Abstract---This review considers the observations concerning the interactions of influenza virus with cholesterol and consequences of these interactions for both the virus and a host cell. There are at least two crucial “touch points”, when IFV deals with cholesterol: first, cholesterol is required for influenza virus entry into the cell. Second, during budding, when new viral particles form their envelopes from plasma membrane of the infected cell, selectively acquiring “raft lipids”, cholesterol and sphingolipids. One possible mechanism ensuring selective accumulation of cholesterol in the viral envelope is the presence of cholesterol-binding motifs (CRAC motifs) in protein M1 and possibly other viral proteins involved in this process. These motifs could be responsible for binding of cell membrane´s cholesterol by the viral protein. The important role of cholesterol in the influenza virus life cycle raises the possibility that lowering cholesterol levels in host cells (e.g., with statins) can be useful in reducing influenza virus infectivity and productivity. However, lowering cholesterol in cell membranes below an optimal level may not be compatible with normal cell function. There is experimental evidence that CRAC-containing peptide derived from influenza virus protein M1 is indeed cytotoxic, and that extraction of membrane cholesterol with mbCD lowers the concentration of the peptide´s cytotoxic effect by an order of magnitude. In the conditions of reduced cholesterol, any infection with enveloped virus sequestering cholesterol from cell membranes may be detrimental, as further lowering cholesterol level in cell membrane during virus budding may lead to cell damage or death. Perhaps to minimize the virus infectivity and the consequences of the massive virus budding, advantageous can be alternative approaches, such as a search for and design of agents that would selectively interfere with cholesterol-dependent virus–cell interactions and inhibit them. Understanding the mechanisms and consequences of these interactions should be useful in the developing of new antiviral drugs.
{"title":"INFLUENZA VIRUS AND CHOLESTEROL: TOUCH POINTS","authors":"Antonina Barkovskaya","doi":"10.18103/mra.v11i9.4399","DOIUrl":"https://doi.org/10.18103/mra.v11i9.4399","url":null,"abstract":"Abstract---This review considers the observations concerning the interactions of influenza virus with cholesterol and consequences of these interactions for both the virus and a host cell. There are at least two crucial “touch points”, when IFV deals with cholesterol: first, cholesterol is required for influenza virus entry into the cell. Second, during budding, when new viral particles form their envelopes from plasma membrane of the infected cell, selectively acquiring “raft lipids”, cholesterol and sphingolipids. One possible mechanism ensuring selective accumulation of cholesterol in the viral envelope is the presence of cholesterol-binding motifs (CRAC motifs) in protein M1 and possibly other viral proteins involved in this process. These motifs could be responsible for binding of cell membrane´s cholesterol by the viral protein. The important role of cholesterol in the influenza virus life cycle raises the possibility that lowering cholesterol levels in host cells (e.g., with statins) can be useful in reducing influenza virus infectivity and productivity. However, lowering cholesterol in cell membranes below an optimal level may not be compatible with normal cell function. There is experimental evidence that CRAC-containing peptide derived from influenza virus protein M1 is indeed cytotoxic, and that extraction of membrane cholesterol with mbCD lowers the concentration of the peptide´s cytotoxic effect by an order of magnitude. In the conditions of reduced cholesterol, any infection with enveloped virus sequestering cholesterol from cell membranes may be detrimental, as further lowering cholesterol level in cell membrane during virus budding may lead to cell damage or death. Perhaps to minimize the virus infectivity and the consequences of the massive virus budding, advantageous can be alternative approaches, such as a search for and design of agents that would selectively interfere with cholesterol-dependent virus–cell interactions and inhibit them. Understanding the mechanisms and consequences of these interactions should be useful in the developing of new antiviral drugs.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135953546","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}
Derek Shendell, Lauren Gonzalez, Elizabeth Kaplun, Juhi Aggarwal, Kimberly Nguyen, Maryanne Campbell
Background: The New Jersey Safe Schools Program provides training courses to secondary school educational professionals to supervise students in work-based learning. COVID-19 suspended in-person training courses and work-based learning. As worksites reopened, concerns persisted regarding implementation of work-based learning, and safety and health. After site visits, participants completed reflection assignments. Methods: We examined statewide data from a three-day training, "Designing and Implementing Student Training Plans," from 61 participants in spring-summer 2020 regarding concerns for work-based learning during COVID-19. Qualitative analysis on open-ended responses determined emerging themes through inductive, qualitative coding in Microsoft Office spreadsheet software, Excel, followed by import of a spreadsheet-based code book to NVivo, a qualitative data analysis software tool. Results: Data revealed supervisor perspectives pertaining to re-establishing work-based learning programs (33%), COVID-19 safety and reopening measures (24%), student safety and health (17%), obstacles for in-person work-based learning (9%), future work-based learning placements (7%), and online work-based learning opportunities (4%). Conclusion: Data suggested adaptations for future in-person work-based learning experiences; future online student work placements and safety and health trainings; and insights on improving in-school learning and occupational education for students.
{"title":"Case study in New Jersey on perceptions and concerns during COVID-19: Lessons for safety and health during future work-based learning","authors":"Derek Shendell, Lauren Gonzalez, Elizabeth Kaplun, Juhi Aggarwal, Kimberly Nguyen, Maryanne Campbell","doi":"10.18103/mra.v11i9.4258","DOIUrl":"https://doi.org/10.18103/mra.v11i9.4258","url":null,"abstract":"Background: The New Jersey Safe Schools Program provides training courses to secondary school educational professionals to supervise students in work-based learning. COVID-19 suspended in-person training courses and work-based learning. As worksites reopened, concerns persisted regarding implementation of work-based learning, and safety and health. After site visits, participants completed reflection assignments. Methods: We examined statewide data from a three-day training, \"Designing and Implementing Student Training Plans,\" from 61 participants in spring-summer 2020 regarding concerns for work-based learning during COVID-19. Qualitative analysis on open-ended responses determined emerging themes through inductive, qualitative coding in Microsoft Office spreadsheet software, Excel, followed by import of a spreadsheet-based code book to NVivo, a qualitative data analysis software tool. Results: Data revealed supervisor perspectives pertaining to re-establishing work-based learning programs (33%), COVID-19 safety and reopening measures (24%), student safety and health (17%), obstacles for in-person work-based learning (9%), future work-based learning placements (7%), and online work-based learning opportunities (4%). Conclusion: Data suggested adaptations for future in-person work-based learning experiences; future online student work placements and safety and health trainings; and insights on improving in-school learning and occupational education for students.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135954628","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}
Siddhartha Mani, Sujata Sen, Kaushik Nag, Sobhan Biswas
their diagnosis is not considered in contemporary acute coronary syndrome patients. This study investigates the incidence and types of arrhythsmias among acute coronary syndrome patients presenting to the emergency department, as well as their association with various factors and patient outcomes. Methods: The current prospective observational study was conducted at a tertiary care center in Kolkata, India. Data were collected from 76 acute coronary syndrome patients admitted between October 2020 and May 2021 to the emergency department. Information was gathered through semi-structured interviews and relevant investigations. Results: The majority of the patients were aged 61-70 years, with three fourth of the study population being male. The incidence of arrhythmia was diagnosed in 77.6% of the patients. The most common arrhythmias were sinus tachycardia, ventricular premature complex, atrial fibrillation, sinus bradycardia, and complete heart block. Arrhythmias were more prevalent among ST-elevation myocardial infarction (62.7%) and unstable angina (8.5%) patients. Patients with Left Ventricular Ejection Fraction ≤ 40% had a higher incidence of arrhythmias (93.5%). The mortality rate during hospital stay was 11.9% among acute coronary syndrome patients with arrhythmias, while all acute coronary syndrome patients without arrhythmia had a 100% survival rate. Conclusion: This study highlights the incidence and types of arrhythmias in acute coronary syndrome patients presenting to the emergency department. It reveals a higher prevalence of arrhythmias in specific subgroups, such as patients with ST-elevation myocardial infarction and those with a reduction in left ventricular function. These findings contribute to our understanding of arrhythmias in acute coronary syndrome and their association with patient outcomes, emphasizing the importance of appropriate management and monitoring in this population.
{"title":"Incidence and Types of Arrhythmias in Acute Coronary Syndrome: An Observational Study","authors":"Siddhartha Mani, Sujata Sen, Kaushik Nag, Sobhan Biswas","doi":"10.18103/mra.v11i9.4372","DOIUrl":"https://doi.org/10.18103/mra.v11i9.4372","url":null,"abstract":"their diagnosis is not considered in contemporary acute coronary syndrome patients. This study investigates the incidence and types of arrhythsmias among acute coronary syndrome patients presenting to the emergency department, as well as their association with various factors and patient outcomes. Methods: The current prospective observational study was conducted at a tertiary care center in Kolkata, India. Data were collected from 76 acute coronary syndrome patients admitted between October 2020 and May 2021 to the emergency department. Information was gathered through semi-structured interviews and relevant investigations. Results: The majority of the patients were aged 61-70 years, with three fourth of the study population being male. The incidence of arrhythmia was diagnosed in 77.6% of the patients. The most common arrhythmias were sinus tachycardia, ventricular premature complex, atrial fibrillation, sinus bradycardia, and complete heart block. Arrhythmias were more prevalent among ST-elevation myocardial infarction (62.7%) and unstable angina (8.5%) patients. Patients with Left Ventricular Ejection Fraction ≤ 40% had a higher incidence of arrhythmias (93.5%). The mortality rate during hospital stay was 11.9% among acute coronary syndrome patients with arrhythmias, while all acute coronary syndrome patients without arrhythmia had a 100% survival rate. Conclusion: This study highlights the incidence and types of arrhythmias in acute coronary syndrome patients presenting to the emergency department. It reveals a higher prevalence of arrhythmias in specific subgroups, such as patients with ST-elevation myocardial infarction and those with a reduction in left ventricular function. These findings contribute to our understanding of arrhythmias in acute coronary syndrome and their association with patient outcomes, emphasizing the importance of appropriate management and monitoring in this population.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135955088","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}
Mohd Hashim, Mohamed Awang, Alarmelu Ramanathan, Mohd Wahab, Mohd Mohd Nor, Edre Aidid
Context: Serum albumin is the major protein of the human plasma, accounting for about 60% of the total plasma protein. Serum albumin levels tend to decline in the plasma due to injury or infection independent of nutritional status. Serum albumin consumption increases in a state of stress. Reduction in serum albumin occurs with intracranial haemorrhages. In a patient with severe head injury, there is a significant decline in serum albumin leading to hypoalbuminemia. Serum albumin can be used as an outcome marker in various critical illnesses, including traumatic brain injury. Aim: To determine that serum albumin is an independent predictor affecting the outcome of patients with severe traumatic brain injury over a 6-month duration Settings and design: This was conducted as prospective cohort study in two neurosurgical centres in the East Coast of Malaysia from June 2020 to June 2021 Subjects and methods: A total of fifty-five patients were admitted to our emergency intensive care, or high dependency unit with varying degrees of severe head injuries. Forty patients fulfilled the inclusion criteria of our study and were recruited for data collection and further analysis. Their serum albumin levels were drawn, analysed, and recorded. Statistical analysis used: Descriptive, univariate and multivariate analyses using Multiple Logistic Regression model were done using SPSS version 26.0. Results: Average age for patients in this study was 42 years old. 87.5% of patients involved in this study were male, while the remaining 12.5% were female. The ethnicity of the majority of patients were Malays (77.5%) and the other ethnicities involved were Chinese, Indians and Bangladeshi, with a total of 22.5%. Multiple intracranial injuries were suffered by 57.5% of our study population, Subdural Hemorrhage, Extradural Hemorrhage, Contusional bleed, and Diffuse Axonal Injury were seen respectively in 20%, 10% 7.5% and 5% of the study population. At six months, the unfavourable outcome for serial serum albumin in patients with severe head injury patients was 62.5%, while the favourable outcome was 37.5%. Serum albumin of 30 g/L or less than 30g/L at day 1,3 and 5 post-trauma was noted to have unfavourable outcomes compared to serum albumin level of more than 30g/L. Conclusion: Serum albumin is an independent predictor of outcome in severe TBI patients. However, larger prospective studies are required to verify these findings.
{"title":"Serum Albumin as Independent Predictor In Determining The Outcome Of Traumatic Brain Injury","authors":"Mohd Hashim, Mohamed Awang, Alarmelu Ramanathan, Mohd Wahab, Mohd Mohd Nor, Edre Aidid","doi":"10.18103/mra.v11i9.4438","DOIUrl":"https://doi.org/10.18103/mra.v11i9.4438","url":null,"abstract":"Context: Serum albumin is the major protein of the human plasma, accounting for about 60% of the total plasma protein. Serum albumin levels tend to decline in the plasma due to injury or infection independent of nutritional status. Serum albumin consumption increases in a state of stress. Reduction in serum albumin occurs with intracranial haemorrhages. In a patient with severe head injury, there is a significant decline in serum albumin leading to hypoalbuminemia. Serum albumin can be used as an outcome marker in various critical illnesses, including traumatic brain injury. Aim: To determine that serum albumin is an independent predictor affecting the outcome of patients with severe traumatic brain injury over a 6-month duration Settings and design: This was conducted as prospective cohort study in two neurosurgical centres in the East Coast of Malaysia from June 2020 to June 2021 Subjects and methods: A total of fifty-five patients were admitted to our emergency intensive care, or high dependency unit with varying degrees of severe head injuries. Forty patients fulfilled the inclusion criteria of our study and were recruited for data collection and further analysis. Their serum albumin levels were drawn, analysed, and recorded. Statistical analysis used: Descriptive, univariate and multivariate analyses using Multiple Logistic Regression model were done using SPSS version 26.0. Results: Average age for patients in this study was 42 years old. 87.5% of patients involved in this study were male, while the remaining 12.5% were female. The ethnicity of the majority of patients were Malays (77.5%) and the other ethnicities involved were Chinese, Indians and Bangladeshi, with a total of 22.5%. Multiple intracranial injuries were suffered by 57.5% of our study population, Subdural Hemorrhage, Extradural Hemorrhage, Contusional bleed, and Diffuse Axonal Injury were seen respectively in 20%, 10% 7.5% and 5% of the study population. At six months, the unfavourable outcome for serial serum albumin in patients with severe head injury patients was 62.5%, while the favourable outcome was 37.5%. Serum albumin of 30 g/L or less than 30g/L at day 1,3 and 5 post-trauma was noted to have unfavourable outcomes compared to serum albumin level of more than 30g/L. Conclusion: Serum albumin is an independent predictor of outcome in severe TBI patients. However, larger prospective studies are required to verify these findings.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135955102","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}
Children’s well-being at school has only recently attracted much attention, in particular when linked to school closure due to the COVID-19 pandemic, the assumption being that children feel well when being able to go to school. However, gifted early readers (i.e., those who have learned to read all by themselves and show good reading skills already at the beginning of primary education) are known to be rather bored in particular in reading lessons if their skills are not promoted according to their accelerated development and needs. Teachers’ lack of knowledge how to provide adequate support for gifted early readers has been linked to detrimental effects on these children’s development and may lead to their school underachievement at early and/or later stages of formal education. In this paper, we aim to shed light onto teachers’ attitudes, beliefs, and knowledge when dealing with gifted early readers in primary school education to find out whether their pedagogical actions in a regular classroom are adequate to meet the gifted early readers’ needs. In an online questionnaire, primary school teachers from Austria (N = 41) who had active experience with early readers were asked to respond to eleven subscales covering child-, teacher-, and school-related factors as well as pedagogical actions in relation to gifted early readers in primary school on a 5-point Likert-scale. The results showed that teachers’ positive attitudes towards children’s advanced skills and beliefs were child-oriented and supportive in general and that they were interested in the child’s competences and reading habits. Their actions were in general not inducing bullying. However, their pedagogical actions did not seem to meet the children’s needs what might be due to a lack of specific knowledge about gifted children, and early readers in particular. Teachers in primary school need professional development opportunities such as training courses for the gifted early readers in order to gain more in-depth knowledge about these children’s needs and how these can be met with adequate pedagogical actions in the regular classroom, how their skills and knowledge can be best promoted to grant healthy development and to prevent boredom, bullying and academic underachievement.
{"title":"Gifted Early Readers’ Health Development and Well-Being: A Survey on Teachers’ Attitudes, Beliefs, Knowledge and Pedagogical Practices in the Regular Classroom","authors":"Julia Festman","doi":"10.18103/mra.v11i8.4355","DOIUrl":"https://doi.org/10.18103/mra.v11i8.4355","url":null,"abstract":"Children’s well-being at school has only recently attracted much attention, in particular when linked to school closure due to the COVID-19 pandemic, the assumption being that children feel well when being able to go to school. However, gifted early readers (i.e., those who have learned to read all by themselves and show good reading skills already at the beginning of primary education) are known to be rather bored in particular in reading lessons if their skills are not promoted according to their accelerated development and needs. Teachers’ lack of knowledge how to provide adequate support for gifted early readers has been linked to detrimental effects on these children’s development and may lead to their school underachievement at early and/or later stages of formal education. In this paper, we aim to shed light onto teachers’ attitudes, beliefs, and knowledge when dealing with gifted early readers in primary school education to find out whether their pedagogical actions in a regular classroom are adequate to meet the gifted early readers’ needs. In an online questionnaire, primary school teachers from Austria (N = 41) who had active experience with early readers were asked to respond to eleven subscales covering child-, teacher-, and school-related factors as well as pedagogical actions in relation to gifted early readers in primary school on a 5-point Likert-scale. The results showed that teachers’ positive attitudes towards children’s advanced skills and beliefs were child-oriented and supportive in general and that they were interested in the child’s competences and reading habits. Their actions were in general not inducing bullying. However, their pedagogical actions did not seem to meet the children’s needs what might be due to a lack of specific knowledge about gifted children, and early readers in particular. Teachers in primary school need professional development opportunities such as training courses for the gifted early readers in order to gain more in-depth knowledge about these children’s needs and how these can be met with adequate pedagogical actions in the regular classroom, how their skills and knowledge can be best promoted to grant healthy development and to prevent boredom, bullying and academic underachievement.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135356159","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.v11i10.4524
Caterina Pisciotta, Rosalind Hill-Kane, Andrew WInters, Cole Hooley, Kerry A. Lee, Takiya Green, Geetha Gopalan
From an implementation science lens, sustaining interventions in large, heterogeneous organizations such as child welfare requires attunement to the inner and outer contexts in which the innovative practice is delivered. This case study describes how one child welfare agency sustained implementation of a modified child mental health intervention since Spring 2019 after formal supports were removed and provides a retrospective look at their experiences. Using qualitative data from interviews with a key informant, this case study employed a priori codes from an existing sustainability framework to organize and understand factors of innovation, adopters, leadership and management, inner context and process, outer context, and outcomes. Findings offer insights for child welfare agencies to consider when sustaining an intervention without research supports, including the intervention’s alignment with the agency’s culture and mission, the agency’s ability to adapt and embed the intervention, and child welfare leadership and staff buy-in to the intervention. Implications for policy, practice, and research are discussed.
{"title":"Sustainability of a Child Mental Health Intervention in Child Welfare Services: Case study","authors":"Caterina Pisciotta, Rosalind Hill-Kane, Andrew WInters, Cole Hooley, Kerry A. Lee, Takiya Green, Geetha Gopalan","doi":"10.18103/mra.v11i10.4524","DOIUrl":"https://doi.org/10.18103/mra.v11i10.4524","url":null,"abstract":"From an implementation science lens, sustaining interventions in large, heterogeneous organizations such as child welfare requires attunement to the inner and outer contexts in which the innovative practice is delivered. This case study describes how one child welfare agency sustained implementation of a modified child mental health intervention since Spring 2019 after formal supports were removed and provides a retrospective look at their experiences. Using qualitative data from interviews with a key informant, this case study employed a priori codes from an existing sustainability framework to organize and understand factors of innovation, adopters, leadership and management, inner context and process, outer context, and outcomes. Findings offer insights for child welfare agencies to consider when sustaining an intervention without research supports, including the intervention’s alignment with the agency’s culture and mission, the agency’s ability to adapt and embed the intervention, and child welfare leadership and staff buy-in to the intervention. Implications for policy, practice, and research are discussed.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"50 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135446933","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.v11i10.4607
José Larios, Howard Terebelo
Since the year 2000, we have seen unprecedented improvement in newly diagnosed multiple myeloma in terms of progression-free survival and a doubling of overall survival in 2009 from 2.5 years to 5 years. Patients treated now expect a median survival of 7.5 years, while those receiving quadruplet therapy, stem cell transplant, and consolidation and maintenance therapy have an expected survival up to 11 years. Factors contributing to these improved outcomes include novel agents, antibodies, B-cell Maturation Agent-directed therapy, chimeric antigen receptor T-cells, bispecific antibodies, selective use of stem cell transplant, and supportive care measures such as bisphosphonates, prophylactic antimicrobials, cytokines, and intravenous immunoglobulins. Incorporation of these novel therapies in conjunction with increasing understanding of the genomic landscape of multiple myeloma and the evolving use of minimal residual disease negativity should persuade the oncology community to treat patients with high-risk smoldering multiple myeloma and guide treatment of early relapse in patients with newly diagnosed multiple myeloma. Here, we review early interventions within the context of genomic changes, minimal residual disease status, and strategies for treating high-risk smoldering multiple myeloma and standard and high-risk newly diagnosed multiple myeloma to improve progression-free survival, overall survival, and provide context for which patients may be considered cured.
{"title":"The Age of Immune-therapy in Multiple Myeloma with a Collective Goal for a Cure","authors":"José Larios, Howard Terebelo","doi":"10.18103/mra.v11i10.4607","DOIUrl":"https://doi.org/10.18103/mra.v11i10.4607","url":null,"abstract":"Since the year 2000, we have seen unprecedented improvement in newly diagnosed multiple myeloma in terms of progression-free survival and a doubling of overall survival in 2009 from 2.5 years to 5 years. Patients treated now expect a median survival of 7.5 years, while those receiving quadruplet therapy, stem cell transplant, and consolidation and maintenance therapy have an expected survival up to 11 years. Factors contributing to these improved outcomes include novel agents, antibodies, B-cell Maturation Agent-directed therapy, chimeric antigen receptor T-cells, bispecific antibodies, selective use of stem cell transplant, and supportive care measures such as bisphosphonates, prophylactic antimicrobials, cytokines, and intravenous immunoglobulins. Incorporation of these novel therapies in conjunction with increasing understanding of the genomic landscape of multiple myeloma and the evolving use of minimal residual disease negativity should persuade the oncology community to treat patients with high-risk smoldering multiple myeloma and guide treatment of early relapse in patients with newly diagnosed multiple myeloma. Here, we review early interventions within the context of genomic changes, minimal residual disease status, and strategies for treating high-risk smoldering multiple myeloma and standard and high-risk newly diagnosed multiple myeloma to improve progression-free survival, overall survival, and provide context for which patients may be considered cured.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"294 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135448761","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.v11i10.4578
Thuy Le-Kumar
Overexpression of human epidermal growth factor receptor 2 (HER2) has classically been associated with decreased overall survival. HER2-positive breast cancer makes up about 15-20% of breast cancers. Overall survival and progression-free survival of HER2 breast cancers have increased due to advancements in therapies. Trastuzumab, a humanized monoclonal antibody, targets HER2 in patients with overexpression. When combined with anthracyclines, which has been the treatment of choice for many years, there is increased cardiotoxicity. Since the discovery of trastuzumab, there have been a myriad of novel agents that target HER2 receptors, however little is known about the cardiotoxic effects of these novel agents. In this review, we describe clinical trials using novel anti-HER2 agents for the treatment of HER2-positive breast cancer and the frequency and severity of cardiotoxicity of these agents.
{"title":"A New Era of HER2 Directed Therapy –A Review of Cardiac Toxicities in Novel AntiHER2 Agents","authors":"Thuy Le-Kumar","doi":"10.18103/mra.v11i10.4578","DOIUrl":"https://doi.org/10.18103/mra.v11i10.4578","url":null,"abstract":"Overexpression of human epidermal growth factor receptor 2 (HER2) has classically been associated with decreased overall survival. HER2-positive breast cancer makes up about 15-20% of breast cancers. Overall survival and progression-free survival of HER2 breast cancers have increased due to advancements in therapies. Trastuzumab, a humanized monoclonal antibody, targets HER2 in patients with overexpression. When combined with anthracyclines, which has been the treatment of choice for many years, there is increased cardiotoxicity. Since the discovery of trastuzumab, there have been a myriad of novel agents that target HER2 receptors, however little is known about the cardiotoxic effects of these novel agents. In this review, we describe clinical trials using novel anti-HER2 agents for the treatment of HER2-positive breast cancer and the frequency and severity of cardiotoxicity of these agents.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"157 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135448765","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.v11i10.4551
Amy Zhang, Keming Gao, Zhengyi Chen Chen
Objectives: This study aimed to assess whether race modifies irritability and immunological inflammation, and their interaction to worsen depression during chemotherapy. Methods: 25 African American and 19 White nonmetastasized breast cancer patients were assessed on irritability, inflammation biomarker (hsCRP and IL-6), and depression at baseline (T 1 ) and after 3 months of chemotherapy (T 2 ). Wilcoxon rank sum test was performed to compare racial groups on these study variables. Generalized estimating equations (GEE) regression models for repeated measures were computed, using the severity of depression as the dependent variable, race, an inflammation biomarker (hsCRP or IL-6), irritability, interactions of these variables, and time as independent variables, controlling for age, baseline depression severity level and its racial difference. Results: The African American cancer patients had significantly higher levels of hsCRP (p = .040) and IL-6 (p = .018) than the White patients at T 2, without a significant baseline difference. In both regression models, the African American patients experiencing greater irritability reported significantly more severe depression at T 2 (p = .0002; .0048). In the regression model containing hsCRP, a negative interaction between irritability and hsCRP level was significantly associated with more severe depression at T 2 (p < .0001). In the regression model containing IL- 6, the African American patients (p = .03), most of whom had higher IL-6 (p < .0001), reported significantly more severe depression at T 2 , while White patients who had higher IL-6 levels also had more severe depression at T 2 (p = .016). Conclusion: Association between irritability and depression was significantly stronger for the African American patients than the White patients in this study, and the level of hsCRP influenced irritability and its association with depression. Identification of contributors to irritability, particularly for African Americans, is important for reducing irritability and depression in cancer patients undergoing chemotherapy. Moreover, the White cancer patients in the study who experienced higher IL-6 levels during chemotherapy were also at a higher risk of worsening depression and required medical attention.
{"title":"Association Between Race and Irritability, Inflammation, and Depression During Chemotherapy","authors":"Amy Zhang, Keming Gao, Zhengyi Chen Chen","doi":"10.18103/mra.v11i10.4551","DOIUrl":"https://doi.org/10.18103/mra.v11i10.4551","url":null,"abstract":"Objectives: This study aimed to assess whether race modifies irritability and immunological inflammation, and their interaction to worsen depression during chemotherapy. Methods: 25 African American and 19 White nonmetastasized breast cancer patients were assessed on irritability, inflammation biomarker (hsCRP and IL-6), and depression at baseline (T 1 ) and after 3 months of chemotherapy (T 2 ). Wilcoxon rank sum test was performed to compare racial groups on these study variables. Generalized estimating equations (GEE) regression models for repeated measures were computed, using the severity of depression as the dependent variable, race, an inflammation biomarker (hsCRP or IL-6), irritability, interactions of these variables, and time as independent variables, controlling for age, baseline depression severity level and its racial difference. Results: The African American cancer patients had significantly higher levels of hsCRP (p = .040) and IL-6 (p = .018) than the White patients at T 2, without a significant baseline difference. In both regression models, the African American patients experiencing greater irritability reported significantly more severe depression at T 2 (p = .0002; .0048). In the regression model containing hsCRP, a negative interaction between irritability and hsCRP level was significantly associated with more severe depression at T 2 (p < .0001). In the regression model containing IL- 6, the African American patients (p = .03), most of whom had higher IL-6 (p < .0001), reported significantly more severe depression at T 2 , while White patients who had higher IL-6 levels also had more severe depression at T 2 (p = .016). Conclusion: Association between irritability and depression was significantly stronger for the African American patients than the White patients in this study, and the level of hsCRP influenced irritability and its association with depression. Identification of contributors to irritability, particularly for African Americans, is important for reducing irritability and depression in cancer patients undergoing chemotherapy. Moreover, the White cancer patients in the study who experienced higher IL-6 levels during chemotherapy were also at a higher risk of worsening depression and required medical attention.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134891427","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.v11i10.4552
Edvard Smith
Dendritic cells can be subdivided into three major subsets. The conventional (classical) dendritic cells (cDCs), also known as myeloid DCs, can be further split into the cDC1 and cDC2 subpopulations. The third subpopulation is the plasmacytoid DC (pDC). The pDCs are unique because they constitute the leukocyte, which secretes the largest amount of interferon (IFN). Since IFNs are crucial in the defence against viruses, it could be hypothesized that reduced IFN production by pDCs could cause susceptibility to viral infections in general. However, this does not seem to be the case, since it was not until the SARS-CoV-2 pandemic that the essential role of pDCs in viral immunity was revealed. In this review we discuss the role of pDCs in the protection against Covid-19 and the mechanisms underlying susceptibility when these cells are malfunctioning as seen in haematological malignancies. In contrast, overactive pDCs can lead to selected autoimmune diseases, where systemic lupus (SLE) is the premier example, demonstrating the yin and yang relationship.
{"title":"The Yin and Yang of Plasmacytoid Dendritic Cells – SARS-CoV-2 Protection versus Susceptibility to Selected Autoimmune Diseases","authors":"Edvard Smith","doi":"10.18103/mra.v11i10.4552","DOIUrl":"https://doi.org/10.18103/mra.v11i10.4552","url":null,"abstract":"Dendritic cells can be subdivided into three major subsets. The conventional (classical) dendritic cells (cDCs), also known as myeloid DCs, can be further split into the cDC1 and cDC2 subpopulations. The third subpopulation is the plasmacytoid DC (pDC). The pDCs are unique because they constitute the leukocyte, which secretes the largest amount of interferon (IFN). Since IFNs are crucial in the defence against viruses, it could be hypothesized that reduced IFN production by pDCs could cause susceptibility to viral infections in general. However, this does not seem to be the case, since it was not until the SARS-CoV-2 pandemic that the essential role of pDCs in viral immunity was revealed. In this review we discuss the role of pDCs in the protection against Covid-19 and the mechanisms underlying susceptibility when these cells are malfunctioning as seen in haematological malignancies. In contrast, overactive pDCs can lead to selected autoimmune diseases, where systemic lupus (SLE) is the premier example, demonstrating the yin and yang relationship.","PeriodicalId":18641,"journal":{"name":"Medical Research Archives","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134980361","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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