1.Quality of care among patients with acute heart failure at the emergency room and adherence of physicians at the University of the Philippines – Philippine General Hospital to the division of cardiovascular medicine – heart failure pathway:A retrospective cohort study.
Mark John D. Sabando ; Felix Eduardo R. Punzalan ; Frances Dominique V. Ho ; Tam Adrian P. Aya-ay ; Kevin Paul Da. Enriquez ; Marie Kirk A. Maramara ; Ronald Allan B. Roderos ; Lauren Kay M. Evangelista
Acta Medica Philippina 2026;60(2):22-32
OBJECTIVES
Clinical pathways (CPs) ensure adherence to heart failure (HF) management guidelines. To optimize quality care in a low resource setting, an evidence-based care pathway for the management of acute HF was implemented at the emergency department (ED) of the Philippine General Hospital (PGH), the designated national tertiary hospital and referral center. This study aimed to describe the characteristics of adults with acute HF admitted at the ED and evaluate the quality of care they received, measured using physician adherence to the hospital’s acute heart failure CP.
METHODSThis was a retrospective, descriptive cohort study. We reviewed the inpatient charts of all adult patients with acute HF admitted to the ED of the PGH and referred to the Division of Cardiovascular Medicine between December 1, 2022 and May 31, 2023. Quality of care was assessed based on adherence to quality indicators adapted from routine and conditional order sets detailed in the pathway. Descriptive statistics was utilized to describe patient characteristics, quality of care, and outcomes.
RESULTSTwo hundred thirty-six (236) patients were included, with a mean age of 51.8 years. Majority were male (53.4%); hypertension (61.4%) and ischemic heart disease (53.8%) were the most common comorbidities, and infection the most common precipitant of decompensation (60.6%). There were optimal adherence rates to routine orders, which included referrals to Internal Medicine and Cardiology, baseline vital signs monitoring, fluid intake and output monitoring, chest radiograph, complete blood count, blood urea nitrogen, sodium, potassium, prothrombin time, partial thromboplastin time, arterial blood gas, urinalysis, and N-terminal pro b-type natriuretic peptide. Conditional orders, such as oxygen support, focused echocardiography, thyroid - stimulating hormone, and the use of vasopressors, diuretics, and venous thromboembolism prophylactic agents, were optimally performed when warranted. However, we noted suboptimal adherence to certain resource-intensive conditional orders, such as hourly monitoring of urine output (61.4%), hooking to cardiac monitor (53.8%), and performance of 12-lead ECG within 10 minutes (56.8%). Further, only 43.9% of patients were referred to the intensive care unit. Troponin I, calcium, magnesium, and albumin were ordered in excess.
CONCLUSIONOverall adherence rate of physicians to the hospital’s Acute Heart Failure Pathway was satisfactory. Work is needed to improve adherence to hourly urine output monitoring, consistent hooking to cardiac monitor, and timely performance of 12-lead ECG – an effort that begins with expanding in-hospital diagnostic equipment and human resource supply. We recommend continuous pathway implementation with periodic evaluation and stakeholder feedback to further improve quality of care.
Human ; Male ; Female ; Middle Aged: 45-64 Yrs Old ; Adult ; Albumins ; Blood ; Blood Urea Nitrogen ; Calcium ; Cardiology ; Chart ; Charts ; Cohort Studies ; Critical Care ; Critical Pathways ; Diagnostic Equipment ; Disease ; Diuretics ; Echocardiography ; Electrocardiography ; Emergencies ; Emergency Service, Hospital ; Equipment And Supplies ; Evaluation Studies As Topic ; Feedback ; Heart ; Heart Diseases ; Heart Failure ; Hormones ; Hospitals ; Hospitals, General ; Humans ; Hypertension ; Indicators And Reagents ; Infection ; Infections ; Inpatients ; Intensive Care Units ; Internal Medicine ; Lead ; Magnesium ; Male ; Medicine ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Nitrogen ; Overall ; Oxygen ; Partial Thromboplastin Time ; Patients ; Peptides ; Philippines ; Physicians ; Potassium ; Prothrombin ; Prothrombin Time ; Quality Of Health Care ; Referral And Consultation ; Sodium ; Statistics ; Tertiary Care Centers ; Thorax ; Thromboembolism ; Thromboplastin ; Thyroid Gland ; Time ; Troponin ; Troponin I ; Universities ; Urea ; Urinalysis ; Urine ; Venous Thromboembolism ; Vital Signs ; Work ; Workforce
2.Development of the nationalaacute myocardial infarction pathway for the implementation of the PhilHealth Ischemic Heart Disease – Acute Myocardial Infarction (PHIC IHD-AMI) benefit package.
Felix Eduardo R. PUNZALAN ; Eric Oliver SISON ; Cecileen Anne M. TUAZON
Philippine Journal of Cardiology 2026;54(1):34-61
BACKGROUND
Ischemic heart disease is the leading cause of mortality in the Philippines. Despite strong recommendations from clinical practice guidelines for reperfusion for acute myocardial infarction (AMI), local data reveal low rates of primary percutaneous coronary intervention (PCI) and early invasive strategies due to financial constraints and system inefficiencies. The recent expansion of the Philippine Health Insurance Corporation (PHIC) AMI benefits package presents an opportunity to improve access to appropriate care. A standardized, evidence-based national clinical pathway is needed to guide healthcare providers and ensure consistent, high-quality care of AMI across various healthcare settings.
OBJECTIVETo develop a standardized, evidence-based national clinical pathway for the management of AMI patients eligible under the PHIC IHD-AMI benefits package.
METHODOLOGYExisting AMI clinical pathways from nine public and private hospitals in the Philippines were collected and reviewed. A multidisciplinary Technical Working Group (TWG) appraised current guidelines using the AGREE II tool and evaluated the collected pathways to identify strengths, gaps and variations in practice. A draft pathway was created and refined through consensus-building with cardiology experts and stakeholders to develop the final pathway.
RESULTSThe final national AMI clinical pathway integrates evidence-based best practices and accounts for differences in institutional resources. It standardizes the use of ECG and cardiac biomarkers for diagnosis, provides clear criteria and timelines for reperfusion therapy, defines indications for coronary angiography and PCI, and recommends optimal medical therapy and cardiac rehabilitation.
CONCLUSIONThe national AMI clinical pathway is a critical step toward improving the quality, equity and efficiency of AMI care in the Philippines. Developed through a collaborative, evidence-based process, it aligns clinical management with international standards while addressing local healthcare system realities. Adoption by PHIC as a quality standard is expected to enhance guideline adherence, inform health policy and financing, and drive improvements in health outcomes. Continued implementation support, monitoring and evaluation are necessary to ensure its impact, particularly in under-resourced or geographically isolated settings.
Myocardial Infarction ; Myocardial Ischemia ; Infarction
3.Implementation of the Philippine Health Insurance Corporation (PHIC) Ischemic Heart Disease - Acute Myocardial Infarction (IHD-AMI) benefits package at the University of the Philippines - Philippine General Hospital (UP-PGH).
Eric Oliver D. SISON ; Cecileen Anne M. TUAZON ; Paul Anthony O. ALAD ; Felix Eduardo R. PUNZALAN
Philippine Journal of Cardiology 2026;54(1):62-71
BACKGROUND
Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality among Filipinos. The guideline-recommended treatment for AMI includes emergency care, early electrocardiogram, emergent coronary angiogram and angioplasty, intensive care, medical management and cardiac rehabilitation. However, the cost of treatment is very high and not affordable for most Filipinos. To address this, the Philippine Health Insurance Corporation (PHIC) released the ischemic heart disease – acute myocardial infarction (IHD-AMI) Benefits Package under Circular No. 2024-0032 on December 21, 2024. This package significantly increased the insurance coverage for AMI to include invasive procedures and cardiac rehabilitation. The UP-Philippine General Hospital (UP-PGH) was the first to implement this package. This paper documents the initial planning, system changes and innovations undertaken by UP-PGH to support implementation.
METHODOLOGYThis qualitative descriptive study used retrospective document review to detail revision of the existing acute coronary syndrome (ACS) pathway and development of the AMl pathway, restructuring of patient flow and upgrades in infrastructure and hospital capabilities. Meeting minutes from the Division of Cardiovascular Medicine and UP-PGH were reviewed to describe the hospital's preparation and implementation process.
RESULTSUP-PGH established an efficient, evidence-based ACS and AMI pathway. Hospital protocols, staffing, infrastructure and equipment were aligned to implement the PHIC IHD-AMI Benefit Package. Key steps included resources upgrade, stakeholder consultations, pathway redesign, workflow development, process alignment and monitoring systems.
CONCLUSIONThe PHIC IHD-AMI Benefit Package can be successfully implemented in a tertiary hospital with catheterization laboratory. The documented process at UP-PGH can serve as a model for other institutions planning to utilize the package.
Myocardial Infarction ; Myocardial Ischemia ; Acute Coronary Syndrome ; Insurance, Health ; Philippines
4.ONE (Onwards towards NCD rEduction) Cavite Project: A multisectoral educational approach to cardiovascular risk factor screening and management.
Deborah Ignacia ONA ; Alberto ATILANO ; Marilou ESPIRITU ; Rey-an Nino GARCIA ; Ardith TAN ; David Raymund SALVADOR
Philippine Journal of Cardiology 2026;54(1):77-83
Ischemic heart disease (IHD) remains the most common cause of death while cerebrovascular disease (CVD) is the third most common in the Philippines. IHD and CVD represent complications resulting from prevalent non-communicable diseases (NCDs) and risk factors which present important opportunities for primary and secondary prevention.
This study aimed to pilot a sustainable multisectoral approach for community-based screening and management of cardiovascular (CV) risk factors and determine the effects of a multisectoral collaboration approach on the rate of screening, prevalence and control rates for selected risk factors.
This is a quality improvement project that determines the baseline prevalence and control rates of CV risk factors followed by intense screening efforts with support from private partnerships. The project's core components are: (a) capacity building (b) information dissemination; (c) service provision; and (d) health monitoring. Rates of screening, prevalence and control were monitored over a two-year period.
A total of 94,125 patients were screened through the ONE Cavite Project over two years (January 2021 to December 2022). A total of 61,271 were newly identified as having hypertension (65.1%), 24,069 diagnosed with diabetes mellitus type 2 (25.6%), 29,257 diagnosed to have dyslipidemia (31.1%) and 13,204 smokers (14.0%) were identified.
Intensification of screening was successful in improving identification of individuals with NCDs. The impact of continued educational support for both providers and patients in this study reaffirmed its role as a central component of NCD diagnosis, management and prevention.
Hypertension ; Diabetes Mellitus ; Dyslipidemias ; Myocardial Ischemia ; Primary Prevention
5.Development of the nationalaacute myocardial infarction pathway for the implementation of the PhilHealth Ischemic Heart Disease – Acute Myocardial Infarction (PHIC IHD-AMI) benefit package.
Felix Eduardo R. PUNZALAN ; Eric Oliver SISON ; Cecileen Anne M. TUAZON
Philippine Journal of Cardiology 2026;54(1):34-61
BACKGROUND
Ischemic heart disease is the leading cause of mortality in the Philippines. Despite strong recommendations from clinical practice guidelines for reperfusion for acute myocardial infarction (AMI), local data reveal low rates of primary percutaneous coronary intervention (PCI) and early invasive strategies due to financial constraints and system inefficiencies. The recent expansion of the Philippine Health Insurance Corporation (PHIC) AMI benefits package presents an opportunity to improve access to appropriate care. A standardized, evidence-based national clinical pathway is needed to guide healthcare providers and ensure consistent, high-quality care of AMI across various healthcare settings.
OBJECTIVETo develop a standardized, evidence-based national clinical pathway for the management of AMI patients eligible under the PHIC IHD-AMI benefits package.
METHODOLOGYExisting AMI clinical pathways from nine public and private hospitals in the Philippines were collected and reviewed. A multidisciplinary Technical Working Group (TWG) appraised current guidelines using the AGREE II tool and evaluated the collected pathways to identify strengths, gaps and variations in practice. A draft pathway was created and refined through consensus-building with cardiology experts and stakeholders to develop the final pathway.
RESULTSThe final national AMI clinical pathway integrates evidence-based best practices and accounts for differences in institutional resources. It standardizes the use of ECG and cardiac biomarkers for diagnosis, provides clear criteria and timelines for reperfusion therapy, defines indications for coronary angiography and PCI, and recommends optimal medical therapy and cardiac rehabilitation.
CONCLUSIONThe national AMI clinical pathway is a critical step toward improving the quality, equity and efficiency of AMI care in the Philippines. Developed through a collaborative, evidence-based process, it aligns clinical management with international standards while addressing local healthcare system realities. Adoption by PHIC as a quality standard is expected to enhance guideline adherence, inform health policy and financing, and drive improvements in health outcomes. Continued implementation support, monitoring and evaluation are necessary to ensure its impact, particularly in under-resourced or geographically isolated settings.
Myocardial Infarction ; Myocardial Ischemia ; Infarction
6.Implementation of the Philippine Health Insurance Corporation (PHIC) Ischemic Heart Disease - Acute Myocardial Infarction (IHD-AMI) benefits package at the University of the Philippines - Philippine General Hospital (UP-PGH).
Eric Oliver D. SISON ; Cecileen Anne M. TUAZON ; Paul Anthony O. ALAD ; Felix Eduardo R. PUNZALAN
Philippine Journal of Cardiology 2026;54(1):62-71
BACKGROUND
Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality among Filipinos. The guideline-recommended treatment for AMI includes emergency care, early electrocardiogram, emergent coronary angiogram and angioplasty, intensive care, medical management and cardiac rehabilitation. However, the cost of treatment is very high and not affordable for most Filipinos. To address this, the Philippine Health Insurance Corporation (PHIC) released the ischemic heart disease – acute myocardial infarction (IHD-AMI) Benefits Package under Circular No. 2024-0032 on December 21, 2024. This package significantly increased the insurance coverage for AMI to include invasive procedures and cardiac rehabilitation. The UP-Philippine General Hospital (UP-PGH) was the first to implement this package. This paper documents the initial planning, system changes and innovations undertaken by UP-PGH to support implementation.
METHODOLOGYThis qualitative descriptive study used retrospective document review to detail revision of the existing acute coronary syndrome (ACS) pathway and development of the AMl pathway, restructuring of patient flow and upgrades in infrastructure and hospital capabilities. Meeting minutes from the Division of Cardiovascular Medicine and UP-PGH were reviewed to describe the hospital's preparation and implementation process.
RESULTSUP-PGH established an efficient, evidence-based ACS and AMI pathway. Hospital protocols, staffing, infrastructure and equipment were aligned to implement the PHIC IHD-AMI Benefit Package. Key steps included resources upgrade, stakeholder consultations, pathway redesign, workflow development, process alignment and monitoring systems.
CONCLUSIONThe PHIC IHD-AMI Benefit Package can be successfully implemented in a tertiary hospital with catheterization laboratory. The documented process at UP-PGH can serve as a model for other institutions planning to utilize the package.
Myocardial Infarction ; Myocardial Ischemia ; Acute Coronary Syndrome ; Insurance, Health ; Philippines
7.ONE (Onwards towards NCD rEduction) Cavite Project: A multisectoral educational approach to cardiovascular risk factor screening and management.
Deborah Ignacia ONA ; Alberto ATILANO ; Marilou ESPIRITU ; Rey-an Nino GARCIA ; Ardith TAN ; David Raymund SALVADOR
Philippine Journal of Cardiology 2026;54(1):77-83
Ischemic heart disease (IHD) remains the most common cause of death while cerebrovascular disease (CVD) is the third most common in the Philippines. IHD and CVD represent complications resulting from prevalent non-communicable diseases (NCDs) and risk factors which present important opportunities for primary and secondary prevention.
This study aimed to pilot a sustainable multisectoral approach for community-based screening and management of cardiovascular (CV) risk factors and determine the effects of a multisectoral collaboration approach on the rate of screening, prevalence and control rates for selected risk factors.
This is a quality improvement project that determines the baseline prevalence and control rates of CV risk factors followed by intense screening efforts with support from private partnerships. The project's core components are: (a) capacity building (b) information dissemination; (c) service provision; and (d) health monitoring. Rates of screening, prevalence and control were monitored over a two-year period.
A total of 94,125 patients were screened through the ONE Cavite Project over two years (January 2021 to December 2022). A total of 61,271 were newly identified as having hypertension (65.1%), 24,069 diagnosed with diabetes mellitus type 2 (25.6%), 29,257 diagnosed to have dyslipidemia (31.1%) and 13,204 smokers (14.0%) were identified.
Intensification of screening was successful in improving identification of individuals with NCDs. The impact of continued educational support for both providers and patients in this study reaffirmed its role as a central component of NCD diagnosis, management and prevention.
Hypertension ; Diabetes Mellitus ; Dyslipidemias ; Myocardial Ischemia ; Primary Prevention
8.Electroacupuncture combined with rehabilitation training improves neurological function of mice with cerebral ischemia by promoting astrocyte transdifferentiation.
Dongning TANG ; Yunyun KANG ; Wenjie HE ; Qing XIA
Journal of Southern Medical University 2025;45(7):1434-1441
OBJECTIVES:
To explore the effects of acupuncture combined with rehabilitation training for promoting transdifferentiation of astrocytes into neurons in mice after cerebral ischemia.
METHODS:
Male C57/BL6J mice were subjected to intracerebral microinjection of an adeno-associated virus carrying the GFAP promoter for NeuroD1 and Ngn2 overexpression in the astrocytes, followed 3 or 12 days later by electrocoagulation of the distal middle cerebral artery. After modeling, the mice were randomly divided into model group without interventions and intervention group treated with electroacupuncture at the acupoints Baihui (GV20), left Hegu (LI4), Neiguan (PC6), Zusanli (ST36), and Yanglingquan (GB34) 24 h after surgery. The mice in the intervention group were housed individually in cages with running wheels, and their activity was recorded every 24 h. Neurological function scores of the mice were assessed on the 1st, 14th, and 21st days after modeling. Transdifferentiation of astrocytes in the target brain regions was observed using double immunofluorescence staining.
RESULTS:
Compared with those in the model group, the mice receiving eletroacupuncture and rehabilitation training showed significant improvement of neurological deficits at 14 and 21 days after modeling. The GFAP promoter of the AAV2/5 vector specifically labeled the local astrocytes, and compared with that that in the model group, the number of AAV-positive cells colabeled with the neuronal marker DCX significantly increased after 14 days of electroacupuncture and rehabilitation intervention, and the number of AAV-positive cells colabeled with the neuronal marker NeuN significantly increased after 21 days of intervention.
CONCLUSIONS
In mice with cerebral ischemia, electroacupuncture and rehabilitation training can promote transdifferentiation of astrocytes into neurons in the ischemic brain region, and the efficiency of transdifferentiation is positively correlated with the improvement of motor function.
Animals
;
Electroacupuncture
;
Astrocytes/cytology*
;
Cell Transdifferentiation
;
Male
;
Mice, Inbred C57BL
;
Brain Ischemia/physiopathology*
;
Mice
;
Neurons/cytology*
;
Doublecortin Protein
9.Electroacupuncture improves myocardial injury in rats with acute myocardial ischemia by inhibiting HPA axis hyperactivity via modulating hippocampal glutamatergic system.
Kun WANG ; Haiyan ZUO ; Jiaojiao ZHANG ; Xin WU ; Wenhui WANG ; Shengbing WU ; Meiqi ZHOU
Journal of Southern Medical University 2025;45(8):1599-1607
OBJECTIVES:
To clarify the role of hippocampal glutamate system in regulating HPA axis in mediating the effect of electroacupuncture (EA) at the heart meridian for improving myocardial injury in rats with acute myocardial ischemia (AMI).
METHODS:
Male SD rats were randomized into sham-operated group, AMI group, EA group, and L-glutamic acid+EA group (n=9). Rat models of AMI were established by left descending coronary artery ligation, and EA was applied at the "Shenmen-Tongli" segment; the rats in L-glutamic acid+EA group were subjected to microinjection of L-glutamic acid into the bilateral hippocampus prior to AMI modeling and EA treatment. Cardiac functions of the rats were evaluated using echocardiography, and ECG and heart rate variation (HRV) were analyzed using PowerLab and LabChart. Pathological changes in the myocardial tissue was examined using HE staining, and serum levels of myocardial enzymes were detected with ELISA. Myocardial expressions of TH and GAP43 were detected with immunohistochemistry, and colocalization of VGLUT1, VGLUT2 and c-fos were observed using immunofluorescence staining; the expressions of VGLUT1, VGLUT2, NMDAR1 and NMDAR2B were detected using Western blotting.
RESULTS:
The rat models of AMI showed significantly decreased LVEF and LVFS and increased serum levels of myocardial enzymes in positive correlation with the HPA axis. Numerous TH- and GAP43-positive cells were observed in the hippocampus, where the expressions of NE and E, neurons colabeled with VGLUT1, VGLUT2 and c-fos, and expressions of VGLUT1, VGLUT2, NMDAR1, NMDAR2B and Glu increased significantly. All these changes were significantly improved by interventions with EA as compared with those in AMI and L-Glutamate+EA groups.
CONCLUSIONS
In rats with AMI, EA at the heart meridian can regulate excessive glutamate release in the hippocampus, thereby inhibiting HPA axis hyperactivity and reducing sympathetic nerve activity to protect the myocardial tissue.
Animals
;
Electroacupuncture
;
Male
;
Rats, Sprague-Dawley
;
Hippocampus/metabolism*
;
Rats
;
Glutamic Acid/metabolism*
;
Myocardial Ischemia/physiopathology*
;
Hypothalamo-Hypophyseal System/physiopathology*
;
Pituitary-Adrenal System/physiopathology*
;
Receptors, N-Methyl-D-Aspartate/metabolism*
10.Gastrodin inhibits ferroptosis to alleviate hypoxic-ischemic brain damage in neonatal mice by activating GPX4/SLC7A11/FTH1 signaling.
Tao GUO ; Bolin CHEN ; Jinsha SHI ; Xianfeng KUANG ; Tengyue YU ; Song WEI ; Xiong LIU ; Rong XIAO ; Juanjuan LI
Journal of Southern Medical University 2025;45(10):2071-2081
OBJECTIVES:
To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect.
METHODS:
Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability.
RESULTS:
Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential.
CONCLUSIONS
Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals
;
Ferroptosis/drug effects*
;
Hypoxia-Ischemia, Brain/drug therapy*
;
Mice
;
Mice, Inbred C57BL
;
Signal Transduction/drug effects*
;
Phospholipid Hydroperoxide Glutathione Peroxidase
;
Glucosides/pharmacology*
;
Animals, Newborn
;
Benzyl Alcohols/pharmacology*
;
Amino Acid Transport System y+/metabolism*


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