Direct oral anticoagulants are recommended as first line therapy for patients with atrial fibrillation and venous thromboembolic disease. Measurement of drug levels or pharmacodynamic effect is not recommended during treatment. Dose adjustments are based on age, weight, kidney function and drug-drug interactions. These adjustments are generally based on an estimate of their effect on drug concentration. DOAC dosing recommendations differ across the world. These differences in prescribing recommendations result in different levels of DOAC exposure in patients with identical clinical characteristics. Additionally, data from clinical trials has shown that drug levels may vary significantly in individual patients with identical clinical characteristics despite taking the same prescribed dose. More concerning is that current prescribing recommendations provide cut points for dose adjustments, as an example age 80 or greater in the case of apixaban in atrial fibrillation, which may result in dramatically higher drug concentrations in patients with significantly higher bleeding risk. Data from outcome trials in both atrial fibrillation and venous thromboembolism have provided mean-median drug concentrations for each of the DOACs. These trial results appear to demonstrate that once a threshold DOAC plasma concentration is reached, higher concentrations fail to provide significant added ischemic stroke reduction while at the same time add an increased risk of bleeding. Bleeding remains a significant problem with DOACs and is associated with an increase in short and long-term mortality, ischemic stroke, myocardial infarction, cost, and drug interruption and discontinuation. Over the past years, our clinic has been assessing DOAC concentration in patients at risk for under or over exposure. Based on our experience, clinical characteristics alone appear to be insufficient, as a significant number of patients with characteristics suggesting high exposure would be under-dosed using a purely clinical approach and an even greater number, who are at elevated risk of bleeding would have had excessive levels, if prescribing were based strictly on the established dose reduction criteria. We propose, and provide our supporting clinical experience, that measuring DOAC levels in select patients will increase the margin of safety of these medications without compromising efficacy.
{"title":"Is there a Role for Measuring Direct Oral Anticoagulant Levels in Select Patients?","authors":"L. Baruch, K. Bhatia, P. Lopez, O. Sherman","doi":"10.18103/mra.v11i1.3527","DOIUrl":"https://doi.org/10.18103/mra.v11i1.3527","url":null,"abstract":"Direct oral anticoagulants are recommended as first line therapy for patients with atrial fibrillation and venous thromboembolic disease. Measurement of drug levels or pharmacodynamic effect is not recommended during treatment. Dose adjustments are based on age, weight, kidney function and drug-drug interactions. These adjustments are generally based on an estimate of their effect on drug concentration. DOAC dosing recommendations differ across the world. These differences in prescribing recommendations result in different levels of DOAC exposure in patients with identical clinical characteristics. Additionally, data from clinical trials has shown that drug levels may vary significantly in individual patients with identical clinical characteristics despite taking the same prescribed dose. More concerning is that current prescribing recommendations provide cut points for dose adjustments, as an example age 80 or greater in the case of apixaban in atrial fibrillation, which may result in dramatically higher drug concentrations in patients with significantly higher bleeding risk. Data from outcome trials in both atrial fibrillation and venous thromboembolism have provided mean-median drug concentrations for each of the DOACs. These trial results appear to demonstrate that once a threshold DOAC plasma concentration is reached, higher concentrations fail to provide significant added ischemic stroke reduction while at the same time add an increased risk of bleeding. Bleeding remains a significant problem with DOACs and is associated with an increase in short and long-term mortality, ischemic stroke, myocardial infarction, cost, and drug interruption and discontinuation. Over the past years, our clinic has been assessing DOAC concentration in patients at risk for under or over exposure. Based on our experience, clinical characteristics alone appear to be insufficient, as a significant number of patients with characteristics suggesting high exposure would be under-dosed using a purely clinical approach and an even greater number, who are at elevated risk of bleeding would have had excessive levels, if prescribing were based strictly on the established dose reduction criteria. We propose, and provide our supporting clinical experience, that measuring DOAC levels in select patients will increase the margin of safety of these medications without compromising efficacy.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75531583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Digitalization of the education system in Indonesia became an important topic in the country’s ministry of Education, Culture, Research, and Technology during the period of COVID as all the schools in the country were closed indefinitely. Online classrooms were adopted nationally to ensure that learning persisted despite the shutdown, with teachers and students communicating digitally on instruction, assessment, reporting, and conversations. After the pandemic, the country has not dropped the technology but rather, has taken several steps towards completely digitizing the education system. A literature review was conducted in this paper to understand how COVID pandemic has been instrumental in bringing digital transformations in Indonesia’s education system. It was found that the country has carried forward, as well as introducing further actions in the efforts to digitize the country’s education system. Intriguingly, Indonesia highlights some of the ways that covid-19 has revitalized the tradition of gotong royong (mutual cooperation) within the current setting, in addition to the influence of digitalization on life. Gotong royong is a technique that is frequently employed to raise public awareness of the harm that results from breaking through social barriers, even in the name of getting back together with families to observe a religious holiday. The idea has given rise to a new view of collectivism that does not require physical proximity for us to keep each other safe in this situation.
{"title":"Influence of COVID in Digitizing and Collective Endeavor in Indonesia","authors":"P. Rimbawati","doi":"10.18103/mra.v11i6.3861","DOIUrl":"https://doi.org/10.18103/mra.v11i6.3861","url":null,"abstract":"Digitalization of the education system in Indonesia became an important topic in the country’s ministry of Education, Culture, Research, and Technology during the period of COVID as all the schools in the country were closed indefinitely. Online classrooms were adopted nationally to ensure that learning persisted despite the shutdown, with teachers and students communicating digitally on instruction, assessment, reporting, and conversations. After the pandemic, the country has not dropped the technology but rather, has taken several steps towards completely digitizing the education system. A literature review was conducted in this paper to understand how COVID pandemic has been instrumental in bringing digital transformations in Indonesia’s education system. It was found that the country has carried forward, as well as introducing further actions in the efforts to digitize the country’s education system. Intriguingly, Indonesia highlights some of the ways that covid-19 has revitalized the tradition of gotong royong (mutual cooperation) within the current setting, in addition to the influence of digitalization on life. Gotong royong is a technique that is frequently employed to raise public awareness of the harm that results from breaking through social barriers, even in the name of getting back together with families to observe a religious holiday. The idea has given rise to a new view of collectivism that does not require physical proximity for us to keep each other safe in this situation.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74553662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.18103/mra.v11i7.2.4091
A. Valle, Aloíso Carvalho, Samir Rahme, A. Araújo, P. Malard, H. Brunel
Homeopathy has become increasingly known and used in various treatments, showing excellent clinical results. One of its most common indications is to help treat chronic diseases, directly improving patients' quality of life, especially those with cancer. Hepatocellular carcinoma is a disease that depends on different factors for its development and the success of its treatment. In this context, searching for new therapeutic tools is essential, and homeopathy seems promising. Therefore, Anonna muricata (soursop/graviola) and Handroanthus impetiginosus (purple ipe) have been studied due to their action potential against tumor cells. This study aimed to evaluate the effect of these medicines combined in 1.1mL ampoules, in homeopathic dilutions, on HepG2 (hepatocellular carcinoma) cells through in vitro tests. Cells were cultivated in 75 cm² culture bottles in an oven with controlled temperature and CO2 quantity (37 ºC, 5% CO2). Then, cells were plated in 96-well plates where treatment was performed using the products at different concentrations. After 48 hours of treatment, cell viability analyses were performed by MTT and quantification of the nitric oxide released using the Griess reaction. Treatment with the Anonna muricata D5 (1x10-5) + Handroanthus impetiginosus D5 (1x10-5) formulation resulted in decreased cell viability and increased nitric oxide production by these cells. These findings indicate that this medicine showed an antitumor effect and can be an ally in treating this type of pathology.
{"title":"Evaluation of cell viability and nitric oxide release after treatment of human hepatocellular carcinoma cells with a homeopathic compound of Graviola (Anonna muricata) and Purple Ipe (Handroanthus impetiginosus)","authors":"A. Valle, Aloíso Carvalho, Samir Rahme, A. Araújo, P. Malard, H. Brunel","doi":"10.18103/mra.v11i7.2.4091","DOIUrl":"https://doi.org/10.18103/mra.v11i7.2.4091","url":null,"abstract":"Homeopathy has become increasingly known and used in various treatments, showing excellent clinical results. One of its most common indications is to help treat chronic diseases, directly improving patients' quality of life, especially those with cancer. Hepatocellular carcinoma is a disease that depends on different factors for its development and the success of its treatment. In this context, searching for new therapeutic tools is essential, and homeopathy seems promising. Therefore, Anonna muricata (soursop/graviola) and Handroanthus impetiginosus (purple ipe) have been studied due to their action potential against tumor cells. This study aimed to evaluate the effect of these medicines combined in 1.1mL ampoules, in homeopathic dilutions, on HepG2 (hepatocellular carcinoma) cells through in vitro tests. Cells were cultivated in 75 cm² culture bottles in an oven with controlled temperature and CO2 quantity (37 ºC, 5% CO2). Then, cells were plated in 96-well plates where treatment was performed using the products at different concentrations. After 48 hours of treatment, cell viability analyses were performed by MTT and quantification of the nitric oxide released using the Griess reaction. Treatment with the Anonna muricata D5 (1x10-5) + Handroanthus impetiginosus D5 (1x10-5) formulation resulted in decreased cell viability and increased nitric oxide production by these cells. These findings indicate that this medicine showed an antitumor effect and can be an ally in treating this type of pathology.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"26 7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74593678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The insulin-like growth factor-1 hormonal axis has emerged in recent years as a promising therapeutic target in oncology. Empirical support to this view was provided by pre-clinical studies showing that insulin-like growth factor-1 receptor expression and activation constitute fundamental prerequisites for breast cancer development. Unfortunately, the vast majority of phase III clinical trials using monoclonal antibodies against the receptor have been disappointing. As a result of these negative outcomes there is an urgent need to identify predictive biomarkers that may identify potential responders. The present review article is aimed at providing an overview of the role of the insulin-like growth factor-1 axis in breast cancer. Circulating insulin-like growth factor-1 constitutes a risk factor for a number of malignancies, including breast cancer, and various members of the insulin-like growth factor-1 system are produced by the tumoral cells or by stromal cells. In addition, we provide evidence that the mechanism of action of insulin-like growth factor-1 involves interactions with the estrogen receptor as well as with the breast cancer gene-1. Finally, lifestyle factors that are related to insulin-like growth factor-1, such as obesity, have been suggested to have an effect on breast cancer.
{"title":"New Insights into the Role of the Insulin-Like Growth Factors in Breast Cancer","authors":"H. Werner","doi":"10.18103/mra.v11i4.3634","DOIUrl":"https://doi.org/10.18103/mra.v11i4.3634","url":null,"abstract":"The insulin-like growth factor-1 hormonal axis has emerged in recent years as a promising therapeutic target in oncology. Empirical support to this view was provided by pre-clinical studies showing that insulin-like growth factor-1 receptor expression and activation constitute fundamental prerequisites for breast cancer development. Unfortunately, the vast majority of phase III clinical trials using monoclonal antibodies against the receptor have been disappointing. As a result of these negative outcomes there is an urgent need to identify predictive biomarkers that may identify potential responders. The present review article is aimed at providing an overview of the role of the insulin-like growth factor-1 axis in breast cancer. Circulating insulin-like growth factor-1 constitutes a risk factor for a number of malignancies, including breast cancer, and various members of the insulin-like growth factor-1 system are produced by the tumoral cells or by stromal cells. In addition, we provide evidence that the mechanism of action of insulin-like growth factor-1 involves interactions with the estrogen receptor as well as with the breast cancer gene-1. Finally, lifestyle factors that are related to insulin-like growth factor-1, such as obesity, have been suggested to have an effect on breast cancer.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78203875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Neuropsychology is a branch of clinical psychology that specializes in brain-behavior relationships by assessing cognition, behavior, and emotion. Neuropsychology was initially developed in the United States and Europe, and their practices have shaped other countries’ practices such as Japan. However, neuropsychology in Japan also has its own unique history. Aims: The present paper aims to discuss the history, work environment and licensure, and prospects of Japanese neuropsychology by comparing them to those in the United States. Methods: Information on four topics, including 1) the history and development of neuropsychology and the license of a clinical neuropsychologist in the United States, 2) the history and current situation of neuropsychology in Japan, 3) the background and process of the licensure in clinical psychology and neuropsychology in Japan, and 4) future directions and recommendations, were gathered through literature searches, official organization websites, and personal communication with clinical psychologists and other professionals in Japan. Results: While clinical neuropsychologists in the United States have a background in clinical psychology, most of the people conducting neuropsychological assessments and research in Japan are physicians, occupational therapists, and speech-language-hearing therapists. This is believed to be due to differences in the system of health insurance, education and training, cultural factors shaping psychology practice in Japan, funding opportunities, and the research environment. Conclusion: The care of patients who have neurological injuries and illnesses is one of the most crucial tasks for clinical neuropsychologists. It is important for clinical neuropsychologists in Japan to improve their knowledge and skills in clinical psychology to match global standards.
{"title":"History and State of Neuropsychology in Japan: A Modest Proposal from a Clinical Psychological Perspective","authors":"M. Pomeroy, Yoko Okamura, Nicholas S Thaler","doi":"10.18103/mra.v11i1.3485","DOIUrl":"https://doi.org/10.18103/mra.v11i1.3485","url":null,"abstract":"Introduction: Neuropsychology is a branch of clinical psychology that specializes in brain-behavior relationships by assessing cognition, behavior, and emotion. Neuropsychology was initially developed in the United States and Europe, and their practices have shaped other countries’ practices such as Japan. However, neuropsychology in Japan also has its own unique history. Aims: The present paper aims to discuss the history, work environment and licensure, and prospects of Japanese neuropsychology by comparing them to those in the United States. Methods: Information on four topics, including 1) the history and development of neuropsychology and the license of a clinical neuropsychologist in the United States, 2) the history and current situation of neuropsychology in Japan, 3) the background and process of the licensure in clinical psychology and neuropsychology in Japan, and 4) future directions and recommendations, were gathered through literature searches, official organization websites, and personal communication with clinical psychologists and other professionals in Japan. Results: While clinical neuropsychologists in the United States have a background in clinical psychology, most of the people conducting neuropsychological assessments and research in Japan are physicians, occupational therapists, and speech-language-hearing therapists. This is believed to be due to differences in the system of health insurance, education and training, cultural factors shaping psychology practice in Japan, funding opportunities, and the research environment. Conclusion: The care of patients who have neurological injuries and illnesses is one of the most crucial tasks for clinical neuropsychologists. It is important for clinical neuropsychologists in Japan to improve their knowledge and skills in clinical psychology to match global standards.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72684150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Lacko, N. Sabnis, Dorota L. Stankowska, Akpedje S Dossou, Rong Ma, Ronald Petty, R. Dickerman, B. Bunnell
The primary focus of this review is lipoprotein-based drug carriers, more specifically, high-density lipoprotein (HDL) type nanoparticles (NPs). These nanostructures are discussed regarding their suitability for clinical applications, particularly for cancer therapy. Poor solubility and insufficient capability to selectively target malignant tumors represent significant challenges facing many anticancer drugs. Nevertheless, we and others have found that most, if not all, of these difficulties, can be overcome by incorporating drugs into lipoprotein nanocarriers1. While not a novel approach, as HDL type NPs have been documented to deliver anticancer agents to cancer cells effectively and tumors2,3,4,5, including those that, on their own (without facilitation), exhibited less than desirable therapeutic efficacy6, due to their desirable features (see below), HDL type drug carriers, at least in our view, hold tremendous promise as facilitators of cancer chemotherapy. One of the key aspects of the HDL-type NP-facilitated drug transport is the receptor-mediated uptake of the payload from the NPs7,8. Consequently, in this review, major emphasis is placed on monitoring the expression of the scavenger receptor type B1 (SR-B1) as a potentially valuable tool for the pre-treatment selection of patients regarding their suitability for advanced, personalized chemotherapy. The main emphasis in this article is on developing novel cancer therapeutics, while approaches for treating other diseases via lipoprotein nanocarriers are briefly discussed.
{"title":"Prospects for developing lipoprotein-based drug transporters for therapeutic applications.","authors":"A. Lacko, N. Sabnis, Dorota L. Stankowska, Akpedje S Dossou, Rong Ma, Ronald Petty, R. Dickerman, B. Bunnell","doi":"10.18103/mra.v11i1.3521","DOIUrl":"https://doi.org/10.18103/mra.v11i1.3521","url":null,"abstract":"The primary focus of this review is lipoprotein-based drug carriers, more specifically, high-density lipoprotein (HDL) type nanoparticles (NPs). These nanostructures are discussed regarding their suitability for clinical applications, particularly for cancer therapy. Poor solubility and insufficient capability to selectively target malignant tumors represent significant challenges facing many anticancer drugs. Nevertheless, we and others have found that most, if not all, of these difficulties, can be overcome by incorporating drugs into lipoprotein nanocarriers1. While not a novel approach, as HDL type NPs have been documented to deliver anticancer agents to cancer cells effectively and tumors2,3,4,5, including those that, on their own (without facilitation), exhibited less than desirable therapeutic efficacy6, due to their desirable features (see below), HDL type drug carriers, at least in our view, hold tremendous promise as facilitators of cancer chemotherapy. One of the key aspects of the HDL-type NP-facilitated drug transport is the receptor-mediated uptake of the payload from the NPs7,8. Consequently, in this review, major emphasis is placed on monitoring the expression of the scavenger receptor type B1 (SR-B1) as a potentially valuable tool for the pre-treatment selection of patients regarding their suitability for advanced, personalized chemotherapy. The main emphasis in this article is on developing novel cancer therapeutics, while approaches for treating other diseases via lipoprotein nanocarriers are briefly discussed.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76499030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yukie M. Lloyd, N. Bobbili, A. Salanti, Philomina Gwanmesia, Josephine Fogako, R. Leke, Diane W Taylor
Background: Women produce antibodies to VAR2CSA when infected with Plasmodium falciparum during pregnancy that reduce disease severity in the current and subsequent pregnancies. In addition to antibody quantity, antibody quality (e.g., avidity) and function (e.g., inhibition of binding and opsonic phagocytosis) are immunologically important. Studies comparing the quantity, avidity and effector mechanisms of antibodies to VAR2CSA in the same group of women with pregnancy outcomes, especially in low transmission areas, are limited. Aims: The purpose of this study was to characterize antibodies to VAR2CSA using four assays, determine the correlation among the assays, and relate this to pregnancy outcome. Methods: A panel of 310 plasma samples from women in Yaoundé (a city with low malaria transmission) who had antibodies to full-length VAR2CSA were screened in assays that measured i) level of antibodies to VAR2CSA, ii) antibody avidity, iii) reduction in binding (RiB) of fluorescent VAR2CSA-coupled beads to fluorescent-CSA-coupled beads, and iv) opsonic phagocytosis using VAR2CSA-coupled beads and human THP1 cells. Results from the assays were compared with clinical information from 614 women who were Ab-negative. Results: A modest association was found among the 4 assays, i.e., as the amount of antibodies increased, a small increase in avidity, RiB and phagocytosis was observed; however, the association between RiB and avidity was poor. When results were dichotomized to above and below the median, antibody avidity, but not antibodies in the other assays, was associated with a significant reduction in prevalence of placental malaria and lower placental parasitemia. However, women who had antibody values above the median in amount (p=0.03), avidity (p=0.006), reduction in binding (p=0.018) and probably phagocytosis (p=0.065) had significantly lower placental parasitemia than women who lacked Abs to VAR2CSA. Conclusions: In this urban setting, women with the highest (above the median) antibody levels, in the four assays had a lower prevalence of placental malaria and placental parasitemia than women who lacked anti-VAR2CSA antibodies. Thus, VAR2CA-based vaccine trials in low transmission areas should consider using all four assays before and after vaccination.
{"title":"The Quantity, Quality and Two Major Effector Functions of Antibodies to VAR2CSA and their Association with Pregnancy Outcomes in a Low Malaria Transmission Area","authors":"Yukie M. Lloyd, N. Bobbili, A. Salanti, Philomina Gwanmesia, Josephine Fogako, R. Leke, Diane W Taylor","doi":"10.18103/mra.v11i8.4187","DOIUrl":"https://doi.org/10.18103/mra.v11i8.4187","url":null,"abstract":"Background: Women produce antibodies to VAR2CSA when infected with Plasmodium falciparum during pregnancy that reduce disease severity in the current and subsequent pregnancies. In addition to antibody quantity, antibody quality (e.g., avidity) and function (e.g., inhibition of binding and opsonic phagocytosis) are immunologically important. Studies comparing the quantity, avidity and effector mechanisms of antibodies to VAR2CSA in the same group of women with pregnancy outcomes, especially in low transmission areas, are limited. Aims: The purpose of this study was to characterize antibodies to VAR2CSA using four assays, determine the correlation among the assays, and relate this to pregnancy outcome. Methods: A panel of 310 plasma samples from women in Yaoundé (a city with low malaria transmission) who had antibodies to full-length VAR2CSA were screened in assays that measured i) level of antibodies to VAR2CSA, ii) antibody avidity, iii) reduction in binding (RiB) of fluorescent VAR2CSA-coupled beads to fluorescent-CSA-coupled beads, and iv) opsonic phagocytosis using VAR2CSA-coupled beads and human THP1 cells. Results from the assays were compared with clinical information from 614 women who were Ab-negative. Results: A modest association was found among the 4 assays, i.e., as the amount of antibodies increased, a small increase in avidity, RiB and phagocytosis was observed; however, the association between RiB and avidity was poor. When results were dichotomized to above and below the median, antibody avidity, but not antibodies in the other assays, was associated with a significant reduction in prevalence of placental malaria and lower placental parasitemia. However, women who had antibody values above the median in amount (p=0.03), avidity (p=0.006), reduction in binding (p=0.018) and probably phagocytosis (p=0.065) had significantly lower placental parasitemia than women who lacked Abs to VAR2CSA. Conclusions: In this urban setting, women with the highest (above the median) antibody levels, in the four assays had a lower prevalence of placental malaria and placental parasitemia than women who lacked anti-VAR2CSA antibodies. Thus, VAR2CA-based vaccine trials in low transmission areas should consider using all four assays before and after vaccination.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76575263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cryptochromes, evolutionally conserved and retained in mammals as transcriptional regulators having a repressive role in the transcription-translation feedback loop, the molecular mechanism behind the control of the endogenous mammalian circadian clock. This clock mechanism regulates the oscillation of a huge number of clock-controlled output genes. This in turn is responsible for modification of the physiological response of most organs and tissues, to coordinate with diurnal and seasonal changes in light and nutrient availability. Cryptochromes have also been found to participate in additional signalling cascades, outside of the circadian system, forming supplementary feedback loops that initiate cross-talk between systems influencing metabolism, inflammation and DNA damage response to maintain cellular homeostasis. This physiological organisation system has developed from Palaeolithic man but is still relevant in our modern world.
{"title":"Cryptochrome: An ancient blue light photoreceptor impacts modern mammalian physiology","authors":"David Smith","doi":"10.18103/mra.v11i1.3523","DOIUrl":"https://doi.org/10.18103/mra.v11i1.3523","url":null,"abstract":"Cryptochromes, evolutionally conserved and retained in mammals as transcriptional regulators having a repressive role in the transcription-translation feedback loop, the molecular mechanism behind the control of the endogenous mammalian circadian clock. This clock mechanism regulates the oscillation of a huge number of clock-controlled output genes. This in turn is responsible for modification of the physiological response of most organs and tissues, to coordinate with diurnal and seasonal changes in light and nutrient availability. Cryptochromes have also been found to participate in additional signalling cascades, outside of the circadian system, forming supplementary feedback loops that initiate cross-talk between systems influencing metabolism, inflammation and DNA damage response to maintain cellular homeostasis. This physiological organisation system has developed from Palaeolithic man but is still relevant in our modern world.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77618723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Infertility is a global crisis affecting 15% of global population. Rapidly declining sperm counts below critical levels demands immediate attention to make fertility treatment widely available; accessible and affordable; the triple aim in healthcare. Though fertility treatments have advanced in recent years manifold, unfortunately many are still away from accessing the available treatment due to various behavioural influences and biases. Infertility not only affects physical health, but also impacts mental, social and emotional health of individuals and society. Unawareness, guilt, shame and coping issues are some of the strong biases/influences that effect healthcare seeking action. Beneficial effects of behavioural economics (should vs would) has been well studied and applied in health policy and treatment interventions, especially in chronic diseases. A systematic understanding of behavioural stages patients go through during fertility treatment journey; from seeking treatment, adjusting to the multiple cycles of anticipation to welcoming a baby can greatly help individuals access available treatment sooner, in the appropriate way and accept the journey for better outcome with less burden. Providers too will be better equipped to help patients in an informed empathetic counselling once they understand the psycho-behavioural transitions of the patients throughout the journey. Fertility policies, patient education can be designed based on behavioural models that can make fertility treatment accessible at community level.
{"title":"BEHAVIOURAL MODEL BASED STRATEGIES FOR BETTER ADOPTION OF INFERTILITY TREATMENT","authors":"Kanika Panda, S. Rath","doi":"10.18103/mra.v11i3.3670","DOIUrl":"https://doi.org/10.18103/mra.v11i3.3670","url":null,"abstract":"Infertility is a global crisis affecting 15% of global population. Rapidly declining sperm counts below critical levels demands immediate attention to make fertility treatment widely available; accessible and affordable; the triple aim in healthcare. Though fertility treatments have advanced in recent years manifold, unfortunately many are still away from accessing the available treatment due to various behavioural influences and biases. Infertility not only affects physical health, but also impacts mental, social and emotional health of individuals and society. Unawareness, guilt, shame and coping issues are some of the strong biases/influences that effect healthcare seeking action. Beneficial effects of behavioural economics (should vs would) has been well studied and applied in health policy and treatment interventions, especially in chronic diseases. A systematic understanding of behavioural stages patients go through during fertility treatment journey; from seeking treatment, adjusting to the multiple cycles of anticipation to welcoming a baby can greatly help individuals access available treatment sooner, in the appropriate way and accept the journey for better outcome with less burden. Providers too will be better equipped to help patients in an informed empathetic counselling once they understand the psycho-behavioural transitions of the patients throughout the journey. Fertility policies, patient education can be designed based on behavioural models that can make fertility treatment accessible at community level.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79792635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The novel coronavirus SARS-CoV-2 pandemic, impacted health systems around the world resulting in a surge in demand for medicines and therapeutic interventions to combat the pandemic. Medicine regulatory agencies played a crucial role in ensuring the safety, quality, and efficacy of medicines. Regulatory agencies streamlined regulatory processes and made them flexible to tackle the urgent need for COVID-19 interventions. The COVID-19 pandemic prompted regulatory agencies on the importance of global regulatory collaboration and harmonization. Following the pandemic, regulatory agencies continually aim to ensure global alignment in regulatory standards, facilitate data sharing, and streamline regulatory processes to optimize their activities and preparedness for future emergencies. Objective: The objective of this study was to have an overview of medicines regulation following the emergence of the COVID-19 pandemic and regulator’s perspective on the associated regulatory adaptations. Method: The study was conducted through qualitative open-ended interviews. It was carried out within the head office of the Ghana Food and Drugs Authority; the sole regulator of medicines in the country. Interviews were audio-recorded with the consent of participants and transcribed for analysis. After transcription data was categorized into themes and analyzed using a generic thematic analysis method. Results: Ghana's medicines regulatory system, governed by the Food and Drugs Authority (FDA) developed a system which encompassed pre-market approval, post-market surveillance, pharmacovigilance activities, and approval of clinical trials, aimed at safeguarding public health. To address the urgent need for COVID-19 treatments and vaccines, regulators worldwide, including Ghana, implemented emergency use authorization (EUA) processes, demonstrated regulatory flexibility by adopting alternative assessment approaches and streamlining processes without compromising safety and quality standards. The Food and Drugs Authority along with other stakeholders and opinion leaders played a crucial role in disseminating accurate information and debunking myths and misconceptions about the pandemic to empower citizens with accurate information, dispel misinformation, and promote adherence to preventive measures. Conclusion: The importance of resourcefulness and the adoption of sustainable practices, working smarter, saving resources, embracing virtual trainings, and introducing dynamic assessment practices have been highlighted to have reshaped activities of the Authority. These lessons can serve as valuable guides in building a more efficient, collaborative, and environmentally conscious future as we continue to navigate the post pandemic world.
{"title":"Covid-19 Pandemic and Medicines Regulation in Ghana: Overview and Perspectives of Regulators","authors":"D. Darko, O. Boateng","doi":"10.18103/mra.v11i8.4292","DOIUrl":"https://doi.org/10.18103/mra.v11i8.4292","url":null,"abstract":"Background: The novel coronavirus SARS-CoV-2 pandemic, impacted health systems around the world resulting in a surge in demand for medicines and therapeutic interventions to combat the pandemic. Medicine regulatory agencies played a crucial role in ensuring the safety, quality, and efficacy of medicines. Regulatory agencies streamlined regulatory processes and made them flexible to tackle the urgent need for COVID-19 interventions. The COVID-19 pandemic prompted regulatory agencies on the importance of global regulatory collaboration and harmonization. Following the pandemic, regulatory agencies continually aim to ensure global alignment in regulatory standards, facilitate data sharing, and streamline regulatory processes to optimize their activities and preparedness for future emergencies. Objective: The objective of this study was to have an overview of medicines regulation following the emergence of the COVID-19 pandemic and regulator’s perspective on the associated regulatory adaptations. Method: The study was conducted through qualitative open-ended interviews. It was carried out within the head office of the Ghana Food and Drugs Authority; the sole regulator of medicines in the country. Interviews were audio-recorded with the consent of participants and transcribed for analysis. After transcription data was categorized into themes and analyzed using a generic thematic analysis method. Results: Ghana's medicines regulatory system, governed by the Food and Drugs Authority (FDA) developed a system which encompassed pre-market approval, post-market surveillance, pharmacovigilance activities, and approval of clinical trials, aimed at safeguarding public health. To address the urgent need for COVID-19 treatments and vaccines, regulators worldwide, including Ghana, implemented emergency use authorization (EUA) processes, demonstrated regulatory flexibility by adopting alternative assessment approaches and streamlining processes without compromising safety and quality standards. The Food and Drugs Authority along with other stakeholders and opinion leaders played a crucial role in disseminating accurate information and debunking myths and misconceptions about the pandemic to empower citizens with accurate information, dispel misinformation, and promote adherence to preventive measures. Conclusion: The importance of resourcefulness and the adoption of sustainable practices, working smarter, saving resources, embracing virtual trainings, and introducing dynamic assessment practices have been highlighted to have reshaped activities of the Authority. These lessons can serve as valuable guides in building a more efficient, collaborative, and environmentally conscious future as we continue to navigate the post pandemic world.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79939213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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