Clinicians' beliefs and attitudes to physical activity and exercise therapy as treatment for knee and/or hip osteoarthritis: a scoping review.

OBJECTIVE: To explore clinicians' attitudes and beliefs about physical activity and exercise therapy as treatment for individuals with knee and/or hip osteoarthritis (OA). METHOD: This was a scoping review, mapping available knowledge about the topic derived from qualitative research designs and methods. A comprehensive search of selected databases (MEDLINE, EMBASE; CINAHL; Web of Science) was conducted and data were analysed thematically. RESULTS: Twelve articles met inclusion criteria. Thematic analysis identified three interrelated main themes: 1) Understandings of OA and its trajectory and management; 2) Attitudes to activity and exercise as part of OA management; 3) Clinicians' perceived knowledge of and expertise in OA management. Findings highlight that many clinicians involved in knee/hip OA management, particularly general practitioners and physiotherapists, perceive OA to be a low priority 'wear-and-tear' disease with expected progression of symptoms, making joint replacement surgery eventually inevitable. Further, many clinicians appear to lack knowledge about and interest in physical activity and exercise therapy in the management of knee/hip OA, and seem to show uncertainty about the effectiveness and safety of physical activity and exercise therapy on joint health. CONCLUSION: Clinicians' attitudes and beliefs about physical activity and exercise therapy in OA seem to reflect an outdated narrative which describes OA as a wear-and-tear disease with inevitable disease progression to joint replacement surgery. Clinicians need to adopt a contemporary narrative, which accurately reflects current knowledge and evidence-based practice, thereby ensuring consistent utilisation of exercise therapy as first-line care as recommended in OA guidelines.

[Occupational stress of air traffic controllers and its influencing factors].

Objective: To investigate the occupational stress status of air traffic controllers (ATC) and analyze its influencing factors. Methods: By using cluster sampling method, 457 ATCs in an air traffic management bureau were selected as the investigation objects. The job content questionnaire (JCQ) and the effort reward imbalance questionnaire (ERI) were used to measure work requirements independent imbalance type and ERI type occupational stress separately and analyze the influencing factors. Results: Of the 457 ATCs, 81.84% (374/457) ATGs had work requirements independent imbalance type of occupational stress and 84.46% (386/457) ATGs had ERI type occupational stress. Univariate analysis showed that the factors of marital status, degree of education, age, length of service, title, job post, family monthly income, views on regular training, occurrence of emergency or unsafe events in last month and monthly night shift frequency had various degrees of influence on the different factor scores of JCQ and ERI (P<0.01) . Logistic regression analysis showed that the level of JCQ type occupational stress of ATCs with junior titles and probationers was higher than those of intermediate/senior titles (P=0.000, 0.000) ; The ERI type occupational stress of probationers and junior titles ATCs was lower than those with intermediate/senior titles (P=0.000) . The ERI and JCQ type occupational stress level of tower post ATCs was higher than that of other two job post ATCs (P=0.001, 0.000, 0.000, 0.000) . The ATCs considering regular training had more disadvantages than advantages showed lower ERI type occupational stress level than those considering more advantages than disadvantages (P=0.000) . The ERI type occupational stress level of ATCs who experienced emergency or unsafe events in last month was higher than those who didn't (P=0.007) . Conclusion: A large proportion of ATCs had occupational stress. Management should adjust its policies and pay were attention to occupational stress of ATLs.

[Research progress on occupational hazard factors of civil aviation employees].

In this paper, the related research on occupational hazards of civil aviation employees at home and abroad is reviewed, and the effects of noise, radioactivity, harmful gas, bad posture, occupational stress, fatigue and many other factors on the health of civil aviation employees are summarized. This paper describes the characteristics of occupational hazard factors and their effects on the health of civil aviation employees in order to provide a basis for the management of civil aviation related units to control occupational hazard factors. The occupational health problems of civil aviation employees need to be paid attention to and managed.

Poor survival after resection of early gastric cancer: extremes of survivorship analysis reveal distinct genomic profile.

A subset of patients with early gastric cancer demonstrate early recurrence and poor survival despite margin-negative resection. This study used an extremes-of-survivorship approach to identify an association between TP53 hotspot mutations co-occurring with loss of heterozygosity and unexpectedly poor survival in early gastric cancer. This distinct genomic profile may be a novel biomarker of poor survival in patients with completely resected early gastric cancer, and warrants large-scale validation. Promising, validation needed.

[Research on comprehensive evaluation system of occupational stress for air traffic controllers].

Objective: To explore the index system and weight of occupational stress risk assessment for civil aviation air traffic controllers (ATC) . Methods: In October 2018, a total of 489 ATC staff from an air traffic administration bureau were selected by cluster sampling. Through ATC questionnaire survey, the basic information, the influencing factors of occupational stress and the degree of occupational stress were understood. Based on the order relation analysis method (GL method) , the influencing factors of ATC occupational stress in civil aviation are evaluated. The fuzzy relation synthesis principle is applied to carry out multi-level fuzzy evaluation on the subordinate degree of occupational stress risk, and the ATC occupational stress risk evaluation system model is established. The weight of each index in the index system is determined, Establish a three-level comprehensive evaluation index system for ATC occupational stress risk, and quantify the occupational stress risk, Each Civil Aviation ATC occupational stress index corresponds to different degree of stress. Results: The influence degree of ATC occupational stress from heavy to light is: work factor, psychological factor, event factor, management factor, physiological factor, equipment factor and environmental factor (weight value is 0.2652, 0.2265, 0.1832, 0.1253, 0.1154, 0.045 5, 0.038 9 respectively) . Conclusion: GL method can be used to comprehensively and quantitatively evaluate the occupational stress risk of Civil Aviation ATC, which may be a feasible way to evaluate the occupational stress risk of Civil Aviation ATC.

[Spindle cell lipoma and pleomorphic lipoma: a clinicopathologic analysis of 65 cases].

Objective: To investigate the clinical and pathological features of spindle cell lipoma (SCL) and pleomorphic lipoma (PL) with emphasis on differential diagnosis. Methods: Sixty-five cases of SCL/PL from the archive of Department of Pathology, Fudan University Shanghai Cancer Center, from August of 2006 to June of 2017, were included in the study. Immunohistochemistry by EnVision method, MDM2 gene amplifycation and DDIT3 gene translocation by fluorescence in situ hybridization(FISH) were detected and the literature was reviewed. Results: There were 53 males and 12 females with age ranging from 26 to 82 years (mean, 57 years; median, 59 years). The majority of the lesions occurred in the neck/posterior neck/nuchal region, upper back and shoulder. A small percentage of lesions developed in the extremities, face and trunk, and rarely in the epiglottis, mediastinum, labium majus and perineum. Clinically, the tumor usually manifested as a slowly growing mass or nodule. It was often encapsulated, ranging from 1 to 13 cm (mean, 4.1 cm; median, 3.5 cm) in size. Microscopically, SCL was composed of mature adipose tissue, bland spindle cells and bright eosinophilic "ropey" collagen fibers that varied in proportion. Of 45 SCL, 28 cases (62.2%) were classical, 6 cases (13.3%) were myxoid, 5 cases (11.1%) were fat-poor, 3 cases (6.7%) were fat-free, and 3 cases (6.5%) were pseudoangiomatoid. PL showed similar features as SCL, but was characterized by the presence of scattered floret giant cells. Of 20 PL, 11 cases (55.0%) were classical, 6 cases (30.0%) were mixed SCL/PL, 3 cases (15.0%) were fat-free. Both SCL and PL contained scattered mast cells in the stroma. By immunohistochemistry, the spindle cells in SCL and the floret giant cells in PL showed strong positivity for CD34 (52/52, 100.0%), bcl-2 (24/26, 92.3%) and CD99 (6/6), whereas they were negative for S-100 protein and STAT6. FISH analysis of MDM2 (17 cases) and DDIT3 (4 cases) was negative in all cases. Follow-up information was available in 32 patients (3 to 96 months), with local recurrence in only one patient. Conclusions: SCL and PL belong to the same entity but may exhibit morphological disparities. Of note, the fat-poor and fat-free variants are easily mistaken for other mesenchymal tumors. Attention should be paid in their differential diagnosis.

[The mechanism of nicotine on human bronchial smooth muscle cell contraction].

Objective: To investigate the molecular mechanism of contractility dysfunction of human bronchial smooth muscle cells induced by nicotine. Methods: Primary human bronchial smooth muscle cells were cultured in vitro. The cells were divided into a control group and a nicotine group which was treated with 10(-5) mol/L nicotine for 48 h and transfected with or without α7nAChR-siRNA (The siNC group, siNC + nicotine group and siα7nAChR + nicotine group). The effects of nicotine on the cell contractile function were examined by collagen gel shrinkage assay. The expressions of α7nAChR and TRPC6 protein in nicotine-treated human bronchial smooth muscle cells were detected by Western blotting. The change of intracellular calcium concentration by nicotine was detected by calcium ion imaging system.Data were analyzed by t test or single factor analysis of variance. Results: The area of collagen gel in the nicotine group (24±8)% was significantly lower than that in the control group (59±14)% (t=3.78, P<0.05). Compared with the control group, the expression of α7nAChR protein in nicotine-induced group (173±16)% was significantly higher than that of controls 100±0)%, t=-6.848, P<0.05. Compared with the siNC group [(72±10)%, (0.79±0.07), (0.41±0.04) and (0.17±0.02) respectively], the collagen gel area of siNC + nicotine group was significantly reduced by (37±10)%. However, the basal calcium level (1.04±0.02), store operated calcium entry level (SOCE, 0.68±0.03) and receptor operated calcium entry level (ROCE, 0.36±0.02) were remarkably elevated in the nicotine treated group (all P<0.05). Furthermore, compared with siNC + nicotine group, the area of collagen gel in siα7nAChR + nicotine group was significantly increased (62±10)%, and the basal calcium level (0.78±0.06), SOCE level (0.39±0.05) and ROCE level (0.15±0.02) were significantly reduced (all P<0.05). Conclusions: Nicotine can increase the expression of TRPC6 protein, SOCE and ROCE level, and increase the intracellular calcium concentration by upregulating the expression of α7nAChR protein, thereby promoting smooth muscle cell contraction.

[Latent tuberculosis infection and associated risk factors among the tuberculosis contacts in one of district in Shanghai].

Objective: To investigate the prevalence of latent tuberculosis infection(LTBI) and associated risk factors among the tuberculosis(TB) contacts in Minhang District of Shanghai. Methods: A self-designed questionnaire was used to acquire socio-demographic information and to assess the degree of exposure to index cases. LTBI screening was performed by T-SPOT.TB assay. Pearson chi-square test and Logistic regression analyses were used to identify the risk factors associated with LTBI among the TB contacts. Results: A total of 137 contacts from 59 mycobacterial (culture) positive pulmonary TB patients were enrolled in this study. In these contacts, there were 54 men and 83 women, with the average age of 42. LTBI was identified in 20% (27/137) of these contacts. Several risk factors were found by logistic analyses in this study. The worse the ventilation in the exposure location was, the more likely to develop LTBI. Contacts aged more than 60 (42.1%) were 3.9 times more likely to develop LTBI than those aged less than 60 (16.1%). Individuals in contact with TB patients for more than 40 h/week(25.8%) had a 4.2 times risk of LTBI as compared to those for less than 40 h/week(6.8%). Conclusion: The prevalence of LTBI was 20% among the TB contacts in this study, highlighting the need of TB screening and intervention among TB contacts.

Identification of conserved microRNAs and their target genes in Nile tilapia (Oreochromis niloticus) by bioinformatic analysis.

MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in posttranscriptional regulation of target genes. miRNAs are involved in multiple biological processes by degrading targeted mRNAs or repressing mRNA translation in various organisms. Their conserved nature in various organisms makes them a good source of new miRNA discovery using comparative genomic approaches. In the present study, conserved Nile tilapia (Oreochromis niloticus) miRNAs were identified using a bioinformatic strategy based on expressed sequence tag and genome survey sequence databases. A total of 21 new miRNAs were detected and were found to belong to 17 families. Using mature miRNA sequences as queries, potential targets for tilapia miRNAs were predicted using a local BLAST program and the miRanda software. Target proteins identified using miRanda and BLAST analyses included transcription factors and molecules important in metabolism, transportation, immunity, stress-related activity, growth, and development. These miRNAs and their targets in tilapia may increase the understanding of the role of miRNAs in regulating the growth and development of tilapia.

Prevalence of hepatitis A viral RNA and antibodies among Chinese blood donors.

Like other developing countries, China was reported to have a relatively high seroprevalence of anti-hepatitis A antibodies (anti-HAV). However, no studies have evaluated the prevalence of anti-HAV and HAV RNA among voluntary blood donors with or without elevated serum alanine transaminase (ALT) levels. Anti-HAV antibodies were detected using an enzyme-linked immunosorbent assay, and reverse transcription quantitative polymerase chain reaction was carried out for detection of HAV RNA. In the current study, we analyzed a total of 450 serum samples with elevated ALT levels (≥40 U/L) and 278 serum samples with non-elevated ALT levels. Seroprevalence rates of anti-HAV were 51.6% in donors with elevated ALT and 41.4% in donors with non-elevated ALT; however, none of the samples was positive for HAV RNA. The results of our study showed lower seroprevalence rates of anti-HAV in blood donors (irrespective of ALT levels) than those in published data on Chinese populations. Although donors with elevated ALT had statistically higher prevalence rates of anti- HAV than did those with non-elevated ALT, none of the serum samples had detectable levels of the active virus. In conclusion, our results demonstrate that the transmission of hepatitis A by blood transfusion will occur rarely.

An individual coding polymorphism and the haplotype of the SPARC gene predict gastric cancer recurrence.

The 5-year survival rate for gastric adenocarcinoma (GA) remains only 40% and biomarkers to identify patients at high risk of tumor recurrence are urgently needed. Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein that mediates cell matrix interactions, and upregulation of SPARC can promote tumor progression and metastasis. This study investigated whether single-nucleotide polymorphisms (SNPs) in SPARC impact the prognosis of GA. Blood or formalin-fixed, paraffin-embedded tissues were obtained from 137 GA patients at the University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was isolated and five SNPs in the SPARC 3'-untranslated region (UTR) were evaluated by DNA sequencing or PCR-restriction fragment length polymorphism. Associations between SNPs and time to tumor recurrence (TTR) were analyzed using Kaplan-Meier curves, log-rank tests, and likelihood-ratio test within logistic or Cox regression model as appropriate. Patients carrying at least one G allele of the SPARC rs1059829 polymorphism (GG, AG) showed a median TTR of 3.7 years compared with 2.1 years TTR for patients with AA (hazard ratio (HR) 0.57; P=0.033). In a multivariate analysis adjusted for T and N category as covariates and stratified by race, hospital and chemotherapy, patients with at least one SPARC rs1059829 G allele (GG, AG) remained significantly associated with superior TTR than patients with AA genotype (adjusted P=0.026). In addition, patients harboring the G-A-A haplotype had the highest risk of tumor recurrence (HR 1.892; adjusted P=0.016). Our findings suggest that SPARC 3'-UTR SNPs may be useful in predicting GA patients at increased risk of recurrence.

Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm.

Mastocytosis is characterized by accumulations of mast cells in various organs (1). Most cases are indolent and confined to the skin, where discrete mast cell infiltrates are associated increased epidermal melanin, a clinical picture known as urticaria pigmentosa (UP). Other forms of mastocytosis combine UP with aggressive involvement of other organs or with haemotologic abnormalities (1-4). It is not known whether all forms of mastocytosis are true neoplasms or whether some might represent reactive hyperplasias (5-7). The c-KIT proto-oncogene encodes a type III receptor tyrosine kinase (KIT) that is critical to the development and survival of mast cells and melanocytes (8-11). The ligand for KIT (KL) can stimulate mast cell development, proliferation, and mediator release (9,12-17), as well as melanocyte proliferation and pigment production (18-20). To determine the role of c-KIT in the pathogenesis of mastocytosis, we examined tissue and cells isolated from a patient with UP and aggressive systemic mastocytosis with massive splenic involvement. We found a mutation that results in constitutive activation and expression of c-KIT in mast cells of both skin and spleen. This is the first in situ demonstration of an activation c-KIT mutation in neoplastic cells. It also demonstrates the clonal and neoplastic nature of this form of mastocytes.

Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis.

BACKGROUND: To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. RESULTS: Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). CONCLUSIONS: Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.

Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma.

BACKGROUND: To characterise recurrence patterns and survival following pathologic complete response (pCR) in patients who received preoperative therapy for localised gastric or gastrooesophageal junction (GEJ) adenocarcinoma. METHODS: A retrospective review of a prospective database identified patients with pCR after preoperative chemotherapy for gastric or preoperative chemoradiation for GEJ (Siewert II/III) adenocarcinoma. Recurrence patterns, overall survival, recurrence-free survival, and disease-specific survival were analysed. RESULTS: From 1985 to 2009, 714 patients received preoperative therapy for localised gastric/GEJ adenocarcinoma, and 609 (85%) underwent a subsequent R0 resection. There were 60 patients (8.4%) with a pCR. Median follow-up was 46 months. Recurrence at 5 years was significantly lower for pCR vs non-pCR patients (27% and 51%, respectively, P=0.01). The probability of recurrence for patients with pCR was similar to non-pCR patients with pathologic stage I or II disease. Although the overall pattern of local/regional (LR) vs distant recurrence was comparable (43% LR vs 57% distant) between pCR and non-pCR groups, there was a significantly higher incidence of central nervous system (CNS) first recurrences in pCR patients (36 vs 4%, P=0.01). CONCLUSION: Patients with gastric or GEJ adenocarcinoma who achieve a pCR following preoperative therapy still have a significant risk of recurrence and cancer-specific death following resection. One third of the recurrences in the pCR group were symptomatic CNS recurrences. Increased awareness of the risk of CNS metastases and selective brain imaging in patients who achieve a pCR following preoperative therapy for gastric/GEJ adenocarcinoma is warranted.

GRP78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients.

BACKGROUND: Recently, the analysis of gastric and colorectal tumor specimens determined that 78-kiloDalton glucose-regulated protein (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism protecting cells against apoptosis and can confer drug resistance. We tested whether functional polymorphisms within the GRP78 gene are related to clinical outcome in gastric and colorectal cancer (CRC) patients. PATIENTS AND METHODS: Blood samples of 234 stage II/III CRC patients at the University of Southern California (USC) and formalin-fixed paraffin-embedded tissues of 137 patients with localized gastric adenocarcinoma (GA) at USC and Memorial Sloan-Kettering Cancer Centers were obtained. GRP78 polymorphisms analyzed on germline DNA were correlated with clinical outcome using univariate and multivariate analyses. RESULTS: GA patients with the combined GRP78 rs391957 C/T and T/T genotype were at higher risk for tumor recurrence and death [hazard ratio (HR) 2.61; P < 0.001 and HR 3.17; P < 0.001, respectively], than those with C/C. These findings were subsequently tested in a CRC cohort where patients with the homozygous T/T genotype were at highest risk for tumor recurrence (HR 2.61; P = 0.015). The results remained significant after adjusting for clinicopathologic determinants. CONCLUSION: These data provide the first evidence that the GRP78 rs391957 polymorphism can predict clinical outcome in localized GA and locally advanced CRC patients.

Genetic variations in angiogenesis pathway genes associated with clinical outcome in localized gastric adenocarcinoma.

BACKGROUND: Angiogenesis has been attributed to be a well-recognized aspect of human cancer biology. As such, proteinase-activated receptor (PAR)-1, endostatin (ES) and interleukin-8 (IL-8) mediate the regulation of early-onset angiogenesis and in turn impact the process of tumor-growth and disease progression. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tissues were obtained from 137 patients with localized gastric cancer at University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was extracted and genotyping was carried out using PCR-restriction fragment length polymorphism-based protocols. RESULTS: In false discovery rate-adjusted univariate analysis, PAR-1 -506 ins/del (P < 0.001), ES +4349 G>A (P = 0.004), and IL-8 -251 T>A (P < 0.0001) were associated with time to tumor recurrence (TTR). Further, PAR-1 -506 ins/del and IL-8 -251 were associated with overall survival (OS). After adjusting for covariates, IL-8 remained significantly associated with TTR (adjusted P = 0.003) and OS (adjusted P = 0.049), whereas ES was significantly associated with TTR (adjusted P = 0.026). CONCLUSIONS: Polymorphisms in PAR-1, ES, and IL-8 may serve as independent molecular prognostic markers in patients with localized gastric adenocarcinoma. The assessment of the patients' individual risk on the basis of interindividual genotypes may therefore help to identify patient subgroups at high risk for poor clinical outcome.

Identification of 17 novel major histocompatibility complex-A alleles in a population of Chinese-origin rhesus macaques.

Rhesus macaques (Macaca mulatta) serve as important animal models for human disease and vaccine research. Although Chinese rhesus macaques are the same species as those of Indian origin, they are from a geographically separated population and possess divergent major histocompatibility complex (MHC) class I A alleles. In an analysis of 65 Chinese rhesus macaques, 17 novel Mamu-A alleles were identified and deposited under the following accession numbers: EU252155-158, EU262737-741, EU418504-505, EU422996, EU418506, EU753185-187, and EU828528. The discovery of these additional MHC class I A sequences indicates a greater diversity and polymorphism of Chinese rhesus macaques in different geographic locations. As the set of Mamu-A alleles in Chinese rhesus macaques differs from the alleles of Indian animals, more work still needs to be carried out to identify these new allele-restricted immune responses with regard to vaccine studies.

Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in China.

OBJECTIVE: In China, Chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) were abandoned for the treatment of falciparum malaria 20 years ago due to resistance. Subsequent field studies showed a trend of declining CQ and SP resistance in the country. The main purpose of this study was to analyse the molecular markers of antimalarial resistance and thereby to assess the possibility of reintroduction of CQ or SP for falciparum malaria treatment. METHODS: Plasmodium falciparum field isolates were collected in 2006-2007 from Hainan and Yunnan provinces, China. Nested PCR-sequencing assays were applied to analyse the SNPs in four genes: P. falciparum chloroquine resistance transporter (pfcrt) gene, multi-drug resistance 1 (pfmdr1) gene, dihydrofolate reductase (dhfr) gene and dihydropteroate synthetase (dhps) gene. RESULTS: We found the widespread presence of point mutations in the dhfr and dhps genes which are associated with SP treatment failure. The molecular analyses also showed the fairly high prevalence of point mutation in the pfcrt gene which is linked to CQ resistance. CONCLUSION: The results of the present study indicate that CQ and SP should not be reintroduced for falciparum malaria treatment in the near future in China.

Allosteric modulation of the NMDA receptor by dihydrolipoic and lipoic acid in rat cortical neurons in vitro.

The mitochondrial cofactor dihydrolipoic acid (DHLA) was observed to potentiate N-methyl-D-aspartate (NMDA), but not non-NMDA, receptor-mediated whole-cell responses in cultured neurons. This potentiation was readily reversed by the oxidizing agent 5,5'-dithio-bis-(2-nitro-benzoic acid) (DTNB). DHLA was unable to increase NMDA responses previously potentiated by dithiothreitol, nor did it have an effect on NMDA receptors alkylated with N-ethylmaleimide. Single-channel recordings revealed that DHLA produced an increase in NMDA channel open frequency, with no change in single-channel conductance or open time. In contrast, lipoic acid reversed the potentiation of NMDA-evoked responses produced by dithiothreitol and had no effect on NMDA receptors previously oxidized by DTNB. DHLA and lipoic acid are pervasively found substances that readily permeate cellular membranes and thus may influence NMDA receptor activity in vivo by modifying its redox site.