Incidence of spine surgery in the South African private healthcare sector: ten-year trends within a large open medical scheme.

PURPOSE: Studies from developed countries suggest a dramatic increase in the utilization of spine surgery in recent decades, however less is known about spine surgery rates in the developing world. The aim of this study was to investigate ten-year trends in the incidence of spine surgery within South Africa's largest open medical scheme. METHODS: This retrospective review included adult inpatient spine surgeries funded by the scheme between 2008 and 2017. The incidence of spine surgery was investigated by age group-overall and for degenerative pathologies, fusion and instrumentation. Surgeons per 100,000 members were determined. Trends were evaluated by linear regression and by crude 10-year change in incidence. RESULTS: A total of 49,575 spine surgeries were included. The incidence of surgery for lumbar degenerative pathology showed a significant upward trend among 60-79 year olds but declined among 40-59 year olds. The incidence of lumbar fusion and lumbar instrumentation declined significantly among 40-59 year olds with little change among 60-79 year olds. The ratio of orthopaedic spinal surgeons decreased from 10.2 to 6.3 per 100,000 members whereas the ratio of neurosurgeons decreased from 7.6 to 6.5 per 100,000. CONCLUSION: Spine surgery in the South African private healthcare sector bears some similarity to developed countries in that it is dominated by elective procedures for degenerative pathology. However, the findings did not reflect the marked increases in the utilization of spine surgery reported elsewhere. It is hypothesized that this may be partly related to differences in the supply of spinal surgery.

Soil CO2 emissions in cropland with fodder maize (Zea mays L.) with and without riparian buffer strips of differing vegetation.

Vegetated land areas play a significant role in determining the fate of carbon (C) in the global C cycle. Riparian buffer vegetation is primarily implemented for water quality purposes as they attenuate pollutants from immediately adjacent croplands before reaching freashwater systems. However, their prevailing conditions may sometimes promote the production and subsequent emissions of soil carbon dioxide (CO2). Despite this, the understanding of soil CO2 emissions from riparian buffer vegetation and a direct comparison with adjacent croplands they serve remain elusive. In order to quantify the extent of CO2 emissions in such an agro system, we measured CO2 emissions simultaneously with soil and environmental variables for six months in a replicated plot-scale facility comprising of maize cropping served by three vegetated riparian buffers, namely: (i) a novel grass riparian buffer; (ii) a willow riparian buffer, and; (iii) a woodland riparian buffer. These buffered treatments were compared with a no-buffer control. The woodland (322.9 ± 3.1 kg ha- 1) and grass (285 ± 2.7 kg ha- 1) riparian buffer treatments (not significant to each other) generated significantly (p = < 0.0001) the largest CO2 compared to the remainder of the treatments. Our results suggest that during maize production in general, the woodland and grass riparian buffers serving a maize crop pose a CO2 threat. The results of the current study point to the need to consider the benefits for gaseous emissions of mitigation measures conventionally implemented for improving the sustainability of water resources.

Secondary non-invasive prenatal screening for fetal trisomy: an effectiveness study in a public health setting.

OBJECTIVE: To evaluate the effectiveness of secondary screening using non-invasive prenatal testing (NIPT) in a routine NHS setting including test performance, turn-around times (TATs) and no-call (failure to obtain result) rates. To examine the influence of maternal and fetal characteristics on test performance. DESIGN: Retrospective cohort. SETTING: London teaching hospital. SAMPLE: A total of 8651 pregnancies undergoing screening for fetal trisomy using NIPT provided by an NHS cell-free DNA screening laboratory - the SAFE laboratory. METHODS: Screening test evaluation and TATs. Univariate and multivariate logistic regression analysis to identify significant predictors of no-call results and reported by low fetal fraction (<2%), very high fetal fraction (>40%) and processing failure. MAIN OUTCOME MEASURES: Test performance, TATs and no-call rates, factors affecting no-call results. RESULTS: Average TAT was 4.0 days (95% CI 4.0-4.2 days). Test sensitivities for trisomies 21 and 13/18 were 98.9% (95% CI 95.9-99.9%) and 90.4% (95% CI 80.0-96.8%), respectively. The overall no-call rate was 32/8651 (0.37%, 95% CI 0.26-0.52%). The overall risk of a no-call result was influenced by gestational age, dichorionic twin pregnancy, history of malignancy and pregnancies affected by trisomy 13/18, but not by maternal weight or use of low-molecular-weight heparin. CONCLUSIONS: High-throughput NIPT can be effectively embedded into a public health NHS setting. TATs of 4 days and no-calls of <0.5% were well within clinically desirable tolerances. Gestational age, maternal weight, assisted reproductive techniques, use of low-molecular-weight heparin and past history of malignancy did not have major impacts on test no-call rates and should not constitute reasons for withholding the option of NIPT from women. TWEETABLE ABSTRACT: Turn-around times of 4 days, no-call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS.

Risk scoring for time to end-stage knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: This study constructs a risk score for patients' progression to end-stage knee osteoarthritis (OA) within 4 years. DESIGN: The Osteoarthritis Initiative (OAI) was a longitudinal study of the onset and progression of knee OA. Using a recent definition of end-stage knee OA, we implement interval-censored survival forests to select predictors of this endpoint. We fit an interval-censored Cox model for time to end-stage knee OA, using the selected predictors. The risk score is the Cox model's fitted linear combination of the nine selected baseline structural and symptomatic knee OA variables. RESULTS: We fit our models on a training set of 2,701 patients, and we evaluate on an independent test set of 1,436 patients. On the test sample, we observe a concordance index of 0.86 between risk score and time to end-stage, AUC of 0.87 for predicting end-stage within 24, 36, and 48 months, and positive predictive values that increase with the risk score. This risk stratification algorithm could enrich clinical trial patient enrollment. By enrolling test sample patients with scores above a threshold, a trial could have included 91% of test set patients who reach end-stage within 4 years while only enrolling 45% of the test sample. CONCLUSION: Using statistical methods, we construct and validate an interpretable risk score for time to end-stage knee OA. This score can help disease-modifying OA treatment developers to select candidates with the highest risk of fast-progressing knee OA.

Multicenter Clinical Evaluation of the Automated Aries Group A Strep PCR Assay from Throat Swabs.

Group A Streptococcus (GAS) is one of the leading causes of bacterial pharyngitis. Early GAS diagnosis is critical for appropriate antibiotic administration that reduces the risk of GAS sequelae and limits spread of the infection. The Aries Group A Strep (GAS) assay (Luminex, Austin, TX) is a fully automated PCR assay for direct detection of GAS in throat swab specimens in less than 2 h with minimum hands-on time. This multicenter prospective study evaluated the clinical performance of the Aries GAS assay compared to that of Streptococcus pyogenes culture. Subjects with symptoms consistent with pharyngitis were enrolled across four sites in the United States, and a throat swab in liquid Amies medium was obtained. Aries and reference testing was performed within 72 and 48 h after sample collection, respectively. Of 623 throat swab specimens from patients with pharyngitis (93.6% <18 years old, 54.3% female), the reference method yielded valid results for 618 specimens. Reference and Aries assay testing showed GAS-positive results for 160 (25.9%) and 166 (26.9%) specimens, respectively. Compared to the reference method, Aries assay sensitivity was 97.5% (95% confidence interval [CI], 93.7% to 99.0%), specificity was 97.8% (95% CI, 96.0 to 98.8%), positive predictive value was 94.0% (95% CI, 89.3% to 96.7%), and negative predictive value was 99.1% (95% CI, 97.7% to 99.7%). There were 10 false-positive and four false-negative detections with the Aries assay. Discrepant analysis with bidirectional sequencing yielded concordant results with the Aries assay for nine of 14 discordant samples. The Aries assay had high sensitivity and specificity for qualitative detection of group A Streptococcus from patients with pharyngitis.

Deep Learning and Glaucoma Specialists: The Relative Importance of Optic Disc Features to Predict Glaucoma Referral in Fundus Photographs.

PURPOSE: To develop and validate a deep learning (DL) algorithm that predicts referable glaucomatous optic neuropathy (GON) and optic nerve head (ONH) features from color fundus images, to determine the relative importance of these features in referral decisions by glaucoma specialists (GSs) and the algorithm, and to compare the performance of the algorithm with eye care providers. DESIGN: Development and validation of an algorithm. PARTICIPANTS: Fundus images from screening programs, studies, and a glaucoma clinic. METHODS: A DL algorithm was trained using a retrospective dataset of 86 618 images, assessed for glaucomatous ONH features and referable GON (defined as ONH appearance worrisome enough to justify referral for comprehensive examination) by 43 graders. The algorithm was validated using 3 datasets: dataset A (1205 images, 1 image/patient; 18.1% referable), images adjudicated by panels of GSs; dataset B (9642 images, 1 image/patient; 9.2% referable), images from a diabetic teleretinal screening program; and dataset C (346 images, 1 image/patient; 81.7% referable), images from a glaucoma clinic. MAIN OUTCOME MEASURES: The algorithm was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for referable GON and glaucomatous ONH features. RESULTS: The algorithm's AUC for referable GON was 0.945 (95% confidence interval [CI], 0.929-0.960) in dataset A, 0.855 (95% CI, 0.841-0.870) in dataset B, and 0.881 (95% CI, 0.838-0.918) in dataset C. Algorithm AUCs ranged between 0.661 and 0.973 for glaucomatous ONH features. The algorithm showed significantly higher sensitivity than 7 of 10 graders not involved in determining the reference standard, including 2 of 3 GSs, and showed higher specificity than 3 graders (including 1 GS), while remaining comparable to others. For both GSs and the algorithm, the most crucial features related to referable GON were: presence of vertical cup-to-disc ratio of 0.7 or more, neuroretinal rim notching, retinal nerve fiber layer defect, and bared circumlinear vessels. CONCLUSIONS: A DL algorithm trained on fundus images alone can detect referable GON with higher sensitivity than and comparable specificity to eye care providers. The algorithm maintained good performance on an independent dataset with diagnoses based on a full glaucoma workup.

The impact of military service on health and well-being.

BACKGROUND: While it is known that some UK Armed Forces (UK AF) personnel and veterans experience physical and mental health problems, the possible future healthcare needs of military veterans are unknown. AIMS: To estimate the number of military personnel who may experience physical and/or psychological health problems associated with their military service. METHODS: Data were obtained via Freedom of Information requests to several sources, including Defence Statistics. Raw data from research studies were also used where available. Data were analysed using meta-analytic methods to determine the rate of physical, mental or comorbid health problems in AF personnel. RESULTS: Musculoskeletal problems were the predominant reason for medical discharge from service. In terms of mental health, meta-analyses estimated that veteran reservists (part-time military members) previously deployed to operational areas had the highest proportion of general health problems (35%), previously deployed veteran regulars (those in full time military employment) and veteran reservists had the highest proportion of post-traumatic stress disorder (9%), and regular personnel with a deployment history had the highest proportion of alcohol problems (14%). Overall, our findings suggest that at least 67515 veterans are likely to suffer from mental and/or physical health problems at some point as a result of their service between 2001 and 2014. CONCLUSIONS: The results of this study highlight that the difficulties personnel may face are largely musculoskeletal or mental health-related. These findings may help with planning the provision of future physical and mental health care and support for those who serve in the UK AF.

Multicenter Diagnostic Accuracy Evaluation of the Luminex Aries Real-Time PCR Assay for Group B Streptococcus Detection in Lim Broth-Enriched Samples.

The vertical transmission of group B Streptococcus (GBS) strains causing neonatal sepsis is one of the leading reasons for neonatal mortality worldwide. The gold standard for GBS detection is enriched culture with or without the aid of chromogenic agars. Given the high risk for morbidity and mortality in this population, high assay sensitivity is required to prevent the personal and economic costs of GBS disease. Nucleic acid amplification tests (NAATs) allow for objective determination of GBS colonization with a sensitivity and a specificity higher than those of traditional culture methods. In this study, we determined the analytical and clinical performance of the Aries GBS assay compared to those of the enrichment culture method, biochemical identification, and the NAATs used at the study sites. Remnant Lim broth samples were used to perform the Aries assay and reference testing. Upon first testing using enriched culture as the reference standard, the Aries GBS assay identified GBS with a 96.1% sensitivity (95% confidence interval [CI], 91.2 to 98.7%) and a 91.4% specificity (95% CI, 88.8 to 93.6%). The test performed with 100% positive agreement (95% CI, 83.2 to 100%) compared to the results of the BD Max GBS assay and 98.0% positive agreement (95% CI, 89.2 to 99.9%) compared to the results of the Cepheid Xpert GBS LB test. Repeatability and reproducibility were maintained in intra- and interlaboratory testing, regardless of the instrument, module, or user who performed the test. The Aries GBS assay can be set up in less than 5 min and produces results in 2 h. The easy setup, with minimal hands-on time, and high assay sensitivity and specificity make this a useful testing option for GBS screening in prepartum women.

The role of citizen science in addressing grand challenges in food and agriculture research.

The power of citizen science to contribute to both science and society is gaining increased recognition, particularly in physics and biology. Although there is a long history of public engagement in agriculture and food science, the term 'citizen science' has rarely been applied to these efforts. Similarly, in the emerging field of citizen science, most new citizen science projects do not focus on food or agriculture. Here, we convened thought leaders from a broad range of fields related to citizen science, agriculture, and food science to highlight key opportunities for bridging these overlapping yet disconnected communities/fields and identify ways to leverage their respective strengths. Specifically, we show that (i) citizen science projects are addressing many grand challenges facing our food systems, as outlined by the United States National Institute of Food and Agriculture, as well as broader Sustainable Development Goals set by the United Nations Development Programme, (ii) there exist emerging opportunities and unique challenges for citizen science in agriculture/food research, and (iii) the greatest opportunities for the development of citizen science projects in agriculture and food science will be gained by using the existing infrastructure and tools of Extension programmes and through the engagement of urban communities. Further, we argue there is no better time to foster greater collaboration between these fields given the trend of shrinking Extension programmes, the increasing need to apply innovative solutions to address rising demands on agricultural systems, and the exponential growth of the field of citizen science.

The ecosystem services of animal microbiomes.

Microbiologists often evaluate microbial community dynamics by formulating functional hypotheses based on ecological processes. Indeed, many of the methods and terms currently used to describe animal microbiomes derive from ecology and evolutionary biology. As our understanding of the composition and functional dynamics of "the microbiome" grows, we increasingly refer to the host as an ecosystem within which microbial processes play out. Even so, an ecosystem service framework that extends to the context of the host has thus far been lacking. Here, we argue that ecosystem services are a useful framework with which to consider the value of microbes to their hosts. We discuss those "microbiome services" in the specific context of the mammalian gut, providing a context from which to develop new hypotheses and to evaluate microbial functions in future studies and novel systems.

Asthma in the elderly and late-onset adult asthma.

Elderly asthmatics are at a higher risk for morbidity and mortality from their asthma than younger patients. There are important age-related physiologic and immunologic changes that complicate the presentation, diagnosis, and management of asthma in the aged population. Evidence suggests that elderly asthmatics are more likely to be underdiagnosed and undertreated. Additionally, elderly patients with asthma have highest rates of morbidity and mortality from their disease than younger patients. The underlying airway inflammation of asthma in this age group likely differs from younger patients and is felt to be non-type 2 mediated. While elderly patients are underrepresented in clinical trials, subgroup analysis of large clinical trials suggests they may be less likely to respond to traditional asthma therapies (ie, corticosteroids). As the armamentarium of pharmacologic asthma therapies expands, it will be critical to include elderly asthmatics in large clinical trials so that therapy may be better tailored to this at-risk and growing population.

Child and adult spinal tuberculosis at tertiary hospitals in the Western Cape, South Africa: 4-year burden and trend.

The aim of this retrospective review was to assess the overall burden and trend in spinal tuberculosis (TB) at tertiary hospitals in the Western Cape Province of South Africa. All spinal TB cases seen at the province's three tertiary hospitals between 2012 and 2015 were identified and clinical records of each case assessed. Cases were subsequently classified as bacteriologically confirmed or clinically diagnosed and reported with accompanying clinical and demographic information. Odds ratios (OR) for severe spinal disease and corrective surgery in child vs. adult cases were calculated. A total of 393 cases were identified (319 adults, 74 children), of which 283 (72%) were bacteriologically confirmed. Adult cases decreased year-on-year (P = 0.04), however there was no clear trend in child cases. Kyphosis was present in 60/74 (81%) children and 243/315 (77%) adults with available imaging. Corrective spinal surgery was performed in 35/74 (47%) children and 80/319 (25%) adults (OR 2.7, 95% confidence interval 1.6-4.5, P = 0.0003). These findings suggest that Western Cape tertiary hospitals have experienced a substantial burden of spinal TB cases in recent years with a high proportion of severe presentation, particularly among children. Spinal TB remains a public health concern with increased vigilance required for earlier diagnosis, especially of child cases.

Orthopaedic Surgeon Density in South Africa.

BACKGROUND: In the era of global surgery, there are limited data regarding the available surgical workforce in South Africa. METHODS: This aim of this study was to determine the orthopaedic surgeon density in South Africa. This involved a quantitative descriptive analysis of all registered specialist orthopaedic surgeons in South Africa, using data collected from various professional societal national databases. RESULTS: The results showed 1.63 orthopaedic surgeons per 100,000 population. The vast majority were male (95%) with under two-thirds (65%) being under the age of 55 years. The majority of the orthopaedic surgeons were found in Gauteng, followed by the Western Cape and Kwa-Zulu Natal. The majority of specialists reportedly worked either full time or part time in the private sector (95%), and the orthopaedic surgeon density per uninsured population (0.36) was far below that of the private sector (8.3). CONCLUSION: Interprovincial differences as well as intersectoral differences were marked indicating geographic and socio-economic maldistribution of orthopaedic surgeons. This parallels previous studies which looked at other surgical sub-disciplines in South Africa. Addressing this maldistribution requires concerted efforts to expand public sector specialist posts as well as quantifying the burden of orthopaedic disease in both private and public sectors before recommendations can be made regarding workforce allocation in the future. LEVEL OF EVIDENCE: IV.

Magnetic resonance imaging of disease progression and resolution in a transgenic mouse model of pulmonary fibrosis.

Pulmonary fibrosis contributes to morbidity and mortality in a range of diseases, and there are no approved therapies for reversing its progression. To understand the mechanisms underlying pulmonary fibrosis and assess potential therapies, mouse models are central to basic and translational research. Unfortunately, metrics commonly used to assess murine pulmonary fibrosis require animals to be grouped and euthanized, increasing experimental difficulty and cost. We examined the ability of magnetic resonance imaging (MRI) to noninvasively assess lung fibrosis progression and resolution in a doxycycline (Dox) regulatable, transgenic mouse model that overexpresses transforming growth factor-α (TGF-α) under control of a lung-epithelial-specific promoter. During 7 wk of Dox treatment, fibrotic lesions were readily observed as high-signal tissue. Mean weighted signal and percent signal volume were found to be the most robust MRI-derived measures of fibrosis, and these metrics correlated significantly with pleural thickness, histology scores, and hydroxyproline content (R = 0.75-0.89). When applied longitudinally, percent high signal volume increased by 1.5% wk-1 (P < 0.001) and mean weighted signal increased at a rate of 0.0065 wk-1 (P = 0.0062). Following Dox treatment, lesions partially resolved, with percent high signal volume decreasing by -3.2% wk-1 (P = 0.0034) and weighted mean signal decreasing at -0.015 wk-1 (P = 0.0028). Additionally, longitudinal MRI revealed dynamic remodeling in a subset of lesions, a previously unobserved behavior in this model. These results demonstrate MRI can noninvasively assess experimental lung fibrosis progression and resolution and provide unique insights into its pathobiology.

Identification and functional characterisation of genetic variants in OLFM2 in children with developmental eye disorders.

Anophthalmia, microphthalmia, and coloboma are a genetically heterogeneous spectrum of developmental eye disorders and affect around 30 per 100,000 live births. OLFM2 encodes a secreted glycoprotein belonging to the noelin family of olfactomedin domain-containing proteins that modulate the timing of neuronal differentiation during development. OLFM2 SNPs have been associated with open angle glaucoma in a case-control study, and knockdown of Olfm2 in zebrafish results in reduced eye size. From a cohort of 258 individuals with developmental eye anomalies, we identified two with heterozygous variants in OLFM2: an individual with bilateral microphthalmia carrying a de novo 19p13.2 microdeletion involving OLFM2 and a second individual with unilateral microphthalmia and contralateral coloboma who had a novel single base change in the 5' untranslated region. Dual luciferase assays demonstrated that the latter variant causes a significant decrease in expression of OLFM2. Furthermore, RNA in situ hybridisation experiments using human developmental tissue revealed expression in relevant structures, including the lens vesicle and optic cup. Our study indicates that OLFM2 is likely to be important in mammalian eye development and disease and should be considered as a gene for human ocular anomalies.

TrueNTH sexual recovery study protocol: a multi-institutional collaborative approach to developing and testing a web-based intervention for couples coping with the side-effects of prostate cancer treatment in a randomized controlled trial.

BACKGROUND: Over half of men who receive treatment for prostate suffer from a range of sexual problems that affect negatively their sexual health, sexual intimacy with their partners and their quality of life. In clinical practice, however, care for the sexual side effects of treatment is often suboptimal or unavailable. The goal of the current study is to test a web-based intervention to support the recovery of sexual intimacy of prostate cancer survivors and their partners after treatment. METHODS: The study team developed an interactive, web-based intervention, tailored to type of treatment received, relationship status (partnered/non-partnered) and sexual orientation. It consists of 10 modules, six follow the trajectory of the illness and four are theme based. They address sexual side effects, rehabilitation, psychological impacts and coaching for self-efficacy. Each includes a video to engage participants, psychoeducation and activities completed by participants on the web. Tailored strategies for identified concerns are sent by email after each module. Six of these modules will be tested in a randomized controlled trial and compared to usual care. Men with localized prostate cancer with partners will be recruited from five academic medical centers. These couples (N = 140) will be assessed prior to treatment, then 3 months and 6 months after treatment. The primary outcome will be the survivors' and partners' Global Satisfaction with Sex Life, assessed by a Patient Reported Outcome Measure Information Systems (PROMIS) measure. Secondary outcomes will include interest in sex, sexual activity, use of sexual aids, dyadic coping, knowledge about sexual recovery, grief about the loss of sexual function, and quality of life. The impact of the intervention on the couple will be assessed using the Actor-Partner Interaction Model, a mixed-effects linear regression model able to estimate both the association of partner characteristics with partner and patient outcomes and the association of patient characteristics with both outcomes. DISCUSSION: The web-based tool represents a novel approach to addressing the sexual health needs of prostate cancer survivors and their partners that-if found efficacious-will improve access to much needed specialty care in prostate cancer survivorship. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT02702453 , registered on March 3, 2016.

Glycaemic control and risk of incident urinary incontinence in women with Type 1 diabetes: results from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

AIMS: To study the impact of glycaemic control on urinary incontinence in women who participated in the Diabetes Control and Complications Trial (DCCT; 1983-1993) and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC; 1994-present). METHODS: Study participants were women who completed, at both years 10 (2003) and 17 (2010) of the EDIC follow-up, the urological assessment questionnaire (UroEDIC). Urinary incontinence was defined as self-reported involuntary leakage of urine that occurred at least weekly. Incident urinary incontinence was defined as weekly urinary incontinence present at EDIC year 17 but not at EDIC year 10. Multivariable regression models were used to examine the association of incident urinary incontinence with comorbid prevalent conditions and glycaemic control (mean HbA1c over the first 10 years of EDIC). RESULTS: A total of 64 (15.3%) women with Type 1 diabetes (mean age 43.6 ± 6.3 years at EDIC year 10) reported incident urinary incontinence at EDIC year 17. When adjusted for clinical covariates (including age, DCCT cohort assignment, DCCT treatment arm, BMI, insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract infection in the last year), the mean EDIC HbA1c was associated with increased odds of incident urinary incontinence (odds ratio 1.03, 95% CI 1.01-1.06 per mmol/mol increase; odds ratio 1.41, 95% CI 1.07-1.89 per % HbA1c increase). CONCLUSIONS: Incident urinary incontinence was associated with higher HbA1c levels in women with Type 1 diabetes, independent of other recognized risk factors. These results suggest the potential for women to modify their risk of urinary incontinence with improved glycaemic control. (Clinical Trials Registry no: NCT00360815 and NCT00360893).

Tool use by a temperate wrasse, California sheephead Semicossyphus pulcher.

Multiple individuals of a temperate reef fish species (California sheephead Semicossyphus pulcher) were observed using an anvil to crush hard-bodied invertebrate prey. Potential implications for this behaviour extend from individuals, which may experience reduced likelihood of injury and increased reproduction, to communities, which could see changes in prey abundance and size-distribution, with particularly important consequences for communities regulated by top-down processes. Until relatively recently, the use of simple tools by fishes was overlooked compared with observations of tool use by primates and birds; however, observations of tool use, and interesting foraging behaviours in general, by aquatic organisms should increase with improved underwater monitoring technology.

Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns.

Intrauterine infection (chorioamnionitis) aggravates neonatal hypoxic-ischemic (HI) brain injury, but the mechanisms linking systemic inflammation to the CNS damage remain uncertain. Here we report evidence for brain influx of T-helper 17 (TH17)-like lymphocytes to coordinate neuroinflammatory responses in lipopolysaccharide (LPS)-sensitized HI injury in neonates. We found that both infants with histological chorioamnionitis and rat pups challenged by LPS/HI have elevated expression of the interleukin-23 (IL-23) receptor, a marker of early TH17 lymphocytes, in the peripheral blood mononuclear cells. Post-LPS/HI administration of FTY720 (fingolimod), a sphingosine-1-phosphate receptor agonist that blocks lymphocyte trafficking, mitigated the influx of leukocytes through the choroid plexus and acute induction of nuclear factor-κB signaling in the brain. Subsequently, the FTY720 treatment led to attenuated blood-brain barrier damage, fewer cluster of differentiation 4-positive, IL-17A-positive T-cells in the brain, less proinflammatory cytokine, and better preservation of growth and white matter functions. The FTY720 treatment also provided dose-dependent reduction of brain atrophy, rescuing >90% of LPS/HI-induced brain tissue loss. Interestingly, FTY720 neither opposed pure-HI brain injury nor directly inhibited microglia in both in vivo and in vitro models, highlighting its unique mechanism against inflammation-sensitized HI injury. Together, these results suggest that the dual hit of systemic inflammation and neonatal HI injury triggers early onset of the TH17/IL-17-mediated immunity, which causes severe brain destruction but responds remarkably to the therapeutic blockade of lymphocyte trafficking.