Search

The discovery of compounds and proteins from plants has greatly contributed to modern medicine, especially in malaria where both quinine and artemisinin have been the cornerstone of therapeutics. Here we describe the first known plant-derived cytokine binding agent. Chlorophyll a-b binding protein AB96, present to varying levels in the leaves of all chlorophyll-containing plants, binds to active TGFβ1. Active TGFβ1 contributes to the pathology of many infectious and neoplastic diseases and therefore, by inhibiting these processes, chlorophyll a-b binding protein opens up new approaches with therapeutic potential.

Mitchell, UH, Owen, PJ, Rantalainen, T, and Belavý, DL. Increased joint mobility is associated with impaired transversus abdominis contraction. J Strength Cond Res 36(9): 2472-2478, 2022-Increased joint mobility is a risk factor for joint injury, but muscle function may be able to compensate for it. Current evidence suggests reduced force production capacity in people with hypermobility. However, little is known about the lumbar spine. The purpose of this cross-sectional study was to assess whether there was a link between joint mobility and transverse abdominis and multifidus muscles contraction, muscles ascribed a core-stability role. Using a modified quantitative version of the Beighton scale (BOM score), we measured joint mobility of 30 middle-aged individuals without low back pain. These scores were correlated with magnetic resonance imaging-derived measures of transverse abdominis and multifidus muscle contraction during a spinal loading maneuver. The level of significance was set for p ≤ 0.05. The results showed greater joint mobility (a higher BOM score) correlated ( r = 0.468; p = 0.009) with reduced transversus abdominis (TrA) shortening during contraction (i.e., less muscle shortening in people with greater joint mobility). The trunk subdomain score exhibited a correlation of 0.354 with TrA length change, but this did not reach statistical significance ( p = 0.055). The subdomains of the BOM score did not correlate significantly with each other ( p ≥ 0.097). No association was seen between multifidus contraction and joint mobility. The results suggest that greater general joint mobility is associated with impaired contraction of the TrA muscle. This should be considered when coaching athletes or treating patients with (functional) spinal instability. The quantitative approach we developed to measure joint mobility could be used in the future studies of global flexibility.

Objectives Stigma contributes to diagnostic delay, disease concealment, and reduced wellbeing for people with multidrug-resistant tuberculosis (MDR-TB) and their communities. Despite the negative effects of stigma, there are no scales to measure stigma in people with MDR-TB. This study aimed to develop and validate a scale to measure stigma in people affected by MDR-TB in Vietnam. Study Design and Setting People with rifampicin-resistant (RR)-MDR-TB who had completed at least 3 months of treatment were invited to complete a survey containing 45 draft stigma items. Data analysis included exploratory factor analysis, internal consistency, content, criterion and construct validity, and test-retest reliability. Results A total of 315 people with RR/MDR-TB completed the survey. Exploratory factor analysis revealed a 14 item RR/MDR-TB stigma scale with four subscales, including guilt, social exclusion, physical isolation, and blame. Internal consistency and test-retest reliability were good (Cronbach’s Alpha = 0.76, ICC = 0.92). Construct validity was adequate with moderate correlations with related constructs. Conclusion Our RR/MDR-TB Scale demonstrated good psychometric properties in Vietnam. This scale will assist in the measurement of stigma in people with RR/MDR-TB. It will also aid in the evaluation of stigma reduction interventions in people with RR/MDR-TB.

Background The greatest risk of infectious disease undernotification occurs in settings with limited capacity to detect it reliably. World Health Organization guidance on the measurement of misreporting is paradoxical, requiring robust, independent systems to assess surveillance rigor. Methods are needed to estimate undernotification in settings with incomplete, flawed, or weak surveillance systems. This study attempted to design a tuberculosis (TB) inventory study that balanced rigor with feasibility for high-need settings. Objective This study aims to design a hybrid TB inventory study for contexts without World Health Organization preconditions. We estimated the proportion of TB cases that were not reported to the Ministry of Health in 2015. The study sought to describe TB surveillance coverage and quality at different levels of TB care provision. Finally, we aimed to identify structural-, facility-, and provider-level barriers to notification and reasons for underreporting, nonreporting, and overreporting. Methods Retrospective partial digitalization of paper-based surveillance and facility records preceded deterministic and probabilistic record linkage; a hybrid of health facilities and laboratory census with a stratified sampling of HFs with no capacity to notify leveraged a priori knowledge. Distinct extrapolation methods were applied to the sampled health facilities to estimate bacteriologically confirmed versus clinical TB. In-depth interviews and focus groups were used to identify causal factors responsible for undernotification and test the acceptability of remedies. Results The hybrid approach proved viable and instructive. High-specificity verification of paper-based records in the field was efficient and had minimal errors. Limiting extrapolation to clinical cases improved precision. Probabilistic record linkage is computationally intensive, and the choice of software influences estimates. Record absence, decay, and overestimation of the private sector TB treatment behavior threaten validity, meriting mitigation. Data management demands were underestimated. Treatment success was modest in all sectors (R=37.9%–72.0%) and did not align with treatment success reported by the state (6665/8770, 75.99%). One-fifth of TB providers (36/178, 20%) were doubtful that the low volume of patients with TB treated in their facility merited mastery of the extensive TB notification forms and procedures. Conclusions Subnational inventory studies can be rigorous, relevant, and efficient in countries that need them even in the absence of World Health Organization preconditions, if precautions are taken. The use of triangulation techniques, with minimal recourse to sampling and extrapolation, and the privileging of practical information needs of local decision makers yield reasonable misreporting estimates and viable policy recommendations.

BACKGROUND The greatest risk of infectious disease undernotification occurs in settings with limited capacity to detect it reliably. World Health Organization guidance on the measurement of misreporting is paradoxical, requiring robust, independent systems to assess surveillance rigor. Methods are needed to estimate undernotification in settings with incomplete, flawed, or weak surveillance systems. This study attempted to design a tuberculosis (TB) inventory study that balanced rigor with feasibility for high-need settings. OBJECTIVE This study aims to design a hybrid TB inventory study for contexts without World Health Organization preconditions. We estimated the proportion of TB cases that were not reported to the Ministry of Health in 2015. The study sought to describe TB surveillance coverage and quality at different levels of TB care provision. Finally, we aimed to identify structural-, facility-, and provider-level barriers to notification and reasons for underreporting, nonreporting, and overreporting. METHODS Retrospective partial digitalization of paper-based surveillance and facility records preceded deterministic and probabilistic record linkage; a hybrid of health facilities and laboratory census with a stratified sampling of HFs with no capacity to notify leveraged a priori knowledge. Distinct extrapolation methods were applied to the sampled health facilities to estimate bacteriologically confirmed versus clinical TB. In-depth interviews and focus groups were used to identify causal factors responsible for undernotification and test the acceptability of remedies. RESULTS The hybrid approach proved viable and instructive. High-specificity verification of paper-based records in the field was efficient and had minimal errors. Limiting extrapolation to clinical cases improved precision. Probabilistic record linkage is computationally intensive, and the choice of software influences estimates. Record absence, decay, and overestimation of the private sector TB treatment behavior threaten validity, meriting mitigation. Data management demands were underestimated. Treatment success was modest in all sectors (R=37.9%–72.0%) and did not align with treatment success reported by the state (6665/8770, 75.99%). One-fifth of TB providers (36/178, 20%) were doubtful that the low volume of patients with TB treated in their facility merited mastery of the extensive TB notification forms and procedures. CONCLUSIONS Subnational inventory studies can be rigorous, relevant, and efficient in countries that need them even in the absence of World Health Organization preconditions, if precautions are taken. The use of triangulation techniques, with minimal recourse to sampling and extrapolation, and the privileging of practical information needs of local decision makers yield reasonable misreporting estimates and viable policy recommendations.

Long‐term care facilities have been identified as a local epicenter of disease among populations vulnerable to coronavirus disease 2019 (COVID‐19). A skilled nursing facility in Washington State was the first major site of COVID‐19 infections in the United States. Many lessons were learned during the events surrounding this outbreak, including how to develop, and the importance of, a coordinated response between emergency medical services and local area hospitals. As these events came early in the U.S. pandemic, unfortunately, disease spread and mortality was high. However, these events also resulted in rapid mobilization of the regional response to the COVID‐19 pandemic. Understanding the events surrounding this outbreak demonstrate some of the challenges involved in responding to acute infectious illnesses within these unique environments and associated vulnerable populations.

There has been an ongoing debate in the healthcare community about what pressure ulcers/injuries are, and how to name, define and classify them. The aim of this discussion paper is to provide a brief theoretical background about pressure ulcer/injury classification, to explain the approach the Guideline Governance Group has taken during the 2019 update of the International Guideline for 'Prevention and Treatment of Pressure Ulcers/Injuries' and to share views on how to best implement pressure ulcer/injury classification. First formal pressure ulcer/injury classifications were introduced in the 1950s and today various pressure ulcer/injury classification systems are used worldwide. Dissimilarities between commonly used classification systems may be considered a limitation that impedes clinical and scientific communication. However, the conceptual meaning of pressure ulcer/injury categories described within the various classification systems is comparable and the current evidence does not indicate that one classification is superior to another. Therefore, the Guideline Governance Group created a crosswalk of the major pressure ulcer/injury classifications in common use across different geographic regions. Clinicians are encouraged to use the classification system adopted by their healthcare setting in the most consistent way. The validity of pressure ulcer/injury classification is closely linked to its intended purpose. Studying measurement properties of pressure ulcer/injury classification systems must follow state-of-the-art methods. Structured educational interventions are helpful for improving diagnostic accuracy and reducing misclassification of pressure ulcers/injuries. Implementation of innovative skin and soft tissue assessments and revised pressure ulcer/injury classifications are only worth implementing, when the diagnostic information improves clinical care.

Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.

The 2020 International Year of the Nurse and the Midwife is an important opportunity to marry nursing science and health policy globally. Nurses and midwives are demonstrating strong intent towards evidence-based practice but often feel they lack the skills to implement it. Examples are provided of ways in which general and advanced practice nurses have succeeded in bringing evidence into practice and then into local and global policy.

The blood pressure response to exercise is exaggerated in the type 1 diabetes mellitus (T1DM). An overactive exercise pressor reflex (EPR) contributes to the potentiated pressor response. However, the mechanism(s) underlying this abnormal EPR activity remains unclear. This study tested the hypothesis that the heightened blood pressure response to exercise in T1DM is mediated by EPR-induced sympathetic overactivity. Additionally, the study examined whether the single muscle afferents are sensitized by PKC (protein kinase C) activation in this disease. Sprague-Dawley rats were intraperitoneally administered either 50 mg/kg streptozotocin (T1DM) or saline (control). At 1 to 3 weeks after administration, renal sympathetic nerve activity and mean arterial pressure responses to activation of the EPR, mechanoreflex, and metaboreflex were measured in decerebrate animals. Action potential responses to mechanical and chemical stimulation were determined in group IV afferents with pPKCα (phosphorylated-PKCα) levels assessed in dorsal root ganglia. Compared with control, EPR (58±18 versus 96±33%; P P P P P

Aerobic exercise training has many known cardiovascular benefits that may promote healthy aging. It is not known if long-term aerobic exercise training is also associated with structural benefits (e.g., lower fat mass, higher areal bone mineral density (BMD) and greater muscle mass). We evaluated these parameters in middle-aged long-term endurance runners compared to sex-, age‐, height-, and weight-matched non-running controls. Total and regional lean and fat mass and areal BMD were assessed by dual-energy X-ray absorptiometry. Sagittal magnetic resonance images captured the cross-sectional area and thickness of the lumbar multifidus. Runners (n = 10, all male) had a mean (standard deviation, SD) age of 49 (4) years, height of 178.9 (4.9) cm, weight of 67.8 (5.8) kg, body mass index (BMI) of 21.4 (1.4) kg/m2 and had been running 82.6 (27.9) km/week for 23 (13) years. Controls (n = 9) had a mean (SD) age of 51 (5) years, height of 176.0 (5.1) cm, weight of 72.8 (7.1) kg, and BMI of 23.7 (2.1) kg/m2. BMI was greater in controls (p = 0.010). When compared to controls on average, runners had a 10 percentage-point greater total body lean mass than controls (p = 0.001) and 14% greater trunk lean mass (p = 0.010), as well as less total body (8.6 kg, p &lt, 0.001), arm (58%, p = 0.002), leg (52%, 0.001), trunk (73%, 0.001), android (91%, 0.001), and gynoid fat mass (64%, 0.001). No differences were observed between groups for BMD outcomes or multifidus size. These results underscore the benefits of endurance running to body composition that carry over to middle-age.

Postsurgical dental pain is mainly driven by inflammation, particularly through the generation of prostaglandins via the cyclooxygenase system. Thus, it is no surprise that numerous randomized placebo-controlled trials studying acute pain following the surgical extraction of impacted third molars have demonstrated the remarkable efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen sodium, etodolac, diclofenac, and ketorolac in this prototypic condition of acute inflammatory pain. Combining an optimal dose of an NSAID with an appropriate dose of acetaminophen appears to further enhance analgesic efficacy and potentially reduce the need for opioids. In addition to being on average inferior to NSAIDs as analgesics in postsurgical dental pain, opioids produce a higher incidence of side effects in dental outpatients, including dizziness, drowsiness, psychomotor impairment, nausea/vomiting, and constipation. Unused opioids are also subject to misuse and diversion, and they may cause addiction. Despite these risks, some dental surgical outpatients may benefit from a 1- or 2-d course of opioids added to their NSAID regimen. NSAID use may carry significant risks in certain patient populations, in which a short course of an acetaminophen/opioid combination may provide a more favorable benefit versus risk ratio than an NSAID regimen.

Using detailed microdata, we document how migration-dependent households are especially vulnerable during the COVID-19 pandemic. We create pre- and post-COVID panel datasets for three populations in Bangladesh and Nepal, leveraging experimental and observational variation in prior migration dependence. We report 25 per cent greater declines in earnings and fourfold greater prevalence of food insecurity among migrant households since March. Causes include lower migration rates, less remittance income per migrant, isolation in origin communities, and greater health risks. We compile a large set of secondary data to demonstrate the extent of vulnerability worldwide and conclude with recommendations for policy targeted at migrants.

Tuberculosis is the deadliest infection of our time, with about 1.3 million deaths in 2017. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a licensed vaccine with up to 100% efficacy against Ebola. The developments that led to the trialing and licensure of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a new, more efficacious TB vaccine. In order to license and deploy such vaccines, trials are needed in a limited number of sites that combine high disease incidence, research infrastructure and expertise. We first chronologically describe our twelve-year experience in building a TB vaccine trial site, an arduous and incremental process in contrast to the recent Ebola outbreak, which illustrates that sites can be set up under great adversity. Due to the striking differences in the vaccine development of the two diseases, we also compare the number of respective human trials between the two diseases, using publicly available data. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While acknowledging pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. We are convinced that TB is a global threat that requires similar concerted effort for elimination. Funding Statement: AERAS, EDCTP and GSK funded the studies included in the manuscript. None had a role in interpreting results in the article or the decision to publish. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The authors stated that ethics approval was obtained for all the studies included, but was not applicable to this article.

Heterotopic ossification (HO) is a known sequela in total ankle arthroplasty. The purpose of this study was to determine the radiographic incidence of HO in fourth-generation total ankle implants including the INFINITY, CADENCE, and VANTAGE. Radiographs were assessed for the incidence and location of HO in each implant using the modified Brooker classification. Seventy-one patients were included. There were 41 INFINITY, 16 CADENCE, and 14 VANTAGE implants. The average radiographic follow-up was 19.7 months. The incidence of HO was 69.0%. Overall, the HO was Class I in 31 cases (63.3%); Class II in 7 cases (14.3%); Class III in 10 cases (20.4%); and Class IV in 1 case (2.0%). For INFINITY; n = 33 patients (80.5%), CADENCE; n = 8 patients (50%); VANTAGE n = 8 patients (57.1%). When comparing INFINITY with CADENCE/VANTAGE, there was a statistically significant difference in presence of HO (P = 0.01). When comparing INFINITY with CADENCE, there was a statistically significant difference in presence of HO (P = 0.04). In the 33 cases of INFINITY with HO, 30 had neutral or posterior coverage, and in 4 cases, the prosthesis did not extend to the posterior tibial cortex (P = 0.005). This study demonstrates a continued high rate of HO with 3 fourth-generation ankle implants in the short term, although many were Class 1 and posterior. The INFINITY had a higher overall incidence of HO. Adequate posterior cortical coverage did not play a role in radiographic presence of HO. Further research is warranted with longer-term follow-up to determine the clinical and radiographic significance of HO. Level of Evidence: Level III: Retrospective comparative

BACKGROUND: Hepatitis C virus infected (HCV+) adults evidence increased rates of psychiatric and cognitive difficulties. This is the first study to use functional magnetic resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. OBJECTIVE: To determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit differences in brain activation during a delay discounting task (DDT), a measure of one’s tendency to choose smaller immediate rewards over larger delayed rewards - one aspect of impulsivity. METHODS: 20 adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. RESULTS: Mixed effects regression analyses of Hard versus Easy trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less activation in the left lateral occipital gyrus, precuneus and superior frontal gyrus. There were also significant interactive effects for Hard – Easy contrasts in the bilateral medial frontal gyrus, left insula, left precuneus, left inferior parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a positive relationship between impulsivity and activation, while the HCV+ group exhibited a negative relationship. Within the HCV+ group, those with high viral load chose immediate rewards more often than those with low viral load, regardless of choice difficulty; those with low viral load chose immediate rewards more often on hard choices relative to easy choices. CONCLUSIONS: Results show that HCV+ patients exhibit greater impulsive behavior when presented with difficult choices, and impulsivity is negatively related to activation in regions important for cognitive control. Thus, interventions that decrease impulsive choice may be warranted with some HCV+ patients.

Continuous peripheral nerve blockade is a common technique in the analgesic management for many procedures. Leakage of local anaesthetic from around the nerve catheter insertion site can increase the chance of catheter dislodgement, risks infective complications, and could divert anaesthetic away from the nerve causing the block to fail. We conducted a randomised controlled trial to assess whether the type of nerve catheter influenced local anaesthetic leak rate. One hundred and ten patients scheduled for elective unilateral total knee arthroplasty were randomised to receive a perineural catheter with either a catheter over needle (CON) system (Pajunk® E-Cath) (PAJUNK® GmbH, Medizintechnologie, Geisingen, Germany), or catheter through needle (CTN) system (Pajunk® SonoLong) (PAJUNK® GmbH, Medizintechnologie, Geisingen, Germany). There was no statistically significant difference in the rate of leaking catheters between groups (CON 1.8% versus CTN 3.7%; P=0.618), however, the overall leak rate was much lower than anticipated from pilot data. The CON system was on average faster to insert (CON 357 seconds versus CTN 482 seconds; P=0.004), but associated with poorer needle visibility under ultrasound (Likert scale 1–5, mean [SD], CON 3.31 [0.96] versus CTN 3.89 [0.84]; P=0.001). All seven instances of inadvertent catheter dislodgement occurred in the CTN group (P=0.006). There was no statistically significant difference between groups in the proportion of patients who had adequate analgesia on day one (CON 80% versus CTN 86.5%; P=0.294) and day two postoperatively (CON 85.5% versus CTN 91.8%; P=0.369). Our findings show the overall leak rate to be very low with both catheter systems; however, the CON system may have advantages in terms of speed of use and rate of inadvertent catheter dislodgement.

An acute bout of distance running decreases Achilles tendon CSA. The purpose of this study was to examine if three-week stretch training of the Achilles tendon alters the Achilles tendon thinning response to running. Thirty-three recreational runners were divided into a control group (n = 17) and an intervention group (n = 16). The intervention included a three-week soleus stretch (knee flexed) and gastrocnemius stretch (knee extended). Three gastrocnemius stretches and three soleus stretches were performed each day, six days per week. Stretches were held for 30 s per repetition for a total duration of 180 s per leg per day. Achilles tendon CSA and range of motion measures were completed pre and post-run before and after the three-week stretching intervention. The runs prior to and following the three-week stretch training intervention both resulted in a 6% decrease in Achilles tendon CSA (p < 0.0001). There was no interaction across time between control and intervention groups in CSA (p = 0.446). Only the intervention group experienced a significant increase in dorsiflexion range of motion following the stretch training (p = 0.009). We therefore conclude that even when an increased dorsiflexion range of motion occurs, three weeks of triceps surae stretching does not alter the response of the Achilles tendon CSA.

Environmental hazards typically are encountered in the gaseous phase; however, selective sensing modalities for identifying and quantitating compounds of interest in an inexpensive, pseudo-real-time format are severely lacking. Here, we present a novel proof-of-concept that combines an Air2Liquid sampler in conjunction with an oil-in-water microfluidic assay for detection of organophosphates. We believe this proof-of-concept will enable development of a new platform technology for semivolatile detection that we have demonstrated to detect 50 pmoles (2 ppb) of neurotoxic organophosphates.

Use of hydrogen gas (H(2)) as an electron donor is common among free-living chemolithotrophic microorganisms. Given the presence of this dissolved gas at deep-sea hydrothermal vents, it has been suggested that it may also be a major electron donor for the free-living and symbiotic chemolithoautotrophic bacteria that are the primary producers at these sites. Giant Riftia pachyptila siboglinid tubeworms and their symbiotic bacteria (“Candidatus Endoriftia persephone”) dominate many vents in the Eastern Pacific, and their use of sulfide as a major electron donor has been documented. Genes encoding hydrogenase are present in the “Ca. Endoriftia persephone” genome, and proteome data suggest that these genes are expressed. In this study, high-pressure respirometry of intact R. pachyptila and incubations of trophosome homogenate were used to determine whether this symbiotic association could also use H(2) as a major electron donor. Measured rates of H(2) uptake by intact R. pachyptila in high-pressure respirometers were similar to rates measured in the absence of tubeworms. Oxygen uptake rates in the presence of H(2) were always markedly lower than those measured in the presence of sulfide, as was the incorporation of (13)C-labeled dissolved inorganic carbon. Carbon fixation by trophosome homogenate was not stimulated by H(2), nor was hydrogenase activity detectable in these samples. Though genes encoding [NiFe] group 1e and [NiFe] group 3b hydrogenases are present in the genome and transcribed, it does not appear that H(2) is a major electron donor for this system, and it may instead play a role in intracellular redox homeostasis. IMPORTANCE Despite the presence of hydrogenase genes, transcripts, and proteins in the “Ca. Endoriftia persephone” genome, transcriptome, and proteome, it does not appear that R. pachyptila can use H(2) as a major electron donor. For many uncultivable microorganisms, omic analyses are the basis for inferences about their activities in situ. However, as is apparent from the study reported here, there are dangers in extrapolating from omics data to function, and it is essential, whenever possible, to verify functions predicted from omics data with physiological and biochemical measurements.

Hypabyssal kimberlites are subvolcanic intrusive rocks crystallised from mantle-derived magmas poor in SiO2 and rich in CO2 and H2O. They are complex, hybrid rocks containing significant amounts of mantle-derived fragments, primarily olivine with rare diamonds, set in a matrix of essentially magmatic origin. Unambiguous identification of kimberlites requires careful petrographic examination combined with mineral compositional analyses. Melt inclusion studies have shown that kimberlite melts contain higher alkali concentrations than previously thought but have not clarified the ultimate origin of these melts. Because of the hybrid nature of kimberlites and their common hydrothermal alteration by fluids of controversial origin (magmatic and/or crustal), the composition of primary kimberlite melts remains unknown.

We present new paleomagnetic and geochemical data from a suite of the similar to 1144-Ma ultramafic lamprophyre dikes that outcrop in the Canadian Shield northeast of Lake Superior (Ontario, Canada). Nineteen of 22 sampled dikes yielded consistent characteristic remanent magnetization directions of normal (n = 5) and reversed (n = 14) polarity. The primary origin of characteristic remanent magnetization is bolstered by positive baked contact tests and a reversal test. The group mean direction (D = 306.4 degrees, I = 72.1 degrees, alpha(95) = 5.5 degrees, N = 19) obtained from the lamprophyre dikes is statistically indistinguishable from the group mean direction (D = 297.4 degrees, I = 65.5 degrees, alpha(95) = 8.3 degrees, N = 8) previously reported for the nearly coeval similar to 1142-Ma Abitibi dikes. The geochemistry of the lamprophyre dikes suggests strong affinity with magmas derived from ocean island basalt-type mantle sources, consistent with the mantle plume hypothesis for the formation of the similar to 1.1-Ga North American Midcontinent Rift. The similarity in age, trend, paleomagnetism, and geochemistry indicates that the lamprophyre and Abitibi dike suites represent the earliest magmatic event associated with the commencement of rifting. The combined mean direction (D = 303.1 degrees, I = 70.2 degrees, alpha(95) = 4.5 degrees, N = 27) corresponds to a paleomagnetic pole at P-lat = 55.8 degrees N, P-long = 220.0 degrees E (A(95) = 7.3 degrees). The new pole merits the highest classification on the Q-scale of paleomagnetic reliability and represents a key pole defining the North American apparent polar wander path during the late Mesoproterozoic. Combined with high-quality data from the similar to 1108-Ma Coldwell Complex, our data indicate an equatorward motion of Laurentia at 3.8 +/- 1.4 cm/year, comparable with the present-day velocities of continental plates, before switching to extremely rapid motion between similar to 1108 and similar to 1099 Ma. Plain Language Summary Similar to a magnetic tape, rocks can retain the direction of ancient Earth's magnetic field. Scientists use this record (known as paleomagnetism) to reconstruct past positions of continents and to decipher the geological history of our planet. We investigated paleomagnetism and chemical composition of the similar to 1.14 Ga-old intrusive rocks called lamprophyres exposed in Northwestern Ontario (Canada). We found that the paleomagnetic field directions recorded in lamprophyres are indistinguishable from those recorded by another similar age suite of basaltic intrusions called the Abitibi dikes, from the same area. The combined data from these rocks allowed us to constrain the position of an ancient supercontinent called Laurentia at similar to 1.14 billions of years ago more accurately than it was possible before. Our results convincingly show that, during that time, Laurentia moved with a velocity comparable to present-day plate velocities, before switching to an extremely rapid motion approximately 35 millions of years later. The lamprophyre and Abitibi rocks also share similar chemical signatures, close to those observed for ocean island basalts (e.g., Hawaii). These observations support the hypothesis that a failed ocean opening attempt called the North American Midcontinent Rift was instigated by the arrival of a hot mantle material upwelling to the Earth surface.

Treatment of rats with the cholesterol pathway inhibitor AY9944 produces an animal model of Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive disease caused by defective cholesterol synthesis. This SLOS rat model undergoes progressive and irreversible degeneration of the neural retina, with associated pathological features of the retinal pigmented epithelium (RPE). Here, we provide further insights into the mechanism involved in the RPE pathology. In the SLOS rat model, markedly increased RPE apical autofluorescence is observed, compared to untreated animals, which correlates with increased levels of A2E and other bisretinoids. Utilizing cultured human induced pluripotent stem cell (iPSC)- derived SLOS RPE cells, we found significantly elevated steady-state levels of 7-dehydrocholesterol (7DHC) and decreased cholesterol levels (key biochemical hallmarks of SLOS). Western blot analysis revealed altered levels of the macroautophagy/autophagy markers MAP1LC3B-II and SQSTM1/p62, and build-up of ubiquitinated proteins. Accumulation of immature autophagosomes was accompanied by inefficient degradation of phagocytized, exogenously supplied retinal rod outer segments (as evidenced by persistence of the C-terminal 1D4 epitope of RHO [rhodopsin]) in SLOS RPE compared to iPSC-derived normal human control. SLOS RPE cells exhibited lysosomal pH levels and CTSD activity within normal physiological limits, thus discounting the involvement of perturbed lysosomal function. Furthermore, 1D4-positive phagosomes that accumulated in the RPE in both pharmacological and genetic rodent models of SLOS failed to fuse with lysosomes. Taken together, these observations suggest that defective phagosome maturation underlies the observed RPE pathology. The potential relevance of these findings to SLOS and the requirement of cholesterol for phagosome maturation are discussed.

This study explores perceptions of recent graduates from UK institutions who have undertaken Early Childhood Studies (ECS) degrees, following on from a similar study nearly two decades ago. Although there are clear similarities, it is the differences which bring a new dimension and focus. Data were gathered from graduates at 11 UK institutions through an electronic questionnaire and a follow-up focus group interview. Analysis of the data demonstrated that the degrees were highly rated by the graduates but not always understood or known about by employers and careers advisors. Sufficient opportunity for spending supervised time in a relevant setting (practice) was regarded as an essential component of the degrees, but this was not always available. Considerable differences in employment opportunities for the graduates in the two studies were evident from the data, as the newer graduates found achieving employment in the sector was often a challenge, unlike the graduates in the earlier study. Despite not often gaining ‘graduate’ employment, almost all participants believed they had improved their employment prospects since completing their programmes. Graduates’ motivations for their programme choice were similar in both studies. The relevance and influence of the programmes, including advocacy and political awareness, and the employment opportunities following their degree programmes, had changed.

The incidence of low back pain (LBP) among elite ballroom dancers is high and understanding associations between muscle morphology and pain may provide insight into treatment or training options. Research has linked multifidus muscle atrophy to LBP in the general and some athletic populations; however, this has not been examined in ballroom dancers. We compared the lumbar multifidus cross-sectional area (CSA) at rest in 57 elite level ballroom dancers (age 23±2.4 years; height, 174±11 cm; mass, 64±10 kg) divided into one of three pain groups, according to their self-reported symptoms, 1) LBP group (n=19), 2) minimal LBP (n=17), and 3) no LBP (n=21). There were no significant difference in demographics between the groups (P>0.05). The LBP group demonstrated significant differences in reported pain and Oswestry Disability Index scores compared to the other two groups. There was no significant difference between groups in multifidus cross-sectional area (P=0.49). Asymmetry was found in all groups with the overall left side being significantly larger than the right (P

OBJECTIVES Early resuscitation may improve outcomes in pediatric traumatic brain injury (TBI). We examined the association between timely treatment of hypotension and hypoxia during early care (prehospital or emergency department locations) and discharge outcomes in children with severe TBI. METHODS Hypotension was defined as systolic blood pressure less than 70 + 2 (age in years), and hypoxia was defined as PaO2 less than 60 mm Hg or oxygen saturation less than 90% in accordance with the 2003 Brain Trauma Foundation guidelines. Timely treatment of hypotension and hypoxia during early care was defined as the treatment within 30 minutes of a documented respective episode. Two hundred thirty-six medical records of children younger than 18 years with severe TBI from 5 regional pediatric trauma centers were examined. Main outcomes were in-hospital mortality and discharge Glasgow Outcome Scale (GOS) score. RESULTS Hypotension occurred in 26% (60/234) during early care and was associated with in-hospital mortality (23.3% vs 8.6%; P = 0.01). Timely treatment of hypotension during early care occurred in 92% (55/60) by use of intravenous fluids, blood products, or vasopressors and was associated with reduced in-hospital mortality [adjusted relative risk (aRR), 0.46; 95% confidence interval, 0.24-0.90] and less likelihood of poor discharge GOS (aRR, 0.54; 95% confidence interval, 0.39-0.76) when compared to children with hypotension who were not treated in a timely manner. Early hypoxia occurred in 17% (41/236) and all patients received timely oxygen treatment. CONCLUSIONS Timely resuscitation during early care was common and associated with lower in-hospital mortality and favorable discharge GOS in severe pediatric TBI.

Perovskite mineral oxides commonly exhibit extensive solid-solution, and are therefore classified on the basis of the proportions of their ideal end-members. A uniform sequence of calculation of the end-members is required if comparisons are to be made between different sets of analytical data. A Microsoft Excel spreadsheet has been programmed to assist with the classification and depiction of the minerals of the perovskite- and vapnikite-subgroups following the 2017 nomenclature of the perovskite supergroup recommended by the International Mineralogical Association (IMA). Compositional data for up to 36 elements are input into the spreadsheet as oxides in weight percent. For each analysis, the output includes the formula, the normalized proportions of 15 end-members, and the percentage of cations which cannot be assigned to those end-members. The data are automatically plotted onto the ternary and quaternary diagrams recommended by the IMA for depiction of perovskite compositions. Up to 200 analyses can be entered into the spreadsheet, which is accompanied by data calculated for 140 perovskite compositions compiled from the literature.

The mineralogy of nine recently discovered dykes (VL1:VL8 and VL10) in the vicinity of Vattikod village, Nalgonda district in Telangana State is described. The mineral assemblage present and their compositions are comparable to those of bona fide lamproites in terms of the presence of phlogopite (Ti-rich, Al-poor phlogopite and tetraferriphlogopite); amphiboles (potassic-arfvedsonite, potassic-richterite, potassic-ferro-richterite, potassic-katophorite, Ti-rich potassic-katophorite, Ti-rich potassic-magnesio-katophorite); Al-poor clinopyroxenes; feldspars (K-feldspar, Ba-K-feldspar and Na-feldspar) and spinels (chromite-magnetite and qandilite-ulvöspinel-franklinite). These dykes have undergone diverse and significant degrees of deuteric alteration as shown by the formation of secondary phases such as: titanite, allanite, hydro-zircon, calcite, chlorite, quartz and cryptocrystalline SiO2. On the basis of their respective mineralogy: the VL4 and VL5 dykes are classified as pseudoleucite-phlogopite lamproite; VL2 and VL3 dykes as pseudoleucite-amphibole-lamproite; and VL6, VL7 and VL8 as pseudoleucite-phlogopite-amphibole-lamproite. VL10 is extensively altered but contains fresh euhedral apatite microphenocrysts together with pseudomorphs after leucite and is classified as a pseudoleucite-apatite-(phlogopite?) lamproite. The mineralogy of the Vattikod lamproite dykes is compared with that of the Ramadugu, Somavarigudem and Yacharam lamproite dykes which also occur in the Ramadugu lamproite field. The lamproites from the Eastern Dharwar Craton are considered as being possible expressions of ancient subduction-related alkaline magmatism along the Eastern Ghats mobile belt.

Physical activity impacts health and disease in multiple body tissues including the intervertebral discs. Fluid flow within the disc is an indicator of disc health that can be observed using diffusion weighted magnetic resonance imaging. We monitored activity levels of 26 participants, age 35-55 yrs, using Actigraph accelerometers for 4 days to evaluate vigorous-intensity activity, moderate to vigorous intensity activity, and sedentary time. Participants underwent structural and diffusion weighted magnetic resonance imaging to evaluate intervertebral disc health and fluid flow. They also underwent bone density scans, carotid artery ultrasounds, a treadmill test, and a physical exam for pain, range of motion, and instability. These measures were used to correlate MRI indicators of intervertebral disc health with participant activity levels. Participants with any vigorous-intensity physical activity compared with no vigorous-intensity activity had significantly greater L5/S1 apparent diffusion coefficient values (p = 0.002), corresponding to higher freedom of diffusive movement for cellular nutrients and metabolic waste. Sagittal T2 values in the L5/S1 were also higher (p = 0.004), corresponding to a higher water content in the discs. Higher apparent diffusion coefficients were also found in participants with more than 30 min compared with less than 30 min of daily moderate to vigorous physical activity (p = 0.03), and in participants with less than 67% awake time as sedentary time compared with more than 67% sedentary time (p = 0.03). Increased dynamic loading through physical activity and decreased static loading from sedentary time benefit intervertebral disc health. Physical activity, particularly vigorous activity, is beneficial in helping maintain intervertebral disc health. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1313-1323, 2018.

The transient receptor potential cation channel mucolipin 1 (TRPML1) channel is a conduit for lysosomal calcium efflux, and channel activity may be affected by lysosomal contents. The lysosomes of retinal pigmented epithelial (RPE) cells are particularly susceptible to build-up of lysosomal waste products because they must degrade the outer segments phagocytosed daily from adjacent photoreceptors; incomplete degradation leads to accumulation of lipid waste in lysosomes. This study asks whether stimulation of TRPML1 can release lysosomal calcium in RPE cells and whether such release is affected by lysosomal accumulations. The TRPML agonist ML-SA1 raised cytoplasmic calcium levels in mouse RPE cells, hesRPE cells, and ARPE-19 cells; this increase was rapid, robust, reversible, and reproducible. The increase was not altered by extracellular calcium removal or by thapsigargin but was eliminated by lysosomal rupture with glycyl-l-phenylalanine-β-naphthylamide. Treatment with desipramine to inhibit acid sphingomyelinase or YM201636 to inhibit PIKfyve also reduced the cytoplasmic calcium increase triggered by ML-SA1, whereas RPE cells from TRPML1−/− mice showed no response to ML-SA1. Cotreatment with chloroquine and U18666A induced formation of neutral, autofluorescent lipid in RPE lysosomes and decreased lysosomal Ca2+ release. Lysosomal Ca2+ release was also impaired in RPE cells from the ATP-binding cassette, subfamily A, member 4−/− mouse model of Stargardt’s retinal dystrophy. Neither TRPML1 mRNA nor total lysosomal calcium levels were altered in these models, suggesting a more direct effect on the channel. In summary, stimulation of TRPML1 elevates cytoplasmic calcium levels in RPE cells, but this response is reduced by lysosomal accumulation.—Gómez, N. M., Lu, W. Lim, J. C., Kiselyov, K., Campagno, K. E., Grishchuk, Y., Slaugenhaupt, S. A., Pfeffer, B., Fliesler, S. J., Mitchell, C. H. Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation.

Digital nerves are intrinsic to the sensory and motor function of the hand. These nerves represent the terminal ramifications of the ulnar, median, and radial nerves and are located distal to the carpal tunnel and Guyon canal. With magnetic resonance imaging, traumatic and nontraumatic abnormalities of the digital nerves can be shown with high contrast as well as high spatial resolution. Digital nerve abnormalities are most commonly posttraumatic in nature; however, infection, inflammatory, vascular malformations, and neoplasms can rarely occur. Magnetic resonance imaging is playing an increasing role in the assessment of peripheral nerve injury throughout the body, and in the hand, which can accurately identify the extent and character of digital nerve abnormalities before operative intervention.

We report the first U–Pb geochronological investigation of schorlomite garnet from carbonatite and alkaline complexes and demonstrate its applicability for U–Pb age determination using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) due to its relatively high U and Th abundances and negligible common Pb content. The comparative matrix effects of laser ablation of zircon and schorlomite are investigated and demonstrate the necessity of a suitable matrix-matched reference material for schorlomite geochronology. Laser-induced elemental fractional and instrumental mass discrimination were externally-corrected using an in house schorlomite reference material (WS20) for U–Pb geochronology. In order to validate the effectiveness and robustness of our analytical protocol, we demonstrate the veracity of U–Pb age determination for five schorlomite samples from: the Magnet Cove complex, Arkansas (USA); the Fanshan ultrapotassic complex, Hebei (China); the Ozernaya alkaline ultramafic complex, Kola Peninsula (Russia); the Alno alkaline–rock carbonatite complex (Sweden); and the Prairie Lake carbonatite complex, Ontario (Canada). The schorlomite U–Pb ages range from 96 Ma to 1160 Ma, and are almost identical to ages determined from other accessory minerals in these complexes and support the reliability of our analytical protocol. Schorlomite garnet U–Pb geochronology is considered to be a promising new technique for understanding the genesis of carbonatites, alkaline rocks, and related rare-metal deposits.

This study reports the mineralogy and petrology, together with the major and trace element composition of pyroxenes, garnets and apatite from ijolite series rocks occurring at the Prairie Lake carbonatite complex, northwestern Ontario, with comparative data for ijolites from the Fen complex, Norway. The ijolites and calcite ijolites (hollaites) of Prairie Lake record the effects of magma mixing, crystal settling, solid-state re-equilibration and deuteric alteration. The Prairie Lake complex was formed by at least three stages of intrusion. The initial stage was predominantly biotite pyroxenite and associated coarse carbonatite veins. The second stage is represented primarily by members of the ijolite series together with meta-ijolites created by solid state re-equilibration of previously crystallized rocks. Differentiation of the magmas which formed the ijolite suite resulted in the formation of calcite ijolites (hollaites) and malignites (potassic nepheline syenites). The final stage was the intrusion of the heterogeneous carbonatites derived from different batches of carbonatite related magmas. These rocks contain xenoliths of ijolite suite rocks, pyroxene apatitite, wollastonite apatitite, and phoscorite. Pyroxene compositions show an evolutionary trend from diopside in biotite pyroxenites through Fe-enriched diopside-augite in ijolites to aegirine in malignites. Clinopyroxene major and trace element data show that the cores of clinopyroxene in biotite pyroxenites formed as antecrysts at depth and were emplaced as part of a later event. Trace element data from pyroxenes, garnets and apatite from Prairie Lake and Fen are similar to each other and those found in carbonatite complexes worldwide. It is proposed that a continuously-filled fractionating magma chamber was not present at Prairie Lake and that the ijolite–malignite members of the complex formed as result of small intrusions of nephelinitic magma into pre-existing ijolites. Similar styles of magmatic evolution by fractional crystallization are indicated for the Prairie Lake, Fen, and Belaya Zima ijolite‑carbonatite complexes and there is no evidence that liquid immiscibility played any role in their petrogenesis.

Date Presented Accepted for AOTA INSPIRE 2021 but unable to be presented due to online event limitations. OTs and other health care professionals frequently experience low back pain. This has been associated with multifidus cross-sectional area in various populations, but not previously in health care workers. This project observed multifidus cross-sectional area in OTs and other health care personnel. A pain group was compared with a nonpain group to assess differences between them. At the S1 level (with a trend at L5), those with more pain had smaller multifidus. Primary Author and Speaker: Robert E. Larson Contributing Authors: Ulrike H. Mitchell, A. Wayne Johnson