In the last four years, TheranostiCentre S.r.l., Berkion Technology LLC and ENEA have patented and fabricated a first prototype of a Compact Neutron Generator (CNG) currently under testing in the ENEA laboratories. Besides the usual applications in the field of materials irradiation, this CNG - producing neutrons of 2.45 MeV energy by using the DD fusion reaction - was conceived for the neutron irradiation of the solid cancer’s tumour bed by means of the Intra-Operative Radiotherapy (IORT) technique, the so-called neutron-IORT (nIORT®). The CNG is self-shielded and light-weight (~120 kg) making possible its remote handling by a robotic arm. Accurate Monte Carlo simulations, modelling the CNG and the “open wound” biological tissues near its irradiation window, demonstrated that the apparatus - operated at 100 kV-10 mA - supplies a neutron flux ~108 cm-2 s-1 and can deliver equivalent dose rates ~2 Gy (RBE)/min. Hence, it can administer very high dose levels in limited treatment times. This article briefly summarizes the main findings of this collaborative research study, the clinical rationales underpinning the nIORT® idea and the potential performances of the CNG for the treatment of solid cancer pathologies. Indeed, the CNG can be installed in an operating room dedicated to nIORT® treatments, without posing any environmental and safety issues. Monte Carlo simulations have been carried out by envisioning the CNG equipped with an IORT applicator, that is an applicator pipe with a tuneable diameter to be inserted in the surgical cavity. By foreseeing the clinical endpoints of the standard IORT protocols, the irradiation performances for potential nIORT® treatments - obtained with an applicator pipe of 6 cm diameter - are here reported for different regimes: from 10 up to 75 Gy (RBE), that can be administered in a single session of about 4 to 30 minutes. Besides the dose peak in the centre of the tumour bed, the almost isotropic neutrons emission allows to irradiate the surroundings side-walls of the tumour bed – usually filled by potential quiescent cancer cells (QCCs) – and therefore reducing the chances of local recurrences by improving the local control of the tumour. The rapid decrease in tissues depth of the dose profile (in few centimetres) will spare the neighbouring organs at risk from harmful radiations. Thus, the CNG apparatus developed for nIORT® applications can potentially improve the resectability rate of a given neoadjuvant cancer treatment and, generally, could satisfy all five R’s criteria of radiotherapy. Furthermore, in comparing with the current IORT techniques with electrons or low-keV X-rays, the nIORT® exploiting a high-flux neutrons beam of 2.45 MeV energy could lead to some significant clinical advantages due to its larger Linear Energy Transfer (LET, ~ 40 keV/m as average) and significantly higher Relative Biological Effectiveness (RBE 16) than all other forms of ionizing radiation.
{"title":"A COMPACT NEUTRON GENERATOR FOR THE NIORT® TREATMENT OF SEVERE SOLID CANCERS","authors":"M. Martellini","doi":"10.18103/mra.v11i3.3799","DOIUrl":"https://doi.org/10.18103/mra.v11i3.3799","url":null,"abstract":"In the last four years, TheranostiCentre S.r.l., Berkion Technology LLC and ENEA have patented and fabricated a first prototype of a Compact Neutron Generator (CNG) currently under testing in the ENEA laboratories. Besides the usual applications in the field of materials irradiation, this CNG - producing neutrons of 2.45 MeV energy by using the DD fusion reaction - was conceived for the neutron irradiation of the solid cancer’s tumour bed by means of the Intra-Operative Radiotherapy (IORT) technique, the so-called neutron-IORT (nIORT®). The CNG is self-shielded and light-weight (~120 kg) making possible its remote handling by a robotic arm. Accurate Monte Carlo simulations, modelling the CNG and the “open wound” biological tissues near its irradiation window, demonstrated that the apparatus - operated at 100 kV-10 mA - supplies a neutron flux ~108 cm-2 s-1 and can deliver equivalent dose rates ~2 Gy (RBE)/min. Hence, it can administer very high dose levels in limited treatment times. This article briefly summarizes the main findings of this collaborative research study, the clinical rationales underpinning the nIORT® idea and the potential performances of the CNG for the treatment of solid cancer pathologies. Indeed, the CNG can be installed in an operating room dedicated to nIORT® treatments, without posing any environmental and safety issues. Monte Carlo simulations have been carried out by envisioning the CNG equipped with an IORT applicator, that is an applicator pipe with a tuneable diameter to be inserted in the surgical cavity. By foreseeing the clinical endpoints of the standard IORT protocols, the irradiation performances for potential nIORT® treatments - obtained with an applicator pipe of 6 cm diameter - are here reported for different regimes: from 10 up to 75 Gy (RBE), that can be administered in a single session of about 4 to 30 minutes. Besides the dose peak in the centre of the tumour bed, the almost isotropic neutrons emission allows to irradiate the surroundings side-walls of the tumour bed – usually filled by potential quiescent cancer cells (QCCs) – and therefore reducing the chances of local recurrences by improving the local control of the tumour. The rapid decrease in tissues depth of the dose profile (in few centimetres) will spare the neighbouring organs at risk from harmful radiations. Thus, the CNG apparatus developed for nIORT® applications can potentially improve the resectability rate of a given neoadjuvant cancer treatment and, generally, could satisfy all five R’s criteria of radiotherapy. Furthermore, in comparing with the current IORT techniques with electrons or low-keV X-rays, the nIORT® exploiting a high-flux neutrons beam of 2.45 MeV energy could lead to some significant clinical advantages due to its larger Linear Energy Transfer (LET, ~ 40 keV/m as average) and significantly higher Relative Biological Effectiveness (RBE 16) than all other forms of ionizing radiation.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87401898","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.v11i7.1.4008
S. Rietveld, A. Latenstein, M. Besselink, J. Haverkamp, J. Haver
Background: In the current literature different diagnosis and treatment strategies for chyle leak after pancreatic surgery are described. In 2017, the International Study Group for Pancreatic Surgery defined a consensus-based definition for diagnosis. However, consensus on the optimal treatment strategy is lacking. Aim: The aim of this multicenter study is to investigate the current treatment and diagnosis of chyle leak after pancreatic surgery in clinical practice in the Netherlands to gain insight into practical applications of chyle leak. Methods: A nationwide survey about the diagnosis and treatment of chyle leak was sent to specialized dieticians and pancreatic surgeons from all 16 pancreatic centers collaborating in the Dutch Pancreatic Cancer Group. Data was quantitative processed according to thematic content analysis and by using descriptive analysis. Results: In total, 16 dieticians from 16 centers and 20 surgeons from 12 centers completed the questionnaire. Analysis showed that the International Study Group for Pancreatic Surgery-definition for chyle leak was used in clinical practice by 31% (n=11) of the respondents. The results show also large nationwide variation in treatment of chyle leak after pancreatic surgery, as well between as within centers. The most common treatment was a step-up approach of nutritional therapies (44% (n=16)), which starts with an enteral fat restricted diet enriched with medium chain fatty acids followed by total parenteral nutrition. Conclusion This study shows that the current diagnosis and treatment strategies for chyle leak after pancreatic surgery in clinical practice on a nationwide scale are different. More comparable studies are needed to define the optimal treatment strategy for chyle leak. There is need for an international multidisciplinary (sub)working group to reach consensus on the treatment strategy of chyle leak and to discuss implementation strategies for clinical practice.
{"title":"Large Variation in Diagnosis and Treatment of Chyle Leak after Pancreatic Surgery: A Nationwide Insight","authors":"S. Rietveld, A. Latenstein, M. Besselink, J. Haverkamp, J. Haver","doi":"10.18103/mra.v11i7.1.4008","DOIUrl":"https://doi.org/10.18103/mra.v11i7.1.4008","url":null,"abstract":"Background: In the current literature different diagnosis and treatment strategies for chyle leak after pancreatic surgery are described. In 2017, the International Study Group for Pancreatic Surgery defined a consensus-based definition for diagnosis. However, consensus on the optimal treatment strategy is lacking. Aim: The aim of this multicenter study is to investigate the current treatment and diagnosis of chyle leak after pancreatic surgery in clinical practice in the Netherlands to gain insight into practical applications of chyle leak. Methods: A nationwide survey about the diagnosis and treatment of chyle leak was sent to specialized dieticians and pancreatic surgeons from all 16 pancreatic centers collaborating in the Dutch Pancreatic Cancer Group. Data was quantitative processed according to thematic content analysis and by using descriptive analysis. Results: In total, 16 dieticians from 16 centers and 20 surgeons from 12 centers completed the questionnaire. Analysis showed that the International Study Group for Pancreatic Surgery-definition for chyle leak was used in clinical practice by 31% (n=11) of the respondents. The results show also large nationwide variation in treatment of chyle leak after pancreatic surgery, as well between as within centers. The most common treatment was a step-up approach of nutritional therapies (44% (n=16)), which starts with an enteral fat restricted diet enriched with medium chain fatty acids followed by total parenteral nutrition. Conclusion This study shows that the current diagnosis and treatment strategies for chyle leak after pancreatic surgery in clinical practice on a nationwide scale are different. More comparable studies are needed to define the optimal treatment strategy for chyle leak. There is need for an international multidisciplinary (sub)working group to reach consensus on the treatment strategy of chyle leak and to discuss implementation strategies for clinical practice.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80602790","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}
Systemic lupus erythematosus (SLE) is a complex autoimmune disease, which can be clinically heterogeneous in the same patient over the disease process and has an unpredictable evolution. Although its prevalence is increasing, SLE remains a rare disease with frequent extra-articular manifestations managed by multiple specialists. Among these, the internist is a key player in the overall coordination of the care pathway. The dramatic improvement in the short-term prognosis of SLE observed over the past few decades has favoured the emergence of more chronic disease-associated morbidities, especially infectious, cardiovascular and/or related to sequelae, notably renal. Thus, every lupologist is confronted with the difficulty of having to address, in an educational, individualised but also systematic way, a certain number of key items on which the short-, medium- and long-term medical future of patients who develop SLE at a relatively young age depend. In recent years, in addition to the creation of a network of reference centres and the drafting of regularly updated national therapeutic guidelines and therapeutic education programs, international consensus about the factors to consider in SLE patients has been reached, including the definition of therapeutic objectives according to a treat-to-target (T2T) strategy. However, the translation of these new objectives/paradigms in real-life has encountered a number of difficulties. As part of a multidisciplinary team involving SLE patients, we developed practical tools in the form of CHECKLISTs addressing the problems of refractory SLE (D2T), the management of comorbidities and toxicities (BASICs), and, more recently, therapeutic de-escalation with a shared medical decision (T2U). It appears that there is an opportunity to transform the care pathway of SLE patients by allowing the implementation of these tools within adaptive structuring of the consultation, which has the advantage of defining a starting point within the care pathway as a common denominator for lupologists, regardless of their specialty or where they work.
{"title":"Towards adaptive structuring of the lupologist’s consultation to transform the care pathway of systemic lupus erythematosus","authors":"","doi":"10.18103/mra.v11i3.3679","DOIUrl":"https://doi.org/10.18103/mra.v11i3.3679","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a complex autoimmune disease, which can be clinically heterogeneous in the same patient over the disease process and has an unpredictable evolution. Although its prevalence is increasing, SLE remains a rare disease with frequent extra-articular manifestations managed by multiple specialists. Among these, the internist is a key player in the overall coordination of the care pathway. The dramatic improvement in the short-term prognosis of SLE observed over the past few decades has favoured the emergence of more chronic disease-associated morbidities, especially infectious, cardiovascular and/or related to sequelae, notably renal. Thus, every lupologist is confronted with the difficulty of having to address, in an educational, individualised but also systematic way, a certain number of key items on which the short-, medium- and long-term medical future of patients who develop SLE at a relatively young age depend. In recent years, in addition to the creation of a network of reference centres and the drafting of regularly updated national therapeutic guidelines and therapeutic education programs, international consensus about the factors to consider in SLE patients has been reached, including the definition of therapeutic objectives according to a treat-to-target (T2T) strategy. However, the translation of these new objectives/paradigms in real-life has encountered a number of difficulties. As part of a multidisciplinary team involving SLE patients, we developed practical tools in the form of CHECKLISTs addressing the problems of refractory SLE (D2T), the management of comorbidities and toxicities (BASICs), and, more recently, therapeutic de-escalation with a shared medical decision (T2U). It appears that there is an opportunity to transform the care pathway of SLE patients by allowing the implementation of these tools within adaptive structuring of the consultation, which has the advantage of defining a starting point within the care pathway as a common denominator for lupologists, regardless of their specialty or where they work.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"149 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86656723","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 effective design, implementation, monitoring, and evaluation of state programs to reduce racial health inequities requires measures of societal resource access (e.g., education, home ownership, voting) and access inequity by race in each state. This paper proposes criteria for the selection of social determinants to assess, and ways to combine data to assess overall access and overall access inequity in states. Access and equity can be compared across geographic regions assessed. Hypotheses regarding the determinants and consequences of access and equity can be examined. Means of validating metrics are proposed. An example of analysis of access and inequity for Blacks and Whites in U.S. states yields surprising results—social determinant access and access equity are generally greatest in southern states. These metrics can be used to target and measure the effects of interventions to advance health equity for racial minority populations. The condition of state access and equity by race indicates the culmination of structural racism.
{"title":"Measuring Social Determinant Access and Equity by Race in U.S. States","authors":"R. Hahn","doi":"10.18103/mra.v11i2.3643","DOIUrl":"https://doi.org/10.18103/mra.v11i2.3643","url":null,"abstract":"The effective design, implementation, monitoring, and evaluation of state programs to reduce racial health inequities requires measures of societal resource access (e.g., education, home ownership, voting) and access inequity by race in each state. This paper proposes criteria for the selection of social determinants to assess, and ways to combine data to assess overall access and overall access inequity in states. Access and equity can be compared across geographic regions assessed. Hypotheses regarding the determinants and consequences of access and equity can be examined. Means of validating metrics are proposed. An example of analysis of access and inequity for Blacks and Whites in U.S. states yields surprising results—social determinant access and access equity are generally greatest in southern states. These metrics can be used to target and measure the effects of interventions to advance health equity for racial minority populations. The condition of state access and equity by race indicates the culmination of structural racism.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"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":"86706362","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}
In December 2019 there was a novel outbreak in Wuhan, China where an unknown respiratory disease known as SARS-COV-2 (COVID-19) started to spread rapidly across the world. In March 2020 the World Health Organisation declared a global pandemic. Over the next few years, the United Kingdom began adapting specific lockdown measures to prevent the spread of the disease, where a vaccination programme was started in December 2020 across the country to help prevent severity and reduce the rate of infection. Since the start of the pandemic, health care professionals have continued to work on effective treatment strategies to help relieve the stress on the health systems and manage the symptoms of the disease across the nation.
{"title":"An overview of lockdown measures, vaccination rollout and other treatment strategies used against COVID-19 in the past triennium since the start of the global pandemic in the United Kingdom","authors":"Carl Paramedic","doi":"10.18103/mra.v11i1.3500","DOIUrl":"https://doi.org/10.18103/mra.v11i1.3500","url":null,"abstract":"In December 2019 there was a novel outbreak in Wuhan, China where an unknown respiratory disease known as SARS-COV-2 (COVID-19) started to spread rapidly across the world. In March 2020 the World Health Organisation declared a global pandemic. Over the next few years, the United Kingdom began adapting specific lockdown measures to prevent the spread of the disease, where a vaccination programme was started in December 2020 across the country to help prevent severity and reduce the rate of infection. Since the start of the pandemic, health care professionals have continued to work on effective treatment strategies to help relieve the stress on the health systems and manage the symptoms of the disease across the nation.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91248621","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}
Neuroblastoma is a solid malignancy observed in pediatric patients that develops when neuroblasts are unable to mature, leading to unregulated proliferation and tumor formation. Neuroblastoma commonly manifests in the adrenal gland, but may also form in the neck, chest, or spinal cord. Neuroblastoma is heterogeneous and aggressive in nature, leading to high treatment failure, morbidity, and mortality rates. Lewis family glycans, as part of the Core 2 O- glycans, play a key role in neuroblastoma malignant cell behavior in MYCN-amplified cell lines. Current treatment approaches for neuroblastoma include chemotherapy, surgery, and radiation. These approaches are faced with physiological and cellular barriers, including the influence of glycosylation in cancer diseases. Studies have confirmed that the inhibition of mucin glycosylation has improved effectiveness of cytotoxic drug agents employed against solid malignancies such as with pancreatic cancer, yet little research is available regarding the influence of glycosylated proteins for other diseases. This article reviews the effect of glycosylation on the development and treatment of neuroblastoma.
{"title":"Influence of glycosylation on the development and treatment of neuroblastoma.","authors":"Robert Campbell","doi":"10.18103/mra.v11i6.3933","DOIUrl":"https://doi.org/10.18103/mra.v11i6.3933","url":null,"abstract":"Neuroblastoma is a solid malignancy observed in pediatric patients that develops when neuroblasts are unable to mature, leading to unregulated proliferation and tumor formation. Neuroblastoma commonly manifests in the adrenal gland, but may also form in the neck, chest, or spinal cord. Neuroblastoma is heterogeneous and aggressive in nature, leading to high treatment failure, morbidity, and mortality rates. Lewis family glycans, as part of the Core 2 O- glycans, play a key role in neuroblastoma malignant cell behavior in MYCN-amplified cell lines. Current treatment approaches for neuroblastoma include chemotherapy, surgery, and radiation. These approaches are faced with physiological and cellular barriers, including the influence of glycosylation in cancer diseases. Studies have confirmed that the inhibition of mucin glycosylation has improved effectiveness of cytotoxic drug agents employed against solid malignancies such as with pancreatic cancer, yet little research is available regarding the influence of glycosylated proteins for other diseases. This article reviews the effect of glycosylation on the development and treatment of neuroblastoma.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89819467","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}
Racheal Baartmans, Mary Mendoza, A. Dickey, H. Hassan
The internal cavity of equine contains symbiotic microorganisms that are collectively referred to as the gut microbiota, which interact with the host immune system from birth. The microorganisms in the gut microbiota are shaped by their interactions with the gut environment throughout the life of the host, i.e., exposure to antibiotics and diet. Lactobacilli are one of the major groups found in the gastrointestinal tracts of humans and animals. Lactobacilli are members of the lactic acid bacteria, and they help to maintain a balanced gut microbiome and stimulate the host’s immune system. In this study six equine Lactobacillus spp. were isolated from three American Quarter horses of different ages (i.e., 1-day post-weaning, 1.5-month post-weaning, and 10-year-old mature gelding). The metabolic properties that allowed the isolates to survive in the harsh environment of the gut were characterized. Thus, we evaluated their abilities to metabolize different carbohydrates and to withstand acidic pH, bile salts, antibiotics, and to inhibit pathogenic bacteria which may be encountered during their passage to the small/large intestine. We also identified the genetic elements that allow the isolates to survive and persist in the host’s gut environment by using data generated from whole genome sequencing. The data indicated that the isolates were metabolically adapted to the age of the host and the type of feed consumed. The characterized isolates are potential probiotic candidates for enhancing the gut health of equines.
{"title":"Genetic and Biochemical Characterization of Six Lactobacillus Isolates from American Quarter Horses","authors":"Racheal Baartmans, Mary Mendoza, A. Dickey, H. Hassan","doi":"10.18103/mra.v11i1.3492","DOIUrl":"https://doi.org/10.18103/mra.v11i1.3492","url":null,"abstract":"The internal cavity of equine contains symbiotic microorganisms that are collectively referred to as the gut microbiota, which interact with the host immune system from birth. The microorganisms in the gut microbiota are shaped by their interactions with the gut environment throughout the life of the host, i.e., exposure to antibiotics and diet. Lactobacilli are one of the major groups found in the gastrointestinal tracts of humans and animals. Lactobacilli are members of the lactic acid bacteria, and they help to maintain a balanced gut microbiome and stimulate the host’s immune system. In this study six equine Lactobacillus spp. were isolated from three American Quarter horses of different ages (i.e., 1-day post-weaning, 1.5-month post-weaning, and 10-year-old mature gelding). The metabolic properties that allowed the isolates to survive in the harsh environment of the gut were characterized. Thus, we evaluated their abilities to metabolize different carbohydrates and to withstand acidic pH, bile salts, antibiotics, and to inhibit pathogenic bacteria which may be encountered during their passage to the small/large intestine. We also identified the genetic elements that allow the isolates to survive and persist in the host’s gut environment by using data generated from whole genome sequencing. The data indicated that the isolates were metabolically adapted to the age of the host and the type of feed consumed. The characterized isolates are potential probiotic candidates for enhancing the gut health of equines.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89668760","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.v11i7.2.4003
C. Mengue, L. Pellanda, M. Parodi, M. Vilela
Background: Among congenital diseases, congenital heart disease is one of the most frequent defects, accounting for high morbidity and mortality rates. Coexistence of ocular sequelae, especially in retinal microvascularization, is frequent, and may be a marker of vascular damage and severity of underlying disease. Aims: To identify ocular anatomical repercussions in children with congenital heart diseases; to describe the prevalence of potential markers associated with retinal vessels using a smartphone. Methods: This was a cross-sectional observational study with children diagnosed with congenital heart disease treated at the Instituto de Cardiologia in Porto Alegre-RS from 4 up to (but not over) 18 years old. Results: Of a total of 218 patients assessed, 206 were included in the study. Mean age was 10.19 years +- 3.88. Uncorrected visual acuity poorer than 0.6 in at least one eye was found in 11.65% (24) of all patients. Regarding retinal findings, estimated mean arterial tortuosity was 437.79 μm, and estimated mean venous tortuosity was 336.41 μm. Taking only the cyanotic group, the arterial mean reached 557.29 μm, and the venous mean reached 401.86 (p=.001 and p=.004, respectively). In the multivariate analysis, estimated mean arterial tortuosity of cyanotic patients undergoing clinical treatment was 699.13 μm versus 489.74 μm for those without clinical treatment (p<0.001). Conclusion: Presence of retinal vascular tortuosity, especially in the arterial bed, is associated with cyanotic CHD. Identification of ocular changes, especially through an easily accessible and universal method such as the smartphone, may have diagnostic and prognostic significance.
{"title":"Identifying Eye Changes in Children and Adolescents with Congenital Heart Disease with the Aid of a Smartphone: An Observational Study","authors":"C. Mengue, L. Pellanda, M. Parodi, M. Vilela","doi":"10.18103/mra.v11i7.2.4003","DOIUrl":"https://doi.org/10.18103/mra.v11i7.2.4003","url":null,"abstract":"Background: Among congenital diseases, congenital heart disease is one of the most frequent defects, accounting for high morbidity and mortality rates. Coexistence of ocular sequelae, especially in retinal microvascularization, is frequent, and may be a marker of vascular damage and severity of underlying disease. Aims: To identify ocular anatomical repercussions in children with congenital heart diseases; to describe the prevalence of potential markers associated with retinal vessels using a smartphone. Methods: This was a cross-sectional observational study with children diagnosed with congenital heart disease treated at the Instituto de Cardiologia in Porto Alegre-RS from 4 up to (but not over) 18 years old. Results: Of a total of 218 patients assessed, 206 were included in the study. Mean age was 10.19 years +- 3.88. Uncorrected visual acuity poorer than 0.6 in at least one eye was found in 11.65% (24) of all patients. Regarding retinal findings, estimated mean arterial tortuosity was 437.79 μm, and estimated mean venous tortuosity was 336.41 μm. Taking only the cyanotic group, the arterial mean reached 557.29 μm, and the venous mean reached 401.86 (p=.001 and p=.004, respectively). In the multivariate analysis, estimated mean arterial tortuosity of cyanotic patients undergoing clinical treatment was 699.13 μm versus 489.74 μm for those without clinical treatment (p<0.001). Conclusion: Presence of retinal vascular tortuosity, especially in the arterial bed, is associated with cyanotic CHD. Identification of ocular changes, especially through an easily accessible and universal method such as the smartphone, may have diagnostic and prognostic significance.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89680628","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}
Upregulation of uncoupling protein 2 (UCP2) is considered a prosurvival mechanism for cancer cells. This prosurvival function is thought to be mediated by UCP2’s uncoupling activity which reduces the production of superoxide in the mitochondria. However, exactly how highly expressed UCP2 regulates cell proliferation, cell cycle, and cell death during the early stage of tumorigenesis has not been studied thoroughly. For this purpose, we generated UCP2 stably overexpressed JB6 Cl-41 cells (a skin cell transformation model) and performed studies to answer the above questions. Our results demonstrated that UCP2 overexpression enhanced cell proliferation, activation of the oncoprotein Fra-1, anchorage-independent growth, 3D spheroids growth, and glucose uptake during skin cell transformation. Next, our results demonstrated that UCP2 overexpression resulted in marked decreases in the proportion of the cells in the G1 phase and an increase of cells in the S phase of the cell cycle, which was accompanied by increased expression of Cyclin E and Cdk2. Lastly, UCP2 overexpression did not enhance or suppress apoptosis during skin cell transformation, as indicated by Annexin V and active caspase 3/7 staining. Taken together, these data suggest that UCP2 upregulation mainly enhances the Fra-1 oncogenic pathway which drives cell proliferation, without inhibiting apoptosis during skin cell transformation.
{"title":"UCP2 Upregulation Increases Fra-1 Expression and S-phase Cell Population without Decreasing Apoptosis during Skin Cell Transformation","authors":"Yunfeng Zhao, Annapoorna Sreedhar, Chunjing Zhang, Noel Jacquet","doi":"10.18103/mra.v11i6.3938","DOIUrl":"https://doi.org/10.18103/mra.v11i6.3938","url":null,"abstract":"Upregulation of uncoupling protein 2 (UCP2) is considered a prosurvival mechanism for cancer cells. This prosurvival function is thought to be mediated by UCP2’s uncoupling activity which reduces the production of superoxide in the mitochondria. However, exactly how highly expressed UCP2 regulates cell proliferation, cell cycle, and cell death during the early stage of tumorigenesis has not been studied thoroughly. For this purpose, we generated UCP2 stably overexpressed JB6 Cl-41 cells (a skin cell transformation model) and performed studies to answer the above questions. Our results demonstrated that UCP2 overexpression enhanced cell proliferation, activation of the oncoprotein Fra-1, anchorage-independent growth, 3D spheroids growth, and glucose uptake during skin cell transformation. Next, our results demonstrated that UCP2 overexpression resulted in marked decreases in the proportion of the cells in the G1 phase and an increase of cells in the S phase of the cell cycle, which was accompanied by increased expression of Cyclin E and Cdk2. Lastly, UCP2 overexpression did not enhance or suppress apoptosis during skin cell transformation, as indicated by Annexin V and active caspase 3/7 staining. Taken together, these data suggest that UCP2 upregulation mainly enhances the Fra-1 oncogenic pathway which drives cell proliferation, without inhibiting apoptosis during skin cell transformation.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"27 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":"90435527","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}
Patients with multiple sclerosis have been subjected to extra levels of stress during the COVID-19 pandemic when they were singled out by governmental regulatory agencies as sufficiently immune-compromised persons that should be in the first group to receive the untested, new COVID-19 vaccine. The designation of these persons in such a high-risk group compounded their anxiety and depression. Early in the disease in 2020-2021, little was known about the disease, the vaccine, or whether their disease-modifying therapies for multiple sclerosis were subjecting them to more immunomodulatory suppression. This review is not comprehensive of all articles written on COVID-19 and multiple sclerosis, but selectively looks at research on COVID-19 and use of low-doses of naltrexone as treatment. Specific causes for anxiety and depression are discussed in light of evidence that suggests that the length of disease, rather than age, sex, or therapy leads to more anxiety. Low-dose naltrexone in combination with other disease-modifying therapies, or alone, reduced the perceived levels of anxiety. These data suggest that clinicians may want to prescribe low-dose naltrexone for early-stage multiple sclerosis patients.
{"title":"A Review of Factors Influencing Anxiety and Depression in Persons with Multiple Sclerosis during the COVID-19 Pandemic","authors":"Patricia McLaughlin, L. Odom, I. Zagon","doi":"10.18103/mra.v11i6.3964","DOIUrl":"https://doi.org/10.18103/mra.v11i6.3964","url":null,"abstract":"Patients with multiple sclerosis have been subjected to extra levels of stress during the COVID-19 pandemic when they were singled out by governmental regulatory agencies as sufficiently immune-compromised persons that should be in the first group to receive the untested, new COVID-19 vaccine. The designation of these persons in such a high-risk group compounded their anxiety and depression. Early in the disease in 2020-2021, little was known about the disease, the vaccine, or whether their disease-modifying therapies for multiple sclerosis were subjecting them to more immunomodulatory suppression. This review is not comprehensive of all articles written on COVID-19 and multiple sclerosis, but selectively looks at research on COVID-19 and use of low-doses of naltrexone as treatment. Specific causes for anxiety and depression are discussed in light of evidence that suggests that the length of disease, rather than age, sex, or therapy leads to more anxiety. Low-dose naltrexone in combination with other disease-modifying therapies, or alone, reduced the perceived levels of anxiety. These data suggest that clinicians may want to prescribe low-dose naltrexone for early-stage multiple sclerosis patients.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78140490","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}