Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in ...Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen Neu N, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ？ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke.展开更多
Self expanding metal stents (SEMS) play an important role in the management of malignant obstructing lesions in the gastrointestinal tract. Traditionally,they have been used for palliation in malignant gastric outlet ...Self expanding metal stents (SEMS) play an important role in the management of malignant obstructing lesions in the gastrointestinal tract. Traditionally,they have been used for palliation in malignant gastric outlet and colonic obstruction and esophageal malignancy. The development of the polyflex stent,which is a removable self expanding plastic stent,allows temporary stent insertion for benign esophageal disease and possibly for patients undergoing neoadjuvant chemotherapy prior to esophagectomy. Potential complications of SEMS insertion include perforation,tumour overgrowth or ingrowth,and stent migration. Newer stents are being developed with the aim of increasing technical and clinical success rates,while reducing complication rates. Other areas of development include biodegradable stents for benign disease and radioactive or drug-eluting stents for malignant disease. It is hoped that,in the future,newer stents will improve our management of these diffi cult conditions and,possibly,provide prognostic as well as symptomatic benefi t in the setting of malignant obstruction.展开更多
Several reports have described an apparently uncommon clinicopathological disorder that is characterized by multifocal stenosing small-intestinal ulceration.Compared to Crohn's disease,the ulcers are not transmura...Several reports have described an apparently uncommon clinicopathological disorder that is characterized by multifocal stenosing small-intestinal ulceration.Compared to Crohn's disease,the ulcers are not transmural and typically remain shallow,and involve only the mucosa and submucosa.The disorder seems to be localized in the jejunum and proximal ileum only,and not the distal ileum or colon.Only nonspecif ic inflammatory changes are present without giant cells or other typical features of granulomatous inflammation.Most patients present clinically with recurrent obstructive events that usually respond to steroids,surgical resection,or both.With the development of newer imaging modalities to visualize the small-intestinal mucosa,such as double-balloon enteroscopy,improved understanding of the long-term natural history of this apparently distinctive disorder should emerge.展开更多
Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria that affects periodontal support tissues.1 If left untreated,it results in loss of periodontal attachment and alveolar bone resorptio...Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria that affects periodontal support tissues.1 If left untreated,it results in loss of periodontal attachment and alveolar bone resorption.Approximately one-half of adults in the United States older than 30 years have periodontal disease.2 Though the disease is initiated by bacterial infection,it activates host defense systems that eventually lead to the degradation of the periodontium.During periodontitis,the disease progress involves further production of pro-inflammatory mediators such as cytokines,proteolytic enzymes like matrix metalloproteinases(MMPs),and their inhibitors.展开更多
Web3,also known as Web 3.0,has recently been attracting increasing attention from industry and academia.Leveraging the potential of blockchain technologies,Web3 has emerged as a pivotal foundation in the realm of meta...Web3,also known as Web 3.0,has recently been attracting increasing attention from industry and academia.Leveraging the potential of blockchain technologies,Web3 has emerged as a pivotal foundation in the realm of metaverse development,which is considered by many as the next-generation Internet.Specifically,Web3 technologies such as smart contracts and protocols like non-fungible tokens(NFTs)have supported the immersive and content-rich experience of current Web3 metaverse projects.展开更多
The separator is an essential component of sodium-ion batteries(SIBs)to determine their electrochemical performances.However,the separator with high mechanical strength,good electrolyte wettability and excellent elect...The separator is an essential component of sodium-ion batteries(SIBs)to determine their electrochemical performances.However,the separator with high mechanical strength,good electrolyte wettability and excellent electrochemical performance remains an open challenge.Herein,a new separator consisting of amphoteric nanofibers with abundant functional groups was fabricated through supramolecular assembly of natural polymers for SIB.The uniform nanoporous structure,remarkable mechanical properties and abundant functional groups(e.g.-COOH,-NH_(2)and-OH)endow the separator with lower dissolution activation energy and higher ion migration numbers.These metrics enable the separator to lower the barrier for desolvation of Na^(+),accelerate the migration of Na^(+),and generate more stable solid electrolyte interphase(SEI)and cathode electrolyte interphase(CEI).The battery assembled with the amphoteric nanofiber separator shows higher specific capacity and better stability than that assembled with glass fiber(GF)separator.展开更多
Background : Adherence to therapy is integral to successfully managing asthma, which requires comprehension of what, when, and how to use medication and diligence in following management plan. Asthma patients from eth...Background : Adherence to therapy is integral to successfully managing asthma, which requires comprehension of what, when, and how to use medication and diligence in following management plan. Asthma patients from ethnic minority groups have more morbidity and reported filling their prescriptions less often. Limited information is available in Canadian literature on ethnic differences in their perceptions of asthma management. We aimed to document patient perceived adherence to asthma therapy among targeted ethno-cultural groups. Methods : We evaluated perceived barriers to therapy adherence, including: cultural beliefs and practices, patient/care-provider communication, self-management knowledge, and medication costs. We conducted a cross sectional study and interviewed 85 Chinese or Punjabispeaking adult asthma patients. Results : Lack of sufficient instructions from physicians, language/communication barriers, lack of skills on how to use inhalers, and high medication costs and medication side effects were most reported barriers to proper self-management practices. Most participants lived with others in the same household and reported high social support from home caregivers. The influence of family on self-management practices was obvious. Conclusion: Better understanding of patient needs, provision of culturally and linguistically appropriate education, and inclusion of home caregivers into the management practices are necessary to improve asthma outcomes in Chinese and Punjabi communities.展开更多
A 69-year-old male with chronic lymphocytic leukemia presented with iron deficiency anemia and post-prandial abdominal fullness. Endoscopy showed a large polyp on a stalk, protruding through the pylorus into the duode...A 69-year-old male with chronic lymphocytic leukemia presented with iron deficiency anemia and post-prandial abdominal fullness. Endoscopy showed a large polyp on a stalk, protruding through the pylorus into the duodenum causing intermittent gastric outlet obstruction. While prolapsing gastric antral polyps are usually benign and hyperplastic, inflammatory or regenerative in type, excisional snare polypectomy here led to complete resolution of his symptoms, but showed a malignant polyp.展开更多
There is recognized increased risk for colorectal cancer in patients with inflammatory bowel disease, particularly in long-standing and extensive ulcerative colitis. There also appears to be an increased rate of intes...There is recognized increased risk for colorectal cancer in patients with inflammatory bowel disease, particularly in long-standing and extensive ulcerative colitis. There also appears to be an increased rate of intestinal cancer in Crohn's disease, including both colon and small bowel sites. In Crohn's disease, evidence suggests that detection of colorectal cancer may be delayed with a worse progno-sis. Some risk factors for cancer in Crohn's disease include the extent of inflammatory change within the colon and the presence of bypassed or excluded segments, inclu-ding rectal "stump" cancer. In addition, the risk for other types of intestinal neoplasms may be increased in Crohn's disease, including lymphoma and carcinoid tumors. Earlier detection of colorectal cancer based on colonoscopy scre-ening and surveillance may be achieved but, to date, this has not translated into a positive survival benefit. Moreo-ver, newer staining methods and evolving micro-endos-copic techniques show promise, but have not significantly altered management. Future research should focus on development of molecular or other bio-markers that might predict future dysplasia or cancer development in Crohn's disease.展开更多
Objective. -To evaluate the psychometric properties of the revised Patient Perception of Migraine Questionnaire (PPMQ-R), which measures satisfaction with migraine treatment. Background. -The original version of the P...Objective. -To evaluate the psychometric properties of the revised Patient Perception of Migraine Questionnaire (PPMQ-R), which measures satisfaction with migraine treatment. Background. -The original version of the PPMQ was developed prior to the introduction of newer migraine treatments, which may have attributes that influence treatment satisfaction. Methods. -Literature review, patient focus groups, and one-on-one patient interviews guided revisions to the original PPMQ. The revised questionnaire was tested in 200 migraine patients visiting neurologists and primary care clinics. At baseline, all subjects completed the PPMQ-R, a migraine-specific quality-of-life measure, and a migraine experience questionnaire; and 125 subjects completed assessments 24 hours after each migraine attack and within 30 days post-baseline. Factor analysis was performed to inform the development of a scoring algorithm, and reliability, validity, and responsiveness of the PPMQ-R were evaluated. Results. -Factor analyses confirmed that the revised questionnaire has five domains measuring satisfaction with efficacy, functionality, ease of use, medication cost, and bothersomeness of medication side effects. A total score can be created by taking the average of efficacy, functionality, and ease of use scores. The PPMQ-R scale scores and Total score demonstrated internal consistency reliability (Cronbach’s α: 0.80 to 0.98) and test-retest reliability (intra-class correlation coefficient: 0.79 to 0.91). Except for the Cost domain, the PPMQ-R scores discriminated among migraine pain severity levels (all P < .05) and levels of impairment in ability to work and perform usual activities (all P < .05). Except for the Ease of Use and Cost domains, mean PPMQ-R scores were significantly higher among patients with no change in treatment and whose pain improved between two consecutive migraine attacks (all P < .01). Conclusion. -The PPMQ-R is a reliable and valid measure of patient satisfaction with acute migraine treatment in women with frequent展开更多
Purines have a recognized importance as intercellular mes- sengers. These molecules play an important role in the de- velopment and maintenance of the central nervous system （CNS）, as well as in its response to path...Purines have a recognized importance as intercellular mes- sengers. These molecules play an important role in the de- velopment and maintenance of the central nervous system （CNS）, as well as in its response to pathological conditions. Both adenine and guanine-based purines can be released from astrocytes, where they play a relevant role as extracel- lular signaling molecules. Particularly, the nucleoside gua- nosine has been proposed as an extracellular molecule that regulates the response of CNS to damage. Following injury, this nucleoside attains high concentrations in the extracel- lular space, where it activates multiple signaling pathways.展开更多
Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. Recently, a monoclonal antibody, designated ...Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. Recently, a monoclonal antibody, designated as RP215, was generated against the ovarian cancer cell line, OC-3-VGH, and was shown to react with CA215, which consisted mainly of these cancer cell-expressed antigen receptors. Experimental evidence has clearly indicated that cancerous immunoglobulins play significant roles in the growth and proliferation of cancer cells in vitro and in vivo. RP215 and anti-antigen receptor antibodies were equally effective in inducing apoptosis and complement-dependent cytotoxicity reactions to cultured cancer cells. Through gene regulation studies, both RP215 and antibodies against antigen-receptors were shown to affect more than a dozen of genes involved in cell proliferation (such as NFκB-1, IgG, P21, cyclin D1, ribosomal P1, and c-fos). Furthermore, selected toll-like receptor genes (TLR- 2, -3, -4, and -9) were also found to be highly regulated by both RP215 and anti-antigen receptor antibodies. For example, RP215 and anti-antigen receptor antibodies were found to both up-regulate TLR-2 and/or TLR-3 and down- regulate TLR-4 and TLR-9 intwo types of cancer cells. Based on these studies, it is reasonable to postulate that cancerous immunoglobulins play important roles in the modulation of the innate immune system to allow the growth and survival of cancer cells within the human body. Consequently, RP215 inits humanized forms may be utilized to target cancer cells for potential therapeutic purposes.展开更多
RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically ...RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.展开更多
Crohn’ s disease is a heterogeneous disorder that involves different sites along the length of the gastrointestinal tract. It is usually characterized by a high rate of strictures and penetrating complications. The p...Crohn’ s disease is a heterogeneous disorder that involves different sites along the length of the gastrointestinal tract. It is usually characterized by a high rate of strictures and penetrating complications. The present study used the modified Vienna classification schema to explore the specific role of age at diagnosis on both disease location and disease behavior. There were 1,015 consecutively evaluated patients, including 449 males and 566 females. Disease was most often localized in the ileocolon and could be most often classified as complex disease (ie, in >70% ) with strictures or penetrating complications. For both males and females, with increasing age at diagnosis, disease became less extensive, more often localized in the colon alone, and disease behavior could be characterized as more complex, especially with penetrating disease complications. These results demonstrate the phenomenon of age dependence in the phenotypic clinical expression of Crohn’ s disease.展开更多
基金supported by the Korea Health Technology R&D Project,Ministry of Health & Welfare(HI12C0381),Republic of Korea
文摘Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen Neu N, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ？ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke.
文摘Self expanding metal stents (SEMS) play an important role in the management of malignant obstructing lesions in the gastrointestinal tract. Traditionally,they have been used for palliation in malignant gastric outlet and colonic obstruction and esophageal malignancy. The development of the polyflex stent,which is a removable self expanding plastic stent,allows temporary stent insertion for benign esophageal disease and possibly for patients undergoing neoadjuvant chemotherapy prior to esophagectomy. Potential complications of SEMS insertion include perforation,tumour overgrowth or ingrowth,and stent migration. Newer stents are being developed with the aim of increasing technical and clinical success rates,while reducing complication rates. Other areas of development include biodegradable stents for benign disease and radioactive or drug-eluting stents for malignant disease. It is hoped that,in the future,newer stents will improve our management of these diffi cult conditions and,possibly,provide prognostic as well as symptomatic benefi t in the setting of malignant obstruction.
文摘Several reports have described an apparently uncommon clinicopathological disorder that is characterized by multifocal stenosing small-intestinal ulceration.Compared to Crohn's disease,the ulcers are not transmural and typically remain shallow,and involve only the mucosa and submucosa.The disorder seems to be localized in the jejunum and proximal ileum only,and not the distal ileum or colon.Only nonspecif ic inflammatory changes are present without giant cells or other typical features of granulomatous inflammation.Most patients present clinically with recurrent obstructive events that usually respond to steroids,surgical resection,or both.With the development of newer imaging modalities to visualize the small-intestinal mucosa,such as double-balloon enteroscopy,improved understanding of the long-term natural history of this apparently distinctive disorder should emerge.
基金the National Institutes of Health grants,RO1DE019802the Pilot Grant of the School of Dentistry,UTHSCSA,131314.
文摘Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria that affects periodontal support tissues.1 If left untreated,it results in loss of periodontal attachment and alveolar bone resorption.Approximately one-half of adults in the United States older than 30 years have periodontal disease.2 Though the disease is initiated by bacterial infection,it activates host defense systems that eventually lead to the degradation of the periodontium.During periodontitis,the disease progress involves further production of pro-inflammatory mediators such as cytokines,proteolytic enzymes like matrix metalloproteinases(MMPs),and their inhibitors.
文摘Web3,also known as Web 3.0,has recently been attracting increasing attention from industry and academia.Leveraging the potential of blockchain technologies,Web3 has emerged as a pivotal foundation in the realm of metaverse development,which is considered by many as the next-generation Internet.Specifically,Web3 technologies such as smart contracts and protocols like non-fungible tokens(NFTs)have supported the immersive and content-rich experience of current Web3 metaverse projects.
基金supported by the Outstanding Youth Team Project of Guangdong Natural Science Foundation(2023B1515040013)Guangdong Basic and Applied Basic Research Foundation(2023A1515012215,2023B1515040013,2023A1515012519)+1 种基金State Key Laboratory of Pulp&Paper Engineering(2023C07,2023PY03)Guangdong Col ege Students’Scientific and Technological Innovation(“Climbing Program”Special Fund,Pdjh2022a0026)
文摘The separator is an essential component of sodium-ion batteries(SIBs)to determine their electrochemical performances.However,the separator with high mechanical strength,good electrolyte wettability and excellent electrochemical performance remains an open challenge.Herein,a new separator consisting of amphoteric nanofibers with abundant functional groups was fabricated through supramolecular assembly of natural polymers for SIB.The uniform nanoporous structure,remarkable mechanical properties and abundant functional groups(e.g.-COOH,-NH_(2)and-OH)endow the separator with lower dissolution activation energy and higher ion migration numbers.These metrics enable the separator to lower the barrier for desolvation of Na^(+),accelerate the migration of Na^(+),and generate more stable solid electrolyte interphase(SEI)and cathode electrolyte interphase(CEI).The battery assembled with the amphoteric nanofiber separator shows higher specific capacity and better stability than that assembled with glass fiber(GF)separator.
文摘Background : Adherence to therapy is integral to successfully managing asthma, which requires comprehension of what, when, and how to use medication and diligence in following management plan. Asthma patients from ethnic minority groups have more morbidity and reported filling their prescriptions less often. Limited information is available in Canadian literature on ethnic differences in their perceptions of asthma management. We aimed to document patient perceived adherence to asthma therapy among targeted ethno-cultural groups. Methods : We evaluated perceived barriers to therapy adherence, including: cultural beliefs and practices, patient/care-provider communication, self-management knowledge, and medication costs. We conducted a cross sectional study and interviewed 85 Chinese or Punjabispeaking adult asthma patients. Results : Lack of sufficient instructions from physicians, language/communication barriers, lack of skills on how to use inhalers, and high medication costs and medication side effects were most reported barriers to proper self-management practices. Most participants lived with others in the same household and reported high social support from home caregivers. The influence of family on self-management practices was obvious. Conclusion: Better understanding of patient needs, provision of culturally and linguistically appropriate education, and inclusion of home caregivers into the management practices are necessary to improve asthma outcomes in Chinese and Punjabi communities.
文摘A 69-year-old male with chronic lymphocytic leukemia presented with iron deficiency anemia and post-prandial abdominal fullness. Endoscopy showed a large polyp on a stalk, protruding through the pylorus into the duodenum causing intermittent gastric outlet obstruction. While prolapsing gastric antral polyps are usually benign and hyperplastic, inflammatory or regenerative in type, excisional snare polypectomy here led to complete resolution of his symptoms, but showed a malignant polyp.
文摘There is recognized increased risk for colorectal cancer in patients with inflammatory bowel disease, particularly in long-standing and extensive ulcerative colitis. There also appears to be an increased rate of intestinal cancer in Crohn's disease, including both colon and small bowel sites. In Crohn's disease, evidence suggests that detection of colorectal cancer may be delayed with a worse progno-sis. Some risk factors for cancer in Crohn's disease include the extent of inflammatory change within the colon and the presence of bypassed or excluded segments, inclu-ding rectal "stump" cancer. In addition, the risk for other types of intestinal neoplasms may be increased in Crohn's disease, including lymphoma and carcinoid tumors. Earlier detection of colorectal cancer based on colonoscopy scre-ening and surveillance may be achieved but, to date, this has not translated into a positive survival benefit. Moreo-ver, newer staining methods and evolving micro-endos-copic techniques show promise, but have not significantly altered management. Future research should focus on development of molecular or other bio-markers that might predict future dysplasia or cancer development in Crohn's disease.
文摘Objective. -To evaluate the psychometric properties of the revised Patient Perception of Migraine Questionnaire (PPMQ-R), which measures satisfaction with migraine treatment. Background. -The original version of the PPMQ was developed prior to the introduction of newer migraine treatments, which may have attributes that influence treatment satisfaction. Methods. -Literature review, patient focus groups, and one-on-one patient interviews guided revisions to the original PPMQ. The revised questionnaire was tested in 200 migraine patients visiting neurologists and primary care clinics. At baseline, all subjects completed the PPMQ-R, a migraine-specific quality-of-life measure, and a migraine experience questionnaire; and 125 subjects completed assessments 24 hours after each migraine attack and within 30 days post-baseline. Factor analysis was performed to inform the development of a scoring algorithm, and reliability, validity, and responsiveness of the PPMQ-R were evaluated. Results. -Factor analyses confirmed that the revised questionnaire has five domains measuring satisfaction with efficacy, functionality, ease of use, medication cost, and bothersomeness of medication side effects. A total score can be created by taking the average of efficacy, functionality, and ease of use scores. The PPMQ-R scale scores and Total score demonstrated internal consistency reliability (Cronbach’s α: 0.80 to 0.98) and test-retest reliability (intra-class correlation coefficient: 0.79 to 0.91). Except for the Cost domain, the PPMQ-R scores discriminated among migraine pain severity levels (all P < .05) and levels of impairment in ability to work and perform usual activities (all P < .05). Except for the Ease of Use and Cost domains, mean PPMQ-R scores were significantly higher among patients with no change in treatment and whose pain improved between two consecutive migraine attacks (all P < .01). Conclusion. -The PPMQ-R is a reliable and valid measure of patient satisfaction with acute migraine treatment in women with frequent
基金funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq#403120/2012-8,#308723/2013-9,#449436/2014-4)Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(CAPES),Brazil
文摘Purines have a recognized importance as intercellular mes- sengers. These molecules play an important role in the de- velopment and maintenance of the central nervous system （CNS）, as well as in its response to pathological conditions. Both adenine and guanine-based purines can be released from astrocytes, where they play a relevant role as extracel- lular signaling molecules. Particularly, the nucleoside gua- nosine has been proposed as an extracellular molecule that regulates the response of CNS to damage. Following injury, this nucleoside attains high concentrations in the extracel- lular space, where it activates multiple signaling pathways.
文摘Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. Recently, a monoclonal antibody, designated as RP215, was generated against the ovarian cancer cell line, OC-3-VGH, and was shown to react with CA215, which consisted mainly of these cancer cell-expressed antigen receptors. Experimental evidence has clearly indicated that cancerous immunoglobulins play significant roles in the growth and proliferation of cancer cells in vitro and in vivo. RP215 and anti-antigen receptor antibodies were equally effective in inducing apoptosis and complement-dependent cytotoxicity reactions to cultured cancer cells. Through gene regulation studies, both RP215 and antibodies against antigen-receptors were shown to affect more than a dozen of genes involved in cell proliferation (such as NFκB-1, IgG, P21, cyclin D1, ribosomal P1, and c-fos). Furthermore, selected toll-like receptor genes (TLR- 2, -3, -4, and -9) were also found to be highly regulated by both RP215 and anti-antigen receptor antibodies. For example, RP215 and anti-antigen receptor antibodies were found to both up-regulate TLR-2 and/or TLR-3 and down- regulate TLR-4 and TLR-9 intwo types of cancer cells. Based on these studies, it is reasonable to postulate that cancerous immunoglobulins play important roles in the modulation of the innate immune system to allow the growth and survival of cancer cells within the human body. Consequently, RP215 inits humanized forms may be utilized to target cancer cells for potential therapeutic purposes.
文摘RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.
文摘Crohn’ s disease is a heterogeneous disorder that involves different sites along the length of the gastrointestinal tract. It is usually characterized by a high rate of strictures and penetrating complications. The present study used the modified Vienna classification schema to explore the specific role of age at diagnosis on both disease location and disease behavior. There were 1,015 consecutively evaluated patients, including 449 males and 566 females. Disease was most often localized in the ileocolon and could be most often classified as complex disease (ie, in >70% ) with strictures or penetrating complications. For both males and females, with increasing age at diagnosis, disease became less extensive, more often localized in the colon alone, and disease behavior could be characterized as more complex, especially with penetrating disease complications. These results demonstrate the phenomenon of age dependence in the phenotypic clinical expression of Crohn’ s disease.
