Potential inhibition of Melaleuca leucadendron L. compounds against the NSP5 SARS CoV-2 protein

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome (SARS-CoV-2), causing a global health emergency as a pandemic disease. The lack of certain drug molecules or treatment strategies to fight this disease makes it worse. Therefore, effective drug molecules are needed to fight COVID-19. Non Structural Protein (NSP5) or called Main Protease (Mpro) of SARS CoV 2, a key component of this viral replication, is considered a key target for anti-COVID-19 drug development. The purpose of this study is to determine whether the compounds in the Melaleuca leucadendron L. plant such as 1,8-cineole, terpene, guaiol, linalol, α-selinenol, β-eudesmol and γ-eudesmol are predicted to have antiviral activity for COVID-19. Interaction of compounds with NSP5 with PDB code 6WNP analyzed using molecular docking with Molegro Virtual Docker. Based on binding affinity, the highest potential as an anti-viral is Terpineol with binding energy (-119.743 kcal/mol). The results of the interaction showed that terpinol has similarities in all three amino acid residues namely Cys 145, Gly 143, and Glu 166 with remdesivir and native ligand. Melaleuca leucadendron L. may represent a potential herbal treatment to act as: COVID-19 NSP5, however these findings must be validated in vitro and in vivo

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Hubungan Riwayat Pemberian ASI Eksklusif dengan Kejadian Infeksi Saluran Pernapasan Akut pada Balita di Puskesmas Junrejo Kota Batu Tahun 2020

ABSTRACT Acute Respiratory Tract Infection (ARI) is acute infection that attacks one or more parts of the respiratory tract, it is from the nose to the pockets of the lung (alveoli) including the adneksa (sinus, middle ear cavity, and pleura). The incidence of ARI in Junrejo Health Center of Batu City during 2019 still quite a lot with 2945 cases, 781 of them experienced by under-five children. Giving exclusive breastfeeding to children can reduce the risk of acute respiratory tract infections in children. The goal of this study is to analyze the relationship between history of exclusive breastfeeding with incident of acute respiratory tract infection in under-five children in Junrejo Public Health Center Batu City 2020. This research is nominal correlative analytic study with design of research is cross sectional study. The number of sample is 65 under- five children with nonprobability sampling type accidental sampling. Data were analyzed by Chi Square and Prevalence Ratio. The results of this study that 58.5% of under-five children didn’t have a history of exclusive breastfeeding and 53.8% have ARI. Based on the Chi Square test results obtained probability value 0.005 <0.01. This shows that there is a relationship between the history of exclusive breastfeeding with the incident of acute respiratory tract infections in under-five children. ABSTRAK Infeksi Saluran Pernapasan Akut (ISPA) adalah infeksi akut yang terdapat pada saluran napas mulai dari hidung sampai alveoli termasuk adneksanya (sinus, rongga telinga tengah, pleura) baik salah satu bagian atau lebih. Kejadian ISPA pada Puskesmas Junrejo Kota Batu selama tahun 2019 masih cukup banyak yaitu 2954 kasus dengan 781 diantaranya dialami balita. Pemberian ASI eksklusif kepada anak dapat menurunkan risiko terjadinya infeksi saluran pernafasan akut pada anak. Penelitian ini bertujuan untuk menganalisis hubungan hubungan riwayat pemberian ASI eksklusif dengan kejadian infeksi saluran pernapasan akut (ISPA) pada balita di Puskesmas Junrejo Kota Batu tahun 2020. Penelitian ini merupakan penelitian analitik korelatif nominal-nominal yang menggunakan desain cross sectional study. Jumlah sampel adalah 65 balita dengan teknik nonprobability sampling tipe accidental sampling. Penelitian ini menggunakan uji Chi Square. Hasil penelitian ini menunjukkan bahwa sebanyak 58,5% balita tidak memiliki Riwayat ASI eksklusif dan sebanyak 53,8% terkena ISPA. Berdasarkan hasil uji Chi Square didapatkan nilai probabilitasnya 0,005<0,01. Hal ini menunjukkan bahwa terdapat hubungan antara riwayat pemberian ASI eksklusif dengan kejadian infeksi saluran pernafasan akut pada balita

Pengaruh Ekstrak Etanol Bawang Dayak (Eleutherine Palmifolia(L) Merr.) Terhadap CDK dan Ekspresi Ki67 Sel Epitel Kolon Mencit Balb/C Model Colitis (Insilico Dan Invivo)

Kanker merupakan kondisi sel yang abnormal dalam pertumbuhan maupun perkembangannya ditandai dengan terjadinya proliferasi sel tidak terkendali, bersifat invasif dan dapat menyebar ke bagian organ sekitar. Prevalensi kanker kolon masih menjadi salah satu kejadian tertinggi. Kejadian kanker kolon dapat meningkat oleh peradangan pada kolon. Patogenesisnya masuknya antigen atau benda asing ke daerah kolon mengakibatkan sekresi sitokin proinflamasi (IL1, IL6, TNF-α, IFN-γ). Terjadinya inflamasi meningkatkan radikal bebas (ROS) yang berkontribusi karsinogenesis kolon. Selain itu, terjadinya mutasi p53 pada mukosa kolon pada peradangan kronis mengakibatkan siklus sel yang tidak terkontrol, ditandai ekspresi Ki67 berlebih dan menurunnya jumlah apoptosis pada sel yang rusak. Terjadinya siklus sel tidak terkontrol menyebabkan peningkatan ekspresi dari CDK1, CDK2 dan CDK4. Hal ini dapat meningkatkan proliferasi sel yang dapat memicu terjadinya perkembangan sel kanker dengan ditandai dengan peningkatan proliferasi ki67 yang meningkat pada fase mitosis (M). Sehingga dalam penelitian ini, bertujuan untuk mengetahui binding afinity tanaman bawang dayak dengan senyawa mayor 1,4 naphthoquinon pada CDK1, CDK2 dan CDK4 serta membuktikan penurunan ekspresi dari Ki67 yang merupakan marker of proliferation. Dalam penelitian ini menggunakan 2 metode yaitu in islico dan in vivo. Secara in silico, data variabel independen dalam penelitian ini, yaitu senyawa 1,4 naphthoquinon yang didapatkan dari PubChem. Sedangkan struktur makromolekul dari variabel dependen yaitu CDK1, CDK2, dan CDK4 dengan data bank protein code (PDB) masing-masing yaitu 6GU6, 6GUC, dan 1GIH. Selanjutnya dilakukan proses docking menggunakan aplikasi Molegro untuk mengetahui binding affinity, guna mengetahui energi ikatan yang terjadi. Untuk menjamin senyawa 1,4 naphthoquinon aman dikonsumsi, dilakukan uji kelayakan yang meliputi uji fisikokimia untuk memprediksi kemampuan senyawa dalam menembus sawar darah otak, serta uji hukum 5 Lipinski untuk menilai kemampuan bioavaibilitas oral. Kemudian juga dilakukan pengujian toksisitas Prediksi fisikokimia didapatkan hasil dari senyawa 1,4 naphthoquinon menunjukkan bahwa telah dipenuhinya hukum 5 Lipinski sehingga dapat diprediksi bahwa senyawa uji memiliki permeabilitas yang baik, dapat diabsorbsi dengan baik dan mempunyai bioavaibilitas oral baik. Selanjutnya, berdasarkan analisis bioinformatika, hasil Rerank Score pada semua native ligand menunjukkan nilai yang lebih kecil dari senyawa 1,4 naphthoquinon. Hal ini berarti native ligand pada reseptor 6GU6, 6GUC, dan 1GIH mempunyai afinitas lebih tinggi dibandingkan dengan senyawa 1,4 naphthoquinon. Sehingga potensi senyawa 1,4 naphthoquinon untuk berikatan dengan dengan ketiga reseptor sangatlah kecil dikarenakan perbedaan energi yang terlalu jauh. Potensi adanya interaksi sterik hanya dimunculkan antara senyawa 1,4 naphthoquinon dengan native ligand A pada reseptor 6GUC, dengan asam amino lys 33(A). Hal ini dapat menunjukkan bahwa senyawa 1,4 naphthoquinon tidak dapat berinteraksi langsung dengan kompleks CDK/cyclin sehingga tidak memiliki potensi untuk menjadi inhibitor CDK1, CDK2 maupun CDK4. Selanjtunya pada prediksi toksisitas senyawa 1,4 naphthoquinon tergolong kelas toksisitas 3 yaitu 50-300 mg/kg kategori toksisitas sedang menurut GHS, serta didapatkan hasil tidak terdapat hepatotoksik, namun memiliki sensitivitas terhadap kulit sehingga perlu dicantumkan peringatan keamanan dalam pelabelannya. Secara in vivo, dikerjakan guna membuktikan pengaruh pemberian ekstrak etanol bawang dayak dapat menurunkan ekspresi Ki67 pada sel epitel kolon dalam bahan biologi tersimpan dari mencit BALB/c yang diinduksi AOM DSS. Sampel terdiri enam kelompok yang berasal dari bahan biologi tersimpan dari kolon mencit BALB/c yang diinduksi AOM DSS. Dua kelompok kontrol yaitu negatif dan positif, tiga kelompok pemberian ekstrak ix bawang dayak dengan dosis masing-masing 0,25 mg/20gBB, 0,50 mg/20gBB, 1,00 mg/20gBB serta satu kelompok pembanding dengan doxorubicin 0,052 mg. Selanjutnya dilakukan pewarnaan IHK menggunakan antibodi primer Ki67. Didapatkan hasil penelitian secara statistik terjadi penurunan proliferasi sel epitel kolon pada ketiga kelompok mencit dengan terapi ekstrak bawang dayak. Dengan penurunan terbaik yaitu pada dosis 1,00 mg/20gBB memberikan hasil penurunan jumlah proliferasi sel epitel 11 ± 1.04 sel/LPB, nilai tersebut paling mendekati dengan kelompok dosis pembanding doxorubicin 0,052 mg (8 ± 0.55 sel/LPB) dan kelompok kontrol negatif (6 ± 1.48 sel/LPB). Sehingga pemberian ekstrak bawang dayak (Eleutherine palmifolia (L.) Merr) dapat menurunkan ekspresi Ki67 pada sel epitel kolon dalam bahan biologi tersimpan dari mencit BALB/c yang diinduksi AOM DSS secara in vivo

Potential Inhibition of Melaleuca leucadendron L. Compounds Against the NSP5 SARS CoV-2 Protein

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome (SARS-CoV-2), causing a global health emergency as a pandemic disease. The lack of certain drug molecules or treatment strategies to fight this disease makes it worse. Therefore, effective drug molecules are needed to fight COVID-19. Non Structural Protein (NSP5) or called Main Protease (Mpro) of SARS CoV 2, a key component of this viral replication, is considered a key target for anti-COVID-19 drug development. The purpose of this study is to determine whether the compounds in the Melaleuca leucadendron L. plant such as 1,8-cineole, terpene, guaiol, linalol, α-selinenol, β-eudesmol and γ-eudesmol are predicted to have antiviral activity for COVID-19. Interaction of compounds with NSP5 with PDB code 6WNP analyzed using molecular docking with Molegro Virtual Docker. Based on binding affinity, the highest potential as an anti-viral is Terpineol with binding energy (-119.743 kcal/mol). The results of the interaction showed that terpinol has similarities in all three amino acid residues namely Cys 145, Gly 143, and Glu 166 with remdesivir and native ligand. Melaleuca leucadendron L. may represent a potential herbal treatment to act as: COVID-19 NSP5, however these findings must be validated in vitro and in vivo.Keywords: COVID-19, In Silico, NSP5/ 6WNP, Melaleuca leucadendron L

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background: Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods: This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was coprioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low-middle-income countries. Results: In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of 'single-use' consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low-middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion: This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high- and low-middle-income countries