Studies reporting the Indian prevalence of Epidermal Growth Factor Receptor (EGFR) mutation are mostly single centers with small sample sizes. This systematic review and meta-analysis summarized the available evidence...Studies reporting the Indian prevalence of Epidermal Growth Factor Receptor (EGFR) mutation are mostly single centers with small sample sizes. This systematic review and meta-analysis summarized the available evidence of EGFR mutation epidemiology in Indian patients with adenocarcinoma (ADC) Non-Small Cell Lung Cancer (NSCLC). We conducted a structured literature search in PubMed, and EMBASE databases from January 2004 through October 2019. The primary outcome of interest was prevalence of EGFR mutation by gender, smoking status, and mutation subtype. The review included 34 studies. EGFR mutation prevalence was 39.5% in patients with ADC, and significantly higher in females, non-smokers, and patients with exon 19 deletions. The EGFR mutation frequency in Indian patients with ADC was higher than reported in Caucasians but at a lower range of that reported in East Asians. These findings support the use of EGFR mutation testing to guide choice of treatment.展开更多
Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors ...Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy;they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.展开更多
Lung cancer is the leading cause of cancer death worldwide,with large variation of the incidence and mortality across regions.Although the mortality of lung cancer has been decreasing,or steady in the US,it has been i...Lung cancer is the leading cause of cancer death worldwide,with large variation of the incidence and mortality across regions.Although the mortality of lung cancer has been decreasing,or steady in the US,it has been increasing in Asia for the past two decades.Smoking is the leading cause of lung cancer,and other risk factors such as indoor coal burning,cooking fumes,and infections may play important roles in the development of lung cancer among Asian never smoking women.The median age of diagnosis in Asian patients with lung cancer is generally younger than Caucasian patients,particularly among never-smokers.Asians and Caucasians may have different genetic susceptibilities to lung cancer,as evidenced from candidate polymorphisms and genome-wide association studies.Recent epidemiologic studies and clinical trials have shown consistently that Asian ethnicity is a favorable prognostic factor for overall survival in non-small cell lung cancer(NSCLC),independent of smoking status.Compared with Caucasian patients with NSCLC,East Asian patients have a much higher prevalence of epidermal growth factor receptor(EGFR) mutation(approximately 30% vs.7%,predominantly among patients with adenocarcinoma and never-smokers),a lower prevalence of K-Ras mutation(less than 10% vs.18%,predominantly among patients with adenocarcinoma and smokers),and higher proportion of patients who are responsive to EGFR tyrosine kinase inhibitors.The ethnic differences in epidemiology and clinical behaviors should be taken into account when conducting global clinical trials that include different ethnic populations.展开更多
In this paper, a double artificial neural network （DANN） algorithm was used to parse near infrared （NIR） reflectance spectrum of Cofrel medicines. The contents of benproperine phosphate, which is the effective ing...In this paper, a double artificial neural network （DANN） algorithm was used to parse near infrared （NIR） reflectance spectrum of Cofrel medicines. The contents of benproperine phosphate, which is the effective ingredient in Cofrel medicines, were accurately nondestructive quantitatively predicted. Compared the results with those of HPLC, the relative errors （RE %） were less than 0.18%. The analytical results could be applied to qualitative control of Cofrel medicines.展开更多
Significant progress has been made in understanding pharmacokinetics (PK),pharmacodynamics (PD),as well as toxicity profiles of therapeutic proteins in animals and humans,which have been in commercial development for ...Significant progress has been made in understanding pharmacokinetics (PK),pharmacodynamics (PD),as well as toxicity profiles of therapeutic proteins in animals and humans,which have been in commercial development for more than three decades.However,in the PK arena,many fundamental questions remain to be resolved.Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans,and from in vitro assays to in vivo readouts,which would ultimately lead to a higher success rate in drug development.In toxicology,it is known,in general,what studies are needed to safely develop therapeutic proteins,and what studies do not provide relevant information.One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity.In this review,we will highlight the emerging science and technology,as well as the challenges around the pharmacokinetic-and safety-related issues in drug development of mAbs and other therapeutic proteins.展开更多
AIM To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1(DGAT1) plays in postprandial gut peptide secretion and signaling.METHODS The standard experimental paradigm utilized to evaluate the incret...AIM To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1(DGAT1) plays in postprandial gut peptide secretion and signaling.METHODS The standard experimental paradigm utilized to evaluate the incretin response was a lipid challenge.Following a lipid challenge,plasma was collected via cardiac puncture at each time point from a cohort of 5-8 mice per group from baseline at time zero to 10 h.Incretin hormones [glucagon like peptide-1(GLP-1),peptide tyrosine-tyrosine(PYY) and glucose dependent insulinotropic polypeptide(GIP)] were then quantitated.The impact of pharmacological inhibition of DGAT1 on the incretin effect was evaluated in WT mice.Additionally,a comparison of loss of DGAT1 function either by genetic ablation or pharmacological inhibition.To further elucidate the pathways and mechanisms involved in the incretin response to DGAT1 inhibition,other interventions [inhibitors of dipeptidyl peptidase-IV(sitagliptin),pancreatic lipase(Orlistat),GPR119 knockout mice] were evaluated.RESULTS DGAT1 deficient mice and wildtype C57/BL6J mice werelipid challenged and levels of both active and total GLP-1 in the plasma were increased.This response was further augmented with DGAT1 inhibitor PF-04620110 treated wildtype mice.Furthermore,PF-04620110 was able to dose responsively increase GLP-1 and PYY,but blunt GIP at all doses of PF-04620110 during lipid challenge.Combination treatment of PF-04620110 and Sitagliptin in wildtype mice during a lipid challenge synergistically enhanced postprandial levels of active GLP-1.In contrast,in a combination study with Orlistat,the ability of PF-04620110 to elicit an enhanced incretin response was abrogated.To further explore this observation,GPR119 knockout mice were evaluated.In response to a lipid challenge,GPR119 knockout mice exhibited no increase in active or total GLP-1 and PYY.However,PF-04620110 was able to increase total GLP-1 and PYY in GPR119 knockout mice as compared to vehicle treated wildtype mice.CONCLUSION Collectively,these data provide some insight into the mechanism by which inhibition of DGAT1 enhances intestinal hormone release.展开更多
Chronic kidney disease(CKD) is recognised as a health concern globally and leads to high rates of morbidity,mortality and healthcare expenditure.CKD is itself an independent risk factor for unfavorable health outcomes...Chronic kidney disease(CKD) is recognised as a health concern globally and leads to high rates of morbidity,mortality and healthcare expenditure.CKD is itself an independent risk factor for unfavorable health outcomes that include cardiovascular disease(CVD).Coronary artery disease is the primary type of CVD in CKD patients and a significant cause of death among renal transplant patients.Traditional and non-traditional risk factors for CVD exist in patients with CKD.Traditional factors include smoking,hypertension,dyslipidemia and diabetes which are highly prevalent in CKD patients.Non-traditional risk factors of CKD are mainly uraemiaspecific and increase in prevalence as kidney function declines.Some examples of uraemia-specific risk factors that have been well documented include low levels of haemoglobin,albuminuria,and abnormal bone and mineral metabolism.Therapeutic interventions targeted at more traditional risk factors which contribute to CVD,have not had the desired effect on lowering CVD events and mortality in those suffering with CKD.Future research is warranted to delineate clear evidence to the benefit of modifying non-traditional risk factors.展开更多
AIM: To discuss the advantages of ultra-high field (7T) for 1H and 13C magnetic resonance spectroscopy (MRS) studies of metabolism.METHODS: Measurements of brain metabolites were made at both 3 and 7T using 1H MRS. Me...AIM: To discuss the advantages of ultra-high field (7T) for 1H and 13C magnetic resonance spectroscopy (MRS) studies of metabolism.METHODS: Measurements of brain metabolites were made at both 3 and 7T using 1H MRS. Measurements of glycogen and lipids in muscle were measured using 13C and 1H MRS respectively.RESULTS: In the brain, increased signal-to-noise ratio (SNR) and dispersion allows spectral separation of the amino-acids glutamate, glutamine and γ-aminobutyric acid (GABA), without the need for sophisticated editing sequences. Improved quantification of these metabolites is demonstrated at 7T relative to 3T. SNR was 36% higher, and measurement repeatability (% coefficients of variation) was 4%, 10% and 10% at 7T, vs 8%, 29% and 21% at 3T for glutamate, glutamine and GABA respectively. Measurements at 7T were used to compare metabolite levels in the anterior cingulate cortex (ACC) and insula. Creatine and glutamate levels were found to be significantly higher in the insula compared to the ACC (P < 0.05). In muscle, the increased SNR and spectral resolution at 7T enables interleaved studies of glycogen (13C) and intra-myocellular lipid (IMCL) and extra-myocellular lipid (EMCL) (1H) following exercise and re-feeding. Glycogen levels were significantly decreased following exercise (-28% at 50% VO2 max; -58% at 75% VO2 max). Interestingly, levels of glycogen in the hamstrings followed those in the quadriceps, despite reduce exercise loading. No changes in IMCL and EMCL were found in the study.CONCLUSION: The demonstrated improvements in brain and muscle MRS measurements at 7T will increase the potential for use in investigating human metabolism and changes due to pathologies.展开更多
Background: Colorectal cancer(CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main c...Background: Colorectal cancer(CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main culprit of cancer metastasis,chemotherapy resistance, and relapse.Methods: To further understand the unique biological properties of cancer stem cells and uncover novel molecular targets to eradicate them, we first established a panel of patient-derived xenograft(PDX) tumor models using tumors surgically removed from human colorectal cancer patients. We then isolated CRC cancer stem cells based on their ALDH activity using fluorescent-activated cell sorting(FACS)and characterized their metabolic properties.Results: Interestingly, we found that the CRC cancer stem cells(ie, CRC cells with higher ALDH activity, or ALDH+) express higher level of antioxidant genes and have lower level of reactive oxygen species(ROS) than non-CRC cancer stem cells(ie, CRC cells with lower ALDH activity, or ALDHà). The CRC cancer stem cells also possess more mitochondria mass and show higher mitochondrial activity. More intriguingly,we observed higher AMP-activated protein kinase(AMPK) activities in these CRC cancer stem cells. Inhibition of the AMPK activity using 2 AMPK inhibitors, Compound C and Iodotubercidin, preferentially induces cell death in CRC cancer stem cells.Conclusion: We propose that AMPK inhibitors may help to eradicate the CRC cancer stem cells and prevent the relapse of CRCs.展开更多
Background: Complicated skin and skin structure infections (cSSSIs) due to Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), are associated with significant morbidity. Re-ducing MRSA carriage ha...Background: Complicated skin and skin structure infections (cSSSIs) due to Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), are associated with significant morbidity. Re-ducing MRSA carriage has been a focus of infection control interventions. The prevalence of MRSA colonization after successful treatment of a MRSA cSSSI is unknown. Methods: Secondary analysis of a randomized controlled trial comparing linezolid and vancomycin for the treatment of MRSA cSSSI. Adult patients that had a colonization culture, confirmed MRSA cSSSI, received at least one dose of study treatment, and had an outcome recorded at end of study. Patient, clinical characteristics and prevalence of colonization were compared by treatment regimens. A multivariate regression model identified predictors of MRSA colonization at EOS. Results: There were 456 patients evaluated. The prevalence of MRSA colonization was higher for vancomycin treated patients compared to linezolid treated patients at end of treatment (EOT) (28% vs. 5%, p < 0.001) and EOS (34% vs. 22%, p < 0.01). Independent predictors of colonization at EOS after treatment for a MRSA cSSSI included diagnosis, primarily driven by abscess, black race, treatment with vancomycin, MRSA mixed infection and male gender. Conclusion: Patients treated with linezolid for a cSSSI had less MRSA colonization at EOT and EOS compared to those treated with vancomycin. Multiple independent predictors of MRSA colonization were identified. Additional studies evaluating the relationship of MRSA colonization after treatment of cSSSI are needed.展开更多
The aim of this study was to determine the prevalence of M. hyopneumoniae infection in suckling pigs. Nasal swabs were collected from 300 suckling pigs originating from five farrow-to-finishing farms. One farm had a c...The aim of this study was to determine the prevalence of M. hyopneumoniae infection in suckling pigs. Nasal swabs were collected from 300 suckling pigs originating from five farrow-to-finishing farms. One farm had a confirmed PRDC problem (farm A) and four other farms previously had a PRDC problem (farms B, C, D and E). Thirty (30) lactating sows in parity 1, 2 and 3 were selected from each farm (Ten sows per parity). Two piglets from each sow were randomly sampled for nasal swab at 3 weeks of age. The samples were analyzed by the nested PCR technique. Forty five per cent (27/60) of nasal swabs from farm A were found positive. On the other hand, a total of 2.08 per cent were found positive (5/240) from farm B, C, D and E. The tendency of piglet infection per sow by parity showed that first parity had more prevalence than the second and the third parity (60%, 55%, 20%), respectively. We have found a correction between M. hyopneumoniae early infection in suckling pigs and a confirmed PRDC problem (farm A) as oppose to farms that did not have a PRDC problem. The strategies to prevent M. hyopneumoniae early infection are to maintain good lactation, antibiotic prevention program and early M. hyopneumoniae展开更多
In September 2012,the US Chinese Anti-Cancer Association(USCACA) hosted two symposiums in Beijing.The USCACA hosted the first joint session at the 7th annual meetings of the Chinese Anti-Cancer Association(CACA),theme...In September 2012,the US Chinese Anti-Cancer Association(USCACA) hosted two symposiums in Beijing.The USCACA hosted the first joint session at the 7th annual meetings of the Chinese Anti-Cancer Association(CACA),themed on "Collaboration between the US and China in Cancer Research." Six experts from the United States and China presented their latest work on basic and translational cancer research.During this symposium,5 young Chinese scholars,returnees after their training in the United States,were honored the"AFCR-USCACA Scholarships Award." The USCACA hosted a second symposium during the 15th annual meeting of the Chinese Society of Clinical Oncology(CSCO),focused on the "US-China Collaboration in Cancer Drug Clinical Development." An international delegation of oncology experts presented the innovative clinical trial strategies and discussed the biomarkers for cancer early detection and clinical trials,targeted therapy,and new drug development.The Oncology Drug Clinical Development and Safety Evaluation Committee was also launched to promote an innovative environment and to provide a collaborative platform for anti-cancer drug development in China.展开更多
Data from a prospective, randomized, open-label, active-controlled, multicenter, Phase 4 study comparing oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infe...Data from a prospective, randomized, open-label, active-controlled, multicenter, Phase 4 study comparing oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections caused by methicillin resistant Staphylococcus aureus was used to determine the association between staphylococcal cassette chromosome mec (SCCmec) type and patient’s clinical presentation, infection severity, intravenous therapy duration and length of stay (LOS). Compared to SCCmec types I, II, and III, SCCmec type IV, PVL+ was associated with more frequent presentation of abscesses, lower severity scores, and shorter intravenous therapy duration and LOS in both treatment groups.展开更多
文摘Studies reporting the Indian prevalence of Epidermal Growth Factor Receptor (EGFR) mutation are mostly single centers with small sample sizes. This systematic review and meta-analysis summarized the available evidence of EGFR mutation epidemiology in Indian patients with adenocarcinoma (ADC) Non-Small Cell Lung Cancer (NSCLC). We conducted a structured literature search in PubMed, and EMBASE databases from January 2004 through October 2019. The primary outcome of interest was prevalence of EGFR mutation by gender, smoking status, and mutation subtype. The review included 34 studies. EGFR mutation prevalence was 39.5% in patients with ADC, and significantly higher in females, non-smokers, and patients with exon 19 deletions. The EGFR mutation frequency in Indian patients with ADC was higher than reported in Caucasians but at a lower range of that reported in East Asians. These findings support the use of EGFR mutation testing to guide choice of treatment.
文摘Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy;they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.
文摘Lung cancer is the leading cause of cancer death worldwide,with large variation of the incidence and mortality across regions.Although the mortality of lung cancer has been decreasing,or steady in the US,it has been increasing in Asia for the past two decades.Smoking is the leading cause of lung cancer,and other risk factors such as indoor coal burning,cooking fumes,and infections may play important roles in the development of lung cancer among Asian never smoking women.The median age of diagnosis in Asian patients with lung cancer is generally younger than Caucasian patients,particularly among never-smokers.Asians and Caucasians may have different genetic susceptibilities to lung cancer,as evidenced from candidate polymorphisms and genome-wide association studies.Recent epidemiologic studies and clinical trials have shown consistently that Asian ethnicity is a favorable prognostic factor for overall survival in non-small cell lung cancer(NSCLC),independent of smoking status.Compared with Caucasian patients with NSCLC,East Asian patients have a much higher prevalence of epidermal growth factor receptor(EGFR) mutation(approximately 30% vs.7%,predominantly among patients with adenocarcinoma and never-smokers),a lower prevalence of K-Ras mutation(less than 10% vs.18%,predominantly among patients with adenocarcinoma and smokers),and higher proportion of patients who are responsive to EGFR tyrosine kinase inhibitors.The ethnic differences in epidemiology and clinical behaviors should be taken into account when conducting global clinical trials that include different ethnic populations.
文摘In this paper, a double artificial neural network （DANN） algorithm was used to parse near infrared （NIR） reflectance spectrum of Cofrel medicines. The contents of benproperine phosphate, which is the effective ingredient in Cofrel medicines, were accurately nondestructive quantitatively predicted. Compared the results with those of HPLC, the relative errors （RE %） were less than 0.18%. The analytical results could be applied to qualitative control of Cofrel medicines.
文摘Significant progress has been made in understanding pharmacokinetics (PK),pharmacodynamics (PD),as well as toxicity profiles of therapeutic proteins in animals and humans,which have been in commercial development for more than three decades.However,in the PK arena,many fundamental questions remain to be resolved.Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans,and from in vitro assays to in vivo readouts,which would ultimately lead to a higher success rate in drug development.In toxicology,it is known,in general,what studies are needed to safely develop therapeutic proteins,and what studies do not provide relevant information.One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity.In this review,we will highlight the emerging science and technology,as well as the challenges around the pharmacokinetic-and safety-related issues in drug development of mAbs and other therapeutic proteins.
文摘AIM To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1(DGAT1) plays in postprandial gut peptide secretion and signaling.METHODS The standard experimental paradigm utilized to evaluate the incretin response was a lipid challenge.Following a lipid challenge,plasma was collected via cardiac puncture at each time point from a cohort of 5-8 mice per group from baseline at time zero to 10 h.Incretin hormones [glucagon like peptide-1(GLP-1),peptide tyrosine-tyrosine(PYY) and glucose dependent insulinotropic polypeptide(GIP)] were then quantitated.The impact of pharmacological inhibition of DGAT1 on the incretin effect was evaluated in WT mice.Additionally,a comparison of loss of DGAT1 function either by genetic ablation or pharmacological inhibition.To further elucidate the pathways and mechanisms involved in the incretin response to DGAT1 inhibition,other interventions [inhibitors of dipeptidyl peptidase-IV(sitagliptin),pancreatic lipase(Orlistat),GPR119 knockout mice] were evaluated.RESULTS DGAT1 deficient mice and wildtype C57/BL6J mice werelipid challenged and levels of both active and total GLP-1 in the plasma were increased.This response was further augmented with DGAT1 inhibitor PF-04620110 treated wildtype mice.Furthermore,PF-04620110 was able to dose responsively increase GLP-1 and PYY,but blunt GIP at all doses of PF-04620110 during lipid challenge.Combination treatment of PF-04620110 and Sitagliptin in wildtype mice during a lipid challenge synergistically enhanced postprandial levels of active GLP-1.In contrast,in a combination study with Orlistat,the ability of PF-04620110 to elicit an enhanced incretin response was abrogated.To further explore this observation,GPR119 knockout mice were evaluated.In response to a lipid challenge,GPR119 knockout mice exhibited no increase in active or total GLP-1 and PYY.However,PF-04620110 was able to increase total GLP-1 and PYY in GPR119 knockout mice as compared to vehicle treated wildtype mice.CONCLUSION Collectively,these data provide some insight into the mechanism by which inhibition of DGAT1 enhances intestinal hormone release.
文摘Chronic kidney disease(CKD) is recognised as a health concern globally and leads to high rates of morbidity,mortality and healthcare expenditure.CKD is itself an independent risk factor for unfavorable health outcomes that include cardiovascular disease(CVD).Coronary artery disease is the primary type of CVD in CKD patients and a significant cause of death among renal transplant patients.Traditional and non-traditional risk factors for CVD exist in patients with CKD.Traditional factors include smoking,hypertension,dyslipidemia and diabetes which are highly prevalent in CKD patients.Non-traditional risk factors of CKD are mainly uraemiaspecific and increase in prevalence as kidney function declines.Some examples of uraemia-specific risk factors that have been well documented include low levels of haemoglobin,albuminuria,and abnormal bone and mineral metabolism.Therapeutic interventions targeted at more traditional risk factors which contribute to CVD,have not had the desired effect on lowering CVD events and mortality in those suffering with CKD.Future research is warranted to delineate clear evidence to the benefit of modifying non-traditional risk factors.
基金Supported by The Haldane-Spearman Consortium for PhD funding for Dr. Gunner F, Swecarb AB for provision of the carbo-hydrate drink，and Pfizer for funding the 1H Repeatability work Dr.Stephenson M was supported by the University of Notting-ham’s Mansfield Fellowship scheme+2 种基金7T work was supported by grant G9900259 from the Medical Research CouncilPfizer and grant G0901321 from the Medical Research CouncilThe 7 T MR Scanner in Nottingham, was funded by a Joint Infrastructure Fund Grant from the Wellcome Trust UK
文摘AIM: To discuss the advantages of ultra-high field (7T) for 1H and 13C magnetic resonance spectroscopy (MRS) studies of metabolism.METHODS: Measurements of brain metabolites were made at both 3 and 7T using 1H MRS. Measurements of glycogen and lipids in muscle were measured using 13C and 1H MRS respectively.RESULTS: In the brain, increased signal-to-noise ratio (SNR) and dispersion allows spectral separation of the amino-acids glutamate, glutamine and γ-aminobutyric acid (GABA), without the need for sophisticated editing sequences. Improved quantification of these metabolites is demonstrated at 7T relative to 3T. SNR was 36% higher, and measurement repeatability (% coefficients of variation) was 4%, 10% and 10% at 7T, vs 8%, 29% and 21% at 3T for glutamate, glutamine and GABA respectively. Measurements at 7T were used to compare metabolite levels in the anterior cingulate cortex (ACC) and insula. Creatine and glutamate levels were found to be significantly higher in the insula compared to the ACC (P < 0.05). In muscle, the increased SNR and spectral resolution at 7T enables interleaved studies of glycogen (13C) and intra-myocellular lipid (IMCL) and extra-myocellular lipid (EMCL) (1H) following exercise and re-feeding. Glycogen levels were significantly decreased following exercise (-28% at 50% VO2 max; -58% at 75% VO2 max). Interestingly, levels of glycogen in the hamstrings followed those in the quadriceps, despite reduce exercise loading. No changes in IMCL and EMCL were found in the study.CONCLUSION: The demonstrated improvements in brain and muscle MRS measurements at 7T will increase the potential for use in investigating human metabolism and changes due to pathologies.
文摘Background: Colorectal cancer(CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main culprit of cancer metastasis,chemotherapy resistance, and relapse.Methods: To further understand the unique biological properties of cancer stem cells and uncover novel molecular targets to eradicate them, we first established a panel of patient-derived xenograft(PDX) tumor models using tumors surgically removed from human colorectal cancer patients. We then isolated CRC cancer stem cells based on their ALDH activity using fluorescent-activated cell sorting(FACS)and characterized their metabolic properties.Results: Interestingly, we found that the CRC cancer stem cells(ie, CRC cells with higher ALDH activity, or ALDH+) express higher level of antioxidant genes and have lower level of reactive oxygen species(ROS) than non-CRC cancer stem cells(ie, CRC cells with lower ALDH activity, or ALDHà). The CRC cancer stem cells also possess more mitochondria mass and show higher mitochondrial activity. More intriguingly,we observed higher AMP-activated protein kinase(AMPK) activities in these CRC cancer stem cells. Inhibition of the AMPK activity using 2 AMPK inhibitors, Compound C and Iodotubercidin, preferentially induces cell death in CRC cancer stem cells.Conclusion: We propose that AMPK inhibitors may help to eradicate the CRC cancer stem cells and prevent the relapse of CRCs.
文摘Background: Complicated skin and skin structure infections (cSSSIs) due to Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), are associated with significant morbidity. Re-ducing MRSA carriage has been a focus of infection control interventions. The prevalence of MRSA colonization after successful treatment of a MRSA cSSSI is unknown. Methods: Secondary analysis of a randomized controlled trial comparing linezolid and vancomycin for the treatment of MRSA cSSSI. Adult patients that had a colonization culture, confirmed MRSA cSSSI, received at least one dose of study treatment, and had an outcome recorded at end of study. Patient, clinical characteristics and prevalence of colonization were compared by treatment regimens. A multivariate regression model identified predictors of MRSA colonization at EOS. Results: There were 456 patients evaluated. The prevalence of MRSA colonization was higher for vancomycin treated patients compared to linezolid treated patients at end of treatment (EOT) (28% vs. 5%, p < 0.001) and EOS (34% vs. 22%, p < 0.01). Independent predictors of colonization at EOS after treatment for a MRSA cSSSI included diagnosis, primarily driven by abscess, black race, treatment with vancomycin, MRSA mixed infection and male gender. Conclusion: Patients treated with linezolid for a cSSSI had less MRSA colonization at EOT and EOS compared to those treated with vancomycin. Multiple independent predictors of MRSA colonization were identified. Additional studies evaluating the relationship of MRSA colonization after treatment of cSSSI are needed.
文摘The aim of this study was to determine the prevalence of M. hyopneumoniae infection in suckling pigs. Nasal swabs were collected from 300 suckling pigs originating from five farrow-to-finishing farms. One farm had a confirmed PRDC problem (farm A) and four other farms previously had a PRDC problem (farms B, C, D and E). Thirty (30) lactating sows in parity 1, 2 and 3 were selected from each farm (Ten sows per parity). Two piglets from each sow were randomly sampled for nasal swab at 3 weeks of age. The samples were analyzed by the nested PCR technique. Forty five per cent (27/60) of nasal swabs from farm A were found positive. On the other hand, a total of 2.08 per cent were found positive (5/240) from farm B, C, D and E. The tendency of piglet infection per sow by parity showed that first parity had more prevalence than the second and the third parity (60%, 55%, 20%), respectively. We have found a correction between M. hyopneumoniae early infection in suckling pigs and a confirmed PRDC problem (farm A) as oppose to farms that did not have a PRDC problem. The strategies to prevent M. hyopneumoniae early infection are to maintain good lactation, antibiotic prevention program and early M. hyopneumoniae
文摘In September 2012,the US Chinese Anti-Cancer Association(USCACA) hosted two symposiums in Beijing.The USCACA hosted the first joint session at the 7th annual meetings of the Chinese Anti-Cancer Association(CACA),themed on "Collaboration between the US and China in Cancer Research." Six experts from the United States and China presented their latest work on basic and translational cancer research.During this symposium,5 young Chinese scholars,returnees after their training in the United States,were honored the"AFCR-USCACA Scholarships Award." The USCACA hosted a second symposium during the 15th annual meeting of the Chinese Society of Clinical Oncology(CSCO),focused on the "US-China Collaboration in Cancer Drug Clinical Development." An international delegation of oncology experts presented the innovative clinical trial strategies and discussed the biomarkers for cancer early detection and clinical trials,targeted therapy,and new drug development.The Oncology Drug Clinical Development and Safety Evaluation Committee was also launched to promote an innovative environment and to provide a collaborative platform for anti-cancer drug development in China.
文摘Data from a prospective, randomized, open-label, active-controlled, multicenter, Phase 4 study comparing oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections caused by methicillin resistant Staphylococcus aureus was used to determine the association between staphylococcal cassette chromosome mec (SCCmec) type and patient’s clinical presentation, infection severity, intravenous therapy duration and length of stay (LOS). Compared to SCCmec types I, II, and III, SCCmec type IV, PVL+ was associated with more frequent presentation of abscesses, lower severity scores, and shorter intravenous therapy duration and LOS in both treatment groups.
