Chikungunya infection in returned travellers: results from the geosentinel network, 2005-2020.

BACKGROUND: Chikungunya is an important travel-related disease because of its rapid geographical expansion and potential for prolonged morbidity. Improved understanding of the epidemiology of travel-related chikungunya infections may influence prevention strategies including education and vaccination. METHODS: We analysed data from travellers with confirmed or probable chikungunya reported to GeoSentinel sites from 2005 to 2020. Confirmed chikungunya was defined as a compatible clinical history plus either virus isolation, positive nucleic acid test or seroconversion/rising titre in paired sera. Probable chikungunya was defined as a compatible clinical history with a single positive serology result. RESULTS: 1202 travellers (896 confirmed and 306 probable) with chikungunya were included. The median age was 43 years (range 0-91; interquartile range [IQR]: 31-55); 707 (58.8%) travellers were female. Most infections were acquired in the Caribbean (28.8%), Southeast Asia (22.8%), South Central Asia (14.2%) and South America (14.2%). The highest numbers of chikungunya cases reported to GeoSentinel were in 2014 (28.3%), 2015 (14.3%) and 2019 (11.9%). The most frequent reasons for travel were tourism (n = 592; 49.3%) and visiting friends or relatives (n = 334; 27.7%). The median time to presentation to a GeoSentinel site was 23 days (IQR: 7-52) after symptom onset. In travellers with confirmed chikungunya and no other reported illnesses, the most frequently reported symptoms included musculoskeletal symptoms (98.8%), fever/chills/sweats (68.7%) and dermatologic symptoms (35.5%). Among 917 travellers with information available, 296 (32.3%) had a pretravel consultation. CONCLUSIONS: Chikungunya was acquired by international travellers in almost 100 destinations globally. Vector precautions and vaccination where recommended should be integrated into pretravel visits for travellers going to areas with chikungunya or areas with the potential for transmission. Continued surveillance of travel-related chikungunya may help public health officials and clinicians limit the transmission of this potentially debilitating disease by defining regions where protective measures (e.g. pretravel vaccination) should be strongly considered.

Intestinal protozoa in returning travellers: a GeoSentinel analysis from 2007 to 2019.

BACKGROUND: Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. METHODS: We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. RESULTS: There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. CONCLUSIONS: This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.

Brazilin-Ce nanoparticles attenuate inflammation by de/anti-phosphorylation of IKKß.

Inflammation is associated with a series of diseases like cancer, cardiovascular disease and infection, and phosphorylation/dephosphorylation modification of proteins are important in inflammation regulation. Here we designed and synthesized a novel Brazilin-Ce nanoparticle (BX-Ce NPs) using Brazilin, which has been used for anti-inflammation in cardiovascular diseases but with narrow therapeutic window, and Cerium (IV), a lanthanide which has the general activity in catalyzing the hydrolysis of phosphoester bonds, to conferring de/anti-phosphorylation of IKKß. We found that BX-Ce NPs specifically bound to Asn225 and Lys428 of IKKß and inhibited its phosphorylation at Ser181, contributing to appreciably anti-inflammatory effect in cellulo (IC50 = 2.5 µM). In vivo mouse models of myocardial infarction and sepsis also showed that the BX-Ce NPs significantly ameliorated myocardial injury and improved survival in mice with experimental sepsis through downregulating phosphorylation of IKKß. These findings provided insights for developing metal nanoparticles for guided ion interfere therapy, particularly synergistically target de/anti-phosphorylation as promising therapeutic agents for inflammation and related diseases.

Dual effects of extra virgin olive oil in acute wounds.

Extra virgin olive oil (EVOO) has proved beneficial effects in skin wound healing of chronic lesions; however, the effects of EVOO in acute wounds are not completely understood. This study investigated the effects of short-term and long-term administration of a diet rich in EVOO on acute wound healing. To check this, mice were fed with a diet rich in EVOO for 1 week (short term), 1 month, or 3 months (long term). The control group received a standard diet. Mouse macrophages were treated in vitro with EVOO or hydroxytyrosol (HT), which is the main EVOO polyphenol. Short-term administration of an EVOO rich diet in vivo increased lipid peroxidation and mRNA levels of pro-inflammatory cytokine levels and impaired acute wound closure. In contrast, long-term administration of an EVOO rich diet resulted in increased mRNA levels of anti-inflammatory cytokines and enhanced acute wound closure. In both in vivo and in vitro assays, the administration of EVOO or HT resulted in a predominantly anti-inflammatory macrophage phenotype. In conclusion, a diet rich in EVOO has a positive effect on acute wound healing that is dependent on the duration of EVOO administration. Short-term EVOO diet supplementation increases oxidative damage and pro-inflammatory responses, which impaired acute wound closure. On the other hand, long-term EVOO supplementation reduces oxidative damage and enhances anti-inflammatory responses, which improved acute wound closure. The effects of EVOO on oxidation and inflammation in acute wounds are linked to the EVOO polyphenol HT.

Olive oil promotes the survival and migration of dermal fibroblasts through Nrf2 pathway activation.

Olive oil has beneficial effects on skin wound healing due to its anti-inflammatory and antioxidant properties; however, the mechanism by which olive oil promotes wound healing is unclear. We evaluated the mechanisms involved in Nrf2 pathway activation by olive oil and its role in cell survival and migration in mouse dermal fibroblasts in a short-term exposition. Our data demonstrated that olive oil and oleic acid promoted reactive oxygen species (ROS) production, while olive oil and hydroxytyrosol stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Olive oil-mediated ROS production increased nuclear factor kappa B p65 expression, while olive oil-stimulated reactive nitrogen species production augmented the levels of Nrf2. Olive oil augmented cell proliferation, cell migration, and AKT phosphorylation, but decreased apoptotic cell number and cleaved caspase-3 levels. The effect of olive oil on cell migration and protein levels of AKT, BCL-2, and Nrf2 were reversed by an Nrf2 inhibitor. In conclusion, the activation of the Nrf2 pathway by olive oil promotes the survival and migration of dermal fibroblasts that are essential for the resolution of skin wound healing.

Comparative transcriptomics analysis reveals a calcineurin B-like gene to positively regulate constitutive and acclimated freezing tolerance in potato.

Freezing stress is a major limiting factor in crop production. To increase frost-hardiness of crops via breeding, deciphering the genes conferring freezing-tolerance is vital. Potato cultivars (Solanum tuberosum) are generally freezing-sensitive, but some potato wild species are freezing-tolerant, including Solanum commersonii, Solanum malmeanum and Solanum acaule. However, the underlying molecular mechanisms conferring the freezing-tolerance to the wild species remain to be deciphered. In this study, five representative genotypes of the above-mentioned species with distinct freezing-tolerance were investigated. Comparative transcriptomics analysis showed that SaCBL1-like (calcineurin B-like protein) was upregulated substantially in all of the freezing-tolerant genotypes. Transgenic overexpression and known-down lines of SaCBL1-like were examined. SaCBL1-like was shown to confer freezing-tolerance without significantly impacting main agricultural traits. A functional mechanism analysis showed that SaCBL1-like increases the expression of the C-repeat binding factor-regulon as well as causes a prolonged higher expression of CBF1 after exposure to cold conditions. Furthermore, SaCBL1-like was found to only interact with SaCIPK3-1 (CBL-interacting protein kinase) among all apparent cold-responsive SaCIPKs. Our study identifies SaCBL1-like to play a vital role in conferring freezing tolerance in potato, which may provide a basis for a targeted potato breeding for frost-hardiness.

Alum Addition Triggers Hypoxia in an Engineered Pit Lake.

Here, we examine the geobiological response to a whole-lake alum (aluminum sulfate) treatment (2016) of Base Mine Lake (BML), the first pilot-scale pit lake established in the Alberta oil sands region. The rationale for trialing this management amendment was based on its successful use to reduce internal phosphorus loading to eutrophying lakes. Modest increases in water cap epilimnetic oxygen concentrations, associated with increased Secchi depths and chlorophyll-a concentrations, were co-incident with anoxic waters immediately above the fluid fine tailings (FFT) layer post alum. Decreased water cap nitrate and detectable sulfide concentrations, as well as increased hypolimnetic phospholipid fatty acid abundances, signaled greater anaerobic heterotrophic activity. Shifts in microbial community to groups associated with greater organic carbon degradation (i.e., SAR11-LD12 subclade) and the SRB group Desulfuromonodales emerged post alum and the loss of specialist groups associated with carbon-limited, ammonia-rich restricted niches (i.e., MBAE14) also occurred. Alum treatment resulted in additional oxygen consumption associated with increased autochthonous carbon production, watercap anoxia and sulfide generation, which further exacerbate oxygen consumption associated with on-going FFT mobilized reductants. The results illustrate the importance of understanding the broader biogeochemical implications of adaptive management interventions to avoid unanticipated outcomes that pose greater risks and improve tailings reclamation for oil sands operations and, more broadly, the global mining sector.

Effects of Rehmannia glutinosa polysaccharides on bone tissue structure and skeletal muscle atrophy in rats with disuse.

PURPOSE: To study effects of Rehmannia glutinosa polysaccharides (RGP) on bone tissue structure and skeletal muscle atrophy in rats with disuse. METHODS: A rat model of disuse osteoporosis combined with muscle atrophy was established by removing the bilateral ovaries of rats and fixing their hind limbs for a long time. Forty SD rats were administered intragastrically for 12 weeks. The bone histomorphometry parameters and the level of oxidative stress were measured. In addition, the changes of muscle atrophy F-box (MAFbx), muscle RING-finger protein-1 (MuRF1), forkhead box O1 (FOXO1) mRNA expression in skeletal muscle of rats were observed. RESULTS: RGP significantly increased the percentage of fluorescence perimeter and bone mineralization deposition rate of the second lumbar vertebrae of rats. It also significantly increased the wet weight ratio and muscle fiber cross-sectional area of the gastrocnemius muscle of rats. At the same time, RGP significantly increased the levels of super oxide dismutase (SOD) and catalase (CAT) in the skeletal muscle of rats, and reduced the content of malondialdehyde (MDA). Rehmannia glutinosa polysaccharides also significantly reduced the expression levels of FOXO1, MAFbx and MuRF1 mRNA in rat skeletal muscle. CONCLUSIONS: RGP could improve the bone structure of osteoporotic rats. It could also improve muscle that atrophy may be related to the inhibition of FOXO1-mediated ubiquitin-proteasome pathway.

Hypericin-mediated photodynamic therapy inhibits growth of colorectal cancer cells via inducing S phase cell cycle arrest and apoptosis.

Colorectal cancer (CRC) is one type of cancer with high morbidity and mortality worldwide. Photodynamic therapy (PDT), a promising new therapeutic approach for cancer, induces tumor damage through photosensitizer-mediated oxidative cytotoxicity. Hypericin is a powerful photosensitizer with pronounced tumor-localizing properties. In this study, we investigated the phototoxic effects of hypericin-mediated PDT (HYP-PDT) in HCT116 and SW620 cells. We validated that HYP-PDT inhibited cell proliferation, triggered intracellular reactive oxygen species generation, induced S phase cell cycle arrest and apoptosis of HCT116 and SW620 cells. Mechanistically, the results of western blot showed that HYP-PDT downregulated CDK2 expression through decreasing the CDC25A protein, which resulted in the decrease of CDK2/Cyclin A complex. Additionally, HYP-PDT induced DNA damage as evidenced by ATM activation and upregulation of p-H2AX. Further investigation showed that HYP-PDT significantly increased Bax expression and decreased Bcl-2 expression, and then, upregulated the expression of cleaved caspase-9, cleaved caspase-3 and cleaved PARP, thereby inducing apoptosis in HCT116 and SW620 cells. In conclusion, our results indicated that the CDC25A/CDK2/Cyclin A pathway and the mitochondrial apoptosis pathway were involved in HYP-PDT induced S phase cell cycle arrest and apoptosis in colorectal cancer cells, which shows HYP could be a probable candidate used for treating colorectal cancer.

Dermal fibroblast phagocytosis of apoptotic cells: A novel pathway for wound resolution.

The effective clearance of apoptotic cells is an essential step in the resolution of healing wounds. In particular, blood vessel regression during wound resolution produces a significant number of apoptotic endothelial cells (ApoEC) that must be cleared. In considering the fate of ApoEC and the presence of fibroblasts during wound resolution, we hypothesized that fibroblasts might serve as phagocytes involved in endothelial cell removal. The current study investigated whether dermal fibroblasts engulf ApoEC, whether this uptake alters the phenotype of dermal fibroblasts, and the biological molecules involved. In both in vitro and in vivo studies, following ApoEC engulfment, fibroblasts acquired a pro-healing phenotype (increased cell migration, contractility, α-smooth muscle actin expression, and collagen deposition). In addition, fibroblast uptake of ApoEC was shown to be mediated in part by the milk fat globule-EGF factor 8 protein/integrin αv ß5 pathway. Our study demonstrates a novel function of fibroblasts in the clearance of ApoEC and suggests that this capability has significant implications for tissue repair and fibrosis.

Effects of Rehmannia glutinosa polysaccharides on bone tissue structure and skeletal muscle atrophy in rats with disuse

ABSTRACT Purpose To study effects of Rehmannia glutinosa polysaccharides (RGP) on bone tissue structure and skeletal muscle atrophy in rats with disuse. Methods A rat model of disuse osteoporosis combined with muscle atrophy was established by removing the bilateral ovaries of rats and fixing their hind limbs for a long time. Forty SD rats were administered intragastrically for 12 weeks. The bone histomorphometry parameters and the level of oxidative stress were measured. In addition, the changes of muscle atrophy F-box (MAFbx), muscle RING-finger protein-1 (MuRF1), forkhead box O1 (FOXO1) mRNA expression in skeletal muscle of rats were observed. Results RGP significantly increased the percentage of fluorescence perimeter and bone mineralization deposition rate of the second lumbar vertebrae of rats. It also significantly increased the wet weight ratio and muscle fiber cross-sectional area of the gastrocnemius muscle of rats. At the same time, RGP significantly increased the levels of super oxide dismutase (SOD) and catalase (CAT) in the skeletal muscle of rats, and reduced the content of malondialdehyde (MDA). Rehmannia glutinosa polysaccharides also significantly reduced the expression levels of FOXO1, MAFbx and MuRF1 mRNA in rat skeletal muscle. Conclusions RGP could improve the bone structure of osteoporotic rats. It could also improve muscle that atrophy may be related to the inhibition of FOXO1-mediated ubiquitin-proteasome pathway.

Improvement of full-thickness rat skin wounds by photobiomodulation therapy (PBMT): A dosimetric study.

Basic dosimetric studies are necessary to support the use of photobiomodulation therapy (PBMT), since the great variety of laser parameters that are reported in the literature have created an obstacle to identifying reproducible results. Thus, the present study evaluates the process of tissue repair after the photobiomodulation therapy, taking into consideration the dose, frequency and the mode of energy delivery used. For this, 6 mm diameter wounds were created on dorsal skin of Wistar rats, and the animals were divided in control and irradiated groups, where L1 and L4 (irradiated with 1 point of 10 J/cm2), L2 and L5 (5 points of 10 J/cm2), L3 and L6 (1 point of 50 J/cm2), respectively for one or multiple days of irradiations. A diode laser, λ 660 nm, 40 mW of power and 0.028 cm2 of spot area was used. Our data showed that the group receiving multiple treatments over the first week post wounding, applied at 10 J/cm2 at each of 5 points on and around the wound (group L5) presented the best improvement of wound closure, higher cytokeratin 10, lower macrophage infiltration, and greater tissue resistance to rupture. We conclude that PBMT improves the skin wound healing process, and the outcomes were directly related to the chosen laser parameters and irradiation mode.

Tai Chi exercise and functional electrical stimulation of lower limb muscles for rehabilitation in older adults with chronic systolic heart failure: a non-randomized clinical trial.

Exercise-based training decreases hospitalizations in heart failure patients but such patients have exercise intolerance. The objectives of the study were to evaluate the effect of 12 weeks of Tai Chi exercise and lower limb muscles' functional electrical stimulation in older chronic heart failure adults. A total of 1,084 older adults with chronic systolic heart failure were included in a non-randomized clinical trial (n=271 per group). The control group did not receive any kind of intervention, one group received functional electrical stimulation of lower limb muscles (FES group), another group practiced Tai Chi exercise (TCE group), and another received functional electrical stimulation of lower limb muscles and practiced Tai Chi exercise (FES & TCE group). Quality of life and cardiorespiratory functions of all patients were evaluated. Compared to the control group, only FES group had increased Kansas City Cardiomyopathy Questionnaire (KCCQ) score (P<0.0001, q=9.06), only the TCE group had decreased heart rate (P<0.0001, q=5.72), and decreased peak oxygen consumption was reported in the TCE group (P<0.0001, q=9.15) and FES & TCE group (P<0.0001, q=10.69). FES of lower limb muscles and Tai Chi exercise can recover the quality of life and cardiorespiratory functions of older chronic heart failure adults (trial registration: Research Registry 4474, January 1, 2015).

Diagnosed Sleep Apnea and Cardiovascular Disease in Atrial Fibrillation Patients: The Role of Measurement Error from Administrative Data.

BACKGROUND: Atrial fibrillation and obstructive sleep apnea are common conditions, but little is known about obstructive sleep apnea and cardiovascular risk among atrial fibrillation patients. METHODS: Using the Truven Health MarketScan databases, we constructed a prospective cohort of atrial fibrillation patients from 2007 to 2014. Atrial fibrillation, obstructive sleep apnea, stroke, myocardial infarction, and confounders were defined using the International Classification of Disease-9-CM codes. We matched individuals with an obstructive sleep apnea diagnosis with up to five individuals without a diagnosis by age, sex, and enrollment date. Cox proportional hazards models adjusted for confounders and high-dimensional propensity scores. We included migraines as a control outcome. Bias analysis used published sensitivities and specificities to generate rate ratios adjusted for obstructive sleep apnea misclassification. RESULTS: We matched 56,969 individuals with an obstructive sleep apnea diagnosis to 323,246 without. During a mean follow-up of 16 months, 3234 incident strokes and 4639 incident myocardial infarctions occurred. After adjustment, obstructive sleep apnea diagnosis was strongly associated with reduced risk of incident stroke (hazard ratio = 0.48, 95% confidence interval = 0.43, 0.53) and myocardial infarction (0.40, [0.37, 0.44]) and a smaller reduced risk of migraines (0.82, [0.68, 0.99]). Bias analysis produced wide-ranging or inestimable rate ratios adjusted for misclassification of obstructive sleep apnea. CONCLUSIONS: Obstructive sleep apnea diagnosis in atrial fibrillation patients was strongly associated with reduced risk of incident cardiovascular disease. We discuss misclassification, selection bias, and residual confounding as potential explanations.

7.0T ultrahigh-field MRI directly visualized the pedunculopontine nucleus in Parkinson's disease patients.

OBJECTIVES: The pedunculopontine nucleus (PPN) is considered a promising new target for neurostimulation in Parkinson's disease (PD) patients with postural instability and gait disturbance that is refractory to other treatment modalities. However, the PPN is typically difficult to visualize with magnetic resonance imaging (MRI) at clinical field strengths, which greatly limits the PPN as a viable surgical target for deep brain stimulation (DBS). Thus, the aim of this study is to directly visualize the PPN based on 7.0T ultrahigh-field MRI. METHODS: Five PD patients were enrolled and scanned using the MP2RAGE sequence on a 7.0T ultrahigh-field MRI scanner. Then, the MP2RAGE sequences were imported into a commercially available navigation system. The coordinates of the directly localized PPN poles were recorded in the navigation system relative to the anterior commissure-posterior commissure plane. RESULTS: Our results indicated that the PPN presented intermediate signal intensity in the 7.0T ultrahigh-field MR images in comparison with the surrounding structure, such as the hypo-intensity of the periaqueductal gray and the hyperintensity of the neighboring white matter tracts, in PD patients. The mean coordinates for the rostral and caudal poles of PPN were 6.50 mm and 7.20 mm lateral, 1.58 mm and 2.21 mm posterior, and 8.89 mm and 13.83 mm relative to the posterior commissure. CONCLUSION: Our findings provide, for the first time, direct visualization of the PPN using the MP2RAGE sequence on a 7.0T ultrahigh-field MRI, which may improve the accuracy of stereotactic targeting of the PPN and improve the outcomes in patients undergoing DBS.

Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis.

Tumor necrosis factor-alpha (TNF-α) plays an important role in autoimmune diseases. Previous studies have investigated the association of TNF-α-238G/A (rs361525) and -308G/A (rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, no agreed conclusion had been made. Therefore, this meta-analysis was conducted to assess the associations of TNF-α-238G/A and -308G/A polymorphisms with RA and SLE risk. A systematic search was conducted in commonly used databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were included. In the overall population, the TNF-α-238A allele was observed to be a protective factor for RA (A vs G: OR=0.75, 95%CI=0.57-0.99, P=0.040) and the TNF-α-308A allele was found to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45-2.19, P<0.001). However, no evidence of association was found between TNF-α-238 G/A polymorphism and SLE nor between -308G/A and RA. In the subgroup analysis, TNF-α-308A allele played a pathogenic role for RA in Latin Americans (A vs G: OR=1.46, 95%CI=1.15-1.84, P=0.002) and for SLE in Latin Americans (A vs G: OR=2.12, 95%CI=1.32-3.41, P=0.002) and Europeans (A vs G: OR=2.03, 95%CI=1.56-2.63, P<0.001), while it played a protective role for RA in Asians (A vs G: OR=0.54, 95%CI=0.32-0.90, P=0.017). No significant association was found between TNF-α-308G/A and SLE susceptibility in Africans and Asians. This meta-analysis demonstrated that TNF-α-238A was associated with decreased risk of RA rather than SLE, while -308G/A polymorphism was associated with SLE rather than RA. Stratification analysis indicated that different ethnicities would have different risk alleles.

What's Old Is New Again: The Re-emergence of Yellow Fever in Brazil and Vaccine Shortages.

Yellow fever outbreaks have continued to occur and caused infection and deaths in travelers from non-endemic regions. Yellow fever vaccine has proven effective, but vaccination decisions require balancing benefits with risks. Of concern is the continued vaccine shortage worldwide, including of the YF-VAX® stockout in North America, which has presented many challenges.

Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis

Tumor necrosis factor-alpha (TNF-α) plays an important role in autoimmune diseases. Previous studies have investigated the association of TNF-α-238G/A (rs361525) and -308G/A (rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, no agreed conclusion had been made. Therefore, this meta-analysis was conducted to assess the associations of TNF-α-238G/A and -308G/A polymorphisms with RA and SLE risk. A systematic search was conducted in commonly used databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were included. In the overall population, the TNF-α-238A allele was observed to be a protective factor for RA (A vs G: OR=0.75, 95%CI=0.57-0.99, P=0.040) and the TNF-α-308A allele was found to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45-2.19, P<0.001). However, no evidence of association was found between TNF-α-238 G/A polymorphism and SLE nor between -308G/A and RA. In the subgroup analysis, TNF-α-308A allele played a pathogenic role for RA in Latin Americans (A vs G: OR=1.46, 95%CI=1.15-1.84, P=0.002) and for SLE in Latin Americans (A vs G: OR=2.12, 95%CI=1.32-3.41, P=0.002) and Europeans (A vs G: OR=2.03, 95%CI=1.56-2.63, P<0.001), while it played a protective role for RA in Asians (A vs G: OR=0.54, 95%CI=0.32-0.90, P=0.017). No significant association was found between TNF-α-308G/A and SLE susceptibility in Africans and Asians. This meta-analysis demonstrated that TNF-α-238A was associated with decreased risk of RA rather than SLE, while -308G/A polymorphism was associated with SLE rather than RA. Stratification analysis indicated that different ethnicities would have different risk alleles.

7. 0T ultrahigh-field MRI directly visualized the pedunculopontine nucleus in Parkinson's disease patients

OBJECTIVES: The pedunculopontine nucleus (PPN) is considered a promising new target for neurostimulation in Parkinson's disease (PD) patients with postural instability and gait disturbance that is refractory to other treatment modalities. However, the PPN is typically difficult to visualize with magnetic resonance imaging (MRI) at clinical field strengths, which greatly limits the PPN as a viable surgical target for deep brain stimulation (DBS). Thus, the aim of this study is to directly visualize the PPN based on 7.0T ultrahigh-field MRI. METHODS: Five PD patients were enrolled and scanned using the MP2RAGE sequence on a 7.0T ultrahigh-field MRI scanner. Then, the MP2RAGE sequences were imported into a commercially available navigation system. The coordinates of the directly localized PPN poles were recorded in the navigation system relative to the anterior commissure-posterior commissure plane. RESULTS: Our results indicated that the PPN presented intermediate signal intensity in the 7.0T ultrahigh-field MR images in comparison with the surrounding structure, such as the hypo-intensity of the periaqueductal gray and the hyperintensity of the neighboring white matter tracts, in PD patients. The mean coordinates for the rostral and caudal poles of PPN were 6.50 mm and 7.20 mm lateral, 1.58 mm and 2.21 mm posterior, and 8.89 mm and 13.83 mm relative to the posterior commissure. CONCLUSION: Our findings provide, for the first time, direct visualization of the PPN using the MP2RAGE sequence on a 7.0T ultrahigh-field MRI, which may improve the accuracy of stereotactic targeting of the PPN and improve the outcomes in patients undergoing DBS.