Barriers to and strategies to address COVID-19 testing hesitancy: a rapid scoping review.
Testing is a foundational component of any COVID-19 management strategy; however, emerging evidence suggests that barriers and hesitancy to COVID-19 testing may affect uptake or participation and often these are multiple and intersecting factors that may vary across population groups. To this end, Health Canada's COVID-19 Testing and Screening Expert Advisory Panel commissioned this rapid review in January 2021 to explore the available evidence in this area. The aim of this rapid review was to identify barriers to COVID-19 testing and strategies used to mitigate these barriers. Searches (completed January 8, 2021) were conducted in MEDLINE, Scopus, medRxiv/bioRxiv, Cochrane and online grey literature sources to identify publications that described barriers and strategies related to COVID-19 testing. From 1294 academic and 97 grey literature search results, 31 academic and 31 grey literature sources were included. Data were extracted from the relevant papers. The most cited barriers were cost of testing; low health literacy; low trust in the healthcare system; availability and accessibility of testing sites; and stigma and consequences of testing positive. Strategies to mitigate barriers to COVID-19 testing included: free testing; promoting awareness of importance to testing; presenting various testing options and types of testing centres (i.e., drive-thru, walk-up, home testing); providing transportation to testing centres; and offering support for self-isolation (e.g., salary support or housing). Various barriers to COVID-19 testing and strategies for mitigating these barriers were identified. Further research to test the efficacy of these strategies is needed to better support testing for COVID-19 by addressing testing hesitancy as part of the broader COVID-19 public health response.


Lipid Abnormalities in Type 2 Diabetes Mellitus Patients with Overt Nephropathy.
Diabetic nephropathy is a major complication of diabetes and an established risk factor for cardiovascular events. Lipid abnormalities occur in patients with diabetic nephropathy, which further increase their risk for cardiovascular events. We compared the degree of dyslipidemia among type 2 diabetes mellitus (T2DM) subjects with and without nephropathy and analyzed the factors associated with nephropathy among them. In this retrospective study, T2DM patients with overt nephropathy were enrolled in the study group (n=89) and without nephropathy were enrolled in the control group (n=92). Both groups were matched for age and duration of diabetes. Data on total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), urea and creatinine were collected from the case sheets. TG/HDL-C ratio, a surrogate marker for small, dense, LDL particles (sdLDL) and estimated glomerular filtration rate (eGFR) were calculated using equations. Multivariate analysis was done to determine the factors associated with eGFR. Dyslipidemia was present among 56.52% of control subjects and 75.28% of nephropathy subjects (P=0.012). The percentage of subjects with atherogenic dyslipidemia (high TG+low HDL-C+sdLDL) was 14.13 among controls and 14.61 among nephropathy subjects. Though serum creatinine was not significantly different, mean eGFR value was significantly lower among nephropathy patients (P=0.002). Upon multivariate analysis, it was found that TC (P=0.007) and HDL-C (P=0.06) were associated with eGFR among our study subjects. Our results show that dyslipidemia was highly prevalent among subjects with nephropathy. Regular screening for dyslipidemia may be beneficial in controlling the risk for adverse events among diabetic nephropathy patients.


Different costimulatory and growth factor requirements for CD4+ and CD8+ T cell-mediated rejection.
Costimulatory signals and growth factor signals play a key role in commanding T cell activation and T cell effector function. However, how costimulatory signals and growth factor signals interact and integrate into the activation program of CD4(+) and CD8(+) T cells during the allograft response remains poorly defined. In the present study we found that either CD4- or CD8-deficient mice can vigorously reject the skin allografts. Blocking rapamycin-sensitive growth factor signals produced long term skin allograft survival in CD4-deficient mice (mean survival time, >120 days), but not in CD8-deficient mice (mean survival time, 20 days). Analysis of CFSE-labeled cells proliferating in the allogeneic hosts revealed that clonal expansion of CD4(+) T cells in vivo was more resistant to growth factor blockade than that of CD8(+) T cells. However, blockade or genetic absence of CD28/CD154 costimulatory molecules rendered CD4(+) T cell-mediated rejection sensitive to rapamycin, and long term skin allograft survival can be readily induced by rapamycin in the absence of CD28/CD154 signals (>100 days). Furthermore, blocking OX40 costimulation induced long term skin allograft survival in CD4-deficient mice and CD8-deficient mice when both CD28 and CD154 were transiently blocked. We conclude that CD4(+) and CD8(+) T cells exhibit distinct sensitivity to growth factor blockade in transplant rejection, and CD28/CD154-independent rejection is sensitive to rapamycin and appears to be supported by OX40 costimulation.


Survey of low ER-positive expression and its correlation with other clinical and pathological factors in breast cancer.
Breast cancer is the most common cancer in women. Owning to the prominent role of biomarkers in molecular classification of breast cancer in recent years, evaluation of estrogen receptor (ER), progesterone receptor (PR), and Her2/neu seems to be required for prognosis and treatment of patients. One-hundred twenty two patients with primary breast carcinoma were selected and immunohistochemistry staining for ER, PR, and Her2/neu were performed on representative paraffin blocks. ER level can be semi-quantified by immunohistochemistry using the H-score. The score, given as the sum of the percent of tumor cells staining multiplied by the intensity level, ranges from 0 to 300 as low, intermediate, and high grades. The statistical association of ER expression with the level of PR and Her2/neu, tumor size, necrosis, microscopic grade, vascular invasion, and lymph node involvement were analyzed using SPSS16 software. Results showed that among 122 studied patients, 44.3% were in the low ER-positive group where most of these cases (22.1%) were Her2/neu negative. Although there was a reciprocal interplay between the expression of ER and Her2/neu, increased expression of ER had a direct relation with PR level. However, there was no statistical relation between ER level with age, tumor size, necrosis, microscopic grade, vascular invasion, and lymph node involvement. The study clearly indicated that low ER group encompasses the high frequency of breast cancer patients. Furthermore, the most cases of low ER patients were in Her2/neu negative group.


Maxillary sinus floor elevation using Beta-Tricalcium-Phosphate (beta-TCP) or natural bone: same inflammatory response.
Sinus elevation is a common procedure to increase bone volume in the atrophic maxilla to allow placement of dental implants. Autogenous bone is the gold standard but is limited in quantity and causes morbidity at the donor site. β-TCP is a synthetic biomaterial commonly used in that purpose. It appears to induce a poor inflammatory response. This study aimed to evaluate the degree of edema of the sinus mucosa after sinus lift surgery according to the type of biomaterial. Forty sinuses (20 patients) were included retrospectively and divided into 2 groups according to the biomaterial that was used: synthetic biomaterial (BTCP group), natural bone (BONE group). A control group (CTRL group) was constituted by the non-grafted maxillary sinuses. Twelve measurements per sinus were realized on pre- and post-operative computed tomography and averaged to provide the sinus membrane thickness value (SM.Th). SM.Th was thicker post-operatively in the BTCP and BONE groups in comparison with the CTRL group and in comparison with pre-operative measurements. No difference was found post operatively between the BTCP and BONE groups. We found that a synthetic biomaterial (β-TCP) induced the same degree of edema, and thus of inflammation, as natural bone. It constitutes therefore an interesting alternative to autogenous bone for maxillary sinus lifts.


Anti-angiogenic properties of chemopreventive drugs: fenretinide as a prototype.
Several cancer chemopreventive agents have been demonstrated to exert antiangiogenic effects. Blocking tumor angiogenesis, a process critical for tumor mass expansion and metastasis, represents an intriguing approach not only to cancer therapy, but also to cancer chemoprevention. We found that angiogenesis is a common and key target of many chemopreventive molecules, where they most likely suppress the angiogenic switch in premalignant tumors, a concept we termed "angioprevention." In this manuscript we use as an example the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR), a molecule with confirmed clinical applications in breast cancer adjuvant therapy to prevent cancer recurrence and under evaluation in neuroblastoma and glioblastoma treatment.


Trends in atmospheric concentrations of weed pollen in the context of recent climate warming in Poznań (Western Poland).
A significant increase in summer temperatures has been observed for the period 1996-2011 in Poznań, Poland. The phenological response of four weed taxa, widely represented by anemophilous species (Artemisia spp., Rumex spp. and Poaceae and Urticaceae species) to this recent climate warming has been analysed in Poznań by examining the variations in the course of airborne pollen seasons. Pollen data were collected by 7-day Hirst-type volumetric trap. Trends in pollen seasons were determined using Mann-Kendall test and Sen's slope estimator, whereas the relationships between meteorological and aerobiological data were established by Spearman's rank correlation coefficient. Significant trends in pollen data were detected. The duration of pollen seasons of all analysed taxa increased (from +2.0 days/year for Urticaceae to +3.8 days/year for Rumex), which can be attributed to a delay in pollen season end dates rather than earlier start dates. In addition, the intensity of Artemisia pollen seasons significantly decreased and correlates with mean July-September daily minimum temperatures (r = -0.644, p < 0.01). In contrast, no significant correlations were found between temperature and characteristics of Rumex pollen seasons. The results of this study show that observed shifts in weed pollen seasons in Poznań, i.e. longer duration and later end dates, might be caused by the recorded increase in summer temperature. This influence was the strongest in relation to Artemisia, which is the taxon that flowers latest in the year. The general lack of significant correlations between Rumex and Urticaceae pollen seasons and spring and/or summer temperature suggests that other factors, e.g. land use practices, could also be partially responsible for the observed shifts in pollen seasons.


Predictors of event-free survival after percutaneous mitral commissurotomy.
To assess the long term functional result after percutaneous mitral commissurotomy and identify the predictors of event-free survival following 10 years of experience. Analysis of clinical, echocardiographic, and haemodynamic variables at baseline and after the procedure by univariate and multivariate analyses (Cox model). University hospital. 532 consecutive patients receiving percutaneous mitral commissurotomy in the same institution. The mean (SD) follow up was 3.8 (4.0) years. Survival at 3, 5, and 7.5 years was 94%, 91%, and 83%, respectively; event-free survival was 84%, 74%, and 52%. Mitral valve anatomy was identified as the strongest independent predictor of event-free survival. Age, cardiothoracic ratio, mean pulmonary artery pressure, and mean echocardiographic mitral gradient after commissurotomy were also found to be independent predictors of long term functional results. Event-free survival was 92%, 84%, and 70% at 3, 5, and 7.5 years in patients with favourable anatomy (echo score = 1), 86%, 73%, and 34% in patients with intermediate anatomy (echo score = 2), and 45%, 25%, and 16% in patients with unfavourable anatomy (echo score = 3). In patients aged < or = 65 years, the event-free survival rate was 80%, 70%, and 45% at 3, 5, and 7.5 years v 52%, 38%, and 17% in patients aged > 65 years. The anatomical form of the mitral valve and the patient's age were the most powerful predictors of event-free survival. Patients with intermediate or unfavourable anatomy and those aged > 65 years have low 5 and 7.5 year event-free survival rates. This must be taken into account when discussing the indications for percutaneous mitral commissurotomy; immediate mitral valve replacement is a reasonable alternative to balloon mitral commissurotomy in patients with higher risk of functional deterioration after the procedure.


Two new combinations in Euploca Nutt. (Heliotropiaceae, Boraginales) and a conspectus of the species of the Guiana Shield area.
Heliotropium foliatum and Tournefortia humilis are transferred to Euploca Nutt. respectively as Euploca foliata comb. n. and Euploca humilis comb. n. A collection from Guyana has been recently identified as Euploca humistrata, a species previously considered a Brazilian endemic. A collection from French Guiana documents for the first time the species in that country. A key to the species of the Guiana Shield area is given. The species of Euploca from the Guiana Shield are listed with synonymy and a brief description: Euploca filiformis, Euploca humilis, Euploca humistrata, Euploca lagoensis, Euploca polyphylla, Euploca procumbens.


Polymer concepts in tissue engineering.
Traumatic injuries, cancer treatment, and congenital abnormalities are often associated with abnormal bone shape or segmental bone loss. Restoration of normal structure and function in these cases requires replacement of the missing bone that may be accomplished by surgical transfer of natural tissue from an uninjured location elsewhere in the body. However, this procedure is limited by availability, adequate blood supply, and secondary deformities at the donor site. One strategy to overcome these problems is to develop living tissue substitutes based on synthetic biodegradable polymers. Three methods of bone regeneration using biodegradable polymers are being studied in our laboratory: tissue induction, cell transplantation, and fabrication of vascularized bone flaps. Injectable polymers are used for filling skeletal defects and guiding bone tissue growth. Their main advantage is minimizing the surgical intervention or the severity of the surgery. Polymer-cell constructs also hold great promise in the field of tissue engineering. They provide a scaffold on which cells grow and organize themselves. As the cells begin to secrete their own extracellular matrix, the polymer degrades and is eventually eliminated from the body, resulting in completely natural tissue replacement. Bone flaps can be fabricated ectopically into precise shapes and sizes. With an attached vascular supply, these flaps can be transferred into areas deficient in vascularity. This article discusses polymer concepts regarding bone tissue engineering and reviews recent advances of our laboratory on guided bone regeneration using biodegradable polymer scaffolds.


A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy.
To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice. We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation. One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001). Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.


Ionic liquid based battery electrolytes using lithium and sodium pseudo-delocalized pyridinium anion salts.
The electrolyte salt plays an important role for the overall performance and safety of lithium- and sodium-ion batteries (LIBs and SIBs, respectively). Here, two new lithium and sodium pseudo-delocalized pyridinium anion based salts were used to prepare ionic liquid (IL) based electrolytes. The Li and Na salts of the 1-methylpyridinum 2,6-dicarboxylate anion (MM26py) were synthesized and dissolved in an IL matrix (Pyr14TFSI) - hence creating mixed anion electrolytes. The obtained electrolytes are stable up to 150 and 200 °C and show ion conductivities of 2.8 and 3.2 mS cm-1 at room temperature, for the LIB and SIB electrolytes, respectively. A competitive effect between the MM26py and the TFSI anions to coordinate the alkali metal cations is observed. Finally, the electrochemical stability windows of 2.3 and 2.5 V, respectively, confirm that these electrolytes can be used practically in medium-voltage LIBs and SIBs.


Action and language integration: from humans to cognitive robots.
The topic is characterized by a highly interdisciplinary approach to the issue of action and language integration. Such an approach, combining computational models and cognitive robotics experiments with neuroscience, psychology, philosophy, and linguistic approaches, can be a powerful means that can help researchers disentangle ambiguous issues, provide better and clearer definitions, and formulate clearer predictions on the links between action and language. In the introduction we briefly describe the papers and discuss the challenges they pose to future research. We identify four important phenomena the papers address and discuss in light of empirical and computational evidence: (a) the role played not only by sensorimotor and emotional information but also of natural language in conceptual representation; (b) the contextual dependency and high flexibility of the interaction between action, concepts, and language; (c) the involvement of the mirror neuron system in action and language processing; (d) the way in which the integration between action and language can be addressed by developmental robotics and Human-Robot Interaction.


Role of lysosomes in silica-induced inflammasome activation and inflammation in absence of MARCO.
MARCO is the predominant scavenger receptor for recognition and binding of silica particles by alveolar macrophages (AM). Previously, it was shown that mice null for MARCO have a greater inflammatory response to silica, but the mechanism was not described. The aim of this study was to determine the relationship between MARCO and NLRP3 inflammasome activity. Silica increased NLRP3 inflammasome activation and release of the proinflammatory cytokine, IL-1β, to a greater extent in MARCO(-/-) AM compared to wild type (WT) AM. Furthermore, in MARCO(-/-) AM there was greater cathepsin B release from phagolysosomes, Caspase-1 activation, and acid sphingomyelinase activity compared to WT AM, supporting the critical role played by lysosomal membrane permeabilization (LMP) in triggering silica-induced inflammation. The difference in sensitivity to LMP appears to be in cholesterol recycling since increasing cholesterol in AM by treatment with U18666A decreased silica-induced NLRP3 inflammasome activation, and cells lacking MARCO were less able to sequester cholesterol following silica treatment. Taken together, these results demonstrate that MARCO contributes to normal cholesterol uptake in macrophages; therefore, in the absence of MARCO, macrophages are more susceptible to a greater inflammatory response by particulates known to cause NLRP3 inflammasome activation and the effect is due to increased LMP.


Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells.
During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N-acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders.


Light-induced pigment aggregation in cultured fish melanophores: spectral sensitivity and inhibitory effects of theophylline and cyclic adenosine-3',5'-monophosphate.
About 20% of xiphophorin fish (Xiphophorus maculatus) dermal melanophores which were cultured in monolayer for 5 to 10 days responded to light directly, exhibiting reversible melanosome aggregation within a few minutes. In order to determine the spectral sensitivity for the light-response, absorbance changes due to the light-induced melanosome aggregation were measured on single melanophores in a range of wavelengths from 370 to 550 nm using a recording microspectrophotometer. The melanophores showed maximum sensitivity to a wavelength of about 410 nm and very little to those longer than 500 nm. 10(-4) to 10(-2) M theophylline and 10(-4) M cAMP had inhibitory effects on the light-response.


The use of curcumin as an effective adjuvant to cancer therapy: A short review.
Turmeric (Curcuma longa) is a popular spice that has been used in Ayurvedic medicine for its ability to treat various common ailments. There have been statistical correlations between turmeric consumption and lower incidences of cancer development, prompting research into its primary component curcumin. Several in vitro and in vivo studies over the last decade into cancer treatment have provided experimental evidence that curcumin contains antiproliferative, antiangiogenic, and apoptotic properties. The results of human clinical trials however, have proven mostly to be inconclusive. This short review provides an insight into the properties of curcumin including its bioavailability, biological activity, and potential usage in clinical trials as a chemotherapeutic drug.


Stochastic Character Mapping of State-Dependent Diversification Reveals the Tempo of Evolutionary Decline in Self-Compatible Onagraceae Lineages.
A major goal of evolutionary biology is to identify key evolutionary transitions that correspond with shifts in speciation and extinction rates. Stochastic character mapping has become the primary method used to infer the timing, nature, and number of character state transitions along the branches of a phylogeny. The method is widely employed for standard substitution models of character evolution. However, current approaches cannot be used for models that specifically test the association of character state transitions with shifts in diversification rates such as state-dependent speciation and extinction (SSE) models. Herein, we introduce a new stochastic character mapping algorithm that overcomes these limitations, and apply it to study mating system evolution over a time-calibrated phylogeny of the plant family Onagraceae. Utilizing a hidden state SSE model we tested the association of the loss of self-incompatibility (SI) with shifts in diversification rates. We found that self-compatible lineages have higher extinction rates and lower net-diversification rates compared with self-incompatible lineages. Furthermore, these results provide empirical evidence for the "senescing" diversification rates predicted in highly selfing lineages: our mapped character histories show that the loss of SI is followed by a short-term spike in speciation rates, which declines after a time lag of several million years resulting in negative net-diversification. Lineages that have long been self-compatible, such as Fuchsia and Clarkia, are in a previously unrecognized and ongoing evolutionary decline. Our results demonstrate that stochastic character mapping of SSE models is a powerful tool for examining the timing and nature of both character state transitions and shifts in diversification rates over the phylogeny.


Propagation of Anaplasma marginale in bovine lymph node cell culture.
Anaplasma marginale was propagated in cell cultures derived from bovine lymph node (LN). Treatment of host cells with diethylaminoethyl dextran (DEAE-D) before inoculation and centrifugation of inoculum onto the monolayers resulted in significant numerical increases of A marginale. The direct fluorescent antibody technique (FAT) was used for detection of the organism in culture. The rat was combined with the standard microscopic count procedure to obtain numerical estimates of the organism in cell culture. Infection of LN cells was irregular, with some cells containing many organisms and others containing none. The organisms were dispersed or in inclusions in the cytoplasm of LN cells. Numerical increases of organisms occurred within 6 hours and these were greatest at 12 to 24 hours. After 24 hours, the organisms decreased rapidly, but small numbers of them were observed for at least 7 days. The average generation time in culture was approximately 17.1 hours.


Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids.
Mitochondrial enoyl-CoA isomerase (ECI1) is an auxiliary enzyme involved in unsaturated fatty acid oxidation. In contrast to most of the other enzymes involved in fatty acid oxidation, a deficiency of ECI1 has yet to be identified in humans. We used wild-type (WT) and Eci1-deficient knockout (KO) mice to explore a potential presentation of human ECI1 deficiency. Upon food withdrawal, Eci1-deficient mice displayed normal blood β-hydroxybutyrate levels (WT 1.09 mM vs. KO 1.10 mM), a trend to lower blood glucose levels (WT 4.58 mM vs. KO 3.87 mM, P=0.09) and elevated blood levels of unsaturated acylcarnitines, in particular C12:1 acylcarnitine (WT 0.03 μM vs. KO 0.09 μM, P<0.01). Feeding an olive oil-rich diet induced an even greater increase in C12:1 acylcarnitine levels (WT 0.01 μM vs. KO 0.04 μM, P<0.01). Overall, the phenotypic presentation of Eci1-deficient mice is mild, possibly caused by the presence of a second enoyl-CoA isomerase (Eci2) in mitochondria. Knockdown of Eci2 in Eci1-deficient fibroblasts caused a more pronounced accumulation of C12:1 acylcarnitine on incubation with unsaturated fatty acids (12-fold, P<0.05). We conclude that Eci2 compensates for Eci1 deficiency explaining the mild phenotype of Eci1-deficient mice. Hypoglycemia and accumulation of C12:1 acylcarnitine might be diagnostic markers to identify ECI1 deficiency in humans.


Double gall bladder with two disease processes.
A double gall bladder is a rare congenital anomaly which is usually diagnosed by preoperative ultrasonography. Either one, or both lobes, of the double gall bladder, may be diseased. We report a patient in whom the two lobes were affected by different disease processes, namely, cholesterosis, and cholelithiasis with mucocele.


Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer.
Natural killer (NK) cell activity and psychological status were measured at baseline and at 3 months into treatment, as part of the National Cancer Institute (NCI) Protocol 79-C-111, randomizing breast cancer patients to lumpectomy/radiation v mastectomy. Patients who were found to have positive axillary lymph nodes also received combination chemotherapy (Adriamycin [Adria Laboratories, Columbus, OH], plus Cytoxan [Mead Johnson Pharmaceuticals, Evansville, IN] or methotrexate, plus 5-fluorouracil [5-FU]). Seventy-five patients were entered onto this behavioral immunology protocol at the time of data analysis. We reported in an earlier publication that NK activity was an important predictor of patient baseline prognosis relevant to nodal status. In that study, by using multiple regression analyses, 51% of the baseline NK activity variance could be accounted for by entering three distress indicators into the equation (patient "adjustment," lack of social support, and fatigue/depression symptoms). On reassessment of NK activity after 3 months, it was found that NK activity was not affected by the interim administration of chemotherapy and/or radiotherapy. However, consistent with our earlier findings, NK activity levels remained markedly lower in patients with positive nodes than in patients with negative nodes (at 60 to 1 effector to target cell [E:T] ratio, mean of 18% lytic activity v mean of 31% lytic activity [t = 1.87, P less than .05]). Even though average levels of NK activity were lower for patients with more tumor burden, there was still a substantial range of NK activity levels within the node positive patient group, as well as within the patient group as a whole. We hypothesized that differences in levels of NK activity could be predicted on the basis of baseline distress factors found to be significant in our earlier report. In fact, we found that we could account for 30% of NK activity level variance at 3 months follow-up on the basis of baseline NK activity, fatigue/depression, and lack of social support. Therefore, although neither radiation nor chemotherapy appeared to affect NK activity, tumor burden was again clearly associated with NK activity levels, and a significant amount of baseline and 3-month NK activity could be predicted on the basis of CNS-mediated effects. At the least, such factors provide a psychological marker of host biological status.


[Position of the Latin American Society of Nutrition (SLAN) on the management of conflict of interest.]
There is solid evidence documenting relationships between the food and beverage industry and academia that shows that industry sponsored research is likely to bias results in favor of industry. In Latin America, examples of these situations have been documented in Mexico, Brazil, Chile, Peru, Colombia, and Ecuador, among others. Due to the urgent need for studying and managing relationships between the food and beverage industry and the field of health and nutrition research, in 2017, the President of the Latin American Society of Nutrition (SLAN) appointed a Conflict of Interest Committee (CCI). The CCI was charged with the development of a proposal of a position for the management of conflict of interest (COI) for consideration by SLAN. This document details the work of CCI, and the position adopted by SLAN.


Role of palliative radiotherapy in brain metastases.
Brain metastases are a common manifestation of systemic cancer and exceed primary brain tumors in number and are a significant cause of neurologic problems. They affect 20-40% of all cancer patients. Aggressive management of brain metastases is effective in both symptom palliation and prolonging the life. Radiotherapy has a major role to play in the management of brain metastases. The aim of the study was to know the outcome of palliative radiotherapy in symptomatic brain metastases in terms of improvement in their performance status. This is a retrospective study of 63 patients diagnosed to have brain metastases and treated with palliative whole brain radiotherapy to a dose of 30 Gy in 10 fractions over two weeks between June 1998 and June 2007. Diagnosis was done in most of the cases with computed tomography scan and in a few with magnetic resonance imaging. Improvement in presenting symptoms has been assessed in terms of improvement in their performance status by using the ECOG scale. Fifty-four patients completed the planned treatment. Eight patients received concurrent Temozolamide; 88% of patients had symptom relief at one month follow-up; 39/54 patients had a follow-up of just one to three months. Hence survival could not be assessed in this study. External beam radiotherapy in the dose of 30 Gy over two weeks achieved good palliation in terms improvement in their performance status in 88% of patients. Addition of concurrent and adjuvant Timozolamide may improve the results.


Altered kidney graft high-energy phosphate metabolism in kidney-transplanted end-stage renal disease type 1 diabetic patients: a cross-sectional analysis of the effect of kidney alone and kidney-pancreas transplantation.
Diabetes, hypertension, dyslipidemia, obesity, nephrotoxicity of certain immunosuppressive drugs, and the persistence of a chronic alloimmune response may significantly affect graft survival in end-stage renal disease (ESRD) type 1 diabetic patients who have undergone kidney transplant. The aim of this study was to ascertain the impact of kidney alone (KD) or combined kidney-pancreas (KP) transplantation on renal energy metabolism. We assessed high-energy phosphates (HEPs) metabolism by using, in a cross-sectional fashion, 31P-magnetic resonance spectroscopy in the graft of ESRD type 1 diabetic transplanted patients who received KD (n = 20) or KP (n = 20) transplant long before the appearance of overt chronic allograft nephropathy (CAN). Ten nondiabetic microalbuminuric kidney transplanted patients and 10 nondiabetic kidney transplanted patients with overt CAN were chosen as controls subjects. Simultaneous KP transplantation patients showed a higher beta-ATP/inorganic phosphorus (Pi) ratio (marker of the graft energy status) versus the other groups, and a positive correlation between beta-ATP/Pi phosphorus ratio and A1C was found. In the analysis limited to the subgroup of normoalbuminuric patients, the difference in beta-ATP/Pi was still detectable in KP patients compared with KD transplantation. KP transplantation was associated with better HEPs than in KD transplantation, suggesting that restoration of beta-cell function positively affects kidney graft metabolism.


Anticonvulsant therapy and suicide risk in affective disorders.
Patients with major affective disorders are more likely to complete suicide than patients in any other medical group. Established risk factors for completed suicide in affective disorders include acute depression (with turmoil, hopelessness, global insomnia, anhedonia, anxiety and/or panic), mixed episodes, rapid cycling, substance abuse, aggression and/or impulsivity, low serotonergic activity, and hypothalamic-pituitary-adrenal axis activation. Although anticonvulsants have mood-stabilizing and antidepressant properties, few data are available on the antisuicide effects of anticonvulsant treatment in manic-depressive patients. On the other hand, as reviewed elsewhere in this issue, massive data have been accumulated on the antisuicide effect of lithium. This article discusses lithium versus anticonvulsants in the prevention of suicide associated with affective disorders and future treatment strategies to reduce this most serious complication of manic-depressive illness.


Raynaud's phenomenon of the nipple: a treatable cause of painful breastfeeding.
Maurice Raynaud first described the vasospasm of arterioles in 1862, and Raynaud's phenomenon is now felt to be common, affecting up to 20% of women of childbearing age. Raynaud's phenomenon has been reported to affect the nipples of breastfeeding mothers and is recognized by many lactation experts as a treatable cause of painful breastfeeding. In 1997, Lawlor-Smith and Lawlor-Smith reported 5 women with Raynaud's phenomenon associated with breastfeeding, but there are few other case reports, and none report the possible relationship between Raynaud's phenomenon of the nipple and previous breast surgery. We report 12 women who breastfed 14 infants, all of whom were seen in 1 pediatric practice and 1 lactation consultation center in San Francisco, California, within the past 3 years. Of the 12 women, 11 were seen between June 2002 and May 2003. All women suffered from extremely painful breastfeeding, with symptoms precipitated by cold temperatures and associated with blanching of the nipple followed by cyanosis and/or erythema. Poor positioning and poor attachment or latch may cause blanching of the nipple and pain during breastfeeding, but 10 of the 12 mothers were evaluated by experienced lactation consultations, who were sure that inappropriate breastfeeding techniques were not contributing factors. Because the breast pain associated with Raynaud's phenomenon is so severe and throbbing, it is often mistaken for Candida albicans infection. It is not unusual for mothers who have Raynaud's phenomenon of the nipple to be treated inappropriately and often repeatedly for C albicans infections with topical or systemic antifungal agents. Eight of our 12 mothers and their infants received multiple courses of antifungal therapy without relief before the diagnosis was made. To diagnose Raynaud's phenomenon accurately, additional symptoms such as precipitation by cold stimulus, occurrence of symptoms during pregnancy or when not breastfeeding, and biphasic or triphasic color changes must be present. All our mothers experienced precipitation of symptoms by cold stimuli and demonstrated biphasic or triphasic color changes, and 6 of the 12 experienced symptoms during pregnancy. Interestingly 3 of 12 mothers also reported a history of breast surgery, including 1 mother who had a fibroadenoma removed and 2 who had breast-reduction surgery. The association between breast surgery/implants and autoimmune disease, including Raynaud's phenomenon, has been discussed extensively, but the association of Raynaud's phenomenon of the nipple during breastfeeding has not been reported previously. Given the small numbers in the study, it is uncertain as to whether this may be a precipitating factor in developing Raynaud's phenomenon. Treatment options include methods to prevent or decrease cold exposure, avoidance of vasoconstrictive drugs/nicotine that could precipitate symptoms, and pharmacologic measures. There are reports in the lay press of the use of herbal medicines, aerobic exercise, and dietary supplements, but because most women with painful breastfeeding require immediate relief of the pain to continue breastfeeding successfully, it is important to offer a treatment plan that will alleviate the pain quickly. Nifedipine, a calcium channel blocker, has been used to treat Raynaud's phenomenon because of its vasodilatory effects. Very little of the medication can be demonstrated in breast milk and thus is safe to use in breastfeeding mothers. Of the 12 mothers in our series, 6 chose to use nifedipine, and all had prompt relief of pain. Only 1 mother developed side effects from nifedipine. Pediatricians and lactation consultants should be aware of this treatable cause of painful breastfeeding and should specifically question their patients, because most mothers will not provide this information to the breastfeeding consultant. Prompt treatment will allow mothers to continue to breastfeed pain free while avoiding unnecessary antifungal therapy.


Suppression of LPS-induced TNF-alpha production in macrophages by cAMP is mediated by PKA-AKAP95-p105.
The activation of macrophages through Toll-like receptor (TLR) pathways leads to the production of a broad array of cytokines and mediators that coordinate the immune response. The inflammatory potential of this response can be reduced by compounds, such as prostaglandin E(2), that induce the production of cyclic adenosine monophosphate (cAMP). Through experiments with cAMP analogs and multigene RNA interference (RNAi), we showed that key anti-inflammatory effects of cAMP were mediated specifically by cAMP-dependent protein kinase (PKA). Selective inhibitors of PKA anchoring, time-lapse microscopy, and RNAi screening suggested that differential mechanisms of PKA action existed. We showed a specific role for A kinase-anchoring protein 95 in suppressing the expression of the gene encoding tumor necrosis factor-alpha, which involved phosphorylation of p105 (also known as Nfkb1) by PKA at a site adjacent to the region targeted by inhibitor of nuclear factor kappaB kinases. These data suggest that crosstalk between the TLR4 and cAMP pathways in macrophages can be coordinated through PKA-dependent scaffolds that localize specific pools of the kinase to distinct substrates.


Experiences of the first days of postpartum psychosis: an interview study with women and next of kin in Sweden.
The aim of this study was to explore accounts of the first days of postpartum psychosis from different perspectives, that is, that of the women and their next of kin. Interviews were conducted with seven women with postpartum psychosis and six interviews were done with the next of kin. The overall theme was Shades of Black with A Ray of Light, revealing a difficult experience of darkness, despair, and suffering. For the women, the experience cannot be shared fully other than with those who have lived through it themselves. For the next of kin, the illness is incomprehensible and it proved difficult to express in words what these relatives believe the women were going through. The women and their next of kin spoke about loss of sleep, being in an unreal world, thoughts that moved from having a wanted to an unwanted baby, being infanticidal, and having suicidal ideation. The women and their next of kin described the situations in different ways. The women gave an account of their illness in the strongest of terms, while the language used by the next of kin was much milder. The findings underscore the importance of recognizing the next of kin as key sources in early recognition of the disorder, which would make early treatment possible and support recovery.


Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report.
The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.


Activity-dependent glassy cell mechanics II: Nonthermal fluctuations under metabolic activity.
The glassy cytoplasm, crowded with bio-macromolecules, is fluidized in living cells by mechanical energy derived from metabolism. Characterizing the living cytoplasm as a nonequilibrium system is crucial in elucidating the intricate mechanism that relates cell mechanics to metabolic activities. In this study, we conducted active and passive microrheology in eukaryotic cells, and quantified nonthermal fluctuations by examining the violation of the fluctuation-dissipation theorem. The power spectral density of active force generation was estimated following the Langevin theory extended to nonequilibrium systems. However, experiments performed while regulating cellular metabolic activity showed that the nonthermal displacement fluctuation, rather than the active nonthermal force, is linked to metabolism. We discuss that mechano-enzymes in living cells do not act as microscopic objects. Instead, they generate meso-scale collective fluctuations with displacements controlled by enzymatic activity. The activity induces structural relaxations in glassy cytoplasm. Even though the autocorrelation of nonthermal fluctuations is lost at long timescales due to the structural relaxations, the nonthermal displacement fluctuation remains regulated by metabolic reactions. Our results therefore demonstrate that nonthermal fluctuations serve as a valuable indicator of a cell's metabolic activities, regardless of the presence or absence of structural relaxations.


Multimodality imaging of aortitis.
Multimodality imaging of aortitis is useful for identification of acute and chronic mural changes due to inflammation, edema, and fibrosis, as well as characterization of structural luminal changes including aneurysm and stenosis or occlusion. Identification of related complications such as dissection, hematoma, ulceration, rupture, and thrombosis is also important. Imaging is often vital for obtaining specific diagnoses (i.e., Takayasu arteritis) or is used adjunctively in atypical cases (i.e., giant cell arteritis). The extent of disease is established at baseline, with associated therapeutic and prognostic implications. Imaging of aortitis may be useful for screening, routine follow up, and evaluation of treatment response in certain clinical settings. Localization of disease activity and structural abnormality is useful for guiding biopsy or surgical revascularization or repair. In this review, we discuss the available imaging modalities for diagnosis and management of the spectrum of aortitis disorders that cardiovascular physicians should be familiar with for facilitating optimal patient care.


Co-recovery of Mn and Fe from pyrolusite and copper slag with hydrometallurgy process: Kinetics and leaching mechanisms.
With the shortage of high-quality raw materials and increasingly strict environmental regulations, the recovery of metals from copper slag and pyrolusite has become a research hotspot. A novel method for simultaneously extracting Mn and Fe from pyrolusite and copper slag has been proposed. Under the optimal conditions (Copper slag / Pyrolusite = 2, H2SO4 = 2 M, liquid-solid ratio = 10, T = 90 ℃, holding time = 60 min), the leaching efficiencies of Mn and Fe can reach 98.28% and 99.04%, respectively. In addition, the treated residue containing 60.04 wt% SiO2 can be used as a raw building material. Through chemical kinetics and mineralogical transformation analyses, Fe2SiO4 in copper slag decomposes to release Fe2+, which can reduce and leach Mn from pyrolusite. The unreacted shrinkage nuclear reaction model under the control of the surface chemical reaction is the most suitable model to describe the process, and when the apparent activation energy is 35.50 kJ/mol, the apparent rate equation is: [Formula: see text].


Ovariectomy and 17beta-estradiol modulate disease progression of a mouse model of ALS.
The incidence of amyotrophic lateral sclerosis (ALS) is higher among men than women but rises in women after the menopause. Estrogens may play a protective role. Treatment with estrogens has been shown to be neuroprotective in models of several neurodegenerative diseases. We therefore determined the effect of ovariectomy on female G93A mSOD1 transgenic mice, and the effect of subsequent treatment with 17beta-estradiol (E2). Ovariectomy led to a significant acceleration of disease progression of the mice, and high-dose E2 treatment significantly delayed disease progression of ovariectomized G93A mSOD1 transgenic mice. We conclude that treatment with E2 may also delay disease progression of post-menopausal women with ALS.


Renal function in aging.
A variety of age-related anatomic and functional alterations in the kidney have been described. Anatomic abnormalities in the aging kidney include a decrease in kidney size, increased glomerular sclerosis, altered tubular structure, and an altered pattern of vascular flow. These anatomic abnormalities are associated with renal functional abnormalities, including decreased renal blood flow, and glomerular filtration rate. Altered renal tubular function, including impaired handling of water, sodium, acid, and glucose, may also be present. Impaired "endocrinologic" functioning manifested by changes in the renin-angiotensin system, vitamin D metabolism, and antidiuretic hormone responsiveness have been reported. The kidney is constantly exposed to the effects of a variety of potentially toxic processes. These range from environmental toxins and drugs, to a variety of chronic medical illnesses including hypertension, diabetes, and atherosclerotic disease. In this context, differentiation of "aging" effects from nephrotoxic effects resulting from these other processes is difficult. It has been argued that hypertension is an important factor in the development and progression of renal insufficiency in the elderly. The relationship between hypertension, glomerular hyperfiltration, atherosclerosis, and progressive renal dysfunction needs further study. Further research may allow the rational recommendation of interventions designed to control age-associated changes in renal function.


Using RNA-seq to determine the transcriptional landscape and the hypoxic response of the pathogenic yeast Candida parapsilosis.
Candida parapsilosis is one of the most common causes of Candida infection worldwide. However, the genome sequence annotation was made without experimental validation and little is known about the transcriptional landscape. The transcriptional response of C. parapsilosis to hypoxic (low oxygen) conditions, such as those encountered in the host, is also relatively unexplored. We used next generation sequencing (RNA-seq) to determine the transcriptional profile of C. parapsilosis growing in several conditions including different media, temperatures and oxygen concentrations. We identified 395 novel protein-coding sequences that had not previously been annotated. We removed > 300 unsupported gene models, and corrected approximately 900. We mapped the 5' and 3' UTR for thousands of genes. We also identified 422 introns, including two introns in the 3' UTR of one gene. This is the first report of 3' UTR introns in the Saccharomycotina. Comparing the introns in coding sequences with other species shows that small numbers have been gained and lost throughout evolution. Our analysis also identified a number of novel transcriptional active regions (nTARs). We used both RNA-seq and microarray analysis to determine the transcriptional profile of cells grown in normoxic and hypoxic conditions in rich media, and we showed that there was a high correlation between the approaches. We also generated a knockout of the UPC2 transcriptional regulator, and we found that similar to C. albicans, Upc2 is required for conferring resistance to azole drugs, and for regulation of expression of the ergosterol pathway in hypoxia. We provide the first detailed annotation of the C. parapsilosis genome, based on gene predictions and transcriptional analysis. We identified a number of novel ORFs and other transcribed regions, and detected transcripts from approximately 90% of the annotated protein coding genes. We found that the transcription factor Upc2 role has a conserved role as a major regulator of the hypoxic response in C. parapsilosis and C. albicans.


Pre-tension generates strongly reversible adhesion of a spatula pad on substrate.
Motivated by recent studies on reversible adhesion mechanisms of geckos and insects, we investigate the effect of pre-tension on the orientation-dependent adhesion strength of an elastic tape adhering on a substrate. Our analysis shows that the pre-tension can significantly increase the peel-off force at small peeling angles while decreasing it at large peeling angles, leading to a strongly reversible adhesion. More interestingly, we find that there exists a critical value of pre-tension beyond which the peel-off force plunges to zero at a force-independent critical peeling angle. We further show that the level of pre-tension required for such force-independent detachment at a critical angle can be induced by simply dragging a spatula pad along a substrate at sufficiently low angles. These results provide a feasible explanation of relevant experimental observations on gecko adhesion and suggest possible strategies to design strongly reversible adhesives via pre-tension.


Lymphocyte transfer in streptozotocin-induced diabetes: adhesion of donor cells to islet endothelium.
The interaction between intravenously transferred lymphocytes derived from spleens of multiple low-dose streptozotocin-diabetic mice with islet, exocrine pancreatic, and gastric mucosal endothelium of nondiabetic recipient mice was investigated by in vivo microscopy. Donor lymphocytes were stained with acridine red in vitro. The adoptive transfer of these cells from diabetic donor animals resulted in significantly increased lymphocyte rolling (4.46 +/- 1.32%, P < 0.05) and adhesion (3.86 +/- 1.04%, P < 0.05) in islets of nondiabetic recipients that had been pretreated with a single subdiabetogenic dose of streptozotocin. No increased endothelial interaction was noted in nonpretreated recipients or in experiments with nondiabetic donors. Rolling (1.19 +/- 0.61 to 2.71 +/- 0.62%) and adhesion (0.61 +/- 0.33 to 2.80 +/- 0.97%) of donor lymphocytes were low in exocrine pancreatic and gastric mucosal control tissue. It is concluded that, in this animal model, lymphocytes from diabetic donors interact preferentially with recipient islet endothelium. However, additional stimulation of recipient islet endothelium by exogenous factors is necessary to enable transferred cells to adhere to pancreatic islets.


Genomic Selection with Allele Dosage in Panicum maximum Jacq.
Genomic selection is an efficient approach to get shorter breeding cycles in recurrent selection programs and greater genetic gains with selection of superior individuals. Despite advances in genotyping techniques, genetic studies for polyploid species have been limited to a rough approximation of studies in diploid species. The major challenge is to distinguish the different types of heterozygotes present in polyploid populations. In this work, we evaluated different genomic prediction models applied to a recurrent selection population of 530 genotypes of Panicum maximum, an autotetraploid forage grass. We also investigated the effect of the allele dosage in the prediction, i.e., considering tetraploid (GS-TD) or diploid (GS-DD) allele dosage. A longitudinal linear mixed model was fitted for each one of the six phenotypic traits, considering different covariance matrices for genetic and residual effects. A total of 41,424 genotyping-by-sequencing markers were obtained using 96-plex and Pst1 restriction enzyme, and quantitative genotype calling was performed. Six predictive models were generalized to tetraploid species and predictive ability was estimated by a replicated fivefold cross-validation process. GS-TD and GS-DD models were performed considering 1,223 informative markers. Overall, GS-TD data yielded higher predictive abilities than with GS-DD data. However, different predictive models had similar predictive ability performance. In this work, we provide bioinformatic and modeling guidelines to consider tetraploid dosage and observed that genomic selection may lead to additional gains in recurrent selection program of P. maximum.


Alterations in plasma non-esterified fatty acid (NEFA) kinetics and relationship with insulin resistance in polycystic ovary syndrome.
Are non-esterified fatty acid (NEFA) kinetics altered in women with polycystic ovary syndrome (PCOS)? Women with PCOS, particularly obese subjects, have dysregulated plasma NEFA kinetics in response to changes in plasma insulin and glucose levels, which are associated with insulin resistance (IR) independently of the fasting plasma NEFA levels. Elevated plasma NEFA levels are associated with IR in many disorders, although the homeostasis of NEFA kinetics and its relationship to IR in women with PCOS is unknown. We prospectively compared insulin sensitivity and NEFA kinetics in 29 PCOS and 29 healthy controls women matched for BMI. This study was conducted in a tertiary institution. Plasma NEFA, glucose and insulin levels were assessed during a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT). Minimal models were used to assess insulin sensitivity (Si) and NEFA kinetics (i.e. model-derived initial plasma NEFA level [NEFA0], phi constant [Φ], reflecting glucose-mediated inhibition of lipolysis and measures of maximum rate of lipolysis [SFFA] and NEFA uptake from plasma [KFFA]). The study provides new evidence that women with PCOS have defective NEFA kinetics characterized by: (i) lower basal plasma NEFA levels, measured directly and modeled (NEFA0), and (ii) a greater glucose-mediated inhibition of lipolysis in the remote or interstitial space (reflected by a lower affinity constant [Φ]). There were no differences, however, in the maximal rates of adipose tissue lipolysis (SFFA) and the rate at which NEFA leaves the plasma pool (KFFA). The differences observed in NEFA kinetics were exacerbated, and almost exclusively observed, in the obese PCOS subjects. Our study did not study NEFA subtypes. It was also cross-sectional and based on women affected by PCOS as defined by the 1990 National Institutes of Health (NIH) criteria (i.e. Phenotypes A and B) and identified in the clinical setting. Consequently, extrapolation of the present data to other phenotypes of PCOS should be made with caution. Furthermore, our data is exploratory and therefore requires validation with a larger sample size. Dysfunction in NEFA kinetics may be a marker of metabolic dysfunction in nondiabetic obese women with PCOS and may be more important than simply assessing circulating NEFA levels at a single point in time for understanding the mechanism(s) underlying the IR of PCOS. This work was supported by NIH grants R01-DK073632 and R01-HD29364 to R.A.; a Career Development Award from MD Medical Group, Moscow, RF, to D.L. and Augusta University funds to Y.-H.C. RA serves as consultant to Ansh Labs, Medtronics, Spruce Biosciences and Latitude Capital. U.E., Z.A., D.L., R.M., Y.-H.C., R.C.B. and Y.D.I.C. have no competing interests to declare. Not applicable.


Towards clinical application of tau PET tracers for diagnosing dementia due to Alzheimer's disease.
The recent development of several tau positron emission tomography (PET) tracers represents a major milestone for the Alzheimer's disease (AD) field. These tau PET tracers bind tau neurofibrillary tangles, a key neuropathological characteristic of AD that is tightly linked to synaptic loss, brain atrophy, and cognitive decline. It is notable that these tau PET tracers show low uptake in most non-AD tauopathies and other neurodegenerative disorders, resulting in a diagnostic specificity that is superior to that of amyloid beta (Aβ) PET and biofluid markers, especially at an older age when incidental Aβ pathology is common. Furthermore, tau PET tracers diagnostically outperform widely used MRI markers. Given its excellent diagnostic performance due to the combination of high sensitivity and specificity for detecting tau pathology in AD dementia, we hypothesize that tau PET can become an important diagnostic tool in specialized clinics for the differential diagnosis of dementia syndromes where AD is among the major possible underlying diseases.


Clinical significance and effect of MTDH/AEG-1 in bladder urothelial cancer: a study based on immunohistochemistry, RNA-seq, and in vitro verification.
Overexpression of metadherin/astrocyte elevated gene-1 (MTDH/AEG-1) has been implicated in various cancers. However, the clinical significance and the potential biological functions of MTDH/AEG-1 in bladder urothelial carcinoma (BUC) are not established. In this study, the expression of MTDH/AEG-1in BUC was measured using the Cancer Genome Atlas (TCGA) database and immunohistochemistry, together with a meta-analysis, to investigate the expression and diagnostic value of MTDH/AEG-1. The possible association between MTDH/AEG-1 expression and the viability, proliferation, and apoptosis in BUC cell lines (T24, HT1376, and RT4) was also assessed in vitro by viability, MTS, colony formation, and caspase-3/7 assays, as well as Hoechst 33342 and propidium iodide (PI) double staining. MTDH/AEG-1 expression was significantly higher in BUC tissues than in normal bladder tissues, according to the TCGA and immunohistochemistry results, and these findings were verified by the meta-analysis. Functional knockdown of MTDH/AEG-1 suppressed BUC cell growth and induced apoptosis. Bioinformatics analyses indicated an involvement of MTDH/AEG-1 in several processes, including RNA binding, protein transport, intracellular transport, and the insulin signaling pathway. We hypothesize that MTDH/AEG-1 could play essential roles in BUC, especially in cell growth and apoptosis, via the insulin signaling pathway."


Extra-skeletal Ewing's sarcoma resembling acute abdomen. Case report.
Extraosseous Ewing's sarcoma is a rare tumor of neuroectodermal origin. It presents mainly in the soft tissue of the extremities and thorax. Histologically, it is similar to Ewing's sarcoma of the bone. We present the case of a male who arrived at the emergency room with acute abdomen, leucocytosis and imaging techniques (abdominal ultrasound and computed tomography) suggestive of complicated diverticular disease. He was treated with emergency surgery. Intraoperative findings were an unsuspected tumor (20 x 15 x 15 cm). Treatment consisted of extirpation of the tumor, separating it from the adjacent viscera and followed by chemotherapy based on epirubicin, cyclophosphamide and vincristine for six cycles. Because the control abdominal CT demonstrated tumor activity in the retroperitoneum adjacent to the ascending colon and cecum, further resection was decided upon. In a review of the literature, no previous reports of extraosseous Ewing's sarcoma were found presenting as acute abdomen. Due to the rarity of this tumor, only case reports or series have been found in the literature without randomized or comparative studies. Surgery was the cornerstone of treatment, without reports of preoperative chemotherapy. If the patient's condition permits, percutaneous needle biopsy is mandatory to obtain optimum treatment as well as to improve prognosis.


Systematic mapping of occluded genes by cell fusion reveals prevalence and stability of cis-mediated silencing in somatic cells.
Both diffusible factors acting in trans and chromatin components acting in cis are implicated in gene regulation, but the extent to which either process causally determines a cell's transcriptional identity is unclear. We recently used cell fusion to define a class of silent genes termed "cis-silenced" (or "occluded") genes, which remain silent even in the presence of trans-acting transcriptional activators. We further showed that occlusion of lineage-inappropriate genes plays a critical role in maintaining the transcriptional identities of somatic cells. Here, we present, for the first time, a comprehensive map of occluded genes in somatic cells. Specifically, we mapped occluded genes in mouse fibroblasts via fusion to a dozen different rat cell types followed by whole-transcriptome profiling. We found that occluded genes are highly prevalent and stable in somatic cells, representing a sizeable fraction of silent genes. Occluded genes are also highly enriched for important developmental regulators of alternative lineages, consistent with the role of occlusion in safeguarding cell identities. Alongside this map, we also present whole-genome maps of DNA methylation and eight other chromatin marks. These maps uncover a complex relationship between chromatin state and occlusion. Furthermore, we found that DNA methylation functions as the memory of occlusion in a subset of occluded genes, while histone deacetylation contributes to the implementation but not memory of occlusion. Our data suggest that the identities of individual cell types are defined largely by the occlusion status of their genomes. The comprehensive reference maps reported here provide the foundation for future studies aimed at understanding the role of occlusion in development and disease.


[A combined radioimmunoassay method for the determination of 17 alpha-hydroxypregnenolone, 17 alpha-hydroxypregnenolone sulfate and 17 alpha-hydroxyprogesterone in human blood].
It is well recognized that in the fetal adrenal cortex, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity is lower and in fetal tissues, steroid sulfokinase (SK) is higher than in the adult. In order to clarify a part of the development processes of the adrenal cortex or steroidgenesis in humans, a combined radioimmunoassay (RIA) method to estimate serum 17 alpha-hydroxypregnenolone (17-OH-delta 5 P), 17 alpha-hydroxypregnenolone sulfate (17-OH-delta 5 P-S) and 17 alpha-hydroxyprogesterone (17-OH-delta 4P) was devised. The method consisted of the following procedures: 1) diethyl ether extraction and chromatographic separation of unconjugated steroids (17-OH-delta 5P and 17-OH-delta 4P), 2) enzymatic hydrolysis of 17-OH-delta 5P-S using the residue of diethyl ether extraction for a material, 3) diethyl ether extraction and chromatographic purification of hydrolyzed 17-OH-delta 5P-S, and 4) RIAs for 17-OH-delta 5-P to estimate 17-OH-delta 5P and 17-OH-delta 5P-S concentration, and for 17-OH-delta 4P. Extracted 17-OH-delta 5P was well separated from 17-OH-delta 4P by Sephadex LH-20 microcolumn chromatography, using a benzene/methanol = 95/5 (v/v) solvent as a mobile phase. Several procedures for hydrolysis or solvolysis of 17-OH-delta 5P-S were compared using available tritiated delta 5-3 beta-hydroxysteroids including dehydroepiandrosterone (DHA), DHA sulfate (DHA-S) and 17-OH-delta 5P, and it was found that the most suitable method was an enzymatic hydrolysis by arylsulfatase from Helix Pomatia in an appropriate condition in which the percent hydrolysis was 92.9 +/- 1.2 (mean +/- SEM)%. The final percent recoveries were 88.7 +/- 1.2% in 17-OH-delta 4P, 90.7 +/- 1.4% in 17-OH-delta 5P and 78.1 +/- 2.1% in 17-OH-delta 5P-S, respectively. A suitable antiserum and its final dilution titer for RIA of 17-OH-delta 5P (hydrolyzed 17-OH-delta 5P-S also) was 1:12,000 dilution of anti-17-OH-delta 5P-3-succinate-BSA serum. An anti-7-oxo-17-OH-delta 5P-7-carboxymethyloxime-BSA serum was considered to be unsuitable for the measurement of hydrolyzed 17-OH-delta 5-P-S, presumably because of a significant cross-reactivity with a large amount of unknown steroid sulfates simultaneously hydrolyzed.(ABSTRACT TRUNCATED AT 400 WORDS)


Direct oral anticoagulants versus vitamin K antagonists: Which one is more effective in atrial fibrillation.
The optimal approach for anticoagulation in patients with bioprosthetic valves and atrial fibrillation (AF) remains a subject of debate. A meta-analysis using updated evidence to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) in patients with AF and bioprosthetic valves to address this controversy. A comprehensive search was conducted in multiple databases, including PubMed, Scopus, Web of Science, ProQuest, and the Cochrane Central Register of Controlled Trials, up until March 2023. The search aimed to identify relevant randomized controlled trials (RCTs) that examined the efficacy and safety outcomes of both direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with bioprosthetic valves and atrial fibrillation. The primary outcomes of interest were major bleeding and all-cause mortality. Our study demonstrated that despite the difference was not significant, the hazard of all-cause mortality was 2.5% higher in the DOAC group (HR = 1.03, 95% CI = [0.88, 1.19], p-value = .75). Similarly, the hazard of stroke (HR = 1.03, 95% CI = [0.87, 1.32], p-value = .71) and major bleeding (HR = 1.11, 95% CI = [0.89, 1.38], p-value = .36) were found to be respectively 3.2 and 10.7% higher in the DOAC group, although the difference was not significant. However, the hazard of intracranial hemorrhage was found to be 28.8 lower in the DOAC treatment group (HR = 0.71, 95% CI = [0.39, 1.31], p-value = .27), which again was not statistically significant. Our meta-analysis demonstrates that in patients undergoing bioprosthetic valve surgery and presenting with AF afterward, DOAC and VKA are similar regarding life-threatening and all-cause mortality outcomes, including major bleeding, stroke, and intracranial hemorrhage.


The human orphan nuclear receptor tailless (TLX, NR2E1) is druggable.
Nuclear receptors (NRs) are an important group of ligand-dependent transcriptional factors. Presently, no natural or synthetic ligand has been identified for a large group of orphan NRs. Small molecules to target these orphan NRs will provide unique resources for uncovering regulatory systems that impact human health and to modulate these pathways with drugs. The orphan NR tailless (TLX, NR2E1), a transcriptional repressor, is a major player in neurogenesis and Neural Stem Cell (NSC) derived brain tumors. No chemical probes that modulate TLX activity are available, and it is not clear whether TLX is druggable. To assess TLX ligand binding capacity, we created homology models of the TLX ligand binding domain (LBD). Results suggest that TLX belongs to an emerging class of NRs that lack LBD helices α1 and α2 and that it has potential to form a large open ligand binding pocket (LBP). Using a medium throughput screening strategy, we investigated direct binding of 20,000 compounds to purified human TLX protein and verified interactions with a secondary (orthogonal) assay. We then assessed effects of verified binders on TLX activity using luciferase assays. As a result, we report identification of three compounds (ccrp1, ccrp2 and ccrp3) that bind to recombinant TLX protein with affinities in the high nanomolar to low micromolar range and enhance TLX transcriptional repressive activity. We conclude that TLX is druggable and propose that our lead compounds could serve as scaffolds to derive more potent ligands. While our ligands potentiate TLX repressive activity, the question of whether it is possible to develop ligands to de-repress TLX activity remains open.


Invertible temporal subband/wavelet filter banks with half-pixel-accurate motion compensation.
Three-dimensional (3-D) subband/wavelet coding with motion compensation has been demonstrated to be an efficient technique for video coding applications in some recent research works. When motion compensation is performed with half-pixel accuracy, images need to be interpolated in both temporal subband analysis and synthesis stages. The resulting subband filter banks developed in these former algorithms were not invertible due to image interpolation. In this paper, an invertible temporal analysis/synthesis system with half-pixel-accurate motion compensation is presented. We look at temporal decomposition of image sequences as a kind of down-conversion of the sampling lattices. The earlier motion-compensated (MC) interlaced/progressive scan conversion scheme is extended for temporal subband analysis/synthesis. The proposed subband/wavelet filter banks allow perfect reconstruction of the decomposed video signal while retaining high energy compaction of subband transforms. The invertible filter banks are then utilized in our 3-D subband video coder. This video coding system does not contain the temporal DPCM loop employed in the conventional hybrid coder and the earlier MC 3-D subband coders. The experimental results show a significant PSNR improvement by the proposed method. The generalization of our algorithm for MC temporal filtering at arbitrary subpixel accuracy is also discussed.


Extensive surface protein profiles of extracellular vesicles from cancer cells may provide diagnostic signatures from blood samples.
Extracellular vesicles (EV) are membranous particles (30-1,000 nm in diameter) secreted by cells. Important biological functions have been attributed to 2 subsets of EV, the exosomes (bud from endosomal membranes) and the microvesicles (MV; bud from plasma membranes). Since both types of particles contain surface proteins derived from their cell of origin, their detection in blood may enable diagnosis and prognosis of disease. We have used an antibody microarray (DotScan) to compare the surface protein profiles of live cancer cells with those of their EV, based on their binding patterns to immobilized antibodies. Initially, EV derived from the cancer cell lines, LIM1215 (colorectal cancer) and MEC1 (B-cell chronic lymphocytic leukaemia; CLL), were used for assay optimization. Biotinylated antibodies specific for EpCAM (CD326) and CD19, respectively, were used to detect captured particles by enhanced chemiluminescence. Subsequently, this approach was used to profile CD19(+) EV from the plasma of CLL patients. These EV expressed a subset (~40%) of the proteins detected on CLL cells from the same patients: moderate or high levels of CD5, CD19, CD31, CD44, CD55, CD62L, CD82, HLA-A,B,C, HLA-DR; low levels of CD21, CD49c, CD63. None of these proteins was detected on EV from the plasma of age- and gender-matched healthy individuals.


Hacking Covid-19 with Technology.
The development, implementation and advancement of technology solutions aimed at combating the COVID-19 outbreak are rapidly taking shape in India. Governments, Venture Capitalists, Academic Institutions, Incubators, Start-ups, and businesses large and small are all doing their part to deploy new innovative solutions as quickly as possible. Various databases were searched to look for different advancements in technology during the current coronavirus pandemic. It is seen that on one end nonpharmacological measure (social distancing, self-isolation, clean hands, and face masks) are time-tested and low-tech ways to help mitigate the viral spread. On the other end, Science and technology sector constituting of data science, machine learning, rapid diagnostic tests, mobile-first telehealth and computational simulation systems for drug development, artificial intelligence, virtual collaboration, and data tracking are complex ways of using the technology that have strengthened our pandemic response.


Bictegravir Plus Tenofovir Alafenamide Nanoformulation as a Long-Acting Pre-Exposure Prophylaxis Regimen: Application of Modeling to Design Non-Human Primate Pharmacokinetic Experiments.
Bictegravir (BIC) and tenofovir alafenamide fumarate (TAF), two potent anti-HIV drugs, had been nanoformulated (nBIC-TAF) to achieve once-a-month PrEP coverage. In-vivo mouse experiments for nBIC-TAF exhibited favorable subcutaneous (SC) pharmacokinetics. To probe the clinical suitability of the nBIC-TAF, as the next step, we intend to study nBIC-TAF in non-human primates (NHP), as the best preclinical model to foster clinical trials. Before entering an expensive NHP study, however, we seek to improve our a priori understanding about nBIC-TAF in higher species, having just mouse data. The mechanism-based pharmacokinetic modeling (MBPK) has been used as an appropriate method for pharmacokinetic modeling and interspecies scaling for nanoformulations. Via the use of MBPK, in this work, we created a model for nBIC-TAF able to predict plasma concentration-time curves in NHP. BIKTARVY is a daily oral combination of BIC, TAF, and emtricitabine (Gilead Science, CA), approved for HIV therapy. Using BIKTARVY equivalent dosages (from their NHP studies), we predicted that, following just one SC dose of nBIC-TAF in NHP, both BIC and tenofovir will have detectable and above in vitro efficacy levels for 28 days. Furthermore, the MBPK was able to provide a mechanistic explanation regarding the long-acting mechanism characterizing nBIC-TAF: nanoparticles stores in the SC space from which drugs slowly dissociate. Dissociated drugs in the SC space then buffer the plasma pool over time, yielding an extended-release effect in the plasma. Overall, we predicted for nBIC-TAF a promising long-acting pharmacokinetic in NHP, potentially usable as monthly PrEP. These results will help investigators to gain confidence for facing regulatory submissions at early stages.


Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated alpha-synuclein gene mutations precede central nervous system changes.
Parkinson disease (PD) is a neurodegenerative disease with motor as well as non-motor signs in the gastrointestinal tract that include dysphagia, gastroparesis, prolonged gastrointestinal transit time, constipation and difficulty with defecation. The gastrointestinal dysfunction commonly precedes the motor symptoms by decades. Most PD is sporadic and of unknown etiology, but a fraction is familial. Among familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes alpha-synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates found in neurons in PD. We set out to develop transgenic mice expressing mutant alpha-synuclein (either A53T or A30P) from insertions of an entire human SNCA gene as models for the familial disease. Both the A53T and A30P lines show robust abnormalities in enteric nervous system (ENS) function and synuclein-immunoreactive aggregates in ENS ganglia by 3 months of age. The A53T line also has abnormal motor behavior but neither demonstrates cardiac autonomic abnormalities, olfactory dysfunction, dopaminergic neurotransmitter deficits, Lewy body inclusions or neurodegeneration. These animals recapitulate the early gastrointestinal abnormalities seen in human PD. The animals also serve as an in vivo system in which to investigate therapies for reversing the neurological dysfunction that target alpha-synuclein toxicity at its earliest stages.


[Abortion and miscarriage in adolescence: an epidemiological study].
This study was conducted at the Santa Izabel Maternity Hospital in the town of Bauru, São Paulo State, Brazil, in order to investigate abortions and miscarriages in adolescence, comparing them to terminations among adult women. The indicators are used to draw up an epidemiological profile of hospitalized women through data collected from documents on women with diagnoses of abortion or miscarriage from 2000 to 2003, regardless of their clinical form. The total number of registered early terminations of pregnancy reached 2,286, with 459 (20.08%) during adolescence, with the complete form being significantly higher among teenagers than adults; a decrease in the occurrence among adolescents was noted, dropping from 30.5% in 2000 to 25.05% in 2001, 23.53% in 2002 and 20.92% in 2003; with adolescents tending to remain in hospital for two or more days. The implementation is stressed of policies and programs addressing sexual and reproductive health and its co-morbidities.


Quantification of muscular activity in the shoulder region during monotonous repetitive work.
The purpose of this preliminary study was to evaluate the degree of myoelectric activity (EMG) in the shoulder muscles during repetitive monotonous work cycles in order to assess the load on the shoulder muscles. The tasks were video recorded and the movements performed were analyzed with a direct computer-based observational method (OS-WALD). The amplitude distribution probability function (ADPF) of the surface EMG from the deltoideus lateralis and trapezius pars descendens muscles was analyzed in 6 persons working on assembly lines. For each subject, "on-site" EMG and video recordings were performed over 10-minute periods at four different workstations on the same day. Force/EMG amplitude calibration curves had been previously calculated for the same subjects using a strain-gauge dynamometer. The results obtained during the working periods were the following: the mean static contraction level, as defined by Jonsson (13), was 1.3% MVC in the trapezius muscle and 0.5% MVC in the deltoid muscle; the medium contraction level was 5.2% MVC in the trapezius and 1.7% MVC in the deltoid; the peak contraction level was 17% MVC in the trapezius and 6.2% MVC in the deltoid. When compared to previously suggested upper limits of ADPF levels, all the contraction levels monitored were below the recommended limits. The assessment of musculoskeletal load in the shoulder region via EMG and video recordings led us to conclude that the work cycles examined were characterized by low-repetitive monotonous work and were well organized in order to avoid the occurrence of musculoskeletal injuries.


Polar Ocean Observations: A Critical Gap in the Observing System and Its Effect on Environmental Predictions From Hours to a Season.
There is a growing need for operational oceanographic predictions in both the Arctic and Antarctic polar regions. In the former, this is driven by a declining ice cover accompanied by an increase in maritime traffic and exploitation of marine resources. Oceanographic predictions in the Antarctic are also important, both to support Antarctic operations and also to help elucidate processes governing sea ice and ice shelf stability. However, a significant gap exists in the ocean observing system in polar regions, compared to most areas of the global ocean, hindering the reliability of ocean and sea ice forecasts. This gap can also be seen from the spread in ocean and sea ice reanalyses for polar regions which provide an estimate of their uncertainty. The reduced reliability of polar predictions may affect the quality of various applications including search and rescue, coupling with numerical weather and seasonal predictions, historical reconstructions (reanalysis), aquaculture and environmental management including environmental emergency response. Here, we outline the status of existing near-real time ocean observational efforts in polar regions, discuss gaps, and explore perspectives for the future. Specific recommendations include a renewed call for open access to data, especially real-time data, as a critical capability for improved sea ice and weather forecasting and other environmental prediction needs. Dedicated efforts are also needed to make use of additional observations made as part of the Year of Polar Prediction (YOPP; 2017-2019) to inform optimal observing system design. To provide a polar extension to the Argo network, it is recommended that a network of ice-borne sea ice and upper-ocean observing buoys be deployed and supported operationally in ice-covered areas together with autonomous profiling floats and gliders (potentially with ice detection capability) in seasonally ice covered seas. Finally, additional efforts to better measure and parameterize surface exchanges in polar regions are much needed to improve coupled environmental prediction.


Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects.
Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in healthy subjects. A double-blind, placebo-controlled, crossover study was performed in 27 healthy volunteers. A cup of either caffeinated or decaffeinated coffee was drunk by the subjects, and reactive hyperemia of finger blood flow was assessed by laser Doppler flowmetry. In an interval of more than 2 days, the same experimental protocol was repeated with another coffee in a crossover manner. Caffeinated coffee intake slightly but significantly elevated blood pressure and decreased finger blood flow as compared with decaffeinated coffee intake. There was no significant difference in heart rate between caffeinated and decaffeinated coffee intake. Importantly, caffeinated coffee intake significantly enhanced post-occlusive reactive hyperemia of finger blood flow, an index of microvascular endothelial function, compared with decaffeinated coffee intake. These results provide the first evidence that caffeine contained in a cup of coffee enhances microvascular function in healthy individuals.


Plasma catecholamines, renin and aldosterone during combined alpha- and beta- adrenoceptor blockade in patients with severe arterial hypertension.
Arterial blood pressure and plasma catecholamines, renin activity and aldosterone concentration in 12 patients with severe essential hypertension were studied before and after combined alpha- and beta- adrenoceptor blockade induced by oral labetalol treatment for 2 months. Frusemide in a fixed dose was employed as a basic antihypertensive agent throughout the study. Blood pressure was adequately controlled in only 6 patients. Mean body weight increased by 1.8 kg and there was a rise in body weight which was inversely correlated with the fall in standing mean blood pressure. The mean plasma noradrenaline concentration decreased from 0.30 to 0.20 ng/ml, whereas plasma adrenaline did not change significantly. Plasma renin activity and aldosterone concentration varied greatly, but the mean values did not change significantly. Change in body weight was correlated inversely with changes in plasma noradrenaline and renin. The results suggest that labetalol, through its combined alpha- and beta- adrenoceptor blocking action, induces a rise in body weight, probably due to sodium and fluid retention, which partly counterbalances its anti-hypertensive effect and partly modifies both renin and sympathetic nervous activity.


Extreme light absorption in thin semiconductor films wrapped around metal nanowires.
Metallic and dielectric nanostructures have highly tunable resonances that have been used to increase light absorption in a variety of photovoltaic materials and device structures. Metal nanowires have also emerged as a promising candidate for high-performance transparent electrodes for local contacts. In this Letter we propose combining these electrical and optical functions. As a first step, we use rigorous solutions to Maxwell's equations to demonstrate theoretically extreme absorption in semiconductor thin films wrapped around metal nanowires. We show that there are two key principles underlying this extraordinary light trapping effect: (1) maximizing the absorption of each individual resonance by ensuring it is critically coupled and (2) increasing the total number of degenerate resonances. Inserting a metal core into a semiconductor nanowire creates such a degeneracy: polarization-dependent Mie resonances are transformed into polarization-independent Fabry-Pérot-like resonances. We demonstrate that, by reducing the polarization sensitivity and increasing the number of critically coupled modes, this hybrid coaxial nanowire geometry substantially outperforms solid semiconducting nanowires, even though the semiconductor volume is significantly reduced. These results suggest that metal nanowires with semiconductor shells might be ideal building blocks for photovoltaic and solar fuel applications.


Transcript profiling during fiber development identifies pathways in secondary metabolism and cell wall structure that may contribute to cotton fiber quality.
A global gene expression profiling study at different stages of fiber development was undertaken on two cotton species cultivated for fiber, Gossypium hirsutum (L.) and G. barbadense (L.). A large proportion of the genome was expressed during both fiber elongation and subsequent secondary cell wall thickening. There was a major shift in abundance of transcripts for gene regulation, cell organization and metabolism between fiber elongation and fiber thickening that was fundamentally similar in both species. Each stage had its own distinctive features represented by specific metabolic and regulatory genes, a number of which have been noted previously. Many of the genes expressed in the fibers were of a similar type and developmental expression to those seen in other fiber-producing plants, indicating a conservation of mechanisms of cell elongation and wall thickening across diverse plant genera. Secondary metabolism and pectin synthesis and modification genes were amongst the most statistically significant differentially expressed categories between the two species during fiber elongation. The gene profiles of the fiber thickening stage, however, were almost identical between the two species, suggesting that their different final fiber quality properties may be established at earlier stages of fiber development. Expression levels of representative phenylpropanoid and pectin modification genes showed high correlations with specific fiber properties in an inter-specific cotton recombinant inbred line (RIL) population, supporting a role in determining fiber quality.


Unstable identity compatibility: how gender rejection sensitivity undermines the success of women in science, technology, engineering, and mathematics fields.
Although the perceived compatibility between one's gender and science, technology, engineering, and mathematics (STEM) identities (gender-STEM compatibility) has been linked to women's success in STEM fields, no work to date has examined how the stability of identity over time contributes to subjective and objective STEM success. In the present study, 146 undergraduate female STEM majors rated their gender-STEM compatibility weekly during their freshman spring semester. STEM women higher in gender rejection sensitivity, or gender RS, a social-cognitive measure assessing the tendency to perceive social-identity threat, experienced larger fluctuations in gender-STEM compatibility across their second semester of college. Fluctuations in compatibility predicted impaired outcomes the following school year, including lower STEM engagement and lower academic performance in STEM (but not non-STEM) classes, and significantly mediated the relationship between gender RS and STEM engagement and achievement in the 2nd year of college. The week-to-week changes in gender-STEM compatibility occurred in response to negative academic (but not social) experiences.


Tuberculosis in an urban area in China: differences between urban migrants and local residents.
The increase in urban migrants is one of major challenges for tuberculosis control in China. The different characteristics of tuberculosis cases between urban migrants and local residents in China have not been investigated before. We performed a retrospective study of all pulmonary tuberculosis patients reported in Songjiang district, Shanghai, to determine the demographic, clinical and microbiological characteristics of tuberculosis cases between urban migrants and local residents. We calculated the odds ratios (OR) and performed multivariate logistic regression to identify the characteristics that were independently associated with tuberculosis among urban migrants. A total of 1,348 pulmonary tuberculosis cases were reported during 2006-2008, among whom 440 (32.6%) were local residents and 908 (67.4%) were urban migrants. Urban migrant (38.9/100,000 population) had higher tuberculosis rates than local residents (27.8/100,000 population), and the rates among persons younger than age 35 years were 3 times higher among urban migrants than among local residents. Younger age (adjusted OR per additional year at risk = 0.92, 95% CI: 0.91-0.94, p<0.001), poor treatment outcome (adjusted OR = 4.12, 95% CI: 2.65-5.72, p<0.001), and lower frequency of any comorbidity at diagnosis (adjusted OR = 0.20, 95% CI: 0.13-0.26, p = 0.013) were significantly associated with tuberculosis patients among urban migrants. There were poor treatment outcomes among urban migrants, mainly from transfers to another jurisdiction (19.3% of all tuberculosis patients among urban migrants). A considerable proportion of tuberculosis cases in Songjiang district, China, during 2006-2008 occurred among urban migrants. Our findings highlight the need to develop and implement specific tuberculosis control strategies for urban migrants, such as more exhaustive case finding, improved case management and follow-up, and use of directly observed therapy (DOT).


Increasing the dialysate sodium concentration based on serum sodium concentrations exacerbates weight gain and thirst in hemodialysis patients.
Most dialysis centers adopt a standard dialysate sodium prescription. While pre-hemodialysis (HD) serum sodium levels remain relatively constant in each individual patient on chronic HD, these levels can vary between different patients. Therefore, a single dialysate sodium prescription may not be appropriate for all patients. Nineteen stable patients on maintenance HD were dialyzed for 9 HD sessions with their current dialysis solutions, followed by another 9 sessions using individualized prescriptions created by aligning dialysate sodium levels to each patient's serum sodium concentration. Patients were divided into 2 groups according to whether the average pre-HD serum sodium concentration was higher than (higher serum sodium group, n = 13) or equal to (equal sodium group, n = 5) the standard dialysate sodium concentration. Pre-HD serum sodium levels remained constant during entire study period in both groups. In higher serum sodium group, interdialytic weight gain increased after implementation of the sodium alignment (2.0 ± 0.3 kg vs. 2.3 ± 0.4 kg; P = 0.008). Thirst scores also increased in patients whose dialysate sodium was increased by 4 mmol/L (n = 7) (6.4 ± 1.5 vs. 7.6 ± 1.5, P = 0.015). There were no significant changes in blood pressure and intradialytic complications. In equal sodium group, significant differences were not observed in any parameters. Our results suggest that alignment of dialysate sodium levels to each patient's serum sodium concentration is of little benefit in hemodynamically stable patients who have pre-HD serum sodium concentrations higher than dialysate sodium concentration.


A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate.
It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.


Psychometric validation of the Growth and Empowerment Measure (GEM) applied with Indigenous Australians.
Empowerment is a complex process of psychological, social, organizational and structural change. It allows individuals and groups to achieve positive growth and effectively address the social and psychological impacts of historical oppression, marginalization and disadvantage. The Growth and Empowerment Measure (GEM) was developed to measure change in dimensions of empowerment as defined and described by Aboriginal Australians who participated in the Family Well Being programme. The GEM has two components: a 14-item Emotional Empowerment Scale (EES14) and 12 Scenarios (12S). It is accompanied by the Kessler 6 Psychological Distress Scale (K6), supplemented by two questions assessing frequency of happy and angry feelings. For validation, the measure was applied with 184 Indigenous Australian participants involved in personal and/or organizational social health activities. Psychometric analyses of the new instruments support their validity and reliability and indicate two-component structures for both the EES (Self-capacity; Inner peace) and the 12S (Healing and enabling growth, Connection and purpose). Strong correlations were observed across the scales and subscales. Participants who scored higher on the newly developed scales showed lower distress on the K6, particularly when the two additional questions were included. However, exploratory factor analyses demonstrated that GEM subscales are separable from the Kessler distress measure. The GEM shows promise in enabling measurement and enhancing understanding of both process and outcome of psychological and social empowerment within an Australian Indigenous context.