Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila.

Sleep pressure and sleep depth are key regulators of wake and sleep. Current methods of measuring these parameters in Drosophila melanogaster have low temporal resolution and/or require disrupting sleep. Here we report analysis tools for high-resolution, noninvasive measurement of sleep pressure and depth from movement data. Probability of initiating activity, P(Wake), measures sleep depth while probability of ceasing activity, P(Doze), measures sleep pressure. In vivo and computational analyses show that P(Wake) and P(Doze) are largely independent and control the amount of total sleep. We also develop a Hidden Markov Model that allows visualization of distinct sleep/wake substates. These hidden states have a predictable relationship with P(Doze) and P(Wake), suggesting that the methods capture the same behaviors. Importantly, we demonstrate that both the Doze/Wake probabilities and the sleep/wake substates are tied to specific biological processes. These metrics provide greater mechanistic insight into behavior than measuring the amount of sleep alone.

Effect of Glucocorticoids on Athletic Performance: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the effects of glucocorticoids in enhancing athletic performance. DESIGN: At least 2 independent reviewers conducted study selection and extracted demographic and outcome data. Relevant outcomes were stratified by administration time frame and the specific type of drug used. Study quality was assessed using the Cochrane Risk-of-Bias tool and the Cochrane Grading of Recommendations Assessment Development and Education scale. Where appropriate, meta-analyses were performed. Data sources: Embase, MEDLINE, and SPORTDiscus were searched from their beginning to April 2020. PARTICIPANTS: Participants of any sex and training status aged 18 to 65 years were included. INTERVENTIONS AND MAIN OUTCOME MEASURES: Any type of published randomized controlled trial (RCT) that examined any enhancement in sport as well as aerobic, anaerobic, or body compositional parameters for glucocorticoids compared with placebo. RESULTS: There is low-to-moderate evidence suggesting that the administration of glucocorticoids may be more beneficial than placebo in enhancing athletic performance. short-term administration of glucocorticoids significantly improved time to exhaustion, maximal force, and total distance travelled. By contrast, acute administration of glucocorticoids predominantly yielded no changes to athletic performance, except for reductions in total work and maximal power output. CONCLUSIONS: Although there is evidence suggesting glucocorticoids have ergogenic effects, these improvements may differ depending on the specific type of drug, dose, and the administration time frame and are also limited by small sample sizes. Therefore, there is a need for large, high-quality RCTs as this may influence future doping policy and athlete care.

Novel DNA Aptameric Sensors to Detect the Toxic Insecticide Fenitrothion.

Fenitrothion is an insecticide belonging to the organophosphate family of pesticides that is widely used around the world in agriculture and living environments. Today, it is one of the most hazardous chemicals that causes severe environmental pollution. However, detection of fenitrothion residues in the environment is considered a significant challenge due to the small molecule nature of the insecticide and lack of molecular recognition elements that can detect it with high specificity. We performed in vitro selection experiments using the SELEX process to isolate the DNA aptamers that can bind to fenitrothion. We found that newly discovered DNA aptamers have a strong ability to distinguish fenitrothion from other organophosphate insecticides (non-specific targets). Furthermore, we identified a fenitrothion-specific aptamer; FenA2, that can interact with Thioflavin T (ThT) to produce a label-free detection mode with a Kd of 33.57 nM (9.30 ppb) and LOD of 14 nM (3.88 ppb). Additionally, the FenA2 aptamer exhibited very low cross-reactivity with non-specific targets. This is the first report showing an aptamer sensor with a G4-quadruplex-like structure to detect fenitrothion. Moreover, these aptamers have the potential to be further developed into analytical tools for real-time detection of fenitrothion from a wide range of samples.

Glucocerebrosidase Deficiency in Drosophila Results in α-Synuclein-Independent Protein Aggregation and Neurodegeneration.

Mutations in the glucosidase, beta, acid (GBA1) gene cause Gaucher's disease, and are the most common genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) excluding variants of low penetrance. Because α-synuclein-containing neuronal aggregates are a defining feature of PD and DLB, it is widely believed that mutations in GBA1 act by enhancing α-synuclein toxicity. To explore this hypothesis, we deleted the Drosophila GBA1 homolog, dGBA1b, and compared the phenotypes of dGBA1b mutants in the presence and absence of α-synuclein expression. Homozygous dGBA1b mutants exhibit shortened lifespan, locomotor and memory deficits, neurodegeneration, and dramatically increased accumulation of ubiquitinated protein aggregates that are normally degraded through an autophagic mechanism. Ectopic expression of human α-synuclein in dGBA1b mutants resulted in a mild enhancement of dopaminergic neuron loss and increased α-synuclein aggregation relative to controls. However, α-synuclein expression did not substantially enhance other dGBA1b mutant phenotypes. Our findings indicate that dGBA1b plays an important role in the metabolism of protein aggregates, but that the deleterious consequences of mutations in dGBA1b are largely independent of α-synuclein. Future work with dGBA1b mutants should reveal the mechanism by which mutations in dGBA1b lead to accumulation of protein aggregates, and the potential influence of this protein aggregation on neuronal integrity.

Marijuana and Its Effects on Athletic Performance: A Systematic Review.

OBJECTIVE: To determine the effects of marijuana on athletic performance. DESIGN: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, AMED, and SPORTDiscus from their beginning to September 2016. Study quality was assessed using the Cochrane collaboration tool for assessing risk of bias and the Cochrane GRADE scale. No meta-analyses were performed for this review. SETTING: Subjects in a track, gym, or recreational ward. PARTICIPANTS: Any primary study which included male and female adults of any athletic background between ages 18 and 65, with no other comorbid conditions. INTERVENTIONS: Any primary study which used marijuana cigarettes and included a control group. MAIN OUTCOME MEASURES: Vital signs, pulmonary measures, physical work capacity, grip strength, and exercise duration were determined to be relevant outcomes. RESULTS: Three trials examined marijuana and its effects on athletic performance. Two trials had a high risk of bias and 1 trial had an unclear risk of bias. The effect of marijuana on outcomes including heart rate, blood pressure, and exercise duration remains unclear. Low quality evidence suggests that treatment, sham, and inactive control groups do not have a significant difference for grip strength. Low quality evidence suggests that there is an ergogenic effect of treatment demonstrated by increased bronchodilation and FEV1 compared with inactive control and that there is an ergolytic effect of treatment demonstrated by decreased physical work capacity compared with sham and inactive control groups. CONCLUSION: Because the number and quality of studies was low, the effects of marijuana on athletic performance remain unclear.

WITHDRAWN: Acupuncture for neck disorders.

BACKGROUND: Neck pain is one of the three most frequently reported complaints of the musculoskeletal system. Treatments for neck pain are varied, as are perceptions of benefit. Acupuncture has been used as an alternative to more conventional treatment for musculoskeletal pain. This review summarises the most current scientific evidence on the effectiveness of acupuncture for acute, subacute and chronic neck pain. This update replaces our 2006 Cochrane review update on this topic. OBJECTIVES: To determine the effects of acupuncture for adults with neck pain, with focus on pain relief, disability or functional measures, patient satisfaction and global perceived effect. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Manual, Alternative and Natural Therapy Index System (MANTIS), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Index to Chiropractic Literature (ICL) from their beginning to August 2015. We searched reference lists, two trial registers and the acupuncture database Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS) in China to 2005. SELECTION CRITERIA: We included published trials that used random assignment to intervention groups, in full text or abstract form. We excluded quasi-randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: Two review authors made independent decisions for each step of the review: article inclusion, data abstraction and assessment of quality of trial methods. We assessed study quality by using the Cochrane Back Review Group 'Risk of bias' tool. We used consensus to resolve disagreements, and when clinical heterogeneity was absent, we combined studies by using random-effects meta-analysis models. MAIN RESULTS: Of the 27 included studies, three represented individuals with whiplash-associated disorders (WADs) ranging from acute to chronic (205 participants), five explored chronic myofascial neck pain (186 participants), five chronic pain due to arthritic changes (542 participants), six chronic non-specific neck pain (4011 participants), two neck pain with radicular signs (43 participants) and six subacute or chronic mechanical neck pain (5111 participants).For mechanical neck pain, we found that acupuncture is beneficial at immediate-term follow-up compared with sham acupuncture for pain intensity; at short-term follow-up compared with sham or inactive treatment for pain intensity; at short-term follow-up compared with sham treatment for disability; and at short-term follow-up compared with wait-list control for pain intensity and neck disability improvement. Statistical pooling was appropriate for acupuncture compared with sham for short-term outcomes due to statistical homogeneity (P value = 0.83; I2 = 20%). Results of the meta-analysis favoured acupuncture (standardised mean difference (SMD) -0.23, 95% confidence interval (CI) -0.20 to -0.07; P value = 0.0006). This effect does not seem sustainable over the long term. Whether subsequent repeated sessions would be successful was not examined by investigators in our primary studies.Acupuncture appears to be a safe treatment modality, as adverse effects are minor. Reported adverse effects include increased pain, bruising, fainting, worsening of symptoms, local swelling and dizziness. These studies reported no life-threatening adverse effects and found that acupuncture treatments were cost-effective.Since the time of our previous review, the quality of RCTs has improved, and we have assessed many of them as having low risk of bias. However, few large trials have provided high-quality evidence. AUTHORS' CONCLUSIONS: Moderate-quality evidence suggests that acupuncture relieves pain better than sham acupuncture, as measured at completion of treatment and at short-term follow-up, and that those who received acupuncture report less pain and disability at short-term follow-up than those on a wait-list. Moderate-quality evidence also indicates that acupuncture is more effective than inactive treatment for relieving pain at short-term follow-up.

Acupuncture for neck disorders.

BACKGROUND: Neck pain is one of the three most frequently reported complaints of the musculoskeletal system. Treatments for neck pain are varied, as are perceptions of benefit. Acupuncture has been used as an alternative to more conventional treatment for musculoskeletal pain. This review summarises the most current scientific evidence on the effectiveness of acupuncture for acute, subacute and chronic neck pain. This update replaces our 2006 Cochrane review update on this topic. OBJECTIVES: To determine the effects of acupuncture for adults with neck pain, with focus on pain relief, disability or functional measures, patient satisfaction and global perceived effect. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Manual, Alternative and Natural Therapy Index System (MANTIS), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Index to Chiropractic Literature (ICL) from their beginning to August 2015. We searched reference lists, two trial registers and the acupuncture database Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS) in China to 2005. SELECTION CRITERIA: We included published trials that used random assignment to intervention groups, in full text or abstract form. We excluded quasi-randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: Two review authors made independent decisions for each step of the review: article inclusion, data abstraction and assessment of quality of trial methods. We assessed study quality by using the Cochrane Back Review Group 'Risk of bias' tool. We used consensus to resolve disagreements, and when clinical heterogeneity was absent, we combined studies by using random-effects meta-analysis models. MAIN RESULTS: Of the 27 included studies, three represented individuals with whiplash-associated disorders (WADs) ranging from acute to chronic (205 participants), five explored chronic myofascial neck pain (186 participants), five chronic pain due to arthritic changes (542 participants), six chronic non-specific neck pain (4011 participants), two neck pain with radicular signs (43 participants) and six subacute or chronic mechanical neck pain (5111 participants).For mechanical neck pain, we found that acupuncture is beneficial at immediate-term follow-up compared with sham acupuncture for pain intensity; at short-term follow-up compared with sham or inactive treatment for pain intensity; at short-term follow-up compared with sham treatment for disability; and at short-term follow-up compared with wait-list control for pain intensity and neck disability improvement. Statistical pooling was appropriate for acupuncture compared with sham for short-term outcomes due to statistical homogeneity (P value = 0.83; I(2) = 20%). Results of the meta-analysis favoured acupuncture (standardised mean difference (SMD) -0.23, 95% confidence interval (CI) -0.20 to -0.07; P value = 0.0006). This effect does not seem sustainable over the long term. Whether subsequent repeated sessions would be successful was not examined by investigators in our primary studies.Acupuncture appears to be a safe treatment modality, as adverse effects are minor. Reported adverse effects include increased pain, bruising, fainting, worsening of symptoms, local swelling and dizziness. These studies reported no life-threatening adverse effects and found that acupuncture treatments were cost-effective.Since the time of our previous review, the quality of RCTs has improved, and we have assessed many of them as having low risk of bias. However, few large trials have provided high-quality evidence. AUTHORS' CONCLUSIONS: Moderate-quality evidence suggests that acupuncture relieves pain better than sham acupuncture, as measured at completion of treatment and at short-term follow-up, and that those who received acupuncture report less pain and disability at short-term follow-up than those on a wait-list. Moderate-quality evidence also indicates that acupuncture is more effective than inactive treatment for relieving pain at short-term follow-up.

Crossover physics in the nonequilibrium dynamics of quenched quantum impurity systems.

A general framework is proposed to tackle analytically local quantum quenches in integrable impurity systems, combining a mapping onto a boundary problem with the form factor approach to boundary-condition-changing operators introduced by Lesage and Saleur [Phys. Rev. Lett. 80, 4370 (1998)]. We discuss how to compute exactly the following two central quantities of interest: the Loschmidt echo and the distribution of the work done during the quantum quench. Our results display an interesting crossover physics characterized by the energy scale T(b) of the impurity corresponding to the Kondo temperature. We discuss in detail the noninteracting case as a paradigm and benchmark for more complicated integrable impurity models and check our results using numerical methods.

Association between a medical school admission process using the multiple mini-interview and national licensing examination scores.

CONTEXT: There has been difficulty designing medical school admissions processes that provide valid measurement of candidates' nonacademic qualities. OBJECTIVE: To determine whether students deemed acceptable through a revised admissions protocol using a 12-station multiple mini-interview (MMI) outperform others on the 2 parts of the Canadian national licensing examinations (Medical Council of Canada Qualifying Examination [MCCQE]). The MMI process requires candidates to rotate through brief sequential interviews with structured tasks and independent assessment within each interview. DESIGN, SETTING, AND PARTICIPANTS: Cohort study comparing potential medical students who were interviewed at McMaster University using an MMI in 2004 or 2005 and accepted (whether or not they matriculated at McMaster) with those who were interviewed and rejected but gained entry elsewhere. The computer-based MCCQE part I (aimed at assessing medical knowledge and clinical decision making) can be taken on graduation from medical school; MCCQE part II (involving simulated patient interactions testing various aspects of practice) is based on the objective structured clinical examination and typically completed 16 months into postgraduate training. Interviews were granted to 1071 candidates, and those who gained entry could feasibly complete both parts of their licensure examination between May 2007 and March 2011. Scores could be matched on the examinations for 751 (part I) and 623 (part II) interviewees. INTERVENTION: Admissions decisions were made by combining z score transformations of scores assigned to autobiographical essays, grade point average, and MMI performance. Academic and nonacademic measures contributed equally to the final ranking. MAIN OUTCOME MEASURES: Scores on MCCQE part I (standardized cut-score, 390 [SD, 100]) and part II (standardized mean, 500 [SD, 100]). RESULTS: Candidates accepted by the admissions process had higher scores than those who were rejected for part I (mean total score, 531 [95% CI, 524-537] vs 515 [95% CI, 507-522]; P = .003) and for part II (mean total score, 563 [95% CI, 556-570] vs 544 [95% CI, 534-554]; P = .007). Among the accepted group, those who matriculated at McMaster did not outperform those who matriculated elsewhere for part I (mean total score, 524 [95% CI, 515-533] vs 546 [95% CI, 535-557]; P = .004) and for part II (mean total score, 557 [95% CI, 548-566] vs 582 [95% CI, 569-594]; P = .003). CONCLUSION: Compared with students who were rejected by an admission process that used MMI assessment, students who were accepted scored higher on Canadian national licensing examinations.

The Effect of Acupuncture on Hand and Wrist Pain Intensity, Functional Status, and Quality of Life in Adults: A Systematic Review.

Objective: This systematic review examined the effects of acupuncture on hand-and-wrist pain intensity, functional status, quality of life, and incidence of adverse effects in adults. Methods: Searches of 6 databases and previous reviews for randomized controlled trials (RCTs) were performed. Each outcome was analyzed for participant conditions, interventions, controls, and follow-up times determined a priori. Active controls were excluded. Follow-up periods were based on Cochrane 5.1.0 guidelines. The results were tabulated and described narratively. Results: In the 10 included RCTs (622 participants), 6 had a low risk of bias. For cryotherapy-induced pain, 1 trial showed significant pain reduction post treatment. For rheumatoid arthritis, 1 trial shown significant pain reduction and function improvements post treatment and short-term. For carpal tunnel syndrome, 1 trial showed significant pain reduction and functional improvements intermediate-term, while 3 trials suggested no significant difference. For tenosynovitis, 1 trial showed significant pain reduction and function improvements short-term. For poststroke impairments, 1 trial showed significant function improvements post treatment and at short-term, while another trial suggested no significant difference. No significant improvements were noted for trapezio-metacarpal joint osteoarthritis. In 2 trials, adverse effects occurred in patients with carpal tunnel syndrome; yet acupuncture appeared to be relatively safe. Conclusions: Acupuncture may be effective and safe for short-term pain reduction and functional improvement in hand-and-wrist conditions. Clinicians should interpret the results with caution due to small sample sizes and clinical heterogeneity. Future research is warranted.

Development of novel fluorescence-based and label-free noncanonical G4-quadruplex-like DNA biosensor for facile, specific, and ultrasensitive detection of fipronil.

Fipronil is a broad-spectrum insecticide widely used in agriculture and residential areas; its indiscriminate use leads to environmental pollution and poses health hazards. Early detection of fipronil is critical to prevent the deleterious effects. However, current insecticide analysis methods such as HPLC, LC/MS, and GC/MS are incompetent; they are costly, immobile, time-consuming, laborious, and need skilled technicians. Hence, a sensitive, specific, and cheap biosensor are essential to containing the contamination. Here, we designed two novel biosensors-the first design relied on fluorescent labeling/quenching, while the second sensor focused on label-free detection using Thioflavin T displacement. Altogether, we identified four candidate aptamers, predicted secondary structures, and performed 3D molecular modeling to predict the binding pocket of fipronil in FiPA6B aptamer. Furthermore, the aptameric sensors showed high sensitivity to fipronil of sub-ppb level LOD, attributed to stringent experimental design. The biosensors displayed high specificity against other phenylpyrazole insecticides and demonstrated robust sensitivity for fipronil in real samples like cabbage and cucumber. Notably, to the best of our knowledge, this is the first demonstration of noncanonical G4-quadruplex-like aptamer binding to fipronil, verified using CD spectroscopy. Such aptasensors possess considerable potential for real-time measurements of hazardous insecticides as point-of-care technology.

Identification and structural analysis of novel malathion-specific DNA aptameric sensors designed for food testing.

Malathion is an organophosphate chemical (OPC) and a toxic contaminant that adversely impacts food quality, human health, biodiversity, and the environment. Due to its small size and unavailability of sensitive sensors, detection of malathion remains a challenging task. Often chromatographic methods employed to analyze OPCs suffer from several shortcomings, including cost, immobility, laboriousness, and unsuitability for point-of-care settings. Hence, developing a specific and sensitive diagnostic sensor for quick and inexpensive food testing is essential. We discovered four unique malathion-specific ssDNA aptamers; designed two independent sensing strategies using fluorescence labeling and Thioflavin T (ThT) displacement. Selected aptamers formed the G4-quadruplex-like (G4Q) structure, which helped develop a label-free detection approach with a 2.01 ppb limit of detection. Additionally, 3D structures of aptamers were generated and validated using a series of computational modeling programs. Furthermore, we explored structural features using CD spectroscopy and molecular docking, probing ligands' binding mode, and revealed vital intermolecular interactions with aptamers. Subsequently, the novel sensors were optimized to detect malathion from food samples. The novel sensors could be further developed to meet the demands of sensing and quantifying toxic contaminants from real food samples in field conditions.

Engineering Novel Aptameric Fluorescent Biosensors for Analysis of the Neurotoxic Environmental Contaminant Insecticide Diazinon from Real Vegetable and Fruit Samples.

BACKGROUND: Diazinon is a widely used organophosphorus neurotoxic insecticide. It is a common environmental contaminant and a hazardous agri-waste. Its detection is critical to control entry into food systems and protect the environment. METHODS: In this study, three single-stranded DNA aptamers specific for diazinon were discovered using the systematic evolution of ligands by the exponential enrichment (SELEX) process. Since aptamer-based sensors are quick and straightforward to analyze, they could potentially replace the time-consuming and labor-intensive traditional methods used for diazinon detection. RESULTS: Here, we show the engineering of novel sensors for diazinon detection with a high affinity (Kd), specificity, and high sensitivity at the ppb level. Moreover, the aptamers were helpful in the simultaneous detection of two other structurally relevant insecticides, fenthion, and fenitrothion. Furthermore, the real vegetable and fruit samples confirmed the specific detection of diazinon using DIAZ-02. CONCLUSIONS: We developed novel biosensors and optimized the assay conditions for the detection of diazinon from food samples, such as vegetables and fruit. The biosensor could be adopted to analyze toxicants and contaminants in food, water, and nature as point-of-care technology.

Decaffeinated coffee and nicotine-free tobacco provide neuroprotection in Drosophila models of Parkinson's disease through an NRF2-dependent mechanism.

Epidemiological studies have revealed a significantly reduced risk of Parkinson's disease (PD) among coffee and tobacco users, although it is unclear whether these correlations reflect neuroprotective/symptomatic effects of these agents or preexisting differences in the brains of tobacco and coffee users. Here, we report that coffee and tobacco, but not caffeine or nicotine, are neuroprotective in fly PD models. We further report that decaffeinated coffee and nicotine-free tobacco are as neuroprotective as their caffeine and nicotine-containing counterparts and that the neuroprotective effects of decaffeinated coffee and nicotine-free tobacco are also evident in Drosophila models of Alzheimer's disease and polyglutamine disease. Finally, we report that the neuroprotective effects of decaffeinated coffee and nicotine-free tobacco require the cytoprotective transcription factor Nrf2 and that a known Nrf2 activator in coffee, cafestol, is also able to confer neuroprotection in our fly models of PD. Our findings indicate that coffee and tobacco contain Nrf2-activating compounds that may account for the reduced risk of PD among coffee and tobacco users. These compounds represent attractive candidates for therapeutic intervention in PD and perhaps other neurodegenerative diseases.

The Efficacy of Acupuncture on Foot and Ankle for Pain Intensity, Functional Status, and General Quality of Life in Adults: A Systematic Review.

Objective: To assess the effect of acupuncture on foot and ankle pain intensity, functional status, quality of life, and incidence of adverse events in adults. Methods: Randomized controlled trials (RCTs) were obtained from a systematic search of 6 major English databases, and a manual search of relevant systematic reviews using Google Scholar. RCTs that compared acupuncture with various forms of sham acupuncture, nonactive and waitlist controls for pain intensity, functional status, and general quality of life were included. Study screening, data extraction, risk of bias assessment, and quality assessment were all performed independently. A narrative synthesis was performed when quantitative pooling was inappropriate. Results: Four RCTs were included, encompassing a total of 211 participants. Due to clinical heterogeneity for all outcomes, quantitative analysis was not appropriate. Our Grades of Recommendation, Assessment, Development and Evaluation rated all outcomes to have either low or very low quality of evidence. With low-quality evidence, acupuncture was shown to be efficacious for participants with plantar fasciitis for pain relief and functional status improvement at short- and intermediate-term follow-ups. Acupuncture was also shown to be efficacious for participants with Achilles tendinopathy for pain relief at short- and intermediate-term follow-ups. No adverse events were reported. Conclusion: There is some evidence to suggest acupuncture to be a safe and efficacious treatment for relieving pain and improving functional status for the foot and ankle. The results of this systematic review should be interpreted with caution due to the limited evidence. Future research should take into consideration the findings of this systematic review.

Chinese herbal medicine for chronic neck pain due to cervical degenerative disc disease.

BACKGROUND: Chronic neck pain with radicular signs or symptoms is a common condition. Many patients use complementary and alternative medicine, including traditional Chinese medicine, to address their symptoms. OBJECTIVES: To assess the efficacy of Chinese herbal medicines in treating chronic neck pain with radicular signs or symptoms. SEARCH STRATEGY: We electronically searched CENTRAL (The Cochrane Library 2009, issue 3), MEDLINE, EMBASE, CINAHL and AMED (beginning to October 1, 2009), the Chinese Biomedical Database and related herbal medicine databases in Japan and South Korea (1979 to 2007). We also contacted content experts and handsearched a number of journals published in China. SELECTION CRITERIA: We included randomized controlled trials with adults with a clinical diagnosis of cervical degenerative disc disease, cervical radiculopathy or myelopathy supported by appropriate radiological findings. The interventions were Chinese herbal medicines, defined as products derived from raw or refined plants or parts of plants, minerals and animals that are used for medicinal purposes in any form. The primary outcome was pain relief, measured with a visual analogue scale, numeric scale or other validated tool. DATA COLLECTION AND ANALYSIS: The data were independently extracted and recorded by two review authors on a pre-developed form. Risk of bias and clinical relevance were assessed separately by two review authors using the twelve criteria and the five questions recommended by the Cochrane Back Review Group. Disagreements were resolved by consensus. MAIN RESULTS: All four included studies were in Chinese; two of which were unpublished. Effect sizes were not clinically relevant and there was low quality evidence for all outcomes due to study limitations and sparse data (single studies). Two trials (680 participants) found that Compound Qishe Tablets relieved pain better in the short-term than either placebo or Jingfukang; one trial (60 participants) found than an oral herbal formula of Huangqi ((Radix Astragali)18 g, Dangshen (Radix Codonopsis) 9 g, Sanqi (Radix Notoginseng) 9 g, Chuanxiong (Rhizoma Chuanxiong)12 g, Lujiao (Cornu Cervi Pantotrichum) 12 g, and Zhimu (Rhizoma Anemarrhenae)12 g) relieved pain better than Mobicox or Methycobal and one trial (360 participants) showed that a topical herbal medicine, Compound Extractum Nucis Vomicae, relieved pain better than Diclofenac Diethylamine Emulgel. AUTHORS' CONCLUSIONS: There is low quality evidence that an oral herbal medication, Compound Qishe Tablet, reduced pain more than placebo or Jingfukang and a topical herbal medicine, Compound Extractum Nucis Vomicae, reduced pain more than Diclofenac Diethylamine Emulgel. Further research is very likely to change both the effect size and our confidence in the results.

Effect of erythropoietin on athletic performance: a systematic review and meta-analysis.

INTRODUCTION: Athletes have attempted to glean the ergogenic benefits of recombinant human erythropoietin (rHuEPO) since it became available in the 1980s. However, there is limited consensus in the literature regarding its true performance-enhancing effects. In fact, some studies suggest there is no conclusive evidence; therefore, it is necessary to evaluate and quantify the strength of the evidence. OBJECTIVE: To determine the effects of erythropoietin on enhancing athletic performance. DESIGN: At least two independent reviewers conducted citation identification through abstract and full-text screening, and study selection, and extracted raw data on demographics, descriptions of interventions and all outcomes to predesigned abstraction forms. Outcomes were stratified by treatment periods and dosages. Study quality was assessed using the Cochrane Risk of Bias Tool and Cochrane Grading of Recommendations Assessment Development and Education (GRADE) scale. Where appropriate, quantitative analysis was performed. DATA SOURCES: EMBASE, MEDLINE and SPORTDiscus were searched from their inception to January 2020. ELIGIBILITY CRITERIA: Trials that examined any enhancement in sport in healthy participants aged 18-65 using rHuEPO compared with placebo were included. RESULTS: Overall, there is low-to-moderate quality evidence suggesting rHuEPO may be more beneficial than placebo in enhancing haematological parameters, pulmonary measures, maximal power output and time to exhaustion independent of dosage. However, these improvements are almost exclusively seen during maximal exercise intensities, which may be less relevant to athletic competition conditions. CONCLUSION: Due to heterogeneity among trials, more high-quality randomised controlled trials with larger sample sizes in conditions that mirror actual competition are needed to further elucidate these effects.

Induction of the phase II detoxification pathway suppresses neuron loss in Drosophila models of Parkinson's disease.

Alpha-synuclein aggregates are a common feature of sporadic Parkinson's disease (PD), and mutations that increase alpha-synuclein abundance confer rare heritable forms of PD. Although these findings suggest that alpha-synuclein plays a central role in the pathogenesis of this disorder, little is known of the mechanism by which alpha-synuclein promotes neuron loss or the factors that regulate alpha-synuclein toxicity. To address these matters, we tested candidate modifiers of alpha-synuclein toxicity using a Drosophila model of PD. In the current work, we focused on phase II detoxification enzymes involved in glutathione metabolism. We find that the neuronal death accompanying alpha-synuclein expression in Drosophila is enhanced by loss-of-function mutations in genes that promote glutathione synthesis and glutathione conjugation. This neuronal loss can be overcome by genetic or pharmacological interventions that increase glutathione synthesis or glutathione conjugation activity. Moreover, these same pharmacological agents suppress neuron loss in Drosophila parkin mutants, a loss-of-function model of PD. Our results suggest that oxidative stress is a feature of alpha-synuclein toxicity and that induction of the phase II detoxification pathway represents a potential preventative therapy for PD.

Predictive validity of the multiple mini-interview for selecting medical trainees.

INTRODUCTION: In this paper we report on further tests of the validity of the multiple mini-interview (MMI) selection process, comparing MMI scores with those achieved on a national high-stakes clinical skills examination. We also continue to explore the stability of candidate performance and the extent to which so-called 'cognitive' and 'non-cognitive' qualities should be deemed independent of one another. METHODS: To examine predictive validity, MMI data were matched with licensing examination data for both undergraduate (n = 34) and postgraduate (n = 22) samples of participants. To assess the stability of candidate performance, reliability coefficients were generated for eight distinct samples. Finally, correlations were calculated between 'cognitive' and 'non-cognitive' measures of ability collected in the admissions procedure, on graduation from medical school and 18 months into postgraduate training. RESULTS: The median reliability of eight administrations of the MMI in various cohorts was 0.73 when 12 10-minute stations were used with one examiner per station. The correlation between performance on the MMI and number of stations passed on an objective structured clinical examination-based licensing examination was r = 0.43 (P < 0.05) in a postgraduate sample and r = 0.35 (P < 0.05) in an undergraduate sample of subjects who sat the MMI 5 years prior to sitting the licensing examination. The correlation between 'cognitive' and 'non-cognitive' assessment instruments increased with time in training (i.e. as the focus of the assessments became more tailored to the clinical practice of medicine). DISCUSSION: Further evidence for the validity of the MMI approach to making admissions decisions has been provided. More generally, the reported findings cast further doubt on the extent to which performance can be captured with trait-based models of ability. Finally, although a complementary predictive relationship has consistently been observed between grade point average and MMI results, the extent to which cognitive and non-cognitive qualities are distinct appears to depend on the scope of practice within which the two classes of qualities are assessed.