Search

Cardiac implantable electronic devices (CIEDs) store information continuously; however, the log of these devices is rarely analyzed in forensic practice. We retrospectively reviewed all cases referred for CIED interrogation by the Los Angeles County Department of Medical Examiner-Coroner between 2001 and 2020. According to the Department's practice, CIED interrogation may be requested for decedents in which details or cause of death are not clear from autopsy and clinical history. The CIED analysis was considered informative for the coroner's investigation either if it detected an arrhythmia or malfunction likely related to decedent's terminal event or if it was essential to determine time of death or identity of decedent. A total of 57 CIEDs were evaluated during the 20-year period. In almost half of cases (26/57: 45.6%), device analysis was informative for coroner's investigation. Arrhythmias likely related to terminal event were commonly detected (21/57: 36.8%). Device malfunction was identified as the likely cause of death in almost 10% of decedents (5/57: 8.8%), including three cases of battery depletion (3/57: 5.3%), one case of misclassification of ventricular tachycardia as supraventricular tachycardia with failure to deliver therapy (1/57: 1.7%), and one case of lead failure due to a broken pacing wire (1/57: 1.7%). Not infrequently, CIED interrogation was essential for determination of time of death (9/57: 15.8%), and there was one case (1/57: 1.7%) in which interrogation was essential for identifying the decedent. Our study shows that postmortem CIED interrogation can provide unique information regarding mechanism and time of death, and decedent's identity.

ObjectiveTo describe the perception of professional climate in health services and policy research (HSPR) and efforts to advance diversity, equity, and inclusion (DEI) in the HSPR workforce and workplaces.Data sourceWe administered the HSPR Workplace Culture Survey online to health services and policy researchers.Study designOur survey examined participants' sociodemographic, educational, and professional backgrounds, their perception on DEI in HSPR, experience with DEI initiatives, feeling of inclusion, and direct and witnessed experiences of discrimination at their institutions/organizations. We calculated sample proportions of responses by gender identity, sexual orientation, race/ethnicity, and disability status and compared them with Fisher's exact test.Data collectionWe administered the survey online from July 28 to September 4, 2020. HSPR professionals and trainees aged 18 and older were eligible to participate. Analyses used complete cases only (n=906; 70.6% completion rate).Principal findings53.4% of the participants did not believe that the current workforce reflects the diversity of communities impacted by HSPR. Although most participants have witnessed various DEI initiatives at their institutions/organizations, nearly 40% characterized these initiatives as "tokenistic." Larger proportions of participants who identified as female, LGBQI+, underrepresented racial/ethnic groups, and those with a disability held this perception than their male, heterosexual, White, and non-disabled counterparts. Current DEI initiatives focused on "planning" activities (e.g., convening task forces) rather than "implementation" activities (e.g., establishing mentoring or network programs). 43.7% of the participants felt supported on their career development, while female, Black, Hispanic/Latino, LGBQI+ participants and those with a disability experienced discrimination at their workplace.ConclusionsDespite an increasing commitment to increasing the diversity of the HSPR workforce and improving equity and inclusion in the HSPR workplace, our results suggest that there is more work to be done to achieve such goals.

Objective National movements have raised awareness of the adverse mental health effects of police brutality. This study examines the relationship between perceived police brutality and unmet need for mental health care. Data sources We used the 2018 Survey of the Health of Urban Residents (N = 4338), a quota sample survey of adults in urban areas in the contiguous United States. Study design Multivariate regressions were used to understand the association between police brutality and unmet need for mental health care. Unmet need was regressed on police brutality (the independent variable), controlling for sociodemographic and health status characteristics of respondents and access to care. We then stratified the sample by experiences of police brutality (no negative encounters with the police, encounters that were perceived as necessary, and encounters that were considered unnecessary) and described how medical mistrust and perceived respect within health care settings were associated with odds of unmet need for each subsample. Data collection Data were collected online. Principal findings Negative police encounters perceived as necessary were associated with greater odds of unmet need compared to no negative police encounters (odds ratio [OR] = 1.98, confidence interval [CI] = 1.30-2.65). Odds of unmet need were also higher among persons with negative and unnecessary police encounters (OR = 1.28, CI = 1.05-1.56). Greater respect was associated with lower odds of unmet need among persons who reported negative unnecessary encounters with the police (OR = 0.88, CI = 0.72-0.97). Medical mistrust was associated with greater odds of unmet need among those with negative unnecessary police encounters (OR = 1.52, CI = 1.12-1.93). Conclusions Persons who are exposed to police brutality are also likely to be those who experience unmet need for mental health care. Ensuring that they feel respected within medical settings and establishing conditions that build trust in medical institutions are important for eliminating unmet need for mental health care.

A high fruit and vegetable (FV) diet reduces asthma exacerbations in adults; this has not been examined in children to date.To investigate the effect of a 6-month, high FV diet on the time to first asthma exacerbation in children with asthma, in a parallel-group, randomized, controlled trial.Children (aged 3-11 years) with asthma, history of exacerbations and usual low FV intake (≤3 serves/day) were randomized to the intervention (high FV diet) or control group (usual diet) for 6 months. The primary outcome was time to first exacerbation requiring medical intervention. Secondary outcomes included exacerbation rate, lung function, plasma TNF-α, CRP, and IL-6, faecal microbiota and peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity and G-protein coupled receptor (GPR) 41/43 and HDAC (1-11) expression.67 children were randomized between September 2015 and July 2018. FV intake (difference in change (∆): 3.5 serves/day, 95% CI: [2.6, 4.4] p 0.001) and plasma total carotenoids (∆: 0.44 µg/ml [0.19, 0.70] p = 0.001) increased after 6 months (intervention vs control). Time to first exacerbation (HR: 0.81, 95% CI: [0.38, 1.69], p = 0.569; control vs. intervention) and exacerbation rate (IRR: 0.84, [0.47, 1.49], p = 0.553; control vs. intervention) were similar between groups. In per-protocol analysis, airway reactance z-scores increased in the intervention versus control group (XA high FV diet did not affect asthma exacerbations over the 6-month intervention, though warrants further investigation as a strategy for improving lung function and protecting against systemic inflammation in children with asthma.

Childhood onset chronic inflammatory demyelinating polyneuropathy (CIDP) often requires long-term immunomodulatory therapy. We report a comprehensive review of our treatment of pediatric CIDP with a focus on high-dose weekly corticosteroids ("pulse oral corticosteroids"), a treatment method that is not commonly reported. We retrospectively reviewed medical records of pediatric patients with CIDP treated at our center between 2000 and 2018 for whom we had at least 12 mo follow-up. Here, we describe the demographics, disease course, treatment regimens, and long-term outcomes of these patients. Twenty-five patients were identified for analysis. Pulse oral corticosteroid monotherapy was the predominant maintenance treatment in 56% of patients. Patients were followed for a median of 4 y. Side effects were seen in a minority of patients. The probability of a normal exam or being off treatment at last follow-up was similar regardless of predominant maintenance therapy. Pulse oral corticosteroid therapy is a safe and effective long-term treatment option in children with CIDP.

Fenpicoxamid (Inatreq™ active), a new fungicide under development by Corteva Agriscience™, Agriculture Division of DowDuPont, is an isobutyryl acetal derivative of the antifungal antibiotic UK-2A. SAR studies around the picolinamide ring and benzyl substituents attached at positions 3 and 8, respectively, of the UK-2A bislactone macrocycle have recently been documented. This study focuses on replacement of the isobutyryl ester group in the 7 position.Thirty analogs, predominantly esters and ethers, were prepared and evaluated for inhibition of mitochondrial electron transport and in vitro growth of Zymoseptoria tritici, Leptosphaeria nodorum, Pyricularia oryzae and Ustilago maydis. Aliphatic substituents containing four to six carbon atoms deliver strong intrinsic activity, the pivaloate ester (ICSubstitution of the isobutyryl ester group of UK-2A generates analogs that retain strong antifungal activity against Z. tritici and other fungi. © 2019 Society of Chemical Industry.

Author(s): Rogers, Jennifer; Stein, Eric; Beck, Marcus; Flint, Kelly; Kinoshita, Alicia; Ambrose, Richard

Oral Presentation - 82. Note: In light of the Covid-19 pandemic, FNM 2020 Local Organising Committee resolved to postpone FNM 2020.

Background The antifungal antibiotic UK-2A strongly inhibits mitochondrial electron transport at the Qi site of the cytochrome bc1 complex. Previous reports have described semi-synthetic modifications of UK-2A to explore the structure-activity relationship (SAR), but efforts to replace the picolinic acid moiety have been limited. Results Nineteen UK-2A analogs were prepared and evaluated for Qi site (cytochrome c reductase) inhibition and antifungal activity. While the majority are weaker Qi site inhibitors than UK-2A (IC50 , 3.8 nM), compounds 2, 5, 13 and 16 are slightly more active (IC50 , 3.3, 2.02, 2.89 and 1.55 nM, respectively). Compared to UK-2A, compounds 13 and 16 also inhibit growth of Zymoseptoria tritici and Leptosphaeria nodorum more strongly, while 2 and 13 provide stronger control of Z. tritici and Puccinia triticina in glasshouse tests. The relative activities of compounds 1-19 are rationalized based on a homology model constructed for the Z. tritici Qi binding site. Physical properties of compounds 1-19 influence translation of intrinsic activity to antifungal growth inhibition and in planta disease control. Conclusions The 3-hydroxy-4-methoxy picolinic acid moiety of UK-2A can be replaced by a variety of o-hydroxy-substituted arylcarboxylic acids that retain strong activity against Z. tritici and other agriculturally relevant fungi. © 2018 Society of Chemical Industry.

Little is known about the effectiveness of fishways for restoring passage to inland (nonanadromous) salmonids. We used PIT telemetry to evaluate the biological effectiveness of a vertical-slot fishway constructed to restore passage of adult Colorado River Cutthroat Trout Oncorhynchus clarkii pleuriticus (CRCT) in a small Rocky Mountain stream. Our objectives were to assess (1) fishway efficacy (whether or not the fishway restored fish passage), (2) approach efficiency (the probability that a tagged fish encountered the fishway; an index of population use), (3) attraction efficiency (the probability that a fish near the fishway located its entrance), and (4) passage efficiency (the probability that a fish entering the fishway navigated successfully through it). To account for antenna detection probabilities and avoid biases that can result from simple, proportion-based calculations, we used a variation of the Cormack–Jolly–Seber model to derive efficiency estimates. The fishway restored passage of ...

The gastrointestinal (GI) microbiome is shaped by host diet, immunity, and other physicochemical characteristics of the GI tract, and perturbations such as antibiotic treatments can lead to persistent changes in microbial constituency and function. These GI microbes also play critical roles in host nutrition and health. A growing body of evidence suggests that the GI microbiome in people with CF is altered, and that these dysbioses contribute to disease manifestations in many organs, both within and beyond the GI tract. Therapies that people with CF receive, even those targeting the respiratory tract, may impact the CF GI microbiome in ways that can influence the outcome of treatment. These new perspectives on the microbial contents of the CF intestine offer new opportunities for preventing a variety of CF-associated disorders. Pediatr Pulmonol. 2016;51:S35-S44. © 2016 Wiley Periodicals, Inc.

Background The discovery of sulfoxaflor (Isoclast™ active) stemmed from a novel scaffold-based approach toward identifying bioactive molecules. It exhibits broad-spectrum control of many sap-feeding insect pests, including aphids, whiteflies, hoppers and Lygus. Systematic modifications of the substituents flanking each side of the sulfoximine moiety were carried out to determine whether these changes would improve potency. Results Structure-activity relationship (SAR) studies showed that, with respect to the methylene linker, both mono- and disubstitution with alkyl groups of varying sizes as well as cyclic analogs exhibited excellent control of cotton aphids. However, against green peach aphids a decrease in activity was observed with substituents larger than ethyl as well as larger cycloalkyl groups. At the terminal tail there appeared to be a narrow steric tolerance as well, with linear groups or small rings more active against green peach aphids than bulkier groups. Conclusion A novel series of compounds exploring the substituents flanking the sulfoximine moiety of sulfoxaflor were prepared and tested for bioactivity against cotton aphids and green peach aphids. SAR studies indicated that a decrease in green peach aphid potency was observed at the methylene linker as well as at the terminal tail with bulkier substituents. A quantitative structure-activity relationship analysis of the compounds revealed significant correlation of activity with two molecular descriptors, vol (volume of a molecule) and GCUT_SMR_3 (molar refractivity). This predictive model helps to explain the observed activity with the various substituents. © 2016 Society of Chemical Industry.

Pacific trout Oncorhynchus spp. in western North America are strongly valued in ecological, socioeconomic, and cultural views, and have been the subject of substantial research and conservation efforts. Despite this, the understanding of their evolutionary histories, overall diversity, and challenges to their conservation is incomplete. We review the state of knowledge on these important issues, focusing on Pacific trout in the genus Oncorhynchus. Although most research on salmonid fishes emphasizes Pacific salmon, we focus on Pacific trout because they share a common evolutionary history, and many taxa in western North America have not been formally described, particularly in the southern extent of their ranges. Research in recent decades has led to the revision of many hypotheses concerning the origin and diversification of Pacific trout throughout their range. Although there has been significant success at addressing past threats to Pacific trout, contemporary and future threats represented by nonnativ...

The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3'untranslated region (3'UTR) contains a highly conserved AU-rich element (ARE) embedded in a sequence that commonly represses gene expression in mesenchymal cells. Computational analyses indicate that this site also may bind several microRNAs (miRNAs). Although miRNAs frequently target AU-rich regions, this ARE is unusual because the miRNAs directly span the ARE. We began to characterize the factors that may regulate Bmp2 expression via this complex site. The activating protein HuR (Hu antigen R, ELAVL1, HGNC:3312) directly binds this ARE and can activate gene expression. An miRNA was demonstrated to reverse HuR-mediated activation. Mutational and RNA-interference evidence also supports an AUF1 (AU-factor-1, HNRNPD, HGNC:5036) contribution to the observed repressive activity of the 3'UTR in mesenchymal cells. A limited number of studies describe how miRNAs interact with ARE-binding proteins that bind adjacent sites. This study is among the first to describe protein/miRNA interactions at the same site.

There is a growing appreciation of the importance of the human microbiome to our normal physiology. This complex microbial ecosystem plays a range of roles, including influencing the development and function of our immune systems, providing essential nutrients, regulating metabolism and protecting us from opportunistic infections. Our increasing understanding of these processes is due, to a large extent, to the development of high-throughput sequencing technologies, providing for the first time a means by which complex microbial dynamics can be detailed. There is also a growing recognition that disruption of commensal microbiota, a phenomenon known as dysbiosis, is associated with several common disorders, including inflammatory bowel disease, type 2 diabetes and oncogenesis. Further, where innate immunity fails to protect us, the microbial communities that colonise the external surfaces of our bodies represent a ready source of infection. This review discusses the mechanisms that govern our interaction with our resident microbiota, both in health and disease, the technological advances that allow us to gain insight into these relationships, and the way in which our growing understanding can inform clinical practice.

The concentration, location, and timing of bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) gene expression must be precisely regulated. Abnormal BMP2 levels cause congenital anomalies and diseases involving the mesenchymal cells that differentiate into muscle, fat, cartilage, and bone. The molecules and conditions that influence BMP2 synthesis are diverse. Understandably, complex mechanisms control Bmp2 gene expression. This review includes a compilation of agents and conditions that can induce Bmp2. The currently known trans-regulatory factors and cis-regulatory elements that modulate Bmp2 expression are summarized and discussed. Bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) is a classical morphogen; a molecule that acts at a distance and whose concentration influences cell behavior. In mesenchymal cells, the concentration of BMP2 influences myogenesis, adipogenesis, chondrogenesis, and osteogenesis. Because the amount, timing, and location of BMP2 synthesis influence the allocation of cells to muscle, fat, cartilage, and bone, the mechanisms that regulate the Bmp2 gene are crucial. Key early mesodermal events that require precise Bmp2 regulation include heart specification and morphogenesis. Originally named for its osteoinductive properties, healing fractures requires BMP2. The human Bmp2 gene also has been linked to osteoporosis and osteoarthritis. In addition, all forms of pathological calcification in the vasculature and in cardiac valves involve the pro-osteogenic BMP2. The diverse tissues, mechanisms, and diseases influenced by BMP2 are too numerous to list here (see OMIM: 112261). However, in all BMP2-influenced pathologies, changes in the behavior and differentiation of pluripotent mesenchymal cells are a recurring theme. Consequently, much effort has been devoted to identifying the molecules and conditions that influence BMP2 synthesis and the complex mechanisms that control Bmp2 gene expression. This review begins with an overview of the Bmp2 gene's chromosomal neighborhood and then summarizes and evaluates known regulatory mechanisms and inducers.

We evaluated the efficacy of portable PIT detectors for tracking long-term fish movement in an open stream environment. In June and October of 2012, we PIT-tagged a total of 190 Colorado River Cutthroat Trout Oncorhynchus clarkii pleuriticus (CRCT) in a 1.7-km segment of a small, montane stream. In the summers of 2012–2013 (15 total occasions), we relocated PIT-tagged trout using portable PIT detectors. The maximum detection distance of 23-mm PIT tags ranged from 6 to 56 cm and varied with detector, detection plane, and tag orientation. Of the CRCT tagged, 38% were never detected and 43% were detected on two or more occasions. Mean detection efficiencies of PIT-tagged trout were 34% and 45% in 2012 and 2013, respectively, and were generally lower than in evaluations of closed systems and less mobile fishes. We observed a smaller range of CRCT than has been observed by others using radiotelemetry, a difference that could be explained by the spatial and temporal limitations of portable PIT detection...

Alumina and aluminosilicate aerogels offer potential for use at temperatures above 700°C, where silica aerogels begin to sinter. Stability of alumina and aluminosilicate pore structures at high temperatures is governed by the starting aerogel structure, which, in turn is controlled by the synthesis route. Structure, morphology, and crystallization behavior are compared for aerogels synthesized from AlCl3 and propylene oxide with those synthesized from a variety of boehmite precursors. The aerogels possessing a crystalline boehmite structure in the as-synthesized condition retained mesoporous structures to temperatures of 1200°C, while the AlCl3-derived aerogels, although exhibiting higher as-synthesized surface areas, crystallized and densified at 980–1005°C.

Some populations of Mountain Whitefish Prosopium williamsoni, a widely distributed native Rocky Mountain salmonid, have experienced catastrophic declines while other populations remain robust. To assess the possibility that the declines have arisen from climate-related factors, several experiments were conducted to determine the upper thermal tolerances of embryos and fry and the effects of temperature on growth. Hatching of eggs was measured at 5.7, 6.4, 8.4, and 10.4°C (three replicates each). Survival and growth of fry were measured for 33 d at 5.7, 8.2, 11.8, 16.5, 19.1, 22.2, and 25.2°C (three replicates each). Mean hatching success was 96.7% (SD, 2.9) at 5.7°C, 98.3% (2.9) at 6.4°C, 90.0% (8.7) at 8.4°C and 38.3% (10.4) at 10.4°C. The ultimate upper incipient lethal temperature for fry was 23.6°C (95% CI, 23.5–23.7°C) after 7 d, which decreased with time to 22.6°C (22.1–23.0°C) after 33 d. The critical thermal maximum was 26.7°C (SD, 0.8) for fry acclimated to 13.4°C. The temperature for ma...

BACKGROUND Larval movement of target pest populations among Bt and non-Bt plants is a major concern in the use of a seed mixture refuge strategy for Bt resistance management. In this study, occurrence and larval movement of the sugarcane borer, Diatraea saccharalis (F.), were evaluated in four planting patterns of non-Bt and Bt plants containing Genuity® SmartStaxTM traits in 2009–2011. The four planting patterns were: (1) a pure stand of 27 Bt plants; (2) one non-Bt plant in the center, surrounded by 26 Bt plants; (3) a pure stand of 27 non-Bt plants; (4) one Bt plant in the center, surrounded by 26 non-Bt plants. Studies were conducted under four conditions: (1) open field with natural infestation; (2) greenhouse with artificial infestations; open field with artificial infestations (3) on the center plants only and (4) on every plant. The major objective of this study was to determine whether refuge plants in a seed mixture strategy could provide a comparable refuge population of D. saccharalis to a ‘structured refuge’ planting. RESULTS Larvae of D. saccharalis showed the ability to move from infested plants to at least four plants away, as well as to adjacent rows, but the majority remained within the infested row. However, the number of larvae found on the non-Bt plants in the mixture plantings was not significantly reduced compared with the pure stand of non-Bt corn. CONCLUSION The results of this study show that refuge plants in a seed mixture may be able to provide a comparable refuge population of D. saccharalis to a structured refuge planting. © 2013 Society of Chemical Industry

Diatraea saccharalis is a major corn borer pest. Midgut serine proteinases are essential for insect growth and development. Alteration of midgut proteinases is responsible for Bt resistance development in some species. To clone midgut trypsin and chymotrypsin cDNAs and to test if the Cry1Ab resistance in D. saccharalis is associated with changes in midgut proteinases, total midgut tryptic and chymotryptic activities, cDNA sequences, and gene expressions of three trypsin and three chymotrypsin genes were comparatively examined between Cry1Ab-susceptible (Cry1Ab-SS) and Cry1Ab-resistant (Cry1Ab-RR) strains. Full-length cDNAs encoding three trypsin- and three chymotrypsin-like proteinases were sequenced from Cry1Ab-SS and Cry1Ab-RR larvae. These cDNAs code for active forms of midgut serine proteinases with all functional motifs, including signal peptide, conserved His-Asp-Ser for the catalytic triad, three pairs of cysteines for disulfide bridge configurations, and conserved substrate specificity determination residues. In general, cDNA and putative protein sequences are highly similar between Cry1Ab-SS and Cry1Ab-RR strains, except for a few nucleotide and predicted amino acid substitutions, whose function need to be further clarified. Total trypsin and chymotrypsin activities were also similar between Cry1Ab-SS and Cry1Ab-RR strains. Transcriptional levels of the trypsin and chymotrypsin genes had numerical difference between Cry1Ab-SS and Cry1Ab-RR strains, but the difference was not statistically significant. Data suggest that the development of Cry1Ab resistance in D. saccharalis was not significantly associated with these trypsins and chymotrypsins. Results clarified the role of six midgut proteinases and provided a foundation for continuing examination of potential involvement of other midgut proteinases in Bt resistance development and other important biochemical processes.

Sugarcane borer, Diatraea saccharalis (F.), is a major target of transgenic maize expressing Bacillus thuringiensis (Bt) proteins in South America and the US mid-south region. Resistance development in target pest populations is a major threat to the sustainable use of Bt crops. In our field trials in 2009, a significant number of live borers and plant injury from D. saccharalis were observed in an experimental SmartStax™ maize line. The objective of this study was to assess the relative susceptibility of two field populations of D. saccharalis collected from non-Bt and Bt maize plants containing SmartStax™ traits to five individual Cry proteins. The five Bt proteins included two proteins (Cry1A.105 and Cry2Ab2) that were expressed in SmartStax™ maize plants and three other common Bt proteins (Cry1Aa, Cry1Ab and Cry1Ac) that were not produced in SmartStax™. Larval mortality and growth inhibition on Bt diet of the fourth generation after field collections were evaluated 7 days after release of neonates on the diet surface. The laboratory bioassays showed that 50% lethal concentration (LC50) values for Cry1A.105 and Cry2Ab2 for the population originated from Bt plants were 3.55- and 1.34-fold greater, respectively, than those of the population collected from non-Bt plants. In contrast, relative to the population from non-Bt plants, the LC50 of the population sampled from Bt plants were 3.85-, 2.5- and 1.64-fold more sensitive to Cry1Aa, Cry1Ab and Cry1Ac, respectively. The results did not provide clear evidence to conclude that the observed field survival of D. saccharalis on Bt plants was associated with increased levels of resistance.

In an effort to explore the thermal limitations of Colorado River cutthroat trout Oncorhynchus clarkii pleuriticus, the critical thermal maxima (T(cmax) ) of 1+ year Lake Nanita strain O. c. pleuriticus were evaluated when acclimated to 10, 15 and 20° C. The mean ±s.d.T(cmax) for O. c. pleuriticus acclimated to 10° C was 24·6 ± 2·0°C (n = 30), for 15° C-acclimated fish was 26·9 ± 1·5° C (n = 23) and for 20° C-acclimated fish was 29·4 ± 1·1° C (n = 28); these results showed a marked thermal acclimation effect (Q₁₀ = 1·20). Interestingly, there was a size effect within treatments, wherein the T(cmax) of larger fish was significantly lower than that of smaller fish acclimated to the same temperature. The critical thermal tolerances of age 0 year O. c. pleuriticus were also evaluated from three separate populations: Lake Nanita, Trapper Creek and Carr Creek reared under 'common-garden' conditions prior to thermal acclimation. The Trapper Creek population had significantly warmer T(cmax) than the Lake Nanita population, but that of the Carr Creek fish had T(cmax) similar to both Trapper Creek and Lake Nanita fish. A comparison of these O. c. pleuriticus T(cmax) results with those of other stream-dwelling salmonids suggested that O. c. pleuriticus are less resistant to rapid thermal fluctuations when acclimated to cold temperatures, but can tolerate similar temperatures when acclimated to warmer temperatures.

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Historically, the majority of centres in the UK practise a pre-plan brachytherapy technique which is limited to prostate volumes 50 mL were compared. RESULTS • Overall PSA relapse-free survival was 98.8%; 97.0% for intermediate-risk patients and 100.0% for low-risk patients. By volume, 98.5% of men with standard prostates were free from PSA relapse compared with 100.0% of men with large prostates. • The mean post-implant D90 was 177.0 Gy; 175.5 Gy in standard prostates and 183.5 Gy in large prostates. • The overall acute urinary retention rate was 1.9%; 1.7% in standard prostates and 2.4% in large prostates. There were three urethral strictures, all in the standard prostate group. The mean IPSS increased to 11 and 14 at 3 months for the standard and large prostate groups, respectively, before settling to 2 above baseline for both groups at 12 months. • There were no rectovesical fistulae. Persistent rectal bleeding was reported by one (0.5%) patient in the standard prostate group. CONCLUSIONS • Prostate brachytherapy is effective in the treatment of low-risk and intermediate-risk prostate cancer. • It is technically possible to deliver a quality implant in a large prostate using real-time brachytherapy. • The treatment itself is well tolerated. Prostate volumes up to 100 mL should not exclude patients from brachytherapy providing either flow rate ≥14 mL/s or symptom score (IPSS) ≤ 10.

The discovery of novel classes of antibiotics has slowed dramatically. This has occurred during a time when the appearance of resistant strains of bacteria has shown a substantial increase. Concern is therefore mounting over our ability to continue to treat infections in an effective manner using the antibiotics that are currently available. While ongoing efforts to discover new antibiotics are important, these must be coupled with strategies that aim to maintain as far as possible the spectrum of activity of existing antibiotics. In many instances, the resistance to antibiotics exhibited by bacteria in chronic infections is mediated not by direct resistance mechanisms, but by the adoption of modes of growth that confer reduced susceptibility. These include the formation of biofilms and the occurrence of subpopulations of ‘persister’ cells. As our understanding of these processes has increased, a number of new potential drug targets have been revealed. Here, advances in our ability to disrupt these systems that confer reduced susceptibility, and in turn increase the efficacy of antibiotic therapy, are discussed.

The Bmp2 3'untranslated region (UTR) sequence bears a sequence conserved between mammals and fishes that can post-transcriptionally activate or repress protein synthesis. We developed a map of embryonic cells in the mouse where this potent Bmp2 regulatory sequence functions by using a lacZ reporter transgene with a 3’UTR bearing two loxP sites flanking the ultra-conserved sequence. Cre-recombinase-mediated deletion of the ultra-conserved sequence caused strong ectopic expression in proepicardium, epicardium and epicardium-derived cells (EPDC) and in tissues with known epicardial contributions (coronary vessels and valves). Transient transfections of reporters in the epicardial/mesothelial cell (EMC) line confirmed this repression. Ectopic expression of the recombined transgene also occurred in the aorta, outlet septum, posterior cardiac plexus, cardiac and extra-cardiac nerves and neural ganglia. Bmp2 is dynamically regulated in the developing heart. 3’UTR-mediated mechanisms that restrain BMP2 synthesis may be relevant to congenital heart and vasculature malformations and to adult diseases involving aberrant BMP2 synthesis.

To assess potential interactions between Bacillus thuringiensis Berliner (Bt) proteins and jasmonic acid (JA)-induced resistance to the fall armyworm, Spodoptera frugiperda Smith & Abbot (Lepidoptera: Noctuidae), three commercial Stoneville cotton cultivars, Gossypium hirsutum L. (Malvaceae) (‘ST 475', a conventional cultivar; ‘ST 4575 BR', a Bollgard® cultivar expressing Cry1Ac protein; and ‘ST 4554B2RF', a Bollgard II® cultivar expressing Cry2Ab2 in addition to Cry1Ac), were treated with JA. Two experiments were conducted with 6-day-old S. frugiperda larvae on three cotton cultivars at two phenological stages. The first experiment was conducted under laboratory conditions and used excised cotton leaves; the second experiment was performed under greenhouse conditions on intact cotton plants. Relative growth rates (RGRs) and leaf area consumed by 6-day-old S. frugiperda larvae were determined for each combination of treatments. Overall, JA treatment and cultivars significantly impacted RGR and leaf area consumption. Significant JA treatment*cultivar interactions were observed for RGR of larvae in the laboratory experiment and for leaf area consumption in the greenhouse experiment. An additional experiment evaluated S. frugiperda neonates on the same JA and cotton cultivar combinations (at a single phenological stage) under laboratory conditions. Neonate survival was determined after 3, 5, and 10 days of feeding, and final larval weight after 10 days of feeding. Overall, JA treatment and cultivars significantly impacted final weight and survival of S. frugiperda. Significant JA treatment*cultivar interactions were observed for final weight and on overall survival of S. frugiperda. Combination of the cotton tissue expressing pyramided Bt proteins with JA treatment demonstrated the greatest negative impact on larval development. Apparent synergism between Bt proteins and JA-induced resistance emphasizes that traditional host plant resistance has a role to play in combination with Bt technology.

BACKGROUND: The commercialization of new insecticides is important for ensuring that multiple effective product choices are available. In particular, new insecticides that exhibit high potency and lack insecticidal cross-resistance are particularly useful in insecticide resistance management (IRM) programs. Sulfoxaflor possesses these characteristics and is the first compound under development from the novel sulfoxamine class of insecticides. RESULTS: In the laboratory, sulfoxaflor demonstrated high levels of insecticidal potency against a broad range of sap-feeding insect species. The potency of sulfoxaflor was comparable with that of commercial products, including neonicotinoids, for the control of a wide range of aphids, whiteflies (Homoptera) and true bugs (Heteroptera). Sulfoxaflor performed equally well in the laboratory against both insecticide-susceptible and insecticide-resistant populations of sweetpotato whitefly, Bemisia tabaci Gennadius, and brown planthopper, Nilaparvata lugens (Stal), including populations resistant to the neonicotinoid insecticide imidacloprid. These laboratory efficacy trends were confirmed in field trials from multiple geographies and crops, and in populations of insects with histories of repeated exposure to insecticides. In particular, a sulfoxaflor use rate of 25 g ha−1 against cotton aphid (Aphis gossypii Glover) outperformed acetamiprid (25 g ha−1) and dicrotophos (560 g ha−1). Sulfoxaflor (50 g ha−1) provided a control of sweetpotato whitefly equivalent to that of acetamiprid (75 g ha−1) and imidacloprid (50 g ha−1) and better than that of thiamethoxam (50 g ha−1). CONCLUSION: The novel chemistry of sulfoxaflor, its unique biological spectrum of activity and its lack of cross-resistance highlight the potential of sulfoxaflor as an important new tool for the control of sap-feeding insect pests. Copyright © 2010 Society of Chemical Industry

We propose the "microbiota-inflammasome" hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long-lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro-inflammatory pathways mediated by the Nod-like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut dysbiosis. In this review we describe MDD/chronic stress-induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive-like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co-morbid conditions. A number of testable predictions surface from this microbiota-gut-inflammasome-brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change.

Summary 1. A high dose ⁄ refuge strategy has been adopted in the USA to manage the risk of Bacillus thuringiensis (Bt) resistance in target pests such as the cotton bollworm (CBW), Helicoverpa zea (Boddie) in transgenic Bt cotton Gossypium hirsutum L. Structured refuges, consisting of non-Bt cotton, have been a mandated part of this strategy to produce non-selected insects that are temporally and spatially synchronous with insects from the Bt crop, diluting Bt resistance alleles through mating. However, the bollworm is highly polyphagous and exploits a large number of crop and weedy hosts concurrently with Bt cotton.

Using an F 1 screen, 352 feral individuals of the sugarcane borer, Diatraea saccharalis (F.) (Lepidoptera: Crambidae), were examined for the presence of Bacillus thuringiensis (Bt)-resistance alleles. These insects represented four geographical populations collected in central and northeastern Louisiana, USA, and one field population from the Gulf Coast area of Texas, USA, during 2006. The F 1 screen used various crosses between field-collected insects and a laboratory strain of CrylAb-resistant D. saccharalis, including both reciprocal crosses and group mating. F 1 neonates of the crosses were screened for Bt resistance on Bt maize leaf tissue. One field-collected individual of D. saccharalis was shown to have a Bt-resistance allele. Based on Bayesian analysis procedures, the Bt-resistance allele frequency in the five populations of D. saccharalis was 0.0028 with a 95% confidence interval of 0.0003-0.0079. The successful identification of a resistance allele in a field collection of insects suggests that the F 1 screening technique could be an effective tool for detecting and monitoring rare Bt-resistance alleles in field populations of D. saccharalis.

Vulnerable populations generally have decreased access to health care, often present with advanced disease processes and experience poorer health outcomes compared to the general population. Here we report on the epidemiology and economics of a vulnerable population with chronic wounds served by an academic medical center that is the tertiary health care provider and referral center for the state of Mississippi. Data are being collected to determine if aggressive management and treatment improves health outcomes. The epidemiology of our population indicates that 48% are over 60 years of age; 45% are between 41–59 years of age; and 7% are under 40 years of age. About 61% are female and almost 39% male. Our vulnerable population is composed of 51.6% African Americans; 6.5% Native Americans; and 3.2% Hispanic Americans; with the remaining population or 38.7% Caucasian. The etiologies of wounds seen are 31% diabetic/neuropathic and 28.5% venous; followed by smaller percentages of surgically treated diabetic and venous wounds. We have found that this population commonly presents with a single wound, but that more than half (>50%) present with two or more wounds. A majority of these individuals (77%) visit the clinic more than two times, with most, or 44% visiting the clinic from two to five times. A smaller percentage, or about 30% visit the clinic six or more times. About 61% are either Medicare or Medicaid, or a combination, while the remainder are covered by private insurance (23%), workman’s compensation (3.2%), or are self-pay (12.9%). Despite this profile, the aggressive integration of a social worker in our clinic results in 35.5% being followed by home health. Thus, we will present data on whether the opening of a specialized treatment center results in better health outcomes in vulnerable populations once individuals receive appropriate referral and treatment.

The anaerobic lifestyle of the intestinal parasite Blastocystis raises questions about the biochemistry and function of its mitochondria-like organelles. We have characterized the Blastocystis succinyl-CoA synthetase (SCS), a tricarboxylic acid cycle enzyme that conserves energy by substrate-level phosphorylation. We show that SCS localizes to the enigmatic Blastocystis organelles, indicating that these organelles might play a similar role in energy metabolism as classic mitochondria. Although analysis of residues inside the nucleotide-binding site suggests that Blastocystis SCS is GTP-specific, we demonstrate that it is ATP-specific. Homology modelling, followed by flexible docking and molecular dynamics simulations, indicates that while both ATP and GTP fit into the Blastocystis SCS active site, GTP is destabilized by electrostatic dipole interactions with Lys 42 and Lys 110, the side-chains of which lie outside the nucleotide-binding cavity. It has been proposed that residues in direct contact with the substrate determine nucleotide specificity in SCS. However, our results indicate that, in Blastocystis, an electrostatic gatekeeper controls which ligands can enter the binding site.

Bone morphogenetic protein 2 (BMP2) is an essential growth factor and morphogen, whose pattern and level of expression profoundly influences development and physiology. We present the novel finding that mycoplasma infection induces BMP2 RNA production in six cell lines of diverse types (mesenchymal, epithelial, and myeloid). Mycoplasma infection triggered the expression of mature secreted BMP2 protein in BEAS-2B cells (immortalized human bronchial epithelial cells), which normally do not express BMP2, and further increased BMP2 production in A549 cells (lung adenocarcinoma cells). Indeed, mycoplasma is as strong an experimental inducer as inflammatory cytokines and retinoic acid. Second, we showed that post-transcriptional mechanisms including regulation of RNA stability, rather than transcriptional mechanisms, contributed to the increased BMP2 expression in mycoplasma-infected cells. Furthermore, a novel G-rich oligonucleotide, AS1411 that binds the post-transcriptional regulator nucleolin induced BMP2 exclusively in infected cells. Finally, BMP2 stimulated proliferation in BEAS-2B cells transformed by chronic mycoplasma infection, as demonstrated by treatment with Noggin, a BMP2 antagonist. These findings have important implications regarding the effects of mycoplasma on BMP2-regulated processes, including cell proliferation, differentiation, and apoptosis.