Loss of TARBP2 Drives the Progression of Hepatocellular Carcinoma via miR-145-SERPINE1 Axis.
The clinical outcomes of hepatocellular carcinoma (HCC) remain dismal. Elucidating the molecular mechanisms for the progression of aggressive HCC holds the promise for developing novel intervention strategies. The transactivation response element RNA-binding protein (TRBP/TARBP2), a key component of microRNA (miRNA) processing and maturation machinery has been shown to play conflicting roles in tumor development and progression. We sought to investigate the expression of TARBP2 in HCC using well-characterized HCC cell lines, patient-derived tissues and blood samples. Additionally, the potential prognostic and diagnostic value of TARBP2 in HCC were analyzed using Kaplan-Meier plots and ROC curve. Cell counting kit-8 (CCK-8), wound healing and transwell assays examined the ability of TARBP2 to induce cell proliferation, migration, and invasion in HCC cell lines. RNA sequencing was applied to identify the downstream elements of TARBP2. The interaction of potential targets of TARBP2, miR-145 and serpin family E member 1 (SERPINE1), was assessed using luciferase reporter assay. TARBP2 expression was down-regulated in HCC cell lines relative to normal hepatocyte cells, with a similar pattern further confirmed in tissue and blood samples. Notably, the loss of TARBP2 was demonstrated to promote proliferation, migration, and invasion in HCC cell lines. Interestingly, the reduction of TARBP2 was shown to result in the upregulation of SERPINE1, also known as plasminogen activator inhibitor (PAI-1), which is a vital gene of the HIF-1 signaling pathway. Knockdown of SERPINE1 rescued the TARBP2-lost phenotype. Moreover, TARBP2 depletion induced the upregulation of SERPINE1 through reducing the processing of miR-145, which directly targets SERPINE1. Finally, overexpression of miR-145 repressed SERPINE1 and rescued the functions in sh-TARBP2 HCC cells. Our findings underscore a linear TARBP2-miR-145-SERPINE1 pathway that drives HCC progression, with the potential as a novel intervention target for aggressive HCC.


Effect of monensin on the performance and nitrogen utilization of lactating dairy cows consuming fresh forage.
We conducted a lactation trial with a fresh forage diet in order to evaluate 1) the effects of monensin on nitrogen metabolism, and 2) the Cornell Net Carbohydrate and Protein System (CNCPS). Thirty Holstein cows in midlactation (eight fitted with ruminal fistulas) were gradually introduced to a fresh forage diet. A concentrate mix based on corn meal was fed before the a.m. and p.m. milking times 0730 and 1730 h, then the fresh forage was fed at 0830 and 1830 h. Fifteen cows each were allocated to a control (no monensin) and a treatment group receiving 350 mg/cow per day of monensin in the p.m. concentrate feeding. A 7-d fecal and urine collection period and a 3-d rumen sampling period were conducted with the fistulated cows. After the lactation study was concluded, the fistulated cows were fed forage regrowth and a 3-d rumen sampling period was repeated. Monensin increased milk production by 1.85 kg. Milk fat and protein concentrations decreased and milk fat and protein yields increased, but the effects were nonsignificant. Monensin did not significantly affect DMI. Ruminal ammonia and the acetate-to-propionate ratio decreased with the addition of monensin in both fed forages. Monensin decreased fecal N output, and increased apparent N digestibility by 5.4%. Because of the decrease in ruminal ammonia and increase in apparent N digestibility, we concluded monensin was sparing amino acids from wasteful rumen degradation with a fresh forage diet. The precision of the CNCPS in predicting performance was high (r2 = 0.76), and the bias was low (overprediction of 3.6%). These results indicate that the CNCPS can be used for dairy cows consuming fresh forage and gives realistic predictions of performance.


Interventions for asymptomatic retinal breaks and lattice degeneration for preventing retinal detachment.
Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these problems is frequently recommended, in spite of the fact that the effectiveness of this therapy is unproven. The purpose of this review was to evaluate the effectiveness of interventions for asymptomatic retinal breaks and lattice degeneration. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 1), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 28 January 2012. Textbooks regarding retinal detachment and the reference lists of relevant reports were reviewed for additional study reports. Experts in the field were contacted for details of other published and unpublished studies. This review was designed to include randomized controlled trials in which one treatment for asymptomatic retinal breaks and lattice degeneration was compared to another treatment or to no treatment. Initially one author assessed the search results and collected relevant studies. Since no studies met the inclusion criteria, no studies were assessed for methodological quality. No data were extracted and no meta-analysis could be performed. No trials were found that met the inclusion criteria for this review. No conclusions could be reached about the effectiveness of surgical interventions to prevent retinal detachment in eyes with asymptomatic retinal breaks and/or lattice degeneration. Some current recommendations for treatment, based upon a consensus of expert opinion, are contradicted by the best available evidence.


Comparison of contact shotgun wounds of the head produced by different gauge shotguns.
A series of 89 contact shotgun wounds of the head were evaluated to compare the extent of wounding produced by different gauge shotguns. Twelve gauge shotguns were the most common, accounting for 69% of the cases, followed by 20 gauge (18%), .410 caliber (10%), and 16 gauge (3%). The mouth was the most common entry site, used in 62% of cases. Comparison of contact intraoral shotgun wounds revealed statistically significant differences between 12 gauge and 20 gauge wounds. Whereas the extent of internal destruction was similar with both gauges, intraoral 12 gauge shotgun wounds caused bursting of the head with lacerations of the face, forehead, and scalp in 74% of cases, while only 9% of 20 gauge wounds produced a similar extent of external disruption. The external head remained fully intact in 55% of 20 gauge intraoral wounds. To account for the threshold effect for head bursting between 20 gauge and 12 gauge shotgun blasts, commercial shotshell and reloading data were analyzed. While there was considerable overlap between the two gauges, a common 12 gauge load would generate 50% more kinetic energy and 40% greater volume of gas than a common 20 gauge load. Comparison of shotgun blasts at entry sites outside of the mouth showed similar differences. Wounds from .410 shotguns were similar to those from 20 gauge weapons, and 16 gauge shotguns produced wounds intermediate between 20 and 12 gauge.


[Dispensing prescriptions to persons affiliated with the Seguro Popular de Salud de México].
Measure and compare the percentage of prescriptions fully dispensed to persons with and without Popular Health Insurance (SPS in Spanish) who use ambulatory and general hospital services associated with the Mexico State Health Services (SESA in Spanish), and taking into account insurance status. SESA user satisfaction was also measured with respect to access to medication. Information for the study was taken from four surveys of SESA ambulatory and hospital units that included probabilistic samples with state representativity. Samples of ambulatory units were selected by stratification according to level of care and association to the SPS service network. The findings indicate that the percentage of prescriptions fully dispensed in SESA ambulatory units has improved, reaching approximately 90%, especially among those units offering services to persons affiliated with SPS. Nevertheless, these percentages continue to be lower than those of ambulatory units associated with social security institutions. Percentages of prescriptions fully dispensed have also improved in SESA hospital units, but continue to be relatively low. In nearly all states, as the percentage of prescriptions fully dispensed has increased, user satisfaction with access to medication has also improved. In 2006 more than 50% of the states had high levels of fully dispensed prescriptions among persons with SPS (> or =90%). The more significant problem exists among hospitals, since only 44% of users who received a prescription in SESA hospitals in 2006 had their prescriptions fully dispensed. This finding requires a review of SPS medication policies, which have favored highly prescribed low-cost medications at ambulatory services at the expense of higher cost and more therapeutically effective medications for hospital care, the latter having a greater impact on household budgets.


Review of fractional photothermolysis: treatment indications and efficacy.
Fractional photothermolysis (FP) is one of the most significant milestones in laser technology and resurfacing. Review of the Medline English literature and recent international conferences regarding FP technology, applications, and indications. Successful conditions treated with nonablative FP reported in the literature include acne scarring; dyschromia and fine wrinkling of photoaging on the face, chest, neck, and hands; melasma; poikiloderma of Civatte; nevus of Ota; scars; minocycline hyperpigmentation; telangiectatic matting; residual hemangioma; granuloma annulare; colloid milium; and disseminated superficial actinic porokeratosis. An advance in 2007 was the introduction of ablative FP (AFP), which results in significantly greater improvement in skin laxity and textural abnormalities. Most recently, AFP has demonstrated significantly greater improvement than nonablative FP in reducing acne scarring and skin redundancy and laxity associated with photoaging. Through the induction of microthermal zones of injury, FP technology stimulates a robust and rapid wound healing response resulting in improvement in a diversity of aesthetic, inflammatory, and preneoplastic skin disorders. Further investigation into the technology and diverse array of cutaneous conditions that can benefit from FP is highly needed.


Effect of ethanol feeding on bone composition in the rat.
The effect of ethanol feeding for a period of 3 months on the mineral and collagen content of bone was determined in the rat. Ethanol feeding resulted in no changes in the density or in the concentrations of calcium, phosphorus, hydroxyproline, or nitrogen in the tibiae. Also, the serum concentrations of calcium, phosphorus, and 25-hydroxyvitamin D were unaffected by ethanol feeding. The development of a mild degree of osteomolacia was suggested, however, by decreases in EDTA-extractable mineral content and in the calcium/hydroxyproline ratio in the tibiae of the ethanol-fed as compared with the control animals. The urinary excretion of glycosaminoglycans was not changed by ethanol-feeding while the urinary excretion of peptide-bound hydroxyproline was increased. The minimal bone changes found after ethanol feeding in this study are an unlikely cause for the observed increases in the urinary excretion of hydroxyproline.


Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders.
The presence of actinic keratoses (AKs) increases a patient's risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.


PEGylated click polypeptides synthesized by copper-free microwave-assisted thermal click polymerization for selective endotoxin removal from protein solutions.
PEGylated click polypeptides (PEG-CPs) containing α-amino side groups as well as PEG segments are designed for selective endotoxin removal from protein solutions. The PEG-CPs are synthesized via copper-free thermal click copolymerization from aspartic (or glutamic) acid-based dialkyne and diazide monomers (containing free amino side groups) and alkyne-terminated mPEGs or dialkyne-terminated PEGs. Microwave-assisting technology is introduced into thermal click chemistry to improve the reaction efficiency. The monomers and polymers are fully characterized using NMR, XPS, and MALDI-TOF MS. After immobilizing the PEGylated click polypeptides onto polystyrene microspheres, the adsorbents exhibit good endotoxin removal selectivity from BSA solutions.


Altered relative expression of BMPs and BMP inhibitors in cartilaginous areas of human fractures progressing towards nonunion.
The present study was conducted to evaluate the hypothesis that an imbalance in the local production of bone morphogenetic proteins (BMPs) and BMP inhibitors exists within the cartilaginous intermediate of nonhealing fractures. Biopsies were recovered intraoperatively from human fractures that, upon follow-up, were found to heal normally or become nonunions. The samples were examined by immunohistochemistry to determine the expression of BMP-2, BMP-14, and the BMP inhibitors noggin and chordin. Expression was determined semiquantitatively based on the area of positive staining per area of cartilage and by determining the number of positively staining cells and the intensity of staining. There was a significant reduction in BMP-2 and BMP-14 expression in cartilaginous areas of nonhealing fractures compared to healing fractures. However, there was no difference in the expression of the BMP inhibitors between the two groups of fractures. This imbalance in the expression of BMPs and BMP inhibitors within cartilaginous areas of developing nonunions may account for their reduced bone forming ability. These data suggest strategies for preventing the development of nonunions by altering levels of BMPs and their inhibitors within fracture sites.


An investigation of the neural circuits underlying reaching and reach-to-grasp movements: from planning to execution.
Experimental evidence suggests the existence of a sophisticated brain circuit specifically dedicated to reach-to-grasp planning and execution, both in human and non-human primates (Castiello, 2005). Studies accomplished by means of neuroimaging techniques suggest the hypothesis of a dichotomy between a "reach-to-grasp" circuit, involving the anterior intraparietal area, the dorsal and ventral premotor cortices (PMd and PMv - Castiello and Begliomini, 2008; Filimon, 2010) and a "reaching" circuit involving the medial intraparietal area and the superior parieto-occipital cortex (Culham et al., 2006). However, the time course characterizing the involvement of these regions during the planning and execution of these two types of movements has yet to be delineated. A functional magnetic resonance imaging study has been conducted, including reach-to-grasp and reaching only movements, performed toward either a small or a large stimulus, and Finite Impulse Response model (Henson, 2003) was adopted to monitor activation patterns from stimulus onset for a time window of 10 s duration. Data analysis focused on brain regions belonging either to the reaching or to the grasping network, as suggested by Castiello and Begliomini (2008). Results suggest that reaching and grasping movements planning and execution might share a common brain network, providing further confirmation to the idea that the neural underpinnings of reaching and grasping may overlap in both spatial and temporal terms (Verhagen et al., 2013). But, although responsive for both actions, they show a significant predominance for either one of the two actions and such a preference is evident on a temporal scale.


Association between clonogenic cell growth and clinical risk group in B-cell chronic lymphocytic leukemia.
Chronic lymphocytic leukemia of B-cell origin (B-CLL) is a disease with a variable clinical course, despite the fact that the neoplastic cells in this disorder are homogeneous with respect to morphology, immunophenotype, and cell cycle stage. To further investigate the heterogeneity observed in the clinical behavior of B-CLL, we determined the phenotype and growth requirements of clonogenic cells from 28 patients with B-CLL from low-, intermediate-, and high-risk groups as defined by the Rai staging system. Using methyl-cellulose as a semi-solid media with feeder cells and/or growth factors, colonies were observed with one or more of the culture conditions tested in 25 of 28 CLLs. Phenotypic analysis of colonies demonstrated that the clonogenic cells uniformly expressed la, CD19, CD20, CD5, and the identical light chain as the original CLL cell cultured. However, heterogeneity was observed in clonogenic B-CLL cell growth among the three different CLL risk groups. Clonogenic cells from patients with low-risk CLL required either irradiated unstimulated T cells, with or without conditioned media (CM) or irradiated activated T cells alone for colony formation. Both the number of colonies (227 +/- 15) as well as the number of cells per colony (220 +/- 82) were large, with a mean cloning efficiency of 0.39%. In contrast, clonogenic cells from patients with intermediate- and high-risk CLL required the combination of both irradiated activated T cells and CM. As compared with the low-risk CLLs, both the number and size of the colonies formed by the intermediate- (74 +/- 17, 70 +/- 39) and high- (83 +/- 28, 40 +/- 14) risk groups were significantly lower (P less than .0001). Similarly, the mean cloning efficiency was significantly reduced to 0.15% and 0.14%, respectively. None of the recombinant cytokines (interleukin 1 [IL-1] to IL-7, tumor necrosis factor, alpha and gamma-interferon, B-cell growth factor, and granulocyte macrophage colony-stimulating factor) alone or in combination with each other could entirely replace the stimulatory effect of the activated T cells. These data suggest that clinical progression of B-CLL is associated with a loss of clonogenic potential in the circulating pool of neoplastic cells, which require as yet undefined factors provided by activated T cells and CM.


Environmental DNA provides information on sediment sources: A study in catchments affected by Fukushima radioactive fallout.
An excessive supply of sediment is observed in numerous rivers across the world where it leads to deleterious impacts. Information on the sources delivering this material to waterbodies is required to design effective management measures, and sediment tracing or fingerprinting techniques are increasingly used to quantify the amount of sediment derived from different sources. However, the current methods used to identify the land use contributions to sediment have a limited discrimination power. Here, we investigated the potential of environmental DNA (eDNA) to provide more detailed information on the plant species found in sediment source areas as a next generation fingerprint. To this end, flood sediment deposits (n = 12) were collected in 2017 in two catchments impacted by the Fukushima radioactive fallout along differing river sections draining forests, cropland or a mix of both land uses. Conventional fingerprints (i.e. fallout radionuclides and organic matter properties) were also measured in these samples. The conventional fingerprint model results showed that most sediment samples contained a dominant proportion of subsoil material. Nevertheless, the eDNA information effectively discriminated the three above-mentioned groups of sediment, with the dominance of tree, shrub and fern species in sediment sampled in rivers draining forests versus a majority of grass, algae and cultivated plant species in sediment collected in rivers draining cropland. Based on these encouraging results, future research should examine the potential of eDNA in mixed land use catchments where the contribution of topsoil to sediment dominates and where the cultivation of land has not been abandoned in order to better characterize the memory effect of eDNA in soils and sediment.


Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta.
Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.


The U.S. food-energy-water system: A blueprint to fill the mesoscale gap for science and decision-making.
Food, energy, and water (FEW) are interdependent and must be examined as a coupled natural-human system. This perspective essay defines FEW systems and outlines key findings about them as a blueprint for future models to satisfy six key objectives. The first three focus on linking the FEW production and consumption to impacts on Earth cycles in a spatially specific manner in order to diagnose problems and identify potential solutions. The second three focus on describing the evolution of FEW systems to identify risks, thus empowering the FEW actors to better achieve the goals of resilience and sustainability. Four key findings about the FEW systems that guide future model development are (1) that they engage ecological, carbon, water, and nutrient cycles most powerfully among all human systems; (2) that they operate primarily at a mesoscale best captured by counties, districts, and cities; (3) that cities are hubs within the FEW system; and (4) that the FEW system forms a complex network.


Core personal competencies important to entering students' success in medical school: what are they and how could they be assessed early in the admission process?
Assessing applicants' personal competencies in the admission process has proven difficult because there is not an agreed-on set of personal competencies for entering medical students. In addition, there are questions about the measurement properties and costs of currently available assessment tools. The Association of American Medical College's Innovation Lab Working Group (ILWG) and Admissions Initiative therefore engaged in a multistep, multiyear process to identify personal competencies important to entering students' success in medical school as well as ways to measure them early in the admission process. To identify core personal competencies, they conducted literature reviews, surveyed U.S and Canadian medical school admission officers, and solicited input from the admission community. To identify tools with the potential to provide data in time for pre-interview screening, they reviewed the higher education and employment literature and evaluated tools' psychometric properties, group differences, risk of coaching/faking, likely applicant and admission officer reactions, costs, and scalability. This process resulted in a list of nine core personal competencies rated by stakeholders as very or extremely important for entering medical students: ethical responsibility to self and others; reliability and dependability; service orientation; social skills; capacity for improvement; resilience and adaptability; cultural competence; oral communication; and teamwork. The ILWG's research suggests that some tools hold promise for assessing personal competencies, but the authors caution that none are perfect for all situations. They recommend that multiple tools be used to evaluate information about applicants' personal competencies in deciding whom to interview.


Chromium(VI)-induced DNA lesions and chromium distribution in rat kidney, liver, and lung.
DNA lesions were detected in rat organ nuclei following an i.p. injection of sodium dichromate. Kidney, liver, and lung nuclei were examined for DNA interstrand cross-links, strand breaks, and DNA-protein cross-links using the alkaline elution technique. The time course for formation of cross-links in kidney nuclei revealed the presence of DNA interstrand and DNA-protein cross-links 1 hr after injection of sodium dichromate. By 40 hr in kidney, DNA interstrand cross-links had been repaired, but DNA-protein cross-links persisted. In liver nuclei, the time course for formation of cross-links after injection of dichromate showed a maximum in DNA-protein cross-linking at 4 hr and a maximum in DNA interstrand cross-linking at 2 hr. By 36 hr, in the liver, both types of lesions had been repaired. In lung nuclei, both DNA interstrand and DNA-protein cross-links were observed 1 hr after dichromate injection; however, by 36 hr, only DNA-protein cross-links persisted. No DNA lesions were detectable in kidney 1 hr after an i.p. injection of chromium(III) chloride. Chromium distribution in rat kidney, liver, and lung was measured and is discussed with respect to the observed DNA lesions. The lung and kidney may be more sensitive than liver to chromium-induced DNA damage, an observation which correlates with the reported toxicity and carcinogenicity data for chromium(VI) in both animals and humans.


A1C underestimates glycemia in HIV infection.
The objective of this study was to determine the relationship between A1C and glycemia in HIV infection. We completed a prospective cross-sectional study of 100 HIV-infected adults with type 2 diabetes (77%) or fasting hyperglycemia (23%) with measured glucose, A1C, mean corpuscular volume (MCV), and fructosamine. A total of 200 HIV-uninfected type 2 diabetic subjects matched for key demographic characteristics served as control subjects. Relative to the control subjects, A1C underestimated glucose by 29 +/- 4 mg/dl in the HIV-infected subjects. Current nucleoside reverse transcriptase inhibitors (NRTIs), higher MCV and hemoglobin, and lower HIV RNA and haptoglobin were associated with greater A1C-glucose discordance. However, only MCV and current NTRI use, in particular abacavir, remained significant predictors in multivariate analyses. Fructosamine more closely reflected glycemia in the HIV-infected subjects. A1C underestimates glycemia in HIV-infected patients and is related to NRTI use. Use of abacavir and increased MCV were key correlates in multivariate analyses. Fructosamine may be more appropriate in this setting.


Rh isoimmunization complicating a triplet gestation. A case report.
A case occurred of Rh isoimmunization complicating a triplet gestation. Management of that extremely rare situation required careful attention to the problems inherent in both multiple pregnancy and isoimmunization. Amniocentesis and frequent antepartum fetal monitoring were the cornerstones of therapy.


Disruption of amygdala-entorhinal-hippocampal network in late-life depression.
Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an emotional discrimination task used previously to examine the relationship between depressive symptoms and amygdala-mediated emotional modulation of hippocampal pattern separation in young adults. We found that hippocampal dentate gyrus (DG)/CA3 activity was reduced during correct discrimination of negative stimuli and increased during correct discrimination of neutral items in DS+ compared to DS- adults. The extent of the latter increase was correlated with symptom severity. Furthermore, DG/CA3 and basolateral amygdala (BLA) activity predicted discrimination performance on negative trials, a relationship that depended on symptom severity. The impact of the BLA on depressive symptom severity was mediated by the DG/CA3 during discrimination of neutral items, and by the lateral entorhinal cortex (LEC) during false recognition of positive items. These results shed light on a novel mechanistic account for amygdala-hippocampal network changes and concurrent alterations in emotional episodic memory in LLD. The BLA-LEC-DG/CA3 network, which comprises a key pathway by which emotion modulates memory, is specifically implicated in LLD. © 2017 Wiley Periodicals, Inc.


Effect of gramicidin A and thallium ions on cation effluxes in frog sartorius muscle.
The effluxes of potassium, rubidium, sodium and lithium from the sartorius muscle of Rana temporaria in magnesium-Ringer solution free of sodium and potassium have been studied with the flame-emission technique. The channel-forming antibiotic gramicidin A (2.5 X X10(-7)-1 X 10(-6) mol/l) enhanced the efflux of potassium and rubidium and increased the rate constants of these effluxes. Gramicidin had small if any effect on sodium and lithium effluxes and rate constants. After 60-100 min in a gramicidin-containing medium, the potassium efflux and the corresponding rate constant reached a steady-state level. This steady-state value depended on gramicidin concentration. Effect of gramicidin on both the potassium efflux and the rate constant was partially reversible. Thallium ions (2.5 X 10(-3) and 5 X 10(-3) mol/l) in sodium- and potassium- free magnesium Ringer solution caused a large increase in effluxes of all the cations examined (K+, Rb+ and Na+) both in presence and absence of gramicidin. Possible mechanisms of gramicidin and thallium effects are discussed.


Evaluations of continuing medical education for chronic obstructive pulmonary diseases.
A continuing medical education program which linked primary care physicians to a source of needed appropriate clinical knowledge at a relatively low cost has been demonstrated. Chronic obstructive pulmonary disease was identified as the health problem; the reference patient population was comprised of coal miner health fund beneficiaries living in a 10-county region. Primary care physicians treating beneficiaries in this region were the eligible program participants. Content of the program was based on multiple sources of information about actual practice needs. Several educational techniques were used in combination to convey the knowledge identified as appropriate in the diagnostic stage. A quasi-experimental program evaluation indicated significant changes in physician knowledge, judgment, and self-reported behavior related to diagnosis and treatment of chronic obstructive pulmonary disease.


The dental pulp: inflammatory markers and vital bleaching.
To evaluate the expression of specific neuropeptides associated with inflammation, substance-P (SP) and calcitonin gene-related peptide (CGRP), after night guard vital bleaching with 10% carbamide peroxide gel. 10 patients with four caries free premolars scheduled for orthodontic extraction had these teeth bleached with 10% Opalescence as follows: tooth #28, no treatment (control); #5, 4 days of bleaching; #12, 2 weeks of bleaching; #21, 2 weeks of bleaching, followed by 2 weeks without treatment. All teeth in the four groups were extracted at the same time. Immediately after extraction the teeth were frozen at -197 degrees C in liquid nitrogen. The pulp samples were prepared for enzyme-linked immunoabsorbent assay (ELISA) to determine the concentrations of the SP, CGRP and total protein in the pulp tissue. The analysis of mean SP and mean CGRP/ng protein/ml resulted in no significant differences among the four groups. It was concluded that the study did not demonstrate an increase in the release of SP and/or CGRP during night guard vital bleaching of teeth with 10% Opalescence.


Rates of electron emission from negatively charged, impact-heated fullerenes.
Thermal emission of electrons is ordinarily considered to be exclusively a property of macroscopic condensed matter. Slow electron emission occurs for certain small metal clusters as well as for silicon and carbon clusters, but the nature of this process has not been established. Electron emission rates have been obtained and analyzed from extensive real-time measurements on negatively charged fullerenes for several sizes and over a wide, continuous range of energies. These results confirm that delayed electron emission is a simple activated process that depends strongly on the internal energy and size of the cluster and that it has a common underlying mechanism, independent of size. However, the Arrhenius form deduced is inconsistent with the emission rate theory used for bulk surfaces. These results allow the question of the correct microscopic description of this newly observed electron emission process to be assessed.


Two hybrid polyoxometalate-pillared metal-organic frameworks.
Two polyoxometalate-pillared 3D compounds, {Cu(5)(2-ptz)(6)(H(2)O)(4)(SiW(12)O(40))}·4H(2)O 1 and {Cu(9)(2-ptz)(12)(H(2)O)(6)(PMo(12)O(40))(2)}·H(2)O 2 (2-ptz = 5-(2-pyridyl)tetrazole) have been constructed based on different polyoxometalate anions, and copper-organic coordination polymer sheets by a hydrothermal method. Magnetic investigations reveal that both 1 and 2 exhibit antiferromagnetic coupling between the Cu(II) ions. Structural studies show the compound 1 exhibits a typical pcu-type net with the Schälfli symbol of {4(12)·6(3)}, and that compound 2 is a (3,4,6)-connected framework with novel {4(4)·6(10)·10}{6(3)}(2){6(5)·8} topology which has not been reported to date.


Are cytological parameters of maize landraces (Zea mays ssp. mays) adapted along an altitudinal cline?
The Northwestern Argentina (NWA) highland region is one of the southernmost areas of native maize cultivation. We studied variations of different cytological parameters, such as DNA contents, presence/absence of B chromosomes (Bs), and number and sequence composition of heterochromatic knobs in ten accessions of four maize landraces growing along a broad altitudinal cline in NWA. The aim of this work was to assess variations in cytological parameters and their relationship with the crop altitude of cultivation, in an adaptive context. The A-DNA content of the A chromosome complements showed 40% of difference between the lowest (4.5 pg) and the highest (6.3 pg) 2C value. This variation could be attributed to differences in number and size of heterochromatic knobs. Fluorescent in situ hybridization studies revealed the sequence composition of each knob, with a higher proportion of knobs composed of 180-bp repeats rather than TR-1 repeats, in all accessions. We also found numerical polymorphisms and the highest frequency of Bs reported in maize to this date. These results lead us to propose that the frequencies and doses of Bs are influenced by the landrace genotypical make-up. The Bs might be maintained in higher frequencies in those accessions having lower heterochromatin content, so as to preserve an optimal nucleotype. Furthermore, selective forces acting along the altitudinal gradient might be modulating the cytological parameters studied, as suggested by the significant correlations found among them.


The first mitochondrial 5-methylcytosine map in a non-model teleost (Oreochromis niloticus) reveals extensive strand-specific and non-CpG methylation.
DNA methylation is one of the main epigenetic mechanisms that regulate gene expression in a manner that depends on the genomic context and varies considerably across taxa. This DNA modification was first found in nuclear genomes of eukaryote several decades ago and it has also been described in mitochondrial DNA. It has recently been shown that mitochondrial DNA is extensively methylated in mammals and other vertebrates. Our current knowledge of mitochondrial DNA methylation in fish is very limited, especially in non-model teleosts. In this study, using whole-genome bisulfite sequencing, we determined methylation patterns within non-CpG (CH) and CpG (CG) contexts in the mitochondrial genome of Nile tilapia, a non-model teleost of high economic importance. Our results demonstrate the presence of mitochondrial DNA methylation in this species predominantly within a non-CpG context, similarly to mammals. We found a strand-specific distribution of methylation, in which highly methylated cytosines were located on the minus strand. The D-loop region had the highest mean methylation level among all mitochondrial loci. Our data provide new insights into the potential role of epigenetic mechanisms in regulating metabolic flexibility of mitochondria in fish, with implications in various biological processes, such as growth and development.


Evaluation of Total Antioxidant Capacity of Saliva in Type 2 Diabetic Patients with and without Periodontal Disease: A Case-Control Study.
Diabetes mellitus (DM) has been linked with oxidative stress and decreased antioxidant defense. A connection has been established between diabetes and periodontal disease. The aim of present study was to compare salivary total antioxidant capacity of type 2 DM patients and healthy subjects with and without periodontal disease. A total of 120 subjects consisting of 30 type 2 DM patients with periodontal disease; 30 type 2 DM patients without periodontal disease; 30 healthy subjects with periodontal disease; 30 healthy subjects without periodontal disease were included in the study. After clinical measurement and samplings, total antioxidant capacity in saliva of type 2 diabetic and healthy subjects were determined, and the data were tested by non-parametric tests. Total antioxidant capacity of the clinical samples was determined spectrophotometrically. The mean salivary total antioxidant capacity was lowest in diabetic patients with periodontitis. Total antioxidant capacity is inversely proportional to the severity of inflammation and can be used as an useful marker of periodontitis in healthy and diabetic patients.


Do psychiatric medications, especially antidepressants, adversely impact maternal metabolic outcomes?
Psychiatric illnesses, particularly depression, are some of the most common complications of pregnancy. Accordingly, pharmacologic treatment of these illnesses is prevalent and increasing. Systematic reviews on psychiatric medication use during pregnancy have shown effects on obstetrical and neonatal outcomes and non-systematic reviews of maternal outcomes suggest higher weight gain and an increased risk of gestational diabetes. However, to date there has not been a systematic review of the effects of these medications on maternal metabolic outcomes. The objective of this study was to assess the relationship between psychiatric medication use during pregnancy and adverse maternal metabolic outcomes [gestational weight gain (GWG), gestational diabetes (GDM) and postpartum weight retention (PPWR)]. Systematic review and meta-analysis were used. We searched Medline, EMBASE, PsychInfo and references. Two reviewers independently performed each step of the systematic review, following the MOOSE guidelines. Of 3080 non-duplicate titles and abstracts, 175 articles underwent full text review. Two moderate quality cohort studies were included. No differences were found for GWG, GDM and PPWR. There were only two studies which met our inclusion criteria, making it difficult to make any definitive conclusions regarding the effects of psychiatric medication on maternal metabolic outcomes. Despite the suggestions in non-systematic reviews that psychiatric medication use during pregnancy results in adverse maternal metabolic sequelae, in this systematic review, we found no evidence of an increased risk of GWG, GDM or PPWR in women with psychiatric illness who took psychiatric medications compared to non-medicated women with psychiatric illness. However, more, high quality studies are needed in this area to determine if there is an association between psychiatric medication use and maternal metabolic outcomes.


Identification of endosymbionts in ticks by broad-range polymerase chain reaction and electrospray ionization mass spectrometry.
Many organisms, such as insects, filarial nematodes, and ticks, contain heritable bacterial endosymbionts that are often closely related to transmissible tickborne pathogens. These intracellular bacteria are sometimes unique to the host species, presumably due to isolation and genetic drift. We used a polymerase chain reaction/electrospray ionization-mass spectrometry assay designed to detect a wide range of vectorborne microorganisms to characterize endosymbiont genetic signatures from Amblyomma americanum (L.), Amblyomma maculatum Koch, Dermacentor andersoni Stiles, Dermacentor occidentalis Marx, Dermacentor variabilis (Say), Ixodes scapularis Say, Ixodes pacificus Cooley & Kohls, Ixodes ricinus (L.), and Rhipicephalus sanguineus (Latreille) ticks collected at various sites and of different stages and both sexes. The assay combines the abilities to simultaneously detect pathogens and closely related endosymbionts and to identify tick species via characterization of their respective unique endosymbionts in a single test.


Correlation between COX-2 gene polymorphism and susceptibility to nasopharyngeal carcinoma.
The aim of this study was to investigate cyclooxygenase-2 (COX-2) gene polymorphism in peripheral blood cells of patients with nasopharyngeal carcinoma (NPC) and normal people, and to explore the correlation between polymorphism and the occurrence of NPC. The genotype and allele distributions of gene loci COX-2-899 (G/C) and COX-2-1195 (G/A) in peripheral blood of 56 normal people and 114 NPC patients were analyzed via reverse transcription-polymerase chain reaction (RT-PCR). The genetic equilibrium was detected by TaqMan genotyping technique. Meanwhile, the risk factors for NPC were analyzed via multivariate logistic regression analysis. Subsequently, the effects of risk factors, clinical features, and gene polymorphism of NPC on the prognosis and survival of patients were analyzed using univariate and multivariate COX regression analysis. Finally, the correlation of smoking, Epstein-Barr (EB) virus infection and COX-2-1195 gene polymorphism with NPC was explored via χ2-test. There was a significant difference in the genotype and allele distributions at COX-2-1195 (G/A) between the two groups (p<0.05). However, no significant differences were observed at COX-2-899 (G/C) between the two groups (p>0.05). According to the results of univariate and multivariate COX regression analysis, smoking and EB virus infection were risk factors for NPC (p<0.05). The χ2-test indicated that there was an evident gene polymorphism at COX-2-1195 in smokers and EB virus-infected people compared to non-smokers and non-infected people (p<0.05). COX-2-1195 gene polymorphism is associated with susceptibility to NPC. Smoking and EB virus infection are major risk factors for NPC, both of which can affect COX-2-1195 gene polymorphism.


There's an App for it: A systematic review of mobile apps providing information about abortion using a revised MARS scale.
Mobile applications (apps) are increasingly being used to access health-related information, but it may be challenging for consumers to identify accurate and reliable platforms. We conducted a systematic review of applications that provide information about abortion. We searched the iTunes and Google Play stores and queried professional networks to identify relevant apps. To evaluate the apps, we used the validated Mobile App Rating Scale (MARS) and added relevant abortion-specific elements. Two reviewers independently rated each app, and we report mean scores on a 5-point scale across the domains of engagement, functionality, esthetics, and information. We also rated app characteristics (including target population and reach), and number of desirable abortion-specific features. We defined recommended apps as those that achieved a score of 4.0 or above for the question: "would you recommend this app to people who may benefit from it?" Our search initially yielded 282 apps and we identified two additional apps through professional mailing lists. Most were irrelevant or not abortion-specific. We excluded 37 apps that sought to discourage users from seeking abortion. Only 10 apps met inclusion criteria for this review. The Euki app had the highest overall score (4.0). Half of the apps achieved a score of 3.0 or greater. Most of the apps had few desirable design features. Some apps provided significant information but had poor functionality. Only four apps met criteria for being recommended: Euki, Safe Abortion by Hesperian, Ipas Mexico, and Marie Stopes Mexico. In conclusion, we found few apps that provide unbiased information about abortion, and their quality varied greatly. App developers and abortion experts should consider designing additional apps that are clinically accurate, unbiased and well-functioning. We registered this review in the PROSPERO database (Registration # CRD42020195802).


Historical evidence of glyphosate exposure from a US agricultural cohort.
In response to the recent review by Gillezeau et al., The evidence of human exposure to glyphosate: A review, Environmental Health 1/19/19, here we report additional glyphosate biomonitoring data from a repository of urine samples collected from United States farmers in 1997-98. To determine if glyphosate exposure could be identified historically, we examined urine samples from a biorepository of specimens collected from US dairy farmers between 1997 and 98. We compared samples from farmers who self-reported glyphosate application in the 8 h prior to sample collection to samples from farm applicators who did not report using glyphosate. Of 18 applicator samples tested, 39% showed detectable levels of glyphosate (mean concentration 4.04 μg/kg; range:1.3-12) compared to 0% detections among 17 non glyphosate applicator samples (p-value < 0.01). One of the applicator samples that tested positive for glyphosate also tested positive for AMPA. Concentrations of glyphosate were consistent with levels reported in the prior occupational biomonitoring studies reviewed by Gillezeau et al.Accurately detecting both glyphosate and AMPA in this small sample of Wisconsin farmers demonstrates a) glyphosate exposures among farmers were occurring 20 years ago, which was prior to the widespread planting of genetically engineered glyphosate tolerant crops first approved in 1996; and b) liquid chromatography tandem mass spectrometry (LC-MS/MS) can be used for sensitive characterization in cryopreserved urine samples. These data offer an important historical benchmark to which urinary levels from current and future biomonitoring studies can be compared.


Oxidative stress, Noxs, and hypertension: experimental evidence and clinical controversies.
Reactive oxygen species (ROS) are signaling molecules that influence many physiological processes. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in chronic diseases including hypertension. Although oxidative stress may not be the sole cause of hypertension, it amplifies blood pressure elevation in the presence of other prohypertensive factors (salt, renin-angiotensin system, sympathetic hyperactivity). A major source for cardiovascular ROS is a family of non-phagocytic NADPH oxidases (Nox1, Nox2, Nox4, Nox5). Other sources of ROS involve mitochondrial electron transport enzymes, xanthine oxidase, and uncoupled nitric oxide synthase. Although evidence from experimental and animal studies supports a role for oxidative stress in the pathogenesis of hypertension, there is still no convincing proof that oxidative stress is a cause of human hypertension. However, what is clear is that oxidative stress is important in the molecular mechanisms associated with cardiovascular and renal injury in hypertension and that hypertension itself can contribute to oxidative stress. The present review addresses the putative function of ROS in the pathogenesis of hypertension and focuses on the role of Noxs in ROS generation in vessels and the kidney. Implications of oxidative stress in human hypertension are discussed, and clinical uncertainties are highlighted.


Malignant mesothelioma cells with characteristic intracytoplasmic vacuolization and lipids.
In this brief report, we described some uncommon cytomorphological features of malignant mesothelioma (MM) cells in pleural effusions. The tumor cells exhibited abundant cytoplasmic vacuolization, with presence of single or multiple eccentric nuclei in several cells. In the Giemsa-stained smear, we observed a glossy spherical material in some cells, which tested positive in Sudan III stain. In immunocytochemical analysis, tumor cells were positive for calretinin, podoplanin, epithelial membrane antigen, and methylthioadenosine phosphorylase; tumor cells were negative for BRCA1-associated protein 1, CD68, and desmin. The intracytoplasmic vacuoles were positive for adipophilin expression.


Ageing in the right place - a prototype of a web-based housing counselling intervention for later life.
Background: Despite a strong desire among most older adults to age in place, there are few widely available services to support planning and preparing for one's future housing needs.Objective: To develop a prototype of a web-based housing counselling intervention for use in later life, by employing a user-centred design.Material and Methods: As the first step in intervention development, we employed a development process based on research circle methodology. Nine older adults participated in three sessions. Findings from literature reviews, a meeting with a technology and design panel (n = 6) and interviews with representatives of nonprofit organizations, companies, and municipalities (n = 7) served as discussion points.Result: An on-paper prototype was derived, composed of the THINK, LEARN and ACT module reflecting different stages of the decision-making process. Each module addressed preferences, health, home and social and financial resources. Key design features and theoretical underpinnings were included.Conclusion and Significance: A user-centred design process can result in services that are aligned with older adults' preferences for obtaining housing information. Services for planning and preparing future housing needs have the potential to increase older adults´ well-being at home as well as reduce costs for care and housing provision by the municipalities.


Pediatric and neonatal extracorporeal life support technology component utilization: are US clinicians implementing new technology?
The objective of this investigation is to describe recent changes made in extracorporeal life support (ECLS) technology in the US Postal survey to directors and coordinators of all 125 US ECLS centers identified by Extracorporeal Life Support Organization as of November 2010, with follow-up of nonrespondents. Spearman coefficients were used to correlate the method of updating knowledge of ECLS technology with the likelihood of changing technology, and to correlate decision-making hierarchy with the likelihood of changing equipment. The response rate was 75% representing 34 states, and the majority of respondents were ECLS coordinators (56.6%). Respiratory diagnosis is the predominant indication for ECLS at any age. Over 40% of centers are using a hollow-fiber oxygenator for neonates and 80% of pediatric patients. Roller pumps are used in 70% of neonatal and pediatric ECLS. Forty-two percent of centers changed the oxygenator type within the past 3 years, while 30% changed both the oxygenator and pump. Less than 10% of centers reported problems with either oxygenator or pump in both neonates and pediatric ECLS. Forty-six percent of respondents that changed oxygenators cited that the primary reason for changing was "clinical preference/experience," while the other half was split between "FDA approval" and "Research results." In 40% of centers, a multidisciplinary group made decisions on changing technology. This survey indicates that over one-half of ECLS centers implemented new technology within the past 3 years. Knowledge of ECLS technology and safe operation of ECLS circuit components is essential in preventing some of the mechanical complications.


Functional histopathology of keloid disease.
Keloid disease is a benign, yet locally aggressive and recurrent cutaneous fibroproliferative condition characterised by excessive scarring. Unique to humans, keloids represent the end-point of a spectrum of abnormal wound healing, are aesthetically disfiguring and can cause major functional impairment. Its heterogeneous phenotype can confound clinical diagnosis leading to mismanagement. This review examines the histological morphology of keloid disease relative to the underlying pathobiology, places it in the context of other cutaneous fibroses and highlights gaps within the literature that hinder differential diagnosis. The pathological similarity to hypertrophic scarring, dermatofibrosarcoma protuberans, dermatofibroma and scleroderma emphasise the importance of detailing the architectural and cellular components of this unique entity. In the papillary dermis keloid tumours show a tongue-like advancing edge that resembles invasive tumour growth. A thickened but flattened epidermis, hyalinised haphazardly arranged collagen bundles that dominate the dermis with subsequent obliteration of the papillary-reticular boundary along with displacement and eventually destruction of skin appendages, exemplify additional hallmark findings associated with keloid disease. Compared to healthy skin, keloid scars show an increased type I/III collagen ratio, decreased fibrillin-1 and decorin expression, increased dermal cellularity and increased expression of fibronectin, versican, elastin and tenascin in the reticular dermis and hyaluronan and osteopontin in the epidermis. We illustrate these "pathognomonic" features of keloid disease by representative micrographs and discuss them in the context of inflammation, hypoxia and tension--as key elements of keloid disease. Finally, we highlight deficits within the keloid research literature as well as discuss important areas for future research in keloid histology.


Topical application of Mentha piperita essential oil accelerates wound healing in infected mice model.
This study was conducted to evaluate the effects of the prepared ointments from Mentha piperita essential oil (M. piperita) on wound healing in the infected mice models. Each circular full-thickness wound was inoculated with 25 × 107 units of Staphylococcus aureus and Pseudomonas aeruginosa bacteria strains. The tissue bacterial count, histological analyses and expression levels of IL-10, TNF-α, TGF-β1, IL-1β, CCL2, CXCL1, VEGF and FGF-2 were assessed to identify the different doses of M. piperita on wound healing. Total tissue bacterial count, edema and inflammation level were declined, but the migration of fibroblasts, collagen synthesis and re-epithelization were increased in treated animals with M. piperita. The expression levels of CCL2, CXCL1, IL-1β, TGF-β1 and IL-10 genes were up-regulated in the M. piperita-treated animals compared to the control group. While the expression of TNF-α, VEGF and FGF-2 was down-regulated in comparison to the control group. This study indicated that M. piperita can be used for treatment of the infected wound.


Density-dependence as a size-independent regulatory mechanism.
The growth function of populations is central in biomathematics. The main dogma is the existence of density-dependence mechanisms, which can be modelled with distinct functional forms that depend on the size of the population. One important class of regulatory functions is the theta-logistic, which generalizes the logistic equation. Using this model as a motivation, this paper introduces a simple dynamical reformulation that generalizes many growth functions. The reformulation consists of two equations, one for population size, and one for the growth rate. Furthermore, the model shows that although population is density-dependent, the dynamics of the growth rate does not depend either on population size, nor on the carrying capacity. Actually, the growth equation is uncoupled from the population size equation, and the model has only two parameters, a Malthusian parameter rho and a competition coefficient theta. Distinct sign combinations of these parameters reproduce not only the family of theta-logistics, but also the van Bertalanffy, Gompertz and Potential Growth equations, among other possibilities. It is also shown that, except for two critical points, there is a general size-scaling relation that includes those appearing in the most important allometric theories, including the recently proposed Metabolic Theory of Ecology. With this model, several issues of general interest are discussed such as the growth of animal population, extinctions, cell growth and allometry, and the effect of environment over a population.


Protein kinase M, the cytosolic counterpart of protein kinase C, remodels the internal cytoskeleton of the mammalian egg during activation.
We have investigated mechanisms by which intracellular signals act to restructure the spatial organization of the cytoskeleton as the mammalian egg is converted into the zygote. Four distinct approaches (one cytological, two biochemical, and one pharmacological) demonstrate protein kinase C (PKC) and its cytosolic active counterpart, PKM, act in succession at the time of egg activation. PKM serves to remodel the internal cytoskeleton. The cytological approach mapped the distribution of kinase over time using the PKC reporter dye, Rim-1, which demonstrated a temporal shift in kinase distribution from its initial site of activation at the plasma membrane to its subsequent association with a cross-linked network of intermediate filaments referred to as sheets. The first of two biochemical analyses, Western blot analysis, demonstrated that eggs activated with calcium ionophore contained PKC in the detergent-soluble fraction and PKM in the sheet enriched fraction. Prior to egg activation, PKM is not detected in the sheet-enriched fraction; only PKC is detected in the detergent-soluble fraction of these eggs. The second biochemical analysis demonstrated, via [32P]ATP labeling of a known PKC substrate, that the PKM generated from activation of PKC in response to activation of eggs with calcium ionophore is an active kinase and is located in the sheet-enriched fraction. In addition, purified forms of PKM, but not PKC, could be shown to act on the internal cytoskeleton when perfused into a permeabilized egg system. Pharmacological treatments demonstrate that elevation of [Ca2+]i does not act directly to alter the internal cytoskeleton of the egg. Our results suggest that this kinase is employed at the time of fertilization to provide an internal chronometer acting first at the cell periphery as PKC and subsequently in the cell interior as PKM.


Dietary Supplement Use in Australian Army Personnel.
Military personnel are reported to use more dietary supplements (DS) than the general population. However, a comprehensive investigation of DS use in Australian Army personnel has not been conducted. This study investigated the prevalence and types of DS used by Australian Army personnel and examined the underpinning reasons and demographic factors influencing this use. A Convenience sample of Australian Army personnel from both Headquarter (desk-based) and Brigade (field-based) environments completed a researcher-designed DS questionnaire. The questionnaire examined 19 types of DS (including sports foods) and reasons for use. Logistic regression, adjusting for age, sex, education, physical activity, BMI, and occupational group were performed. A total of 667 personnel completed the questionnaire. Overall, 74.5% of personnel reported using ≥1 DS/day, with ~26% reporting use of ≥5 types of DS at least once/week. The most common DS used daily were caffeine (48.4%), vitamin and mineral supplements (34.8%), protein powders (27.9%), creatine (13.3%), and amino acids (13.2%). Reasons for use in descending order were "to provide energy," "performance," "general health," "I like it," "muscle gain," "hydration," "endurance," "convenience," and "weight loss." Using ≥5 DS/week was associated with a higher level of education (p = 0.034), physical activity >10 h/week (p < 0.0005) and having an occupation as a physical training instructor (p = 0.040). If military personnel choose to utilize DS, it is important they are used in a safe, legal and effective manner. Education and up to date guidance on the rapidly evolving range of DS available are therefore necessary.


Smart polymeric nanocarriers for small nucleic acid delivery.
In recent decades, nucleic acid therapeutics have been attracting much attention because of their potential as treatments for various diseases that require high target specificity. Nevertheless, the number of approved nucleic acid drugs is very limited due to substantially poor bioavailability, thereby generating the need for nucleic acid delivery carriers. A variety of delivery formulations have been reported so far. This review particularly describes polymer-based delivery carriers for systemic administration, highlighting the potential of biological environment-responsive chemistry for overcoming the biological barriers to nucleic acid delivery.


An androgen receptor switch underlies lineage infidelity in treatment-resistant prostate cancer.
Cancers adapt to increasingly potent targeted therapies by reprogramming their phenotype. Here we investigated such a phenomenon in prostate cancer, in which tumours can escape epithelial lineage confinement and transition to a high-plasticity state as an adaptive response to potent androgen receptor (AR) antagonism. We found that AR activity can be maintained as tumours adopt alternative lineage identities, with changes in chromatin architecture guiding AR transcriptional rerouting. The epigenetic regulator enhancer of zeste homologue 2 (EZH2) co-occupies the reprogrammed AR cistrome to transcriptionally modulate stem cell and neuronal gene networks-granting privileges associated with both fates. This function of EZH2 was associated with T350 phosphorylation and establishment of a non-canonical polycomb subcomplex. Our study provides mechanistic insights into the plasticity of the lineage-infidelity state governed by AR reprogramming that enabled us to redirect cell fate by modulating EZH2 and AR, highlighting the clinical potential of reversing resistance phenotypes.


Effects of maleic acid on renal phosphorus transport: role of dietary phosphorus.
The effects of maleic acid on renal phosphate (Pi) transport were examined by clearance and brush-border membrane vesicle (BBMV) transport studies. In normal rats, maleic acid 50 mg.kg body wt-1.h-1 increased the phosphaturia (P less than 0.001). Intraperitoneal administration of a similar dose of maleic acid decreased the BBMV uptake of Pi but not glucose. In rats fed a low-phosphate diet (0.03%), the maleic acid-induced phosphaturia was blunted, but the inhibitory effect on the BBMV transport of Pi persisted. In chronic parathyroidectomized rats fed a low-phosphate diet, where the filtered load of Pi was higher than in the previous groups, the phosphaturia was abolished, but the inhibition of the BBMV transport of Pi was sustained. Both the in vitro incubation of BBMVV and in vivo administration of maleic acid were associated with a competitive inhibition of Pi transport. These studies indicate that the maleic acid-induced phosphaturia is expressed at the apical membrane entry step of Pi, and the enhanced distal tubular reabsorption accounts for the lack of phosphaturia in dietary Pi deprivation.


Outcome of Pediatric Forearm Fracture Reductions Performed by Pediatric Emergency Medicine Providers Compared With Reductions Performed by Orthopedic Surgeons: A Retrospective Cohort Study.
The aim of this study was to describe the outcome differences between board-certified orthopedists and pediatric emergency medicine (PEM) physicians conducting forearm fracture reductions. We performed an analysis of patients between 1 and 14 years of age who presented to the emergency department (ED) with a forearm fracture requiring reduction. Data collected included reducing provider (PEM or orthopedist) and prereduction, postreduction, and follow-up fracture angles and displacements of both radius and ulna. We collected costs of care, both in the ED and at follow-up, as well as length-of-stay data. χ Tests and Fisher exact test compared associations between categorical variables; 2-sample t tests compared the PEM and orthopedic groups. Regression models were used to control for injury severity confounders. Of the 222 fractures, orthopedists reduced 135, and PEM doctors reduced 87. Based on fracture angle and displacement, the orthopedic group tended to have slightly more complicated cases. After adjusting for age and time to follow-up, fractures reduced by orthopedists were less likely to require remanipulation (adjusted odds ratio, 0.30; P = 0.020). The PEM group had a significantly lower length of stay (59.4 minutes shorter; P < 0.001) and a small overall saving in charges ($273.90; P = 0.47). Orthopedists performed better in maintaining fracture reductions compared with PEM physicians but lengthened the ED stay for our patients. There was no significant difference in cost.


Impact of Pratylenchus penetrans on Soybean Grown in Wisconsin, U.S.A.
Models were developed to quantify the impact of Pratylenchus penetrans to the early season growth and yield of soybean in field and greenhouse environments and to estimate yield loss because of P. penetrans in Wisconsin. There was a negative linear relationship between initial nematode population densities (Pi) and shoot and total plant weight at V2 and yield, pod number, seed number, and seed mass at harvest in the field. Relative yield loss, modeled for the second year of the field experiment, suggested a loss of 4.5% for yield and between 2.4 and 2.8% for yield components at the mean field Pi value. Negative linear relationships were demonstrated for the relative loss in those variables as well as for harvest index and shoot, root, and total plant weight at harvest in the greenhouse. Stress imposed by P. penetrans began within 2 weeks after planting and continued through harvest. Estimates of the percent loss attributed to each nematode Pi value were 0.020% for yield, 0.015% for pod number, and 0.017% for seed number. Pratylenchus spp. was the most widely prevalent pest nematode among samples submitted to a statewide nematode testing program. Molecular identification of a subset of 63 samples suggested 15% were infested with P. penetrans at a mean Pi value of 197 P. penetrans per 100 cm3 soil. Yield loss because of P. penetrans, estimated from prevalence data and our empirical greenhouse model, ranged from 0.23 to 2.76% among Wisconsin's agricultural districts. The cumulative impact for all Pratylenchus spp. is likely much greater, given this loss estimate does not account for the monoecious species present in 79% of the samples.


Non-human primate models for understanding the impact of the microbiome on pregnancy and the female reproductive tract†.
The microbiome has been shown, or implicated to be involved, in multiple facets of human health and disease, including not only gastrointestinal health but also metabolism, immunity, and neurology. Although the predominant focus of microbiome research has been on the gut, other microbial communities such as the vaginal or cervical microbiome are likely involved in physiological homeostasis. Emerging studies also aim to understand the role of different microbial niches, such as the endometrial or placental microbial communities, on the physiology and pathophysiology of reproduction, including their impact on reproductive success and the etiology of adverse pregnancy outcomes (APOs). The study of the microbiome during pregnancy, specifically how changes in maternal microbial communities can lead to dysfunction and disease, can advance the understanding of reproductive health and the etiology of APOs. In this review, we will discuss the current state of non-human primate (NHP) reproductive microbiome research, highlight the progress with NHP models of reproduction, and the diagnostic potential of microbial alterations in a clinical setting to promote pregnancy health. NHP reproductive biology studies have the potential to expand the knowledge and understanding of female reproductive tract microbial communities and host-microbe or microbe-microbe interactions associated with reproductive health through sequencing and analysis. Furthermore, in this review, we aim to demonstrate that macaques are uniquely suited as high-fidelity models of human female reproductive pathology.


Independent and Combined Association of Lifestyle Behaviours and Physical Fitness with Body Weight Status in Schoolchildren.
(1) Background: Lifestyle behaviours and physical fitness play a critical role in the development of childhood obesity. It has been demonstrated in this study that self-reported physical fitness is representative of a healthy lifestyle and thus is associated with a lower incidence of overweight/obesity. The objective of this study was to analyse the independent and combined association of lifestyles (physical activity, screen time, diet and hours of sleep) and self-reported physical fitness with body weight in schoolchildren. (2) Methods: This study performed a descriptive and cross-sectional analysis. The study sample consisted of 864 schoolchildren between 8−9 years old from 26 schools of the province of Cádiz. To measure lifestyles and self-reported physical fitness, questionnaires were administered to both schoolchildren and families. To obtain the body weight status, the children were measured by body mass index (BMI). To verify the influence of lifestyles and self-reported physical fitness on the body weight status of schoolchildren, a combined score of lifestyles and self-reported physical fitness was calculated. (3) Results: Schoolchildren who followed healthier lifestyles and presented good physical fitness had a better body weight status (p < 0.001). Schoolchildren who had less healthful lifestyles and bad physical fitness had a 10.34 times higher risk of being overweight or obese (p = 0.004). (4) Conclusions: It has been shown that there is an independent and combined association between lifestyles and physical fitness on the body weight of the schoolchildren. We have suggested strategies to get children to adopt healthy lifestyles and good physical fitness to maintain a healthy body weight and prevent obesity.


Parenting and childhood irritability: Negative emotion socialization and parental control moderate the development of irritability.
Irritability, characterized by anger in response to frustration, is normative in childhood. While children typically show a decline in irritability from toddlerhood to school age, elevated irritability throughout childhood may predict later psychopathology. The current study (n = 78) examined associations between trajectories of irritability in early childhood (ages 2-7) and irritability in adolescence (age 12) and tested whether these associations are moderated by parenting behaviors. Results indicate that negative emotion socialization moderated trajectories of irritability - relative to children with low stable irritability, children who exhibited high stable irritability in early childhood and who had parents that exhibited greater negative emotion socialization behaviors had higher irritability in adolescence. Further, negative parental control behavior moderated trajectories of irritability - relative to children with low stable irritability, children who had high decreasing irritability in early childhood and who had parents who exhibited greater negative control behaviors had higher irritability in adolescence. In contrast, positive emotion socialization and control behaviors did not moderate the relations between early childhood irritability and later irritability in adolescence. These results suggest that both irritability in early childhood and negative parenting behaviors may jointly influence irritability in adolescence. The current study underscores the significance of negative parenting behaviors and could inform treatment.


Inhibition of immune functions by antiviral drugs.
Immune functions were evaluated in vitro for PBMC isolated from healthy donors and cultured with the antiviral agents, 3'-azido-3'-deoxythymidine (AZT), ribavirin, ganciclovir, 2'3'-dideoxyinosine (ddI), or acyclovir. To identify methods for assessing the effects of antiviral drugs on immune cells, the PBMC response to mitogens, Con A, or phytohemagglutinin was evaluated from measurements of [3H]thymidine and [14C]-leucine incorporation, cell growth, cellular RNA, DNA, and protein levels, and the PBMC proliferative cycle (i.e., progression from G0----G1----S----G2 + M). At clinically relevant concentrations, AZT, ribavirin, or ganciclovir diminished PBMC responsiveness to mitogen. The numbers of proliferating cells in G1, S, and G2 + M phases of the cell cycle, DNA content, and [3H]thymidine uptake were decreased in cultures treated with AZT, ribavirin, or ganciclovir. AZT or ribavirin but not ganciclovir reduced RNA and protein in the cultures and inhibited cell growth. Whereas AZT, ribavirin, or ganciclovir were antiproliferative, ddI or acyclovir had little, if any, effect on PBMC mitogenesis. The inhibitory effects of antivirals on immune cells may contribute to the immune deterioration observed in patients following prolonged use of the drugs.


The Employment Quality of Persons with Disabilities: Findings from a National Survey.
Labour market integration is a widely accepted strategy for promoting the social and economic inclusion of persons with disabilities. But what kinds of jobs do persons with disabilities obtain following their integration into the labour market? In this study, we use a novel survey of workers to describe and compare the employment quality of persons with and without disabilities in Canada. We administered an online, cross-sectional survey to a heterogeneous sample of workers in Canada (n = 2,794). We collected data on sixteen different employment conditions (e.g., temporary contract, job security, flexible work schedule, job lock, skill match, training opportunities, and union membership). We used latent class cluster analysis to construct a novel typology of employment quality describing four distinct 'types' of employment: standard, portfolio, instrumental, and precarious. We examined associations between disability status, disability type, and employment quality. Persons with disabilities reported consistently lower employment quality than their counterparts without disabilities. Persons with disabilities were nearly twice as likely to report low-quality employment in the form of either instrumental (i.e., secure but trapped) or precarious (i.e., insecure and unrewarding) employment. This gap in employment quality was particularly pronounced for those who reported living with both a physical and mental/cognitive condition. There are widespread inequalities in the employment quality of persons with and without disabilities in Canada. Policies and programs aiming to improve the labour market situation of persons with disabilities should emphasize the importance of high-quality employment as a key facet of social and economic inclusion.


Model of local hydrogen permeability in stainless steel with two coexisting structures.
The dynamics of hydrogen in metals with mixed grain structure is not well understood at a microscopic scale. One of the biggest issues facing the hydrogen economy is "hydrogen embrittlement" of metal induced by hydrogen entering and diffusing into the material. Hydrogen diffusion in metallic materials is difficult to grasp owing to the non-uniform compositions and structures of metal. Here a time-resolved "operando hydrogen microscope" was used to interpret local diffusion behaviour of hydrogen in the microstructure of a stainless steel with austenite and martensite structures. The martensite/austenite ratios differed in each local region of the sample. The path of hydrogen permeation was inferred from the time evolution of hydrogen permeation in several regions. We proposed a model of hydrogen diffusion in a dual-structure material and verified the validity of the model by simulations that took into account the transfer of hydrogen at the interfaces.


Pneumocystis carinii: recognition of the infection in albino rats using different stains.
Pneumocystis carinii is a commensal protozoan which may cause pneumonia in hosts with compromised immune status and may end fatally. Since effective management of pneumocystic pneumonia depends on rapid and accurate recognition of the disease, so, the present study aims to throw lights on the best staining method for cytodiagnosis of this organism with the sequential pathological changes in the infected lungs. An immunosuppression state was induced in albino rats for 6-8 weeks then rats were sacrificed weekly & lungs were examined for infection using different stains. In stained smears, intracystic bodies have been identified using Giemsa, Papanicolaou & Toluidine blue stains. On the other hand, cysts were inspected in paraffin sections using Gomori methenamine silver nitrate (GMS) & weight gram stains. Histopathologically, in sections stained with H & E, features of Pneumocystis carinii pneumonia were obvious, foamy exudation, inflammatory infiltration formed mainly of histiocytes, plasma cells, lymphocytes, thickening of alveolar septa and lastly formation of hyaline membrane in some alveoli.


The localization of laminin and fibronectin on the Schwann cell basal lamina.
The localization of laminin and fibronectin was examined on the basal laminae of Schwann cells. Basal laminae from sciatic nerves were isolated by sonication, and the localization of laminin and fibronectin on such isolated basal laminae was studied by immunoferritin histochemistry. Laminin was localized mainly on the cellular side (i.e. the side originally facing the Schwann cell plasma membrane) of the basal laminae. On the other hand, fibronectin was found to be present as aggregates only on the interstitial side (i.e., the side originally facing the endoneurial connective tissue) of the basal laminae. Thus, the locations of laminin and fibronectin were distinctly different. It is presumed that laminin might be involved in the attachment of axons and Schwann cells to the basal laminae, while fibronectin mediates the adhesion of the basal laminae to connective tissue elements, including the collagen fibrils. These findings are discussed from a standpoint of nerve regeneration through the basal laminae scaffolds of Schwann cells.


Overview of medical physics education and research programs in a non-academic environment.
Northwest Medical Physics Center (NMPC) is a nonprofit organization that provides clinical physics support to over 35 radiation therapy facilities concentrated in the Pacific Northwest. Although clinical service is the primary function of NMPC, the diverse array of clinical sites and physics expertise has allowed for the establishment of structured education and research programs, which are complementary to the organization's clinical mission. Three clinical training programs have been developed at NMPC: a therapy medical physics residency program accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP), an Applied Physics Technologist (APT) program, and a summer undergraduate internship program. A partnership has also been established with a major radiation oncology clinical vendor for the purposes of validating and testing new clinical devices across multiple facilities. These programs are managed by a dedicated education and research team at NMPC, made up of four qualified medical physicists (QMPs). The education and research work has made a significant contribution to the organization's clinical mission, and it has provided new training opportunities for early-career physicists across many different clinical environments. Education and research can be incorporated into nonacademic clinical environments, improving the quality of patient care, and increasing the number and type of training opportunities available for medical physicists.


Evidence of thermal metamorphism on the C, g, B, and f asteroids.
Reflectance spectra (0.3 to 2.6 micrometers) of 14 C, G, B, and F asteroids and 21 carbonaceous chondrite powders are compared in detail. Only three thermally metamorphosed CM-Cl chondrites that have a weak ultraviolet absorption are shown to have close counterparts among those asteroids. Reflectance spectra of heated Murchison CM2 chondrite are compared with the average C and G type asteroid spectra. Murchison heated at 600 degrees to 1000 degrees C exhibits a similar weak ultraviolet absorption and provides the best analog for those spectra. Comparison of ultraviolet absorption strengths between 160 C, G, B, and F asteroids and carbonaceous chondrites suggests that surface minerals of most of those asteroids are thermally metamorphosed at temperatures around 600 degrees to 1000 degrees C.


Prognostic value of shock index in patients admitted with non-ST-segment elevation myocardial infarction: the ARIC study community surveillance.
Shock index (SI), defined as the ratio of heart rate (HR) to systolic blood pressure (SBP), is easily obtained and predictive of mortality in patients with ST-segment elevation myocardial infarction. However, large-scale evaluations of SI in patients with non-ST-segment elevation myocardial infarction (NSTEMI) are lacking. Hospitalizations for acute myocardial infarction were sampled from four US areas by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. Shock index was derived from the HR and SBP at first presentation and considered high when ≥0.7. From 2000 to 2014, 18 301 weighted hospitalizations for NSTEMI were sampled and had vitals successfully obtained. Of these, 5753 (31%) had high SI (≥0.7). Patients with high SI were more often female (46% vs. 39%) and had more prevalent chronic kidney disease (40% vs. 32%). TIMI (Thrombolysis in Myocardial Infarction) risk scores were similar between the groups (4.3 vs. 4.2), but GRACE (Global Registry of Acute Coronary Syndrome) score was higher with high SI (140 vs. 118). Angiography, revascularization, and guideline-directed medications were less often administered to patients with high SI, and the 28-day mortality was higher (13% vs. 5%). Prediction of 28-day mortality by SI as a continuous measurement [area under the curve (AUC): 0.68] was intermediate to that of the GRACE score (AUC: 0.87) and the TIMI score (AUC: 0.54). After adjustments, patients with high SI had twice the odds of 28-day mortality (odds ratio = 2.02; 95% confidence interval: 1.46-2.80). The SI is easily obtainable, performs moderately well as a predictor of short-term mortality in patients hospitalized with NSTEMI, and may be useful for risk stratification in emergency settings.


EZH2 Influences mdDA Neuronal Differentiation, Maintenance and Survival.
Over the last decade several components have been identified to be differentially expressed in subsets of mesodiencephalic dopaminergic (mdDA) neurons. These differences in molecular profile have been implied to be involved in the selective degeneration of the SNc neurons in Parkinson's disease. The emergence and maintenance of individual subsets is dependent on different transcriptional programs already present during development. In addition to the influence of transcription factors, recent studies have led to the hypothesis that modifications of histones might also influence the developmental program of neurons. In this study we focus on the histone methyltransferase EZH2 and its role in the development and maintenance of mdDA neurons. We generated two different conditional knock out (cKO) mice; an En1Cre driven cKO, for deletion of Ezh2 in mdDA progenitors and a Pitx3Cre driven cKO, to study the effect of post-mitotic deletion of Ezh2 on mdDA neurons maturation and neuronal survival. During development Ezh2 was found to be important for the generation of the proper amount of TH+ neurons. The loss of neurons primarily affected a rostrolateral population, which is also reflected in the analysis of the subset marks, Ahd2 and Cck. In contrast to early genetic ablation, post-mitotic deletion of Ezh2 did not lead to major developmental defects at E14.5. However, in 6 months old animals Cck was found ectopically in the rostral domain of mdDA neurons and Ahd2 expression was reduced in more mediocaudal positioned cells. In addition, Pitx3Cre driven deletion of Ezh2 led to a progressive loss of TH+ cells in the VTA and these animals display reduced climbing behavior. Together, our data demonstrates that Ezh2 is important for the generation of mdDA neurons during development and that during adult stages Ezh2 is important for the preservation of proper neuronal subset identity and survival.


Development of a fluoroscopically guided robotic assistant for instrument placement in pelvic trauma surgery.
Purpose: A method for fluoroscopic guidance of a robotic assistant is presented for instrument placement in pelvic trauma surgery. The solution uses fluoroscopic images acquired in standard clinical workflow and helps avoid repeat fluoroscopy commonly performed during implant guidance. Approach: Images acquired from a mobile C-arm are used to perform 3D-2D registration of both the patient (via patient CT) and the robot (via CAD model of a surgical instrument attached to its end effector, e.g; a drill guide), guiding the robot to target trajectories defined in the patient CT. The proposed approach avoids C-arm gantry motion, instead manipulating the robot to acquire disparate views of the instrument. Phantom and cadaver studies were performed to determine operating parameters and assess the accuracy of the proposed approach in aligning a standard drill guide instrument. Results: The proposed approach achieved average drill guide tip placement accuracy of 1.57 ± 0.47 mm and angular alignment of 0.35 ± 0.32 deg in phantom studies. The errors remained within 2 mm and 1 deg in cadaver experiments, comparable to the margins of errors provided by surgical trackers (but operating without the need for external tracking). Conclusions: By operating at a fixed fluoroscopic perspective and eliminating the need for encoded C-arm gantry movement, the proposed approach simplifies and expedites the registration of image-guided robotic assistants and can be used with simple, non-calibrated, non-encoded, and non-isocentric C-arm systems to accurately guide a robotic device in a manner that is compatible with the surgical workflow.


[Idiopathic hemochromatosis, analysis of 19 cases].
We studied 19 patients with idiopathic haemochromatosis between 12,000 patients by the Department of Internal Medicine. By 17 the diagnosis was made very late with severe state of chronic liver disease, only two went to consult because transaminases were increased without exploration in routinary examination. Hepatomegalie was constant exploratory feature (100%) followed by impaired hydrocarbonated metabolism (52%). The biochemical usual pattern was: hipersideremie, decreased transferrin and increased transaminases activities in all the patients. Increased iron urinary excretion (more than 8 g/24 h) with desferroxiamine administration is a useful biochemical feature if because severe liver disease the biopsy punction was not indicated due to impaired hemostasia. Because the serious illness with late diagnosis and the normal survival if the diagnosis is early the iron metabolism would be useful screening as in another countries.


Effector loss drives adaptation of Pseudomonas syringae pv. actinidiae biovar 3 to Actinidia arguta.
A pandemic isolate of Pseudomonas syringae pv. actinidiae biovar 3 (Psa3) has devastated kiwifruit orchards growing cultivars of Actinidia chinensis. In contrast, A. arguta (kiwiberry) is not a host of Psa3. Resistance is mediated via effector-triggered immunity, as demonstrated by induction of the hypersensitive response in infected A. arguta leaves, observed by microscopy and quantified by ion-leakage assays. Isolates of Psa3 that cause disease in A. arguta have been isolated and analyzed, revealing a 51 kb deletion in the exchangeable effector locus (EEL). This natural EEL-mutant isolate and strains with synthetic knockouts of the EEL were more virulent in A. arguta plantlets than wild-type Psa3. Screening of a complete library of Psa3 effector knockout strains identified increased growth in planta for knockouts of four effectors-AvrRpm1a, HopF1c, HopZ5a, and the EEL effector HopAW1a -suggesting a resistance response in A. arguta. Hypersensitive response (HR) assays indicate that three of these effectors trigger a host species-specific HR. A Psa3 strain with all four effectors knocked out escaped host recognition, but a cumulative increase in bacterial pathogenicity and virulence was not observed. These avirulence effectors can be used in turn to identify the first cognate resistance genes in Actinidia for breeding durable resistance into future kiwifruit cultivars.


Wireless substitution: state-level estimates from the National Health Interview Survey, January-December 2007.
This report presents state-level estimates of the percentage of households that do not have a landline telephone, but do have at least one wireless telephone. These wireless-only households made up 14.7% of U.S. households in 2007. The report also presents state-level estimates of the percentage of adults living in wireless-only households. These wireless-only adults made up 13.6% of U.S. adults in 2007. A two-sample modeling strategy was used to estimate the prevalence of wireless-only households and adults by state. This modeling was based on data from the 2007 National Health Interview Survey and the 2008 Current Population Survey's Annual and Social Economic Supplement. The results show that the prevalence of wireless-only households and adults in 2007 varied substantially across states. State-level estimates ranged from 5.1% (Vermont) to 26.2% (Oklahoma) of households and from 4.0% (Delaware) to 25.1% (Oklahoma) of adults. In addition, approximately one out of four adults (25.4%) living in the District of Columbia were wireless-only.


Management of cardiac diseases in liver transplant recipients: Comprehensive review and multidisciplinary practice-based recommendations.
Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.


PCR-Based Rapid Identification System Using Bridged Nucleic Acids for Detection of Clarithromycin-Resistant Mycobacterium avium-M. intracellulare Complex Isolates.
The nontuberculous mycobacteria (NTM) cause miscellaneous disorders in humans, especially in the lungs, which present with a variety of radiological features. To date, knowledge of the pathogenic role of the Mycobacterium avium-intracellulare complex (MAC) in the human lung and the definitive criteria for initiating multidrug therapy are still lacking. However, there is little doubt that clarithromycin is the most efficacious drug among the various treatment regimens for lung NTM. In this study, with the use of a bridged nucleic acid (BNA) probe a detection system based on a real-time PCR (BNA-PCR) for the identification of the point mutations at position 2058 or 2059 in domain V of the 23S rRNA gene responsible for clarithromycin resistance was developed and has been assessed using MAC isolates from clinical samples. Out of 199 respiratory specimens, the drug susceptibility test demonstrated 12 strains resistant to clarithromycin, while the BNA-PCR showed 8 strains carrying the point mutation at position 2058 or 2059 of the 23S rRNA gene. This system revealed that there were mycobacterial strains resistant to clarithromycin which do not carry previously identified resistance genes. This paper documents a novel system for detecting clarithromycin-resistant strains and demonstrates that although these mutations are tacitly assumed to account for >90% of the reported resistant mutants, there is a significant fraction of resistant mutants that do not harbor these mutations. Therefore, unknown mechanisms affecting clarithromycin resistance remain to be elucidated.


Pilot feasibility study of the method of water infusion without air insufflation in sedated colonoscopy.
One study in sedated patients demonstrated a reduction in pain score but not midazolam dosage when warm water infusion was used to manage colonic spasm. We describe pilot data with a modified warm water infusion technique. We tested the hypothesis that patients receiving even only half of the usual dose of sedation medications would have acceptable cecal intubation and tolerate the procedure well, based on retrospective review of prospectively collected data from a single Veterans Affairs (VA) medical center. Group 1 included 32 consecutive patients who received full-dose and group 2 included 43 consecutive patients who received half-dose premedication. Insertion of colonoscope was aided by warm water infusion in lieu of air insufflation. Pain scores during insertion, cecal intubation rate, and total amount of medications were monitored. The novel technique permitted equal cecal intubation rate at reduced total dose of medications. Pain scores were not significantly different. The uncontrolled nonrandomized observational nature of the data is one limitation. The nonsignificant difference in pain scores may be affected by a type II error. These pilot data suggest that insertion is feasible without air when water infusion is used. The novel technique may be a useful adjunct for minimizing the dosage of sedation medications without adversely affecting cecal intubation. Further study is needed to compare air insufflation and water infusion with regard to patient tolerance and success, particularly in the presence of an on-demand sedation policy.