Objective: To identify antigenic proteins from the salivary glands of female Anopheles maculatus using a proteomic approach to find the biomarker candidate for serological tools.Methods: The identification of antigeni...Objective: To identify antigenic proteins from the salivary glands of female Anopheles maculatus using a proteomic approach to find the biomarker candidate for serological tools.Methods: The identification of antigenic proteins of Anopheles maculatus salivary gland used these techniques: one-dimensional gel electrophoresis(sodium dodecyl sulfate polyacrylamide gel electrophoresis), western blot, and liquid chromatography–mass spectrometry.Results: The proteins that have molecular weight(MW) 43 and 34 k Da were the antigenic protein. Computational bioinformatic analysis by Mascot Server revealed seven novel hypothetical proteins(MW: 43 k Da) and two novel hypothetical proteins(MW:34 k Da). Further analysis(BLASTP, antigenicity, epitope mapping, and specificity analysis) showed that two novel proteins were identified as apolipoprotein D and cathepsin D in Anopheles darlingi.Conclusions: The identified proteins are potential to be developed as a biomarker of mosquito bite's exposure.展开更多
BACKGROUND Adolescent idiopathic scoliosis remains a major problem due to its high incidence,high risk,and high cost.One of the aims of the management in scoliosis is to correct the deformity.Many techniques are avail...BACKGROUND Adolescent idiopathic scoliosis remains a major problem due to its high incidence,high risk,and high cost.One of the aims of the management in scoliosis is to correct the deformity.Many techniques are available to correct scoliosis deformity;however,they are all far from ideal to achieve three-dimensional correction in scoliosis.AIM To develop a set of tools named Scoliocorrector Fatma-UI(SCFUI)to aid threedimensional correction and to evaluate the efficacy,safety,and functional outcome.METHODS This study consists of two stages.In the first stage,we developed the SCFUI and tested it in finite element and biomechanical tests.The second stage was a single-blinded randomized clinical trial to evaluate the SCFUI compared to direct vertebral rotation(DVR).Forty-four subjects with adolescent idiopathic scoliosis were randomly allocated into the DVR group(n=23)and SCFUI group(n=21).Radiological,neurological,and functional outcome was compared between the groups.RESULTS Finite element revealed the maximum stress of the SCFUI components to be between 31.2-252 MPa.Biomechanical analysis revealed the modulus elasticity of SCFUI was 9561324±633277 MPa.Both groups showed improvement in Cobb angle and sagittal profile,however the rotation angle was lower in the SCFUI group(11.59±7.46 vs 18.23±6.39,P=0.001).Neurological and functional outcome were comparable in both groups.CONCLUSION We concluded that SCFUI developed in this study resulted in similar coronal and sagittal but better rotational correction compared to DVR.The safety and functional outcomes were also similar to DVR.展开更多
Monoclonal antibodies (mAbs) have made significant progress in the treatment of Alzheimer''s disease (AD). However, mAbs are associated with adverse effects, including Amyloid-Related Imaging Abnormality (ARIA...Monoclonal antibodies (mAbs) have made significant progress in the treatment of Alzheimer''s disease (AD). However, mAbs are associated with adverse effects, including Amyloid-Related Imaging Abnormality (ARIA), which manifests as edema or effusion (ARIA-E) and hemorrhage (ARIA-H). The mechanisms behind these effects are not yet fully understood. Moreover, spontaneous ARIA has been insufficiently explored, and mAb therapies, particularly lecanemab, have mainly focused on patients with theAPOE-ε4 allele carrier. This review aims to address this gap by examining the mechanisms of spontaneous ARIA, ARIA induced by mAbs, and the influence of genetic variants on ARIA development. The autoantibody-Aβ-mediated immune response targets excessive Aβ deposits, increasing immune activity through microglial reactivity. The heightened immune response, driven by Aβ accumulation in blood vessels, promotes angiopathy and inflammation, potentially contributing to spontaneous ARIA. TheAPOE-ε4 allele carrier is more strongly associated with ARIA-E because it redistributes Aβ deposition from the brain to blood vessels, influencing microglial reactivity. The redistribution enhances vascular integrity and reduces the risk of ARIA-H. However, it also increases the likelihood of ARIA-E due to Aβ accumulation in the vasculature, triggering inflammation. In contrast, the development of ARIA-H is linked to increasedTREM2 expression and microglial reactivity, leading to impaired vascular integrity and disrupted matrix remodeling, which worsens the condition. Additionally, the adverse effects of mAbs may extend beyond theAPOE-ε4 allele, possibly impacting other genetic variants involved in microglial reactivity, Aβ redistribution, and vascular integrity.展开更多
The rising incidence and death rates linked to Alzheimer's disease(AD)highlight an urgent issue.Genetic screening is celebrated as a significant advancement for its early detection capabilities,pinpointing those a...The rising incidence and death rates linked to Alzheimer's disease(AD)highlight an urgent issue.Genetic screening is celebrated as a significant advancement for its early detection capabilities,pinpointing those at risk before the emergence of symptoms.Yet,the limited availability of these technologies highlights a critical gap in widespread application.This review pivots to the potential of presymptomatic clinical assessments as a readily available,economical,and simple strategy for early detection.Traditionally,AD diagnosis relies on the late-stage identification of cognitive deterioration,functional impairments,and neuropsychiatric symptoms,coinciding with advanced brain degeneration.Conversely,emerging research identifies early indicators preceding significant degeneration,manifesting years before clinical symptoms.We introduce a mnemonic,MEMORIES,to categorize these prodromal:Metabolism changes,Eye/visual impairments,March(refer to gait disturbances),Olfactory dysfunction,Rhythm(blood pressure and heart rate),Insensitivity of the tongue,Ears(hearing loss),and Stool alterations.Recognizing these prodromal through clinical examinations provides a valuable strategy for initiating preventative actions against brain degeneration.This approach advocates for broadening the screening lens beyond genetic screening to encompass clinical evaluations,enhancing early detection and intervention opportunities for AD.展开更多
Introduction: Expert opinions presented in legal proceedings should be scientifically accountable, which is known as evidence-based practice (EBP). Although forensic medical expert opinions are essential in legal proc...Introduction: Expert opinions presented in legal proceedings should be scientifically accountable, which is known as evidence-based practice (EBP). Although forensic medical expert opinions are essential in legal proceedings, the methods used to formulate them are not always evidence based or based on standard methods. In forensic medicine, EBP has not been explicitly applied, including in Indonesia. One potential approach to formulate evidence-based expert opinions is called INtegration of Forensic Epidemiology and the Rigorous EvaluatioN of Causation Elements (INFERENCE). In addition, there is also no universal guideline for making forensic pathological reports. One prospective guideline is named the Principles of Evidence-based Reporting in FORensic Medicine-Pathology version (PERFORM-P). Methods: This article describes the validation process of INFERENCE and PERFORM-P in Indonesia. This study uses a mixed method through three interrelated phases, i.e., (1) a cross-sectional survey to determine the characteristics of Indonesian forensic doctors and their current practice, (2) the adaptation and validation process of the two tools through a review by the Indonesian College of Forensic Medicine, and (3) a one-group pre-postintervention study to assess the validity and reliability of forensic medical expert opinions formulated using Indonesian-INFERENCE (i-INFERENCE) and reported using Indonesian-PERFORM-P (i-PERFORM-P). Results and Discussion: In general, both tools received a positive reception and can potentially be used in the Indonesian setting with some additions/clarifications in the user manuals. Participants envision that both tools will be most useful in complex cases. Conclusions: By obtaining the i-INFERENCE and the i-PERFORM-P, it is hoped that Indonesian forensic medical doctors are better equipped in analyzing and reporting complex cases, and the implementation of EBP can be improved.展开更多
基金Funded by a Doctorate Research Grant of the Directorate General of Higher Education Indonesia(Grant No.435/UN25.3.1/LT.6/2014)
文摘Objective: To identify antigenic proteins from the salivary glands of female Anopheles maculatus using a proteomic approach to find the biomarker candidate for serological tools.Methods: The identification of antigenic proteins of Anopheles maculatus salivary gland used these techniques: one-dimensional gel electrophoresis(sodium dodecyl sulfate polyacrylamide gel electrophoresis), western blot, and liquid chromatography–mass spectrometry.Results: The proteins that have molecular weight(MW) 43 and 34 k Da were the antigenic protein. Computational bioinformatic analysis by Mascot Server revealed seven novel hypothetical proteins(MW: 43 k Da) and two novel hypothetical proteins(MW:34 k Da). Further analysis(BLASTP, antigenicity, epitope mapping, and specificity analysis) showed that two novel proteins were identified as apolipoprotein D and cathepsin D in Anopheles darlingi.Conclusions: The identified proteins are potential to be developed as a biomarker of mosquito bite's exposure.
基金The study was reviewed and approved by the Ethical Committee Faculty of Medicine,University of Indonesia(Approval No.KET-615/UN2.F1/ETIK/PPM.00.02/2020)Ethical Committee of Fatmawati General Hospital(Approval No.DM 01.01/VIII.2/1294/2020).
文摘BACKGROUND Adolescent idiopathic scoliosis remains a major problem due to its high incidence,high risk,and high cost.One of the aims of the management in scoliosis is to correct the deformity.Many techniques are available to correct scoliosis deformity;however,they are all far from ideal to achieve three-dimensional correction in scoliosis.AIM To develop a set of tools named Scoliocorrector Fatma-UI(SCFUI)to aid threedimensional correction and to evaluate the efficacy,safety,and functional outcome.METHODS This study consists of two stages.In the first stage,we developed the SCFUI and tested it in finite element and biomechanical tests.The second stage was a single-blinded randomized clinical trial to evaluate the SCFUI compared to direct vertebral rotation(DVR).Forty-four subjects with adolescent idiopathic scoliosis were randomly allocated into the DVR group(n=23)and SCFUI group(n=21).Radiological,neurological,and functional outcome was compared between the groups.RESULTS Finite element revealed the maximum stress of the SCFUI components to be between 31.2-252 MPa.Biomechanical analysis revealed the modulus elasticity of SCFUI was 9561324±633277 MPa.Both groups showed improvement in Cobb angle and sagittal profile,however the rotation angle was lower in the SCFUI group(11.59±7.46 vs 18.23±6.39,P=0.001).Neurological and functional outcome were comparable in both groups.CONCLUSION We concluded that SCFUI developed in this study resulted in similar coronal and sagittal but better rotational correction compared to DVR.The safety and functional outcomes were also similar to DVR.
文摘Monoclonal antibodies (mAbs) have made significant progress in the treatment of Alzheimer''s disease (AD). However, mAbs are associated with adverse effects, including Amyloid-Related Imaging Abnormality (ARIA), which manifests as edema or effusion (ARIA-E) and hemorrhage (ARIA-H). The mechanisms behind these effects are not yet fully understood. Moreover, spontaneous ARIA has been insufficiently explored, and mAb therapies, particularly lecanemab, have mainly focused on patients with theAPOE-ε4 allele carrier. This review aims to address this gap by examining the mechanisms of spontaneous ARIA, ARIA induced by mAbs, and the influence of genetic variants on ARIA development. The autoantibody-Aβ-mediated immune response targets excessive Aβ deposits, increasing immune activity through microglial reactivity. The heightened immune response, driven by Aβ accumulation in blood vessels, promotes angiopathy and inflammation, potentially contributing to spontaneous ARIA. TheAPOE-ε4 allele carrier is more strongly associated with ARIA-E because it redistributes Aβ deposition from the brain to blood vessels, influencing microglial reactivity. The redistribution enhances vascular integrity and reduces the risk of ARIA-H. However, it also increases the likelihood of ARIA-E due to Aβ accumulation in the vasculature, triggering inflammation. In contrast, the development of ARIA-H is linked to increasedTREM2 expression and microglial reactivity, leading to impaired vascular integrity and disrupted matrix remodeling, which worsens the condition. Additionally, the adverse effects of mAbs may extend beyond theAPOE-ε4 allele, possibly impacting other genetic variants involved in microglial reactivity, Aβ redistribution, and vascular integrity.
文摘The rising incidence and death rates linked to Alzheimer's disease(AD)highlight an urgent issue.Genetic screening is celebrated as a significant advancement for its early detection capabilities,pinpointing those at risk before the emergence of symptoms.Yet,the limited availability of these technologies highlights a critical gap in widespread application.This review pivots to the potential of presymptomatic clinical assessments as a readily available,economical,and simple strategy for early detection.Traditionally,AD diagnosis relies on the late-stage identification of cognitive deterioration,functional impairments,and neuropsychiatric symptoms,coinciding with advanced brain degeneration.Conversely,emerging research identifies early indicators preceding significant degeneration,manifesting years before clinical symptoms.We introduce a mnemonic,MEMORIES,to categorize these prodromal:Metabolism changes,Eye/visual impairments,March(refer to gait disturbances),Olfactory dysfunction,Rhythm(blood pressure and heart rate),Insensitivity of the tongue,Ears(hearing loss),and Stool alterations.Recognizing these prodromal through clinical examinations provides a valuable strategy for initiating preventative actions against brain degeneration.This approach advocates for broadening the screening lens beyond genetic screening to encompass clinical evaluations,enhancing early detection and intervention opportunities for AD.
文摘Introduction: Expert opinions presented in legal proceedings should be scientifically accountable, which is known as evidence-based practice (EBP). Although forensic medical expert opinions are essential in legal proceedings, the methods used to formulate them are not always evidence based or based on standard methods. In forensic medicine, EBP has not been explicitly applied, including in Indonesia. One potential approach to formulate evidence-based expert opinions is called INtegration of Forensic Epidemiology and the Rigorous EvaluatioN of Causation Elements (INFERENCE). In addition, there is also no universal guideline for making forensic pathological reports. One prospective guideline is named the Principles of Evidence-based Reporting in FORensic Medicine-Pathology version (PERFORM-P). Methods: This article describes the validation process of INFERENCE and PERFORM-P in Indonesia. This study uses a mixed method through three interrelated phases, i.e., (1) a cross-sectional survey to determine the characteristics of Indonesian forensic doctors and their current practice, (2) the adaptation and validation process of the two tools through a review by the Indonesian College of Forensic Medicine, and (3) a one-group pre-postintervention study to assess the validity and reliability of forensic medical expert opinions formulated using Indonesian-INFERENCE (i-INFERENCE) and reported using Indonesian-PERFORM-P (i-PERFORM-P). Results and Discussion: In general, both tools received a positive reception and can potentially be used in the Indonesian setting with some additions/clarifications in the user manuals. Participants envision that both tools will be most useful in complex cases. Conclusions: By obtaining the i-INFERENCE and the i-PERFORM-P, it is hoped that Indonesian forensic medical doctors are better equipped in analyzing and reporting complex cases, and the implementation of EBP can be improved.