Extreme heat exposure of host plants indirectly reduces solitary bee fecundity and survival.

Extreme heat poses a major threat to plants and pollinators, yet the indirect consequences of heat stress are not well understood, particularly for native solitary bees. To determine how brief exposure of extreme heat to flowering plants affects bee behaviour, fecundity, development and survival we conducted a no-choice field cage experiment in which Osmia lignaria were provided blueberry (Vaccinium corymbosum), phacelia (Phacelia tanacetifolia) and white clover (Trifolium repens) that had been previously exposed to either extreme heat (37.5°C) or normal temperatures (25°C) for 4 h during early bloom. Despite a similar number of open flowers and floral visitation frequency between the two treatments, female bees provided with heat-stressed plants laid approximately 70% fewer eggs than females provided with non-stressed plants. Their progeny received similar quantities of pollen provisions between the two treatments, yet larvae consuming pollen from heat-stressed plants had significantly lower survival as larvae and adults. We also observed trends for delayed emergence and reduced adult longevity when larvae consumed heat-stressed pollen. This study is the first to document how short, field-realistic bursts of extreme heat exposure to flowering host plants can indirectly affect bee pollinators and their offspring, with important implications for crop pollination and native bee populations.

A novel blood based triage test for colorectal cancer in primary care: a pilot study.

BACKGROUND: The majority of colorectal cancers (CRCs) are detected after symptomatic presentation to primary care. Given the shared symptoms of CRC and benign disorders, it is challenging to manage the risk of missed diagnosis. Colonoscopy resources cannot keep pace with increasing demand. There is a pressing need for access to simple triage tools in primary care to help prioritise patients for referral. AIM: To evaluate the performance of a novel spectroscopy-based CRC blood test in primary care. DESIGN & SETTING: Mixed-methods pilot study of test performance and GP focus group discussions in South Wales. METHOD: Patients on the urgent suspected cancer (USC) pathway were recruited for the Raman spectroscopy (RS) test coupled to machine learning classification ('Raman-CRC') to identify CRC within the referred population. Qualitative focus group work evaluated the acceptability of the test in primary care by thematic analysis of focus group theorising. RESULTS: A total of 532 patients aged ≥50 years referred on the USC pathway were recruited from 27 GP practices. Twenty-nine patients (5.0%) were diagnosed with CRC. Raman-CRC identified CRC with sensitivity 95.7%, specificity 69.3% with area under curve (AUC) of 0.80 compared with colonoscopy as the reference test (248 patients). Stage I and II cancers were detected with 78.6% sensitivity. Focus group themes underlined the convenience of a blood test for the patient and the test's value as a risk assessment tool in primary care. CONCLUSION: The findings support this novel, non-invasive, blood-based method to prioritise those patients most likely to have CRC. Raman-CRC may accelerate access to diagnosis with potential to improve cancer outcomes.

Heat of the moment: extreme heat poses a risk to bee-plant interactions and crop yields.

Extreme heat events threaten the development, functioning, and success of bee pollinators and crops that rely on pollinators for high yields. While direct effects of extreme heat and climate warming have gained more attention, the indirect effects on bees and crops remain largely unexplored. Extreme heat can directly alter the nutritional value of floral rewards, which indirectly contributes to lower bee survival, development, and reproduction with implications for pollination. Phenological mismatches between bee activity and crop flowering are also expected. Heat-stressed crop plants with reduced floral rewards may reduce bee foraging and nesting, limiting pollination services. Understanding how extreme heat affects bee-crop interactions will be essential for resilient production of pollinator-dependent crops in this era of climate change.

Auricular Acupuncture to Facilitate Outpatient Opioid Weaning: A Randomized Pilot Study.

Objective: The purpose of this study was to integrate acupuncture within the standard of care during outpatient opioid tapering and assess impact of this treatment on cumulative withdrawal symptoms, psychologic distress, and pain. Methods: This prospective randomized controlled pilot study administered the National Acupuncture Detoxification Association protocol following monthly opioid tapering. A total of 9 participants were randomized into the intervention group and compared with 6 participants who underwent the standard of care for outpatient opioid tapering. All providers prescribing medication management to both groups were blinded. Psychologic distress was evaluated using the hospital anxiety and depression scale (HADS). The clinical institute narcotic assessment (CINA) measured subjective withdrawal symptoms and pain was assessed using the numerical rating scale (NRS). Results: Overall anxiety appeared slightly higher in the acupuncture group (HADS 7.0 compared with 6.5), however, depression was lower when compared with the standard of care group (HADS 4.0 compared with 6.5). The standard of care group reported more intense withdrawal symptoms (CINA 9.0 compared with 3.5) as well as higher pain scores (NRS 6.5 compared with 5.0). There were no statistically significant differences among the standard of care and acupuncture groups. Conclusions: This study suggests that auricular acupuncture may be implemented within the standard of care for patients undergoing outpatient opioid weaning regimens. Although results were not statistically significant, they support future research and reveal a promising expansion of treatment options for patients physically dependent on opioid medication. Clinical Trials.gov ID: NCT02882048.

Hypnosis for refractory severe neuropathic pain: A case study.

Chronic pain not only has the greatest negative effect on quality of life compared with other chronic health problems but also contributes to the greatest disability worldwide. Management of chronic neuropathic pain is particularly challenging given its association with other pain processes, the fact that less than half of patients respond to a single pain medication, and the lack of evidence regarding combination therapy (i.e. a treatment regimen that combines several scheduled pain medications) safety and efficacy. Given these challenges, there is a growing interest in the application of complementary and alternative medicine (CAM) therapies such as yoga, acupuncture, and hypnosis. We present the case of a 67-year-old male with severe diabetic neuropathy refractory to first, second, and third-line treatments. His disabling pain precipitated premature retirement, contributing to severe depression with suicidality requiring hospitalization. Ultimately, he experienced relief through an integrative health regimen, and he identified hypnosis as the most effective therapy for his pain. Through individual and group sessions, recordings, and daily self-hypnosis, he improved both his chronic pain symptomatology and quality of life, simultaneously decreasing opioid use. Simulation modeling analysis of his pain ratings over time showed that they reliably decreased after engaging in hypnosis, r = -.33, p =.001. A growing body of research suggests that hypnosis is beneficial as part of an integrative treatment approach to chronic pain and enhances the efficacy of other therapies. Our medically challenging case study supports that hypnosis may serve as a viable and durable treatment for chronic neuropathic pain.

Chronic pain and associated factors in Maputo, Mozambique: a pilot study.

INTRODUCTION: Studies estimate that 20% of adults suffer from chronic pain. A meta-analysis in low- and middle-income countries (LMICs) found 34% had chronic pain. There are few studies on pain prevalence gathered in Africa. This study surveyed the capital city of Mozambique. METHODS: This was a cross-sectional study employed in a community setting. The Vanderbilt Global Pain Survey comprised questions on the behaviour and attitudes of respondents regarding pain, including previously validated metrics: the Pain Catastrophizing Scale, the World Health Organization Disability Assessment Schedule, the Brief Pain Inventory, Widespread Pain Index and Symptom Severity Score, and the Michigan Body Map. RESULTS: Ninety-seven surveys were completed out of 100. Pain every day lasting for more than 6 months in their lifetime was reported as 39.2% (CI: 29.4-49.6), and 52% of respondents had pain the day of the interview. However, the pain resulted in little difficulty with activities of daily living and maintaining relationships (61%-89%). Although none reported mental health disorders, 53.6% had experienced a traumatic event in their life, with 45.2% having related nightmares, anxiety, or fear. Most respondents (99%) would take oral medication if it helped their pain, with a large proportion willing to spend significant money for these (49% would pay >US$40) and willing to travel long distances to get help (55.2% would travel >40 kilometer). CONCLUSION: The prevalence of chronic pain in Maputo, Mozambique is similar to the average for LMICs. Trends in high-income countries suggest that multimodal pain management and multidisciplinary treatments may improve optimal pain control in LMICs.

Biological Control of Asparagus Pests Using Synthetic Herbivore-Induced Volatiles.

Natural enemies can be important regulators of pests in agroecosystems, and they often rely on volatile chemical cues to find hosts. Herbivore-induced plant volatiles (HIPVs) have been a focal point in many studies that seek to increase the efficacy of biological control programs by increasing recruitment and retention of natural enemies. Our research sought to explore the role of HIPVs in asparagus agroecosystems to answer the following questions: 1) What is the composition of HIPV produced by asparagus ferns following feeding by a chewing herbivore? 2) Do field deployed lures baited with synthetic asparagus HIPVs attract natural enemies? and 3) Can HIPV lures increase biological control of asparagus pests? Volatiles were field collected from the headspace of healthy asparagus ferns, mechanically damaged ferns, and ferns fed upon by asparagus beetle larvae (Crioceris asparagi L.) (Coleoptera: Chrysomelidae). We found that asparagus beetle damaged asparagus had significantly higher concentrations of (E)-ß-ocimene, (E,E)-α-farnesene, and (1)-tetradecanol than healthy or mechanically damaged ferns. Field experiments demonstrated that lures baited with isolates of ocimene and farnesene attracted parasitoids without attracting pests, but had no impact on predator recruitment. Finally, we determined that overall parasitism rates were not increased by synthetic HIPV lures but found evidence that lures may increase parasitism of asparagus miner (Ophiomyia simplex Loew) (Diptera: Agromyzidae) by pteromalids.

Chronic Pain and Associated Factors in India and Nepal: A Pilot Study of the Vanderbilt Global Pain Survey.

BACKGROUND: Evaluation and treatment of chronic pain worldwide are limited by the lack of standardized assessment tools incorporating consistent definitions of pain chronicity and specific queries of known social and psychological risk factors for chronic pain. The Vanderbilt Global Pain Survey (VGPS) was developed as a tool to address these concerns, specifically in the low- and middle-income countries where global burden is highest. METHODS: The VGPS was developed using standardized and cross-culturally validated metrics, including the Brief Pain Inventory and World Health Organization Disability Assessment Scale, as well as the Pain Catastrophizing Scale, the Fibromyalgia Survey Questionnaire along with queries about pain attitudes to assess the prevalence of chronic pain and disability along with its psychosocial and emotional associations. The VGPS was piloted in both Nepal and India over a 1-month period in 2014, allowing for evaluation of this tool in 2 distinctly diverse cultures. RESULTS: Prevalence of chronic pain in Nepal and India was consistent with published data. The Nepali cohort displayed a pain point prevalence of 48%-50% along with some form of disability present in approximately one third of the past 30 days. Additionally, 11% of Nepalis recorded pain in 2 somatic sites and 39% of those surveyed documented a history of a traumatic event. In the Indian cohort, pain point prevalence was approximately 24% to 41% based on the question phrasing, and any form of disability was present in 6 of the last 30 days. Of the Indians surveyed, 11% reported pain in 2 somatic sites, with only 4% reporting a previous traumatic event. Overall, Nepal had significantly higher chronic pain prevalence, symptom severity, widespread pain, and self-reported previous traumatic events, yet lower reported pain severity. CONCLUSIONS: Our findings confirm prevalent chronic pain, while revealing pertinent cultural differences and survey limitations that will inform future assessment strategies. Specific areas for improvement identified in this VGPS pilot study included survey translation methodology, redundancy of embedded metrics and cultural limitations in representative sampling and in detecting the prevalence of mental health illness, catastrophizing behavior, and previous traumatic events. International expert consensus is needed.

Rac1 GTPase acts downstream of αPS1ßPS integrin to control collective migration and lumen size in the Drosophila salivary gland.

During collective migration of the Drosophila embryonic salivary gland, the distal gland cells mediate integrin-based contacts with surrounding tissues while proximal gland cells change shape and rearrange. Here, we show that αPS1ßPS integrin controls salivary gland migration through Rac1 GTPase which downregulates E-cadherin in proximal and distal gland cells, and promotes extension of actin-rich basal membrane protrusions in the distal cells. In embryos mutant for multiple edematous wings (mew), which encodes the αPS1 subunit of the αPS1ßPS integrin heterodimer, or rac1 and rac2 GTPases, salivary gland cells failed to migrate, to downregulate E-cadherin and to extend basal membrane protrusions. Selective inhibition of Rac1 in just the proximal or distal gland cells demonstrate that proximal gland cells play an active role in the collective migration of the whole gland and that continued migration of the distal cells depends on the proximal cells. Loss of rac1rac2 also affected gland lumen length and width whereas, loss of mew affected lumen length only. Activation of rac1 in mew mutant embryos significantly rescued the gland migration, lumen length and basal membrane protrusion defects and partially rescued the E-cadherin defects. Independent of mew, Rac regulates cell shape change and rearrangement in the proximal gland, which is important for migration and lumen width. Our studies shed novel insight into a Rac1-mediated link between integrin and cadherin adhesion proteins in vivo, control of lumen length and width and how activities of proximal and distal gland cells are coordinated to result in the collective migration of the entire salivary gland.

Idiopathic peripheral neuropathy responsive to sympathetic nerve blockade and oral clonidine.

A 52-year-old female presented with idiopathic stocking-glove neuropathy. She underwent a series of right and left stellate ganglion blocks with ropivacaine and clonidine, followed by lumbar sympathetic blocks. This resulted in complete symptom relief for two weeks. These procedures were repeated after a two-month interval; at that time she was still experiencing partial relief from the first series. She again remained completely pain free for several weeks following the injections. As the pain partially returned, daily oral clonidine was initiated and resulted in almost complete cessation of her symptoms, which persisted at a three-month follow-up examination.

Validation of a detailed scoring checklist for use during advanced cardiac life support certification.

INTRODUCTION: Defining valid, reliable, defensible, and generalizable standards for the evaluation of learner performance is a key issue in assessing both baseline competence and mastery in medical education. However, before setting these standards of performance, the reliability of the scores yielding from a grading tool must be assessed. Accordingly, the purpose of this study was to assess the reliability of scores generated from a set of grading checklists used by nonexpert raters during simulations of American Heart Association (AHA) Megacodes. METHODS: The reliability of scores generated from a detailed set of checklists, when used by 4 nonexpert raters, was tested by grading team leader performance in 8 Megacode scenarios. Videos of the scenarios were reviewed and rated by trained faculty facilitators and a group of nonexpert raters. The videos were reviewed "continuously" and "with pauses." The grading made by 2 content experts served as the reference standard, and 4 nonexpert raters were used to test the reliability of the checklists. RESULTS: Our results demonstrate that nonexpert raters are able to produce reliable grades when using the checklists under consideration, demonstrating excellent intrarater reliability and agreement with a reference standard. The results also demonstrate that nonexpert raters can be trained in the proper use of the checklist in a short amount of time, with no discernible learning curve thereafter. Finally, our results show that a single trained rater can achieve reliable scores of team leader performance during AHA Megacodes when using our checklist in a continuous mode because measures of agreement in total scoring were very strong [Lin's (Biometrics 1989;45:255-268) concordance correlation coefficient, 0.96; intraclass correlation coefficient, 0.97]. CONCLUSIONS: We have shown that our checklists can yield reliable scores, are appropriate for use by nonexpert raters, and are able to be used during continuous assessment of team leader performance during the review of a simulated Megacode. This checklist may be more appropriate for use by advanced cardiac life support instructors during Megacode assessments than the current tools provided by the AHA.

Pak1 control of E-cadherin endocytosis regulates salivary gland lumen size and shape.

Generating and maintaining proper lumen size and shape in tubular organs is essential for organ function. Here, we demonstrate a novel role for p21-activated kinase 1 (Pak1) in defining the size and shape of the Drosophila embryonic salivary gland lumen by regulating the size and elongation of the apical domain of individual cells. Pak1 mediates these effects by decreasing and increasing E-cadherin levels at the adherens junctions and basolateral membrane, respectively, through Rab5- and Dynamin-dependent endocytosis. We also demonstrate that Cdc42 and Merlin act together with Pak1 to control lumen size. A role for Pak1 in E-cadherin endocytosis is supported by our studies of constitutively active Pak1, which induces the formation of multiple intercellular lumens in the salivary gland in a manner dependent on Rab5, Dynamin and Merlin. These studies demonstrate a novel and crucial role for Pak1 and E-cadherin endocytosis in determining lumen size and shape, and also identify a mechanism for multiple lumen formation, a poorly understood process that occurs in normal embryonic development and pathological conditions.

Evolutionary analysis of the cis-regulatory region of the spicule matrix gene SM50 in strongylocentrotid sea urchins.

An evolutionary analysis of transcriptional regulation is essential to understanding the molecular basis of phenotypic diversity. The sea urchin is an ideal system in which to explore the functional consequence of variation in cis-regulatory sequences. We are particularly interested in the evolution of genes involved in the patterning and synthesis of its larval skeleton. This study focuses on the cis-regulatory region of SM50, which has already been characterized to a considerable extent in the purple sea urchin, Strongylocentrotus purpuratus. We have isolated the cis-regulatory region from 15 individuals of S. purpuratus as well as seven closely related species in the family Strongylocentrotidae. We have performed a variety of statistical tests and present evidence that the cis-regulatory elements upstream of the SM50 gene have been subject to positive selection along the lineage leading to S. purpuratus. In addition, we have performed electrophoretic mobility shift assays (EMSAs) and demonstrate that nucleotide substitutions within Element C affect the ability of nuclear proteins to bind to this cis-regulatory element among members of the family Strongylocentrotidae. We speculate that such changes in SM50 and other genes could accumulate to produce altered patterns of gene expression with functional consequences during skeleton formation.

CD22 is a functional ligand for SH2 domain-containing protein-tyrosine phosphatase-1 in primary T cells.

The intracellular Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase (SHP-1) has been characterized as a negative regulator of T cell function, contributing to the definition of T cell receptor signaling thresholds in developing and peripheral mouse T lymphocytes. The activation of SHP-1 is achieved through the engagement of its tandem SH2 domains by tyrosine-phosphorylated proteins; however, the identity of the activating ligand(s) for SHP-1, within mouse primary T cells, is presently unresolved. The identification of SHP-1 ligand(s) in primary T cells would provide crucial insight into the molecular mechanisms by which SHP-1 contributes to in vivo thresholds for T cell activation. Here we present a combination of biochemical and yeast genetic analyses indicating CD22 to be a T cell ligand for the SHP-1 SH2 domains. Based on these observations we have confirmed that CD22 is indeed expressed on mouse primary T cells and capable of associating with SHP-1. Significantly, CD22-deficient T cells demonstrate enhanced proliferation in response to anti-CD3 or allogeneic stimulation. Furthermore, the co-engagement of CD3 and CD22 results in a raising of TCR signaling thresholds hence demonstrating a previously unsuspected functional role for CD22 in primary T cells.