investigate tunneling decay in a magnetic field. Because of broken time-reversal symmetry, the standard WKB technique does not apply. The decay rate and the outcoming wave packet are found from the analysis of the set of the particle Hamiltonian trajectories and its singularities in complex space. The results are applied to tunneling from a strongly correlated 2D electron system in a magnetic field parallel to the layer. We show in a simple model that electron correlations strongly affect the tunneling rate.


Undiagnosed tuberculosis associated with hemophagocytic lymphohistiocytosis due to improper use of corticosteroid.
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hematologic disease segregated into familial (primary) and acquired (secondary) subtypes. Hyperinflammation and HLH occur when the immune system fails to clear activated macrophages and histiocytes. Infections, malignancies, and rheumatologic disorders are the major triggers leading to HLH. Miliary tuberculosis is a serious disease with a lymphohematogenous spread of Mycobacterium tuberculosis, which is known to be one of the causative agents of HLH. Miliary tuberculosis and HLH have atypical presentations which are similar to routine diseases. Hence, physicians may face challenges to diagnose and treat these complications. We report the case of a 60-year-old man with a history of prolonged fever, shortness of breath, jaundice, altered mental status, undiagnosed lower back pain, and overuse of parenteral betamethasone. Miliary tuberculosis was diagnosed by diffuse, vague random micronodules in both lungs and positive acid-fast bacilli in bronchoalveolar lavage and bone marrow aspiration and biopsy. Moreover, compatible presentation and pancytopenia, hypertriglyceridemia, high serum level of ferritin and fibrinogen-derived products, and evidence of hemophagocytosis on bone marrow aspirate led to the diagnosis of HLH. Unfortunately, despite nearly two months of an anti-tuberculosis regimen (standard and salvage) and eight doses of etoposide, he eventually passed away after clinical improvement. Irrational and indiscriminate use of glucocorticoids can be a devastating cause of the spread of tuberculosis and its rare complications, such as HLH.


Identification of the G protein-coupled estrogen receptor (GPER) in human prostate: expression site of the estrogen receptor in the benign and neoplastic gland.
Estrogens are involved in growth, differentiation and pathogenesis of human prostate through the mediation of the classical estrogen receptors ERα and ERβ. The G protein-coupled estrogen receptor (GPER) is a 'novel' mediator of estrogen signaling which has been recently recognized in some human reproductive tissues, but its expression in the prostate gland is still unknown. Here, we investigated GPER in benign (from 5 patients) and neoplastic prostatic tissues (from 50 patients) by immunohistochemical analysis and Western blotting. Normal areas of benign prostates revealed a strong GPER immunoreactivity in the basal epithelial cells while luminal epithelial cells were unreactive and stromal cells were weakly immunostained. GPER was also immunolocalized in adenocarcinoma samples but the immunoreactivity of tumoral areas decreased from Gleason pattern 2 to Gleason pattern 4. Furthermore, a strong GPER immunostaining was also revealed in cells of pre-neoplastic lesions (high-grade prostatic intra-epithelial neoplasia). Western blot analysis of benign and tumor protein extracts showed the presence of a ~42 kDa band, consistent with the GPER molecular weight. An increase in both pAkt and p cAMP-response-binding protein (pCREB) levels was also observed in poorly differentiated PCa samples. Finally, this work identified GPER in the epithelial basal cells of benign human prostate, with a different localization with respect to the classical estrogen receptors. Furthermore, the expression of GPER in prostatic adenocarcinoma cells was also observed but with a modulation of the immunoreactivity according to tumor cell arrangements.


Influence of musical groove on postural sway.
Timescales of postural fluctuation reflect underlying neuromuscular processes in balance control that are influenced by sensory information and the performance of concurrent cognitive and motor tasks. An open question is how postural fluctuations entrain to complex environmental rhythms, such as in music, which also vary on multiple timescales. Musical groove describes the property of music that encourages auditory-motor synchronization and is used to study voluntary motor entrainment to rhythmic sounds. The influence of groove on balance control mechanisms remains unexplored. We recorded fluctuations in center of pressure (CoP) of standing participants (N = 40) listening to low and high groove music and during quiet stance. We found an effect of musical groove on radial sway variability, with the least amount of variability in the high groove condition. In addition, we observed that groove influenced postural sway entrainment at various temporal scales. For example, with increasing levels of groove, we observed more entrainment to shorter, local timescale rhythmic musical occurrences. In contrast, we observed more entrainment to longer, global timescale features of the music, such as periodicity, with decreasing levels of groove. Finally, musical experience influenced the amount of postural variability and entrainment at local and global timescales. We conclude that groove in music and musical experience can influence the neural mechanisms that govern balance control, and discuss implications of our findings in terms of multiscale sensorimotor coupling. (PsycINFO Database Record


Genetic and biochemical identification of the glutamate synthase structural gene in Neurospora crassa.
Neurospora crassa cells require glutamate synthase activity for growth under ammonium-limiting conditions. Despite the physiological importance of glutamate synthase, little is known about the genetics of its expression. To identify the glutamate synthase structural gene, we isolated three new mutants lacking this activity. All mutations are recessive to the wild-type allele and belong to the same complementation group as the previously described en(am)-2 (C24) mutation. Two lines of evidence indicate that en(am)-2 is the structural gene for glutamate synthase in N. crassa. The en(am)-2+ gene shows a gene dosage effect on enzyme activity, and some mutants lacking glutamate synthase activity have cross-reacting material. These data suggest that the mutations are located in the structural gene for N. crassa glutamate synthase.


An antiviral role for antimicrobial peptides during the arthropod response to alphavirus replication.
Alphaviruses establish a persistent infection in arthropod vectors which is essential for the effective transmission of the virus to vertebrate hosts. The development of persistence in insects is not well understood, although it is thought to involve the innate immune response. Using a transgenic fly system expressing a self-replicating viral RNA genome analog, we have previously demonstrated antiviral roles of the Drosophila Imd (immune deficiency) and Jak-STAT innate immunity pathways in response to alphavirus replication. In the present study, comparative microarray analysis of flies harboring an alphavirus replicon and control green fluorescent protein flies identified 95 SINrep-sensitive genes. Furthermore, a subset of these genes is regulated by Rel or STAT transcription factors of the Imd and Jak-STAT pathways, respectively. We identified two antimicrobial peptide genes, attC and dptB, which are SINrep sensitive and regulated by STAT and Rel, respectively. SINrep flies heterozygous for attC had an increased viral RNA level, while knocking down dptB in SINrep flies resulted in impaired development. When injected with whole virus, the double-stranded RNA knockdowns of either attC or dptB showed a significant increase in virus titers. Our data demonstrate an antiviral response involving the Imd and Jak-STAT mediated expression of dptB and attC.


The empty sella.
Empty sella (ES) is an extension or herniation of the subarachnoid space into the pituitary fossa through an incompetent sellar diaphragm that is commonly associated with clinical manifestations and endocrine abnormalities. The ES may occur secondary to a variety of pituitary disorders or as a primary entity. The pathogenesis of the primary ES appears to be multifactorial though the precise mechanisms remain unclear. The etiology of ES in children may differ from that in adults and is not uncommon in the presence of pituitary disorders. Patients with the ES should always undergo endocrine, neurologic, and ophthalmologic evaluation at the time of initial presentation and should be monitored as determined by the initial results. Treatment should be individualized as the clinical features and biochemical abnormalities vary widely among patients from the asymptomatic state with a normal hormone profile to sight-threatening visual disturbances, CSF rhinorrhea, and panhypopituitarism. The ES should not be considered as merely an incidental finding and clinicians should be aware of its varying presentations and ramifications.


Genetic Evidence for Sexuality in Cochliopodium (Amoebozoa).
Microbial eukaryotes, including amoeboids, display diverse and complex life cycles that may or may not involve sexual reproduction. A recent comprehensive gene inventory study concluded that the Amoebozoa are ancestrally sexual. However, the detection of sex genes in some lineages known for their potentially sexual life cycle was very low. Particularly, the genus Cochliopodium, known to undergo a process of cell fusion, karyogamy, and subsequent fission previously described as parasexual, had no meiosis genes detected. This is likely due to low data representation, given the extensive nuclear fusion observed in the genus. In this study, we generate large amounts of transcriptome data for 2 species of Cochliopodium, known for their high frequency of cellular and nuclear fusion, in order to study the genetic basis of the complex life cycle observed in the genus. We inventory 60 sex-related genes, including 11 meiosis-specific genes, and 31 genes involved in fusion and karyogamy. We find a much higher detection of sex-related genes, including 5 meiosis-specific genes not previously detected in Cochliopodium, in this large transcriptome data. The expressed genes form a near-complete recombination machinery, indicating that Cochliopodium is an actively recombining sexual lineage. We also find 9 fusion-related genes in Cochliopodium, although no conserved fusion-specific genes were detected in the transcriptomes. Cochliopodium thus likely uses lineage specific genes for the fusion and depolyploidization processes. Our results demonstrate that Cochliopodium possess the genetic toolkit for recombination, while the mechanism involving fusion and genome reduction remains to be elucidated.


Inducing and viewing the rotational motion of a single molecule
Tunneling electrons from the tip of a scanning tunneling microscope were used to induce and monitor the reversible rotation of single molecules of molecular oxygen among three equivalent orientations on the platinum(111) surface. Detailed studies of the rotation rates indicate a crossover from a single-electron process to a multielectron process below a threshold tunneling voltage. Values for the energy barrier to rotation and the vibrational relaxation rate of the molecule were obtained by comparing the experimental data with a theoretical model. The ability to induce the controlled motion of single molecules enhances our understanding of basic chemical processes on surfaces and may lead to useful single-molecule devices.


Inhibition of prostaglandin E2-induced phosphoinositide metabolism by phorbol ester in bovine adrenal chromaffin cells.
In bovine adrenal chromaffin cells, prostaglandin E2 (PGE2) stimulates the formation of inositol phosphates and Ca2+ mobilization through its specific receptor [Yokohama, Tanaka, Ito, Negishi, Hayashi & Hayaishi (1988) J. Biol. Chem. 263, 1119-1122]. Here we show that PGE2-induced phosphoinositide metabolism was blocked by pretreatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). Using intact cells, we also examined the inhibitory effect of TPA on the individual steps of the activation process of phosphoinositide metabolism. The inhibition was observed within 1 min and complete by 10 min after addition of 1 microM-TPA, and half-maximal inhibition by TPA occurred at 20 nM. TPA prevented Ca2+ mobilization induced by PGE2, but not by the Ca2+ ionophore ionomycin. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate did not inhibit the formation of inositol phosphates and Ca2+ mobilization by PGE2. TPA treatment affected neither the high-affinity binding of [3H]PGE2 to intact cells and membrane fractions nor the ability of guanosine 5'-[gamma-thio]triphosphate to decrease the binding in membrane fractions. TPA also abolished phosphoinositide metabolism induced by muscarinic-receptor activation. NaF plus AlCl3 and ionomycin caused the accumulation of inositol phosphates, probably by directly activating a GTP-binding protein(s) and phospholipase C respectively; neither accumulation was inhibited by TPA treatment. These results suggest that protein kinase C serves as a feedback regulator for PGE2-induced phosphoinositide metabolism. The site of action of TPA appears to be distal to the coupling of the receptor to GTP-binding protein, but on a component(s) specific to the agonist-induced phosphoinositide metabolism.


M2Align: parallel multiple sequence alignment with a multi-objective metaheuristic.
Multiple sequence alignment (MSA) is an NP-complete optimization problem found in computational biology, where the time complexity of finding an optimal alignment raises exponentially along with the number of sequences and their lengths. Additionally, to assess the quality of a MSA, a number of objectives can be taken into account, such as maximizing the sum-of-pairs, maximizing the totally conserved columns, minimizing the number of gaps, or maximizing structural information based scores such as STRIKE. An approach to deal with MSA problems is to use multi-objective metaheuristics, which are non-exact stochastic optimization methods that can produce high quality solutions to complex problems having two or more objectives to be optimized at the same time. Our motivation is to provide a multi-objective metaheuristic for MSA that can run in parallel taking advantage of multi-core-based computers. The software tool we propose, called M2Align (Multi-objective Multiple Sequence Alignment), is a parallel and more efficient version of the three-objective optimizer for sequence alignments MO-SAStrE, able of reducing the algorithm computing time by exploiting the computing capabilities of common multi-core CPU clusters. Our performance evaluation over datasets of the benchmark BAliBASE (v3.0) shows that significant time reductions can be achieved by using up to 20 cores. Even in sequential executions, M2Align is faster than MO-SAStrE, thanks to the encoding method used for the alignments. M2Align is an open source project hosted in GitHub, where the source code and sample datasets can be freely obtained: https://github.com/KhaosResearch/M2Align. email@example.com. Supplementary data are available at Bioinformatics online.


Assessing the Role of Different Heterogeneous Regions in DCE-MRI for Predicting Molecular Subtypes of Breast Cancer based on Network Architecture Search and Vision Transformer.
Breast cancer, the most common female malignancy, is highly heterogeneous, manifesting as different molecular subtypes. It is clinically important to distinguish between these molecular subtypes due to marked differences in prognosis, treatment and survival outcomes. In this study, we first performed convex analysis of mixtures (CAM) analysis on both intratumoral and peritumoral regions in DCE-MRI to generate multiple heterogeneous regions. Then, we developed a vision transformer (ViT)-based DL model and performed network architecture search (NAS) to evaluate all the combination of different heterogeneous regions for predicting molecular subtypes of breast cancer. Experimental results showed that the input plasma from both peritumoral and intratumoral regions, and the fast-flow kinetics from intratumoral regions were critical for predicting different molecular subtypes, achieving an area under receiver operating characteristic curve (AUROC) value of 0.66-0.68.Clinical Relevance- This study reduces the redundancy in multiple heterogeneous subregions and supports the precise prediction of molecular subtypes, which is of potential importance for the medicine care and treatment planning of patients with breast cancer.


Diagnostic accuracy of 3.0 Tesla magnetic resonance imaging for the detection of articular cartilage lesions of the talus.
Talar chondral defects can be a source of persistent ankle pain and disability. If untreated, there is an increased risk of osteoarthritis. The purpose of our study was to determine diagnostic accuracy of 3T MRI in detecting Outerbridge grades 3 and 4 articular cartilage lesions of the talus in a clinical setting, utilizing a standardized clinical MRI protocol. Patients who had a 3T ankle MRI and subsequent ankle surgery, by a single surgeon, were included in this study. MRI exams were performed 180 days or less before surgery. Seventy-nine ankles in 78 patients (mean age of 42.3 years) were included in this study. Mean body mass index was 26.3. A standard clinical MRI exam was performed on a 3T MRI scanner. Mean days from MRI to surgery was 39 days. All MRI exams were read and findings recorded by a musculoskeletal radiologist. Arthroscopic examination was performed by a single orthopaedic surgeon. Detailed arthroscopic findings and demographic data were collected prospectively and stored in a data registry. Of the 78 patients, 31 (39.2%) reported previous ankle surgery. Pain was the primary reason for seeking medical attention as reported by 95% of patients, followed by instability in 44% and loss of function with 42%. Prevalence of Outerbridge grade 3 and 4 talar articular cartilage defects identified at arthroscopy was 17.7%. The 3T MRI demonstrated a sensitivity of 0.714, specificity of 0.738, positive predictive value of 0.370, and negative predictive value of 0.923. Sensitivity and specificity levels were acceptable for detection of grades 3 and 4 articular cartilage defects of the talar dome using 3T MRI. The high negative predictive value may be beneficial in preoperative planning. While these values are acceptable, a high index of suspicion should be maintained in the appropriate clinical setting.


Measurement-based care for refractory depression: a clinical decision support model for clinical research and practice.
Despite years of antidepressant drug development and patient and provider education, suboptimal medication dosing and duration of exposure resulting in incomplete remission of symptoms remains the norm in the treatment of depression. Additionally, since no one treatment is effective for all patients, optimal implementation focusing on the measurement of symptoms, side effects, and function is essential to determine effective sequential treatment approaches. There is a need for a paradigm shift in how clinical decision making is incorporated into clinical practice and for a move away from the trial-and-error approach that currently determines the "next best" treatment. This paper describes how our experience with the Texas Medication Algorithm Project (TMAP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial has confirmed the need for easy-to-use clinical support systems to ensure fidelity to guidelines. To further enhance guideline fidelity, we have developed an electronic decision support system that provides critical feedback and guidance at the point of patient care. We believe that a measurement-based care (MBC) approach is essential to any decision support system, allowing physicians to individualize and adapt decisions about patient care based on symptom progress, tolerability of medication, and dose optimization. We also believe that successful integration of sequential algorithms with MBC into real-world clinics will facilitate change that will endure and improve patient outcomes. Although we use major depression to illustrate our approach, the issues addressed are applicable to other chronic psychiatric conditions including comorbid depression and substance use disorder as well as other medical illnesses.


Smoking and pre-existing co-morbidities as risk factors for developing severity of COVID-19 infection: Evidence from a field hospital in a rural area of Bangladesh.
Since August 2020; the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) in collaboration with UNICEF has been operating a COVID-19 field hospital at the Teknaf sub-district of Cox's Bazar in Bangladesh. This paper is focused on estimating the effects of a history of tobacco smoking and pre-existing co-morbidities on the severity of COVID-19 infection among adult patients admitted into the aforesaid hospital. We conducted a retrospective data analysis of COVID-19 adult patients hospitalized from August 27, 2020 to April 20, 2022. Based on inclusion criteria; a total of 788 admitted patients were included in the analysis. We conducted a Chi-squared test and Fisher's exact test for the categorical variables to see their associations. Multinomial logistic regression models were performed to explore the risk factors for the severity of COVID-19 infection. Among 788 patients, 18.4%, 18.8%, 13%, 7.1%, 3.4%, and 1.9% have had a history of smoking, hypertension, diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD), and asthma respectively. Overall, the mean age of the patients was 40.3 ± 16.4 years and 51% were female. In multivariate analysis, history of smoking and co-morbidities were identified as the risk factors for the severity of COVID-19 infection; the history of smoking was found linked with an increase in the risk of developing critical, severe, and moderate level of COVID-19 infection- notably 3.17 times (RRR = 3.17; 95% CI: 1.3-7.68), 2.98 times (RRR = 2.98; 95% CI: 1.87-4.76) and 1.96 times (RRR = 1.96; 95% CI: 1.25-3.08) respectively more than the patients who never smoked. It was evident that patients with at least one of the selected co-morbidities such as hypertension, diabetes, COPD, CVD, and asthma exhibited a significantly higher likelihood of experiencing severe illness of COVID-19 compared to patients without any co-morbidity. History of tobacco smoking and pre-existing co-morbidities were significantly associated with an increased severity of COVID-19 infection.


Interaction between the soluble F1 ATPase and its naturally occurring inhibitor protein. Studies using hydrophilic high-performance liquid chromatography and immunoelectron microscopy.
Binding of the isolated ATPase (F1) to its naturally occurring inhibitor protein was studied by two novel, independent techniques. High-pressure gel permeation chromatography revealed one tight binding site (Kd = 0.46 microM) for the inhibitor on F1, and a number of weak, non-specific sites. Use of an antibody directed against a non-binding region of the inhibitor protein demonstrated the formation of inhibitor/F1/immunoglobulin G complexes of 1:1:1 and 2:2:1 stoichiometry, but not of the putatively more stable cyclic 4:2:2 complexes. It was concluded that, despite the presence of three beta-subunits, only one site per F1 molecule is available for binding its inhibitor protein.


Polytopic vector analysis of soil, dust, and serum samples to evaluate exposure sources of PCDD/Fs.
As part of the University of Michigan Dioxin Exposure Study, soil, household dust, and serum samples were collected from more than 750 households in five populations around the city of Midland and in Jackson and Calhoun Counties, Michigan, USA. Polytopic vector analysis, a type of receptor model, was applied to better understand the potential sources of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans found in these samples and to quantify the contributions of the sources in each matrix across populations. The results indicated that source signatures found in soil are similar to those found in dust, reflecting various combustion profiles, pentachlorophenol, and graphite electrode sludge. The profiles associated with contamination in the Tittabawassee River, likely related to historical discharges from the Dow Chemical Company facility in Midland, exhibited the largest differences among the regional populations sampled. Differences in serum source contributions among the study populations were consistent with some of the regional differences observed in soil samples. However, the age trends of these differences suggested that they are related to past exposures, rather than ongoing sources.


Protective Effects of Matricaria chamomilla Extract on Torsion/ Detorsion-Induced Tissue Damage and Oxidative Stress in Adult Rat Testis.
There is some evidence indicating that Matricaria chamomile (MC) had protective effects on ischemiareperfusion. In the present study, a rat model was used to investigate the effect of hydroalcoholic extract of MC on torsion/detorsion-induced testis tissue damage. In this experimental study, 28 male Wistar rats were randomly divided into 4 groups as follows: G1, Sham operated; G2, testicular torsion/detorsion (T/D); G3, rats with testicular torsion/detorsion that received 300 mg/kg of MC extracts 30 minutes before detorsion (T/DMC); and G4, healthy rats that received 300 mg/kg of MC extracts (MC). Also, the reperfusion period was 24 hours. After blood sampling, the oxidative stress marker [e.g. superoxide dismutase (SOD) levels], blood levels of testosterone, and anti-oxidant enzyme levels [e.g. glutathione peroxidase (GPx)] were assessed by ELISA methods. Serum activity of malondialdehyde (MDA) was evaluated by spectrophotometry. Another assessment was carried out by histomorphometry, 24-hour post-procedure. The histological parameters investigated by Johnson's scores (JS), also the seminiferous tubule diameter (STD) and the height of the germinal epithelium (HE) measured using the linear eyepiece grids using light microscopy. Histological features significantly differed between sham and the other groups. The levels of SOD, GPx, and testosterone hormone were significantly decreased in T/D group as compared to sham group, while these parameters increased in T/DMC group as compared to T/D group. During ischemia, the MDA levels increased; however, treatment with MC extract decreased the MDA levels in G3 and G4 groups. Results of the present study demonstrated that MC can protect the testis tissue against torsion/detorsioninduced damages by suppressing superoxide production.


Systems immunology spanning tumors, lymph nodes, and periphery.
The immune system defines a complex network of tissues and cell types that orchestrate responses across the body in a dynamic manner. The local and systemic interactions between immune and cancer cells contribute to disease progression. Lymphocytes are activated in lymph nodes, traffic through the periphery, and impact cancer progression through their interactions with tumor cells. As a result, therapeutic response and resistance are mediated across tissues, and a comprehensive understanding of lymphocyte dynamics requires a systems-level approach. In this review, we highlight experimental and computational methods that can leverage the study of leukocyte trafficking through an immunomics lens and reveal how adaptive immunity shapes cancer.


Characterizing polarization management in a p-HMPD system.
It has been a common challenge to operate optical see-through head-mounted displays in well-lit environments due to the low image brightness and contrast compared with the direct view of a real-world scene. This problem is aggravated in the design of a see-through head-mounted projection display (HMPD) in which the projected light is split twice by a beam splitter and further attenuated greatly by a retroreflective screen. A polarizing head-mounted projection display (p-HMPD) design was recently proposed to enhance the overall flux transfer efficiency and thus increase the brightness and contrast of displayed images. Different from the conventional nonpolarizing HMPD designs, the light polarization states in the p-HMPD system are deliberately manipulated to maximize the flux transfer efficiency, which can potentially result in three times higher efficiency than that of a nonpolarizing HMPD. By measuring the Mueller matrices of the major elements in both a p-HMPD and a nonpolarizing HMPD, we characterize the polarization dependence of each element on incident angles and wavelengths, and also investigate the depolarization effect of the retroreflective screen. Based on these experimental results, we further examine the overall luminance efficiencies of the two types of systems and analyze how various aspects of display performances are affected by the angular and chromatic dependence of the polarization components.


Irreparable Radial Nerve Palsy Due to Delayed Diagnostic Management of a Giant Lipoma at the Proximal Forearm Resulting in a Triple Tendon Transfer Procedure: Case report and Brief Review of Literature.
Non-traumatic radial nerve palsy (RNP) caused by local tumors is a rare and uncommon entity. A 62-year-old female presented with a left non-traumatic RNP, initially starting with weakness only. It was caused by a benign giant lipoma at the proximal forearm that was misdiagnosed over a period of 2 years. The slowly growth of the tumor led to an irreparable overstretching-related partial nerve disruption. For functional recovery of the patient, a triple tendon transfer procedure had to be performed. Four months after surgery, the patient was completely able to perform her activities of daily living again. At the 10-months follow-up, strength of wrist extension, thumb's extension and abduction, and long fingers II-V extension had all improved to grade 4 in Medical Research Council scale (0-5). In order to restore motion, the patient reported that she would undergo the same triple tendon transfer procedure a second time where necessary. Due to the initially misdiagnosed tumor, there was an overall delayed duration of time for functional recovery of the patient. The triple tendon transfer procedure offers a useful and reliable method to restore functionality for patients sustaining irreparable RNP. However, it must be noted critically with our patient that this procedure probably would have been avoided. Initially, there was weakness only by entrapment of the radial nerve. RNP caused by local tumors are uncommon but known from the literature, and so it should be considered generally in differential diagnosis of non-traumatic RNP.


Nucleotide sequence of tobacco mosaic virus RNA.
Oligonucleotide primers have been used to generate a cDNA library covering the entire tobacco mosaic virus (TMV) RNA sequence. Analysis of these clones has enabled us to complete the viral RNA sequence and to study its variability within a viral population. The positive strand coding sequence starts 69 nucleotides from the 5' end with a reading frame for a protein of Mr 125,941 and terminates with UAG. Readthrough of this terminator would give rise to a protein of Mr 183,253. Overlapping the terminal five codons of this readthrough reading frame is a second reading frame coding for a protein of Mr 29,987. This gene terminates two nucleotides before the initiator codon of the coat protein gene. Potential signal sequences responsible for the capping and synthesis of the coat protein and Mr 29,987 protein mRNAs have been identified. Similar sequences within these reading frames may be used in the expression of sets of proteins that share COOH-terminal sequences.


Immunology of paraneoplastic syndromes: overview.
Cancers that cause disturbances of organs or tissues remote from the site of the tumor or its metastases are called paraneoplastic syndromes. The nervous system can be affected at virtually any site, including the neuromuscular junction (e.g., Lambert-Eaton myasthenic syndrome, myasthenia gravis). Paraneoplastic syndromes affecting the central nervous system are characterized by (1) high titers of antibodies that react with both the cancer and the affected portion of the nervous system, (2) specifically reacting T cells in the blood and cerebrospinal fluid, and (3) autopsy evidence of neuronal destruction, inflammatory infiltrates, and antibody penetration. Clinically, paraneoplastic syndromes affecting the central nervous system are usually subacute in onset, rapid in evolution, and cause severe damage, but generally stabilize after several months with or without treatment. Immune suppression does not appear to be particularly effective in treating these disorders. Treatment of the underlying cancer sometimes ameliorates symptoms.


Psychological and behavioral characteristics of suicide attempts and non-suicidal self-injury in Chinese adolescents.
Suicide attempts (SA) and non-suicidal self-injury (NSSI) are prevalent in adolescents and important risk factors of suicide death. Both SA and NSSI are associated with multiple psychosocial, behavioral, biological and genetic factors. This study examined similarities and differences in psychological vulnerability and internalizing and externalizing problems between adolescents with SA and NSSI. Participants consisted of 11,831 students and had a mean age of 14.97 (SD = 1.46) years. Students completed a structured questionnaire to report their demographic information, psychological characteristics, internalizing and externalizing problems, SA and NSSI. Based on the history of NSSI and SA in the last year, the sample was divided into four groups: non-self-harm (NSH), NSSI only, SA only, and NSSI+SA. Multivariate analyses of covariance and post-hoc pairwise comparisons were performed for multiple comparisons. Compared with NSH group, adolescents with either NSSI or SA scored significantly higher on trait anger, impulsiveness, hopelessness, internalizing and externalizing problems. NSSI+SA group and SA only group scored significantly higher than NSSI only group but both did not score significantly different on most psychological and behavioral variables. Limitations include reliance on self-reported measures and cross-sectional survey. Psychological and behavioral profiles between adolescents with SA and NSSI are similar but are more severe in suicide attempters. The findings highlight the necessity of assessing psychological and behavioral problems for prevention and early intervention of adolescent self-harm.


Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study.
Type 2 diabetes mellitus (T2DM) is a condition defined by hyperglycaemia, but also often presents with dyslipidaemia and suppressed HDL cholesterol. Mendelian randomization studies have suggested a causal link between low HDL cholesterol and T2DM. However, influences of gender, polymorphisms and lifestyle, all known to influence HDL cholesterol, have not been fully explored in a prospective cohort. In 2001-2002, a random sample of 1514 males (18-87 years old) and 1528 females (18-89 years old) were recruited in the ATTICA study. The 10-year follow-up (2011-2012) included 1485 participants. Lipids and lipoproteins levels, glucose and insulin levels were measured together with apolipoprotein A1 (apoA1) 75 G/A genotype, which is known to influence HDL-cholesterol. In total, 12.9% of the study sample developed T2DM within the 10-year follow-up period. In multivariable models, for each mg/dL increase in apoA1 levels in males, 10-year T2DM risk decreased 1.02%; while every unit increase in apoB/LDL-cholesterol ratio increased risk 4-fold. Finally, for every unit increase in triglycerides/apoA1 ratio, the risk increased 85%. HOMA-IR independently predicted T2DM 10-year incidence only for carriers of GG polymorphism (all, p < 0.05), but not in carriers of the GA polymorphism (all, p > 0.05). ApoA1 was associated with decreased T2DM risk and TG/ApoA1 and apoB/LDL were associated with increased risk of T2DM, only in males. ApoA1 polymorphism, which is associated with lower HDL cholesterol, influenced the predictive effects of HOMA-IR on T2DM incidence, which appeared to be moderated by physical activity, suggesting potential scope for more targeted preventative strategies.


Single-state measurement of electrical conductivity of warm dense gold.
We report on a single-state measurement of electrical conductivity of warm dense gold in the solid to plasma transition regime. This is achieved using the idealized slab plasma approach of isochoric heating of ultrathin samples by a femtosecond laser, coupled with femtosecond probe measurements of reflectivity and transmission. The experiment also reveals the time scale associated with the disassembly of laser heated solid.


Developmental Origins of Health and Disease (DOHaD): Implications for health and nutritional issues among rural children in China.
In China, with fast economic growth, health and nutrition status among the rural population has shown significant improvement in the past decades. On the other hand, burden of non-communicable diseases and prevalence of related risk factors such as overweight and obesity has also increased. Among rural children, the double burden of malnutrition and emerging overweight and obesity has been neglected so far. According to the theory of Developmental Origin of Health and Diseases (DOHaD), malnutrition, including both undernutrition (stunting and wasting) and over-nutrition (overweight and obesity) during childhood is closely related to worsened health outcomes during adulthood. Such a neglected problem is attributable to a complicated synergy of social and environmental factors such as parental migration, financial situation of the household, child-rearing knowledge and practices of the primary caregivers, and has implications for public health. Based on literature review of lessons from the field, intervention to address malnutrition among rural children should be a comprehensive package, with consideration of their developmental environment and geographical and socioeconomic diversity. The scientific evidence on DOHaD indicates the probability and necessity of prevention of adult disease by promotion of maternal and child health and reducing malnutrition by provision of high-quality complementary foods, promotion of a well-balanced dietary pattern, and promotion of health literacy in the public would bring a potential benefit to reduce potential risk of diseases.


Loss of nucleus accumbens low-frequency fluctuations is a signature of chronic pain.
Chronic pain is a highly prevalent disease with poorly understood pathophysiology. In particular, the brain mechanisms mediating the transition from acute to chronic pain remain largely unknown. Here, we identify a subcortical signature of back pain. Specifically, subacute back pain patients who are at risk for developing chronic pain exhibit a smaller nucleus accumbens volume, which persists in the chronic phase, compared to healthy controls. The smaller accumbens volume was also observed in a separate cohort of chronic low-back pain patients and was associated with dynamic changes in functional connectivity. At baseline, subacute back pain patients showed altered local nucleus accumbens connectivity between putative shell and core, irrespective of the risk of transition to chronic pain. At follow-up, connectivity changes were observed between nucleus accumbens and rostral anterior cingulate cortex in the patients with persistent pain. Analysis of the power spectral density of nucleus accumbens resting-state activity in the subacute and chronic back pain patients revealed loss of power in the slow-5 frequency band (0.01 to 0.027 Hz) which developed only in the chronic phase of pain. This loss of power was reproducible across two cohorts of chronic low-back pain patients obtained from different sites and accurately classified chronic low-back pain patients in two additional independent datasets. Our results provide evidence that lower nucleus accumbens volume confers risk for developing chronic pain and altered nucleus accumbens activity is a signature of the state of chronic pain.


Keeping children out of hospitals: parents' and physicians' perspectives on how pediatric hospitalizations for ambulatory care-sensitive conditions can be avoided.
Avoidable hospitalization conditions (AHCs) are hospitalizations that potentially can be avoided with timely, appropriate outpatient care. The specific reasons for avoidability, and parents and physicians' perspectives on the proportion of actually avoidable pediatric AHCs, have not been examined adequately. To identify how pediatric hospitalizations might be avoided, and to determine the proportion of avoidable AHCs according to parents and physicians of hospitalized children. Cross-sectional survey of parents, primary care physicians (PCPs), and inpatient attending physicians (IAPs) of a consecutive series of children who were admitted with AHCs to an urban hospital in a 14-month period. The 554 hospitalized children had a median age of 4 years; most were poor (median annual family income: 12,000 dollars), nonwhite (91%), and had public (73%) or no (16%) health insurance. The most frequent AHC diagnoses were asthma (43%), dehydration/gastroenteritis (16%), pneumonia (11%), seizure disorder (8%), and skin infections (8%). Only 25% of parents said that their child's admission was avoidable, compared with 29% of PCPs and 32% of IAPs. The proportion of AHC hospitalizations assessed as avoidable varied according to the source or combination of sources, from 13% for agreement among all 3 sources to 46% as identified by any 1 of the 3 sources. PCPs (71%) and IAPs (48%) significantly more often than parents (35%) cited parent/patient-related reasons for how hospitalizations could have been avoided, including adhering to and refilling medications, better outpatient follow-up, and avoiding known disease triggers. Parents (48%) significantly more often than PCPs (18%) and IAPs (37%) cited physician-related reasons for how hospitalizations could have been avoided, including better education by physicians about the child's condition, and better quality of care. Multivariate analyses revealed that an age >or=11 years, an asthma diagnosis, working poor family income, and having no health insurance were associated with approximately double to triple the odds of an avoidable hospitalization. The proportion of AHCs assessed as avoidable varies from 13% to 46%, depending on the source. Adolescents, children with asthma, children from working-poor families, and uninsured children are at greatest risk for avoidable hospitalizations. Many pediatric hospitalizations might be avoided if parents and children were better educated about the child's condition, medications, the need for follow-up care, and the importance of avoiding known disease triggers. Direct assessment by parents and physicians of hospitalized children can be an informative way to examine the proportion of avoidable pediatric hospitalizations and how they can be prevented.