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"ABSTRACTPurpose: Duodenal adenoma and adenocarcinoma (AC) are rare tumors, and few studies have examined their genetic features. We aimed to determine the key genetic changes in duodenal adenoma and AC, and to clarify the possible involvement of the adenoma-carcinoma sequence in duodenal tumor carcinogenesis.Methods: Nineteen duodenal tumors collected by endoscopic mucosal resection or surgical resection were classified as AC, adenoma with high-grade dysplasia (HGD), or adenoma with low-grade dysplasia (LGD) per the World Health Organization tumor classification. When a tumor contained two or more components with different dysplasia grades, the highest grade was assigned as the tumor grade. Representative areas of these components with different grades were microdissected and evaluated by a genomic analysis. Mutational hotspots involving 50 oncogenes and tumor suppressor genes were analyzed by next-generation sequencing, and their association with the dysplasia grade was investigated.Results: We analyzed 27 tumor components of AC or adenoma, with 11 normal mucosal samples obtained from 19 patients with duodenal tumors. The most prevalent abnormality among 50 genes tested was the KRAS mutation, which was detected in 12/19 (63.2%) patients, followed by APC and TP53 mutations (47.4 and 36.8%, respectively). According to the tumor dysplasia grading of each component, KRAS mutations were found in 5/8 (62.5%) tumors with AC components, 6/9 (66.7%) tumors with HGD components, and 3/10 (30.0%) tumors with LGD components. TP53 mutations were found in 4/8 (50.0%) tumors with AC components, 3/9 (33.3%) tumors with HGD components, and 1/10 (10.0%) tumors with LGD components. APC mutations were found in 2/8 (25.0%) tumors with AC components, 6/9 (66.7%) tumors with HGD components, and 5/10 (50.0%) tumors with LGD components. Notably, an APC:T1556fs mutation was detected in six cases (31.6%), five of which were adenoma cases. Furthermore, STK11 mutations were confirmed in 2/8 (25.0%) AC cases and in 1/11 (9.1%) adenoma cases.Conclusion: APC:T1556fs and STK11 mutations found in duodenal adenomas/ACs highlight the importance of proteins encoded by these genes in tumor development. APC mutations were identified in duodenal adenomas more frequently than in duodenal ACs, which differed from the observations of typical adenoma-carcinoma sequences seen in colorectal cancer, suggesting the limited involvement of this mechanism in duodenal cancer development."

"Kulit sebagai organ terbesar dan terluar dari tubuh manusia yang langsung berhadapan dengan lingkungan luar menjadi pertahanan fisik lini pertama sekaligus tempat kolonisasi mikrobiota komensal dalam mencegah invasi patogen. Identifikasi komposisi mikrobiota kulit menarik dilakukan untuk mengetahui interaksi antar mikrobiota sehingga mikrobiota kulit komensal yang bersifat probiotik dapat dikembangkan menjadi bahan aktif terapeutik mikrobioma kulit untuk menjaga kesehatan kulit. Keberagaman mikrobiota kulit dipengaruhi oleh beberapa faktor, salah satunya adalah faktor etnis. Penelitian ini mempelajari pengaruh faktor etnis pada dewasa muda pria dan wanita yang mewakili etnis Papua, Jawa, dan keturunan Tionghoa terhadap profil mikrobioma kulit. DNA genomik mikrobiota dari sampel kulit wajah diekstraksi dan disekuens dengan metode Next Generation Sequencing lalu dilakukan analisis diversitas alfa dan beta. Berdasarkan analisis alfa dengan indeks OTU yang dterobservasi, Shannon, dan Faiths PD, diversitas dalam grup tertinggi terdapat pada grup etnis Papua dan terendah pada grup etnis keturunan Tionghoa, namun diversitas alfa ketiga grup tidak berbeda signifikan secara statistik. Analisis beta dilakukan berdasarkan kualitatif dan kuantitatif menunjukkan pengaruh faktor etnis pada profil mikrobioma kulit antar etnis yang signifikan secara statistik serta pengelompokkan yang baik berdasarkan hasil PCoA pada indeks Jaccard, disimilaritas Bray Curtis, Unweighted, dan Weighted. Bakteri yang bersifat komensal dan dominan selanjutnya dapat dikembangkan menjadi bacterial cocktail maupun formula postbiotik untuk terapi mikrobiota kulit dengan pertimbangan interaksi komposisi mikrobiota kulit pada etnis terkait.

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Skin as the largest and the outermost part of human body that directly exposed to the outer environment serves as the first physical barrier and colonised by commensal bacteria to prevent pathogen invasion. Identifying composition of commensal skin microbiota is interesting to know the interaction between the microbiota so the commensal skin microbiota who has probiotic effect can be developed as active substance of skin microbiome therapeutic to maintain skin health. The skin microbiome diversity is influenced by several factors, one of them is ethnicity. This study shows the influence of ethnicity factor in Papuans, Javanese, and Chinese descent young adults on skin microbiome profiles. The microbiota genomic DNA are extracted from the face skin samples and sequenced with Next Generation Sequencing method to be further analysed on its alpha and beta diversity. According to alpha diversity analysis with observed OTU, Shannon, and Faiths PD indices, the greatest alpha diversity shown in Papuans, while the smallest is shown in the Chinese descent group, but alpha diversity differences between three groups are not statistically significant. Beta diversity was assessed by the use of Jaccard index, Bray Curtis dissimilarity, Unweighted and Weighted Unifrac with PCoA shows the difference skin microbiome profiles according to ethnicity and is statistically significant between ethnic group. The characterised commensal and dominant bacteria can be further developed as bacterial cocktail and postbiotic formula as skin microbiome therapeutic with interaction between skin microbiota composition within each ethnicity taking into account."

"Latar belakang: Antibiotik gentamisin (GEN), klindamisin (CLI) dan minosiklin (MIN) digunakan dalam penanganan infeksi Staphylococcus aureus kebal metisilin (methicillin-resistant Staphylococcus aureus, MRSA). Teknologi next-generation sequencing (NGS) merupakan metode mutakhir yang digunakan untuk pemetaan pola kekebalan kuman untuk pengendalian infeksi di suatu fasilitas pelayanan kesehatan. Penelitian ini bertujuan untuk mengetahui profil genom isolat MRSA klinis melalui pemeriksaan NGS. Metode: Proses sequencing DNA menggunakan Illumina® MiSeq dilakukan pada 92 isolat MRSA klinis yang diperoleh dari pasien yang dirawat di Hiroshima University Hospital, Hiroshima, Jepang sehingga didapatkan masing-masing susunan genom de novo. Susunan genom de novo tersebut kemudian dianalisis in silico menggunakan ResFinder sehingga didapatkan profil genom kekebalan antibiotik kuman. Data ini kemudian dianalisis bersama data fenotip kadar hambat minimum (KHM) GEN, CLI, dan MIN.Hasil: Penelitian ini menunjukkan MRSA aac(6')aph(2")+,spc+, ermA+,tetM+ merupakan isolat terbanyak (42/92) dan memiliki KHM GEN >16 mg/L (40/42), CLI >4 mg/L (26/42) dan MIN >8 mg/L MIN (30/42). Deteksi gen aac(6')aph(2") berhubungan dengan KHM GEN (p<0,001), deteksi gen ermA berhubungan dengan KHM CLI (p<0,001) dan deteksi gen tetM berhubungan dengan KHM MIN (p<0,001). Deteksi bersamaan aac(6')aph(2")-spc-ermA-tetM berkorelasi dengan KHM GEN (φc= 0,398, p <0,001), CLI (φc= 0,448, p <0,001) dan MIN (φc= 0,515, p <0,001). Kesimpulan: Penelitian ini menunjukkan korelasi fenotip KHM dan genotip kekebalan antibiotik GEN, CLI dan MIN pada MRSA. Teknologi NGS berpotensi sebagai uji cepat deteksi kekebalan antibiotik pada kasus infeksi MRSA yang merupakan bagian dari upaya pengendalian infeksi.

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Background: Gentamicin (GEN), clindamycin (CLI) and minocycline (MIN) are amongst the widely used antibiotic treatments in methicillin-resistant Staphylococcus aureus (MRSA) infection. The emerging next-generation sequencing (NGS) technology provides antibiotic resistance pattern mapping to be inferred as a consideration in healthcare infection control policy. The subjective of this study is to reveal genomic resistome using NGS and to correlate the resistome with the phenotype of antibiotic resistance represented as minimum inhibitory concentration (MIC) between clinically isolated MRSA specimens.Methods: Illumina® MiSeq was used to sequence and to de novo assembly the genomic DNA of 92 MRSA specimens obtained from the patients treated in Hiroshima University Hospital, Hiroshima, Japan. Resistome was determined by feeding the de novo genome assembly to ResFinder annotation tool prior to correlation analysis with MIC data. These procedures were performed during GEN, CLI and MIN susceptibility observation.Results: The aac(6')aph(2")+,spc+, ermA+,tetM+ MRSA strains were revealed to be predominant (42/92) of which were possessing GEN MIC >16 mg/L (40/42), CLI MIC >4 mg/L (26/42) and MIN MIC >8 mg/L MIN (30/42). This study also revealed the correlation of aac(6')aph(2") and GEN MIC (p<0.001), ermA and CLI MIC (p<0.001), and tetM and MIN MIC (p<0.001). Simultaneous detection of aac(6')aph(2")-spc-ermA-tetM was correlated with GEN MIC (φc= 0.398, p <0.001), CLI MIC (φc=0.448, p <0.001), and MIN MIC (φc= 0.515, p <0.001).Conclusions: This study showed correlation between the MIC and resistome of GEN, CLI and MIN in MRSA. The emerging NGS technology provides promising method in rapid detection of antibiotic resistance in MRSA thus feasible for infection control near in the future."

"ABSTRAKLatar Belakang: Metode seleksi embrio terbaik banyak dikembangkan untuk memperoleh transfer embrio tunggal dalam siklus fertilisasi in vitro (FIV). Blastokista merupakan tahap embrio terbaik yang didapat dari embrio dengan morfologi normal atau 2 pro-nukleus (2PN) maupun morfologi abnormal atau 3 pro-nukleus (3PN). Transfer blastokista masih memberikan tingkat keberhasilan implantasi dan kehamilan yang rendah karena penilaian morfologi yang baik tidak selalu mempunyai status kromosom yang baik. Aneuploidi dan mosaik diketahui masih ditemukan dalam populasi blastokista, sehingga perlu diketahui faktor-faktor yang menyebabkan kelainan tersebut. Tujuan dari penelitian ini adalah mengetahui hubungan antara morfologi dan perkembangan blastokista dengan kejadian aneuploidi dan mosaik, serta faktor yang mempengaruhinya.Metode: Penelitian dilakukan dengan metode potong lintang. Embrio diperoleh dari siklus FIV dan dikultur sampai tahap blastokista, penilaian morfologi blastokista dilakukan menggunakan skoring Gardner dengan 3 parameter yaitu grade ekspansi blastokista, inner cell mass, dan tropektoderm. pre-implantation genetic testing for aneuploidi (PGT-A) dilakukan dengan cara biopsi blastokista pada hari ke 5 atau 6 dan analisis kromosom dilakukan menggunakan metode Next Generation Sequencing (NGS). Hubungan antara morfologi blastokista dan status kromosom serta faktor yang mempengaruhinya kemudian dianalisis.Hasil: Didapatkan 70 embrio dari 25 pasien, dengan pembagian 45 embrio 2PN dan 25 embrio 3PN. Frekuensi aneuploidi pada sampel 2PN dan 3PN berturut turut 42% dan 4%, sedangkan mosaik 2PN 16% dan 3PN 8%, pada embrio 3PN juga didapati kromosom triploid sebesar 52%. Didapatkan hubungan bermakna antara grade tropektoderm embrio 2PN dengan status kromosom (p<0,05), sedangkan embrio 3PN tidak didapati hubungan antara parameter morfologi dengan kromosom. Blastokista dengan grade ³3AA memiliki persentase euploidi sebesar 46%. Usia maternal, usia paternal, jumlah oosit, laju fertilisasi, volume dan motilitas sperma berhubungan dengan status kromosom (p<0,05).Kesimpulan: Grading blastokista berhubungan dengan status kromosom, dan usia maternal merupakan faktor yang paling berhubungan dengan kejadian aneuploidi dan mosaik.

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ABSTRACTBackground: Several method of assessing embryo viability have been employed over these year to obtain single embryo transfer in IVF cycle. Blastocyst, known as the best morphological embryo derived from both normal or 2 pronucleus (2PN) and 3 pronucleus (3PN) still not give the best implantation and pregnancy rate. However, morphology assesment only did not properly evaluate chromosomal status of the embryos. A good morphology blastocyst still can harbour aneuploidy and mosaic, and it is needed to find factor that effect aneuploidy and mosaic. Therefore, the aim of this study was to investigate the correlation between blastocyst morphology with aneuploidy, mosaicism and other related factor.Methods: A cross-sectional study to compare blastocyst morphology with chromosomal status. Embryo collected from IVF-ICSI cyles then cultured until blastocyst stage, Blastocyst scoring was done by Gardner scoring system with 3 parameter including blastocyst expansion, inner cell mass and tropectoderm. Preimplantation genetic testing for aneuploidi (PGT-A) was done by tropectoderm biopsy on day 5 or 6 which were the screened for chromosomal status by Next Generation Sequencing (NGS) method. The relationship between blastocyst morphology and chromosomal status and other related factor were evaluated.Results: A total 70 blastocyst were collected, 45 derived from 2PN zygot and the other 25 from 3PN zygot. The frequency of aneuploid in 2PN and 3PN continuosly 42% and 4%, meanwhile mosaic frequency were 15% and 8%. Triploidy chromosome were found 52% in 3PN embryo. Tropectoderm grading and chromosomal status was found significally different (p<0.05), while in 3PN embryo there in no correlation between blastocyst morphology and chromosomal status. >3AA blasctocyst grading had higher euploidy percentage compare to <3AA grading. Maternal age, oocyte number, fertilization rate, sperm volume and sperm motility have correlation with chromosomal status (p<0.05).Conclusions: Blastocyst grading had correlation with chromosomal status, and maternal age is the key factor that affect aneuploidy and mosaicism."

"Mikrobiota saluran pencernaan neonatus merupakan modulator respon imun yang berpengaruh terhadap kesehatan dan penyakit bagi neonatus. Perkembangan mikrobiota saluran pencernaan neonatus dipengaruhi oleh beberapa faktor baik faktor maternal maupun faktor neonatal yang secara langsung maupun tidak langsung mempengaruhi kolonisasi mikrobiota usus neonatus pada masa awal kehidupannya. Masa awal kehidupan neonatus (≤ 1 bulan setelah lahir) merupakan periode kritis dalam menentukan kesehatan neonatus jangka panjang maupun jangka pendek. Kolonisasi mikrobiota saluran pencernaan yang menyimpang atau disbiosis pada awal kehidupannya dapat meningkatkan risiko terhadap penyakit yang berkaitan dengan perkembangan sistem imunitasnya seperti alergi, obesitas, diabetes, dan lain-lain. Dengan demikian, ulasan ini membahas tentang peranan mikrobiota saluran pencernaan neonatus pada masa awal kehidupan dalam mendukung kesehatan neonatus dengan mengetahui kolonisasi mikrobiota saluran pencernaan yang simbiosis. Sekuensing amplikon gen target 16S rRNA menggunakan metode NGS merupakan metode yang paling banyak digunakan untuk mengkarakterisasi keragaman mikroba. Sampel mekonium atau feses sebagai representatif lingkungan saluran pencernaan neonatus dikumpulkan dan dilakukan ekstraksi DNA kemudian gen target diamplifikasi dengan PCR. Amplikon yang diperoleh disekuensing dan dikarakterisasi secara bioinformatik untuk menentukan mikroba yang ada dalam sampel serta kelimpahan relatifnya. Selain itu, analisis berbasis teknologi molekuler seperti sekuensing gen target 16S rRNA menggunakan metode NGS dan analisis bioinformatik berperan penting dalam memperluas pengetahuan tentang ekosistem saluran cerna yang kompleks dari sampel mekonium dan feses neonatus. Dalam rangka menciptakan mikrobiota saluran pencernaan yang baik dan mendukung kesehatan neonatus pada masa awal kehidupannya dapat dilakukan dengan melakukan intervensi pada faktor-faktor yang mempengaruhi perkembangannya. Intervensi seperti merencanakan kelahiran normal, menjaga asupan nutrisi yang seimbang selama masa kehamilan dan juga menyusui, menghindari paparan antibiotik selama kehamilan dan pada neonatus, dan memberikan ASI kepada neonatus terbukti dapat memodulasi perkembangan mikrobiota saluran pencernaan neonatus yang sehat.

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Neonatal gut microbiota is a modulator of the immune response that influences health and disease for neonates. The development of the neonatal gut microbiota is influenced by several factors, both maternal and neonatal factors that directly or indirectly affect the colonization of neonatal gut microbiota in early life. The early-life period of neonatal life (≤ 1 month after birth) is a critical period in determining the long-term and short-term health of neonates. Aberrant colonization of gut microbiota or dysbiosis in early life can increase the risk of diseases related to the development of the immune system such as allergies, obesity, diabetes, and others. Thus, this review discusses the role of the neonatal gut microbiota in early life in supporting neonatal health by knowing the symbiosis colonization of the gut microbiota. The sequencing of 16S rRNA target gene amplicons using the NGS method is the most widely used method to characterize microbial diversity. Meconium or faecal samples as a representative environment of the neonatal digestive tract are collected and DNA extracted then the target gene is amplified by PCR. The obtained amplicons are sequenced and bioinformaticly characterized to determine the microbes present in the sample and their relative abundance. In addition, analysis based on molecular technologies such as 16S rRNA target gene sequencing using the NGS method and bioinformatic analysis play an important role in expanding our knowledge about complex gastrointestinal ecosystems from meconium and neonatal faecal samples. In sum, creating a good gut microbiota and supporting neonatal health in their early-life period can be done by intervening on factors that influence its development. Interventions such as planning a normal birth, maintaining a balanced nutritional intake during pregnancy and lactating, avoiding antibiotic exposure during pregnancy and in neonates, and breastfeeding for neonates are proven to modulate the development of healthy neonatal gut microbiota."

"Latar belakang: Clinically significant prostate cancer (csPCa) merupakan kanker prostat yang mempunyai kemungkinan progresi lokal, metastasis, rekurensi, dan kematian yang sedang hingga tinggi, serta tata laksana yang lebih agresif. Penelitian ini bertujuan untuk membantu diagnosis antara csPCa dan bukan csPCa menggunakan rasio apparent diffusion coefficient (rADC) lesi prostat dengan urine. Metode: Penelitian dilakukan pada lesi prostat kategori 3-5 prostate imaging-reporting and data system yang telah dibiopsi prostat transperineal tertarget magnetic resonance imaging (MRI) dengan ultrasound/MRI fusion software di Rumah Sakit Umum Pusat Nasional Dokter Cipto Mangunkusumo pada Juni 2019 hingga Maret 2021. rADC lesi prostat dengan urine merupakan perbandingan rerata nilai apparent diffusion coefficient (ADC) lesi prostat dan urine di vesica urinaria pada MRI prostat peta ADC potongan aksial multi-institusi. rADC lesi prostat dengan urine antara csPCa (adenokarsinoma asinar prostat dengan skor Gleason ≥7) dan bukan csPCa (jaringan prostat nonneoplastik atau adenokarsinoma asinar prostat dengan skor Gleason 6) dibandingkan dan ditentukan nilai titik potongnya menggunakan receiver operating curve. Hasil: Terdapat perbedaan rADC lesi prostat dengan urine yang bermakna antara 19 lesi prostat yang merupakan csPCa dan 35 lesi prostat yang bukan merupakan csPCa, dengan nilai tengah rADC lesi prostat dengan urine pada csPCa 0,21 (0,11-0,33), nilai tengah rADC lesi prostat dengan urine pada bukan csPCa 0,43 (0,30-0,61), dan nilai p <0,001. Nilai titik potong rADC lesi prostat dengan urine dalam membedakan csPCa dan bukan csPCa adalah 0,30 dengan sensitivitas 94,73% dan spesifisitas 100%, area under curve 0,998 (IK95% 0,994-1,000), serta nilai p <0,001. Kesimpulan: rADC lesi prostat dengan urine dapat membantu diagnosis csPCa dan bukan csPCa pada lesi prostat sebelum biopsi prostat yang tidak invasif, mudah dikerjakan, serta tidak membutuhkan persiapan dan pemeriksaan tambahan.

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Background: Clinically significant prostate cancer (csPCa) is prostate cancer with moderate to high probability of local progression, metastasis, recurrence, and death, as well as more aggressive management. This study aims to aid diagnose between csPCa and non-csPCa using apparent diffusion coefficient ratio (rADC) of prostate-lesion-to-urine.

Methods: This study analyze prostate lesions with prostate imaging-reporting and data system category 3-5 that underwent magnetic resonance imaging (MRI)-targeted transperineal prostate biopsy using ultrasound/MRI fusion software at Rumah Sakit Umum Pusat Nasional Dokter Cipto Mangunkusumo from June 2019 to March 2021. rADC of prostate-lesion-to-urine is defined as comparison between mean apparent diffusion coefficient (ADC) value of prostate lesion and urine in urinary bladder from axial section of ADC map of multi-institutional prostate MRI. rADC of prostate-lesion-to-urine between csPCa (acinar adenocarcinoma of the prostate with Gleason score ≥7) and non-csPCa (non-neoplastic prostate tissue or acinar adenocarcinoma of the prostate with Gleason score 6) is compared and the cutoff point is determined using receiver operating curve.

Results: There is significance rADC of prostate-lesion-to-urine difference between 19 prostate lesions with csPCa and 35 prostate lesions with non-csPCa, with mean rADC of prostate-lesion-to-urine in csPCa is 0.21 (0.11-0.33), mean rADC of prostate-lesion-to-urine in non-csPCa is 0.43 (0.30-0.61), and p value is <0.001. The cut-off value of rADC of prostate-lesion-to-urine to differentiate between csPCa and non-csPCa is 0.30, with 94.73% sensitivity and 100% specificity, area under curve is 0.998 (CI95% 0.994-1.000), and p value is <0.001.

Conclusion: rADC of prostate-lesion-to-urine may help diagnose between csPCa and non-csPCa in prostate lesions before prostate biopsy, which is non-invasive, easy to perform, does not require additional preparation and examination."