Associations between meteorological variation and hospitalisations for rotavirus infections in Kuala Lumpur, Malaysia.

Objectives: Rotavirus (RoV) infections have emerged as a significant public health concern around the world. Understanding the relationship between climatic conditions and hospitalisations due to RoV infections can help engage effective prevention strategies. This study aims to investigate the potential associations between meteorological variability and RoV-related hospitalisations in Kuala Lumpur, Malaysia. Methods: Hospitalization data from a tertiary teaching hospital in Kuala Lumpur over a twelve-year period were retrospectively collected. Concurrently, meteorological data were obtained from the Malaysian Meteorological Department (MetMalaysia) including variables of temperature, humidity, precipitation, and atmospheric pressure to further demonstrate relationship with RoV-associated hospitalisations. Results: The results indicated positive correlations between increased rainfall, rainy days, humidity, and RoV-related hospitalisations, suggesting the influence of environmental factors on the transmission of RoV. Conclusions: This study highlights positive associations between meteorological variations and hospitalizations for RoV infections in Kuala Lumpur, Malaysia. Further investigations, including national-level data, are needed to deepen our understanding of these associations, particularly within the context of Malaysia and to develop targeted interventions for disease prevention and control.

RYR2 receptor gene mutation associated with catecholaminergic polymorphic ventricular tachycardia in children: a case report & literature review.

Background: Ryanodine receptor 2 (RYR2) gene mutation causing catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the identified causes of sudden death in adults and children. Case Description: We report a case of RYR2 gene mutation presented with cardiac arrest and recurrent syncopal attack with accidental finding of cardiac tumour. For the systematic review, we used four databases (Scopus, PubMed, Ovid and Google Scholar) to search articles with the terms "RYR2 gene mutation" and "catecholaminergic polymorphic ventricular tachycardia (CPVT)". Fourteen studies were chosen and reviewed together with our reported patient. Most of the patients presented initially with syncopal attack and developed cardiac arrest later. Some of them presented with both syncopal attack and seizures precipitated by exercise or stress. We found that 43.8% of patients shared similar variants or coding effects in RYR2 gene mutation. Demographically, the mean age at presentation is 11 years old with 53% of reported cases were male. Conclusions: Refractory arrhythmias cardiac arrest not responding to adrenaline should raise the suspicion towards RYR2 gene mutations. Recognition of this condition is important as it affects the outcome of resuscitation. Untimely diagnosis of RYR2 gene mutations with appropriate use of pharmacological agents during resuscitation is important to ensure a better outcome.

Assessing the impact of COVID-19 on epidemiological changes of severe pediatric respiratory syncytial virus infections in Malaysia.

Introduction: Respiratory syncytial virus (RSV) is one of the leading causes of hospitalization and mortality among children with respiratory tract infections. The non-pharmaceutical preventive measures against severe acute respiratory syndrome coronavirus (COVID-19) may have reduced the transmission of RSV, altering its tropical epidemiological seasonality. Thus, this study represents the first attempt to evaluate changes in RSV epidemiology in the context of COVID-19 pandemic in Malaysia. Methods: Conducted at a tertiary hospital in Kuala Lumpur, Malaysia, this retrospective study analyzed collated data of children aged <12 years who were admitted for severe respiratory infections from 2017 to 2022. Time series models were used to predict the differences between actual and forecasted RSV cases, while logistic regression assessed the statistical association between RSV and COVID-19. Results: Among the 4,084 children analyzed, we reported a significant inverse relationship between RSV and COVID-19 infections during the pandemic (2020-2021) (p < 0.05). In 2020, the RSV positivity rate sharply declined to 8.3 and 5.9%, respectively, in the two prominent seasons. Time series analysis showed a tremendous decrease in cases compared to the expected values, with reductions of 98.3% in the first season and 95.7% in the second season. However, following the lifting of the restriction order in 2022, RSV infections rose sharply with a positivity rate of 36.3%, higher than pre-COVID-19 pandemic levels. Conclusion: This study provides evidence of increasing RSV cases post-COVID-19 pandemic, due to immunity debt. Hence, the healthcare system must be prepared to address future RSV outbreaks with the appropriate implementation of prophylaxis and public health measures.

Understanding Challenges of Genetic Testing on Neuromuscular Disorders from the Parental Lens.

Neuromuscular disorders, characterized by progressive muscle degeneration and weakness, present substantial challenges to both affected individuals and their families. Genetic testing assumes a pivotal role in facilitating early diagnosis, intervention, treatment, and informed family planning for these conditions. The objective of this qualitative study is to delve into the knowledge, awareness, and perceptions surrounding genetic testing within the cohort of parents caring for individuals with neuromuscular disorders in Malaysia. A semi-structured interview approach was employed to elicit data from parents of individuals diagnosed with neuromuscular disorders, encompassing those with clinical diagnoses and those diagnosed through genetic testing. Examination of the interview responses yielded nine overarching themes, which furnish invaluable insights into the perspectives of Malaysian parents concerning genetic testing. The study discerned several challenges associated with genetic testing, notably encompassing the limited awareness among parents, the financial constraints associated with genetic testing, and the perceived significance of genetic testing in the context of neuromuscular disorders. The findings suggest that the level of knowledge and awareness pertaining to genetic testing for neuromuscular disorders among parents in Malaysia varies, with initial levels of awareness ranging from relatively low to reasonably sufficient prior to and following the birth of an affected child. However, the investigation revealed that parents tended to cultivate more favorable perceptions regarding genetic testing subsequent to their experience with genetic counseling. This underscores the potential for heightened awareness and comprehension as a consequence of the personal experience of parenting an affected child confirmed through genetic testing and genetic counseling, ultimately influencing parental awareness.

Concomitant Kawasaki Disease and Rotavirus Infection-More Than Just a Coincidence: A Case Report.

The definitive role of viral infections, such as rotavirus, in causing Kawasaki disease (KD) remains uncertain. However, the intriguing observation of concomitant rotavirus infection and KD suggests a potential association. This study aimed to investigate this relationship. We reported a case of concomitant KD and rotavirus infection complicated by hyponatraemia and anasarca. For the systematic review, we used three large databases, namely PubMed, Ovid, and Scopus, to search articles with the terms "Kawasaki" and "rotavirus". We also used Google Scholar as our secondary source. We included articles that fulfilled the following criteria: (i) articles reporting on children aged 18 and below; (ii) articles reporting on patients infected with rotavirus prior to or concomitant with KD; and (iii) articles written in English only. Three articles were included and analysed in combination with our reported patient. All patients exhibited gastrointestinal symptoms, including diarrhoea and vomiting, in addition to non-resolving fevers, which eventually manifested more signs and symptoms to support the diagnosis of KD. Stool samples from all patients revealed positive rotavirus antigens. Two patients (n = 2) were noted to have hyponatraemia and hypoalbuminaemia. Three (n = 3) manifested coronary artery abnormalities (CAA). Even though the relationship is not fully understood yet, it is known that the combination of these two pathologies can cause catastrophic immune responses and complications.

Transition practice for primary immunodeficiency diseases in Southeast Asia: a regional survey.

Introduction: With increased diagnostic capabilities and treatment modalities in the field of primary immunodeficiencies (PID), many pediatric patients survive beyond childhood and experience a change of care to the adult-oriented healthcare system. Unfortunately, the transition pathways for PID are less clearly defined, resulting in deterioration of quality of care in adulthood. Hence, this is the first regional study to address PID clinicians' opinions on practices and challenges of transition care in 7 Southeast Asia (SEA) countries. Methods: We adopted a cross-sectional study design through an online survey platform to enquire opinions of transition practices from expert representatives in 7 SEA countries. Results: Regionally, 3 out 7 countries reported having no practice of transition care. Among cited challenges were reluctant adaptation by patients and caregivers to unfamiliarized adult healthcare systems, inadequate ratio of adult immunologists to patients and lack of facilities for transfer. Discussion and conclusion: Our study provides evidence to advocate policy makers on the importance of standardized integration of transition practice towards betterment of transiting PID patients into adulthood.

Tuberculous chylothorax in paediatric population-a case report and systematic review of the literature.

Background: Chylothorax as part of the clinical spectrum of tuberculosis (TB) is a rare entity, especially among children. However, it is crucial for clinicians to be able to identify, correlate, and diagnose chylothorax as it poses significant morbidity to patients. Case Description: We report on a paediatric case of pleural TB complicated with complex chylothorax, and systematically reviewing the literature for cases of tuberculous chylothorax among children particularly looking at the (I) demographic, (II) clinical presentations, (III) radiological findings, and (IV) investigations among this cohort of patients. The systematic review complied to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used three separate databases, namely PubMed, Ovid, and Scopus to search for articles with terms "chylothorax", "tuberculosis", and "children". We included article reporting on: (I) children aged below 18; (II) infected by Mycobacterium TB, and (III) written in English only. We reviewed the publications from the inception up to August 2022. After an extensive search, 7 articles were reviewed. We included 10 patients from all the reports. Most common symptoms reported were intermittent fever (n=6) and chronic cough (n=5). Other symptoms include shortness of breath and chest discomfort due to fluid accumulation and/or effusion. Typical TB symptoms like night sweat, loss of weight, and loss of appetite were present in some of the reported patients. Chest radiography was the most used diagnostic imaging modality, in which all of the reported cases noted presence of pleural effusion, with some cases proceeded with computer tomography (CT) of thorax to aid in the diagnosis. Most of the patients had lymphadenopathies and all patients underwent pleural tapping for analysis and symptomatic relief. From the pleural fluid milky appearance and biochemistry correlation, the diagnosis of chylothorax was established in all 10 patients. Every patient was tested positive for TB infection. Conclusions: Most of the cases showed similar clinical presentation, radiological findings, and laboratory investigations particularly the classic analysis findings of pleural fluid. Even though TB is not a common cause of chylothorax, clinicians should have raised suspicion of it especially after gathering full history and correlating it with the other findings.

Immunomodulatory Role of Vitamin D on Gut Microbiome in Children.

Vitamin D plays a role in regulating the immune system and can be linked to the alteration of the gut microbiome, which leads to several immunological diseases. This systematic review aims to explore the relationship between Vitamin D and children's gut microbiome, as well as its impact towards the immune system. We have systematically collated relevant studies from different databases concerning changes in the gut microbiome of children from infants to 18 years old associated with Vitamin D and the immunological pathways. The studies utilized 16S rRNA sequencing analysis of fecal matter with or without Vitamin D supplementation and Vitamin D levels. Ten studies were selected for the review, among which eight studies showed significant alterations in the gut microbiome related to Vitamin D supplementation or Vitamin D levels. The taxa of the phylum Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria are the most altered in these studies. The alteration of the taxa alters the Th1 and Th2 pathways and changes the immune response. We will discuss how Vitamin D may contribute to the activation of immune pathways via its effects on intestinal barrier function, microbiome composition, and/or direct effects on immune responses. In conclusion, the studies examined in this review have provided evidence that Vitamin D levels may have an impact on the composition of children's gut microbiomes.

Primary immunodeficiencies (PID) Life Index in Southeast Asia: A comparative analysis of PID Principles of Care (PoC).

Objective: To analyze the implementation of the Principles of Care (PoC) in primary immunodeficiencies (PID) in Southeast Asia (SEA) countries - six years after its call of action. Methodology: Using the newly developed PID Life Index software, the index of implementation of principles of care in the management of PIDs patients involving the six participating SEA countries (Cambodia, Indonesia, Malaysia, Vietnam, Thailand, and Philippines) were extracted. For each of the six separate principles, the index from the six countries will be compared and presented based on the calculated index. Results: Comparative analysis of the six principles of care of PID in the SEA countries showed low diagnostic rate with minimal availability of diagnostic tests options. Generally, almost all SEA countries provide curative treatments, vaccines, and anti-infectious therapies although the reimbursement scheme varied in relieving patients' financial burden. We also highlighted the active involvement of patient organizations in SEA, with main areas of work focused on advocacy and increasing awareness among public and healthcare professionals. Discussion and conclusion: It is applaudable that the SEA continent is gradually strengthening its work in management of PID, especially in Thailand and Vietnam. However, more emphasis must be placed among stakeholders in SEA countries towards successful implementation of the PoC for a holistic management of PID patients.

Scoping Review on Epigenetic Mechanisms in Primary Immune Thrombocytopenia.

Immune Thrombocytopenia (ITP) is an autoimmune blood disorder that involves multiple pathways responsible for the homeostasis of the immune system. Numerous pieces of literature have proposed the potential of immune-related genes as diagnostic and prognostic biomarkers, which mostly implicate the role of B cells and T cells in the pathogenesis of ITP. However, a more in-depth understanding is required of how these immune-related genes are regulated. Thus, this scoping review aims to collate evidence and further elucidate each possible epigenetics mechanism in the regulation of immunological pathways pertinent to the pathogenesis of ITP. This encompasses DNA methylation, histone modification, and non-coding RNA. A total of 41 studies were scrutinized to further clarify how each of the epigenetics mechanisms is related to the pathogenesis of ITP. Identifying epigenetics mechanisms will provide a new paradigm that may assist in the diagnosis and treatment of immune thrombocytopenia.

Determining the Relationship of Meteorological Factors and Severe Pediatric Respiratory Syncytial Virus (RSV) Infection in Central Peninsular Malaysia.

Respiratory syncytial virus (RSV) is the most common pathogen causing viral respiratory tract infections among younger children worldwide. The influence of meteorological factors on RSV seasonal activity is well-established for temperate countries; however, in subtropical countries such as Malaysia, relatively stable temperate climates do not clearly support this trend, and the available data are contradictory. Better understanding of meteorological factors and seasonality of RSV will allow effective strategic health management relating to RSV infection, particularly immunoprophylaxis of high-risk infants with palivizumab. Retrospectively, from 2017 to 2021, we examined the association between various meteorological factors (rainfall, rainy days, temperature, and relative humidity) and the incidence of RSV in children aged less than 12 years in Kuala Lumpur, Malaysia. RSV activity peaked in two periods (July to August and October to December), which was significantly correlated with the lowest rainfall (p < 0.007) and number of rainy days (p < 0.005). RSV prevalence was also positively associated with temperature (p < 0.006) and inversely associated with relative humidity (p < 0.006). Based on our findings, we recommend that immunoprophylaxis with palivizumab be administered in children aged less than 2 years where transmission of RSV is postulated to be the highest after the end of two monsoon seasons.

Knowledge, awareness, and perception on genetic testing for primary immunodeficiency disease among parents in Malaysia: a qualitative study.

Background: Primary Immunodeficiency Disease (PID), also known as Inborn Errors of Immunity (IEI), comprises a group of rare genetic disorders that impair the body's immune responses. These conditions result from monogenic germline mutations that affect the function of genes governing the innate and adaptive immune system. Therefore, individuals with PID are more susceptible to infectious diseases, allergies, and autoimmune and autoinflammatory conditions. The prevalence of PID has been on the rise, with the number of classified diseases reaching 404, and 430 genetic defects reported to cause these conditions. However, in Malaysia, genetic testing for PID is currently limited and needs to be outsourced to overseas laboratories, posing financial challenges for families. Moreover, limited research has focused on the knowledge and awareness of genetic testing among parents of children with PID in Malaysia. This study aims to address this gap and provide valuable insights into the knowledge, awareness, and perception of genetic testing among this specific population. Method: This qualitative cross-sectional study utilised online open-ended, semi-structured focus group interviews to explore the perceptions and experiences of parents of children with Primary Immunodeficiency (PID). Participants were recruited through convenience sampling from the Malaysian Patient Organisation for Primary Immunodeficiencies (MyPOPI), a non-governmental organisation dedicated to providing support and raising awareness about PID. The study spanned from May 2023 to July 2023 and included participants from diverse regions of Malaysia who had undergone different diagnostic journeys in various hospitals. Result: The focus group discussions yielded 11 sub-themes that highlighted the experiences, understanding and challenges of the participants regarding genetic testing based on the semi-structured questions. These sub-themes were then grouped into four main themes that are awareness and understanding of genetic testing, the journey towards diagnosis and treatment, emotional impact and psychological factors, and the importance of medical experts in diagnosing and managing PID, as well as public perception and awareness. Conclusion: In conclusion, this study highlights the diverse knowledge, awareness, and perception surrounding genetic testing for PID. Factors such as access to services, family history, and personal circumstances shape individuals' understanding of genetic testing. The importance of healthcare professionals, along with the need for improved accessibility and targeted communication strategies, is underscored to enhance understanding and reduce stigma surrounding genetic testing for rare diseases like PID.

Genetics of Cholesterol-Related Genes in Metabolic Syndrome: A Review of Current Evidence.

Metabolic syndrome (MetS) refers to a cluster of metabolic dysregulations, which include insulin resistance, obesity, atherogenic dyslipidemia and hypertension. The complex pathogenesis of MetS encompasses the interplay between environmental and genetic factors. Environmental factors such as excessive nutrients and sedentary lifestyle are modifiable and could be improved by lifestyle modification. However, genetic susceptibility to MetS, a non-modifiable factor, has attracted the attention of researchers, which could act as the basis for future diagnosis, prognosis, and therapy for MetS. Several cholesterol-related genes associated with each characteristic of MetS have been identified, such as apolipoprotein, lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and adiponectin. This review aims to summarize the genetic information of cholesterol-related genes in MetS, which may potentially serve as biomarkers for early prevention and management of MetS.

Kawasaki Disease with Hepatobiliary Manifestations.

Background and Objectives: Kawasaki Disease (KD) incidence has been on the rise globally throughout the years, particularly in the Asia Pacific region. KD can be diagnosed based on several clinical criteria. Due to its systemic inflammatory nature, multi-organ involvement has been observed, making the diagnosis of KD more challenging. Notably, several studies have reported KD patients presenting with hepatobiliary abnormalities. Nonetheless, comprehensive data regarding the hepatobiliary manifestations of KD are limited in Malaysia, justifying a more in-depth study of the disease in this country. Thus, in this article, we aim to discuss KD patients in Malaysia with hepatobiliary manifestations. Materials and Methods: A total of six KD patients with hepatobiliary findings who presented at Hospital Canselor Tuanku Muhriz (HCTM) from 2004 to 2021 were selected and included. Variables including the initial presenting signs and symptoms, clinical progress, laboratory investigations such as liver function test (LFT), and ultrasound findings of hepatobiliary system were reviewed and analyzed. Results: Out of these six KD patients, there were two patients complicated with hepatitis and one patient with gallbladder hydrops. Different clinical features including jaundice (n = 3) and hepatomegaly (n = 4) were also observed. All patients received both aspirin and intravenous immunoglobulin (IVIG) as their first-line treatment and all of them responded well to IVIG. The majority of them (n = 5) had a complete recovery and did not have any cardiovascular and hepatobiliary sequelae. Conclusions: Despite KD mostly being diagnosed with the classical clinical criteria, patients with atypical presentations should always alert physicians of KD as one of the possible differential diagnoses. This study discovered that hepatobiliary manifestations in KD patients were not uncommon. More awareness on the epidemiology, diagnosis, and management of KD patients with hepatobiliary manifestations are required to allow for the initiation of prompt treatment, thus preventing further complications.

Thromboprophylaxis for inpatient with advanced cancer receiving palliative care: A retrospective study.

OBJECTIVES: The benefits and risks of thromboprophylaxis usage in patients with advanced cancer at the end of their lives remain unknown, especially with the lack of randomized studies. This study aimed to describe the clinical use of thromboprophylaxis in those patients under palliative care. METHODS: A retrospective cohort study. It was performed on patients admitted to the Palliative Care Center. RESULTS: A total of 719 patients were enrolled in the study. The mean age was 62.97 (13.65) years. Venous thromboembolism (VTE) incidence was 5.4% (n = 39). At the time of admission, 31.29% (n = 225) of patients were on thromboprophylaxis. At death time, 17.5% (n = 126) of patients were on thromboprophylaxis (41.3% on primary and 58.7% on secondary thromboprophylaxis). The incidence of clinically suspected fatal VTE was 6.5% (n = 47). Surprisingly, clinically suspected VTE was higher statistically in patients with thromboprophylaxis rather than in non-thromboprophylaxis (p < .001). By using linear regression, only higher PPI scores on admission were independent negative predictors of length of stay (OR:4.429, 95% CI: 5.460-3.398, p < .001). The development of clinically suspected fatal VTE, whatever the status of thromboprophylaxis, did not affect the length of stay. CONCLUSIONS: Thromboprophylaxis does not decrease the risk of clinically suspected fatal VTE in patients with advanced disease in their terminal phase. Patients with poor performance status and a short prognosis are unlikely to benefit from thromboprophylaxis.

Prescribing Practices of Intravenous Immunoglobulin in Tertiary Care Hospitals in Malaysia: A Need for a National Guideline for Immunoglobulin Use.

Rational use of drug involves the use of medicine as per clinical guidelines. Given the steady increase in the clinical utility of intravenous immunoglobulin (IVIG) either as licensed or off-label use, concerns are being raised about the possibility of supply shortages that could significantly impact patient care. Therefore, there is a need to regulate and to promote the rational use of this valuable medication. This cross-sectional chart review study attempts to evaluate the prescribing patterns of IVIG at two tertiary hospitals in Malaysia. Patients' medical files and dispensing records were examined and compared with current guidelines. A total of 348 prescriptions for IVIG were written during the 1-year study period. The highest usage of IVIG was for neurological (47.9%), immunological (27.5%), and hematological conditions (20%). The number of prescriptions with the US Food and Drug Administration (FDA) licensed indications and off-label indications was 148 (42.5%) and 200 (57.5%), respectively. Age (OR: 1.02, 95% CI: 1.01-1.03, p = 0.003) and those admitted to the critical care units (OR: 11.11, 95% CI: 5.60-22.05, p < 0.001) were significant factors for receiving IVIG for an off-label indication. Most prescriptions (79%) had appropriate dosing. Significant factors associated with receiving inappropriate dose of IVIG include age (OR: 0.93, 95% CI: 0.89-0.97, p = 0.001) and those admitted to the critical care units (OR: 10.15, 95% CI: 3.81-27.06, p < 0.001). This study advocates the development and implementation of evidence-based clinical guidelines with prioritization protocol to ensure rational use of IVIG.

Clinical Manifestations and Laboratory Findings of Kawasaki Disease: Beyond the Classic Diagnostic Features.

Kawasaki disease (KD) has shown a marked increase in trend over the globe, especially within the last two decades. Kawasaki disease is often seen in the paediatric population below five years old, while it is rare for those who are beyond that age. Up to this date, no exact causes has been identified although KD was found more than half a century ago. The underlying pathogenesis of the disease is still unelucidated, and researchers are trying to unlock the mystery of KD. To further complicate the diagnosis and the prompt management, a specific biomarker for the diagnosis of KD is yet to be discovered, making it hard to differentiate between KD and other diseases with a similar presentation. Nonetheless, since its discovery, clinicians and scientists alike had known more about the different clinical aspects of typical KD. Thus, this article intends to revisit and review the various clinical manifestations and laboratory characteristics of KD in order to guide the diagnosis of KD.

Living through the COVID-19 Pandemic: Impact and Lessons on Dietary Behavior and Physical Well-Being.

The aim of this review is to highlight the spectrum on which human behavior has been affected by blanket restriction measures and on a wider scale, the COVID-19 pandemic. Some of the human behaviors that have been impacted by the COVID-19 lockdown are dietary behavior and nutrition, food options and food delivery usage, physical activity and sedentary behaviors. This is important in planning effective public health strategies with minimal detriment to all subsets of society as well as improving the distribution of government aid to populations that are more severely affected. Our main purpose is to present the literature from a rapidly growing pool of scientific research to hopefully enable a better and more comprehensive understanding of the effects of this pandemic and the lessons learnt from the accompanying restrictions, as well as policy recommendations that can be made in national pandemic responses in the future.

The PID Life Index: an interactive tool to measure the status of the PID healthcare environment in any given country.

BACKGROUND: The "Primary Immunodeficiencies (PIDs) principles of care" were published in 2014 as the gold standard for care of patients with PIDs, setting a common goal for stakeholders to ensure that patients with PID have access to appropriate care and good quality of life. Since then, IPOPI (the International Patient Organisation for Primary Immunodeficiencies), has been working with national PID patient organisations as well as collaborating with scientific and medical institutions and experts to bring these principles closer to the day-to-day life of individuals with PIDs. METHOD: The six PID Principles of Care were revised to consider advances in the field, as well as political developments that had occurred after their initial publication in 2014. Based on this revision the list was updated, and a new principle was added. The six established principles were: diagnosis, treatment, universal health coverage, specialised centres, national patient organisations and registries. Each principle was structured and measured through a series of criteria, and was given the same weight, as they have been considered to all be equally important. Specific weights were attributed to the criteria depending on their relevance and importance to quantify the principle. The index was translated into a survey for data collection: initially involving data from selected countries for a pilot, followed by integration of data from IPOPI's national member organisations and key countries. RESULTS: The PID Life Index was developed in 2020 to assess the status of the PID environment and the implementation of the 6 principles worldwide. The Index allows for benchmarking countries either according to a set of principles and criteria or based on the user's preferences. This can be displayed in an interactive map or through a data visualisation system. CONCLUSION: The PID Life Index has been developed successfully and has potential to become an important source of information for PID stakeholders, to increase awareness and information as well as support advocacy initiatives on PIDs nationally, regionally or globally.

Molecular-Signaling Pathways of Ginsenosides Rb in Myocardial Ischemia-Reperfusion Injury: A Mini Review.

Reperfusion injury following myocardial ischemia remained a challenge for optimal treatment of myocardial infarction. Ginsenosides Rb (G-Rb), the primary components of ginsenoside, have been reported to exert cardioprotective effects via numerous mechanisms. G-Rb1 mediate cardioprotective effects via various signaling pathways, including mitochondrial apoptotic pathway, PI3K/Akt/mTOR, HIF-1α and GRF91, RhoA, p38α MAPK, and eNOS. G-Rb2 activates the SIRT-1 pathway, while G-Rb3 promotes both JNK-mediated NF-κB and PERK/Nrf2/HMOX1. Generally, ginsenosides Rb1, 2, and 3 modulates oxidative stress, inflammation, and apoptosis, contributing to the improvement of structural, functional and biochemical parameters. In conclusion, G-Rb, particularly G-Rb1, have vast potential as a supplement in attenuating reperfusion injury. Translation into a clinical trial is warranted to confirm the beneficial effects of G-Rb.