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"Defisiensi enzim 5 alfa-reduktase tipe 2 (D5AR2) merupakan penyakit genetik, yang disebabkan gangguan konversi testosteron (T) menjadi dihidrotestosteron (DHT). Diagnosis D5AR2 pada umumnya ditegakkan dengan rasio T/DHT dan analisis DNA gen SRD5A2, namun rasio T/DHT sering tidak konklusif, sehingga diperlukan pemeriksaan alternatif dalam diagnosis D5AR2, dalam hal ini dipilih rasio metabolit 5β/5αsteroid urin yakni rasio etiokolanolon/androsteron (Et/An) urin karena telah dilaporkan oleh beberapa peneliti dan juga karena tersedia di Indonesia. Penelitian ini bertujuan untukmembandingkan akurasi rasio T/DHT dan Et/An urin dalam diagnosis penyandang dan pembawa sifat D5AR2. Selain itu mengetahui pola mutasi gen SRD5A2 dan hubungan genotipe-fenotipe. Studi deskriptif potong-lintang dilakukan untuk mengetahui pola mutasi gen SRD5A2 dan hubungan genotipe-fenotipe dilakukandi Lembaga Eijkman, Jakarta sejak Juli 2016–September 2018. Studi komparatif dilakukan untuk membandingkan akurasi rasio T/DHT (dilakukan di Laboratorium Terpadu FKUI) dan rasio Et/An urin (dilakukan di Laboratorium Kesehatan Daerah DKI Jakarta) dalam mendiagnosis penyandang dan pembawa sifat D5AR2, dilanjutkan dengan analisis kurva ROC (receiver operating characteristics) masing-masing rasio, dengan baku emas analisis DNA gen SRD5A2. Enam puluh enam subjek penyandang 46,XY DSD dan 95 subjek keluarga peyandang direkrut dalam penelitian ini. Hasil analisis DNA gen SRD5A2 membagi subjek penyandang 46,XY DSD menjadi 37 subjek penyandang D5AR2 dan 29 subjek bukan penyandang D5AR2, dan subjek keluarga menjadi 53 subjek pembawa sifat dan 42 subjek bukan pembawa sifat D5AR2. Rasio T/DHT tidak berbeda bermakna antara penyandang dan bukan penyandang D5AR2, dan juga tidak berbeda bermakna antara pembawa sifat dan bukan pembawa sifat D5AR2. Nilai AUC rasio Et/An urin dalam mendiagnosis penyandang D5AR2 adalah 79,7% (IK 95% 69,0–90,4%, p < 0,001). Dengan nilai titik potong >0,95 didapatkan sensitivitas rasio Et/An urin dalam diagnosis D5AR2 adalah 67,57% dan spesifisitas 86,21%. Dengan nilai titik potong >0,99 didapatkan sensitivitas rasio Et/An urin dalam mendiagnosis pembawa sifat D5AR2 adalah 67,92% dan spesifisitas73,81%. Kombinasi rasio Et/An urin subjek penyandang dan salah satu keluarga dekatnya meningkatkan perkiraan akurasi diagnostik menjadi sangat baik (AUC menjadi 84,1% (IK 95% 74,3–93,9%, p < 0,001), dengan sensitivitas sangat baik (89,19%), namun spesifisitas kurang baik (57,69%). Enam jenis mutasi baru dideteksi, yaitu c.34delGinsCCAGC, R50H, W136stop, G191R, F194I, I253V, dan 7 mutasi lain. Tidak ada hubungan nyata genotipe dan fenotipe.

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The 5 alpha-reductase type 2 deficiency (5ARD2) is a genetic condition associated with impairment in conversion of testosterone (T) to dihydrotestosterone (DHT), leading to undervirilization in 46,XY individuals. Diagnosis of 5ARD2 is mainly established by T/DHT ratio and molecular analysis. Yet, the T/DHT ratio often yielded in conflicting results, and the available urinary ratio of etiocholanolone/androsterone (Et/An) was selected as an alternative test.

This study aimedto compare the accuracy of T/DHT and urinary Et/An ratios in diagnosing 5ARD2 cases and carriers and to elaborate the molecular characteristics of SRD5A2 gene in 5ARD2 cases and the genotype and phenotype correlations.

Descriptive and comparative cross-sectional studies were conducted at the Eijkman Institute, Jakarta in year 2016–2018. The accuracy of T/DHT and Et/An ratios were compared using ROC (receiver operating characteristics) curve analysis in the cases and carriers group with molecular analysis of SRD5A2 gene as the gold standard. The molecular characterization of SRD5A2 gene and genotype-phenotype correlations were described.

Sixty six 46,XY DSD subjects and 95 subjects of their family members, who gave written consent or parental approval were recruited. Thirty seven 5ARD2 cases and 29 control were identified in 46,XY DSD subjects, and 53 carriers and 42 control of family members were confirmed by molecular analysis of SRD5A2 gene. The T/DHT ratios were not different significantly in cases and carriers group, while the AUC (area under the curve) of urinary Et/An showed 79.7% (95% CI 69.0–90.4%, p < 0.001). After determining cutoff values for diagnosing cases (>0.95) and carriers (>0.99), the sensitivity and specificity of urinary Et/An ratio in cases groups were 67.57% and 86.21%, respectively, and in carrier groups 67.92% and 73.81%, respectively. Simultaneous urinary Et/An ratios of cases and one of their closed family members increased the diagnostic accuracy with AUC of 84.1% (95% CI 74.3–93.9%, p < 0,001) and sensitivity 89.19%, yet the specificity of only 57.69%. Six novel mutations (c.34delGinsCCAGC, R50H, W136stop, G191R, F194I, and I253V), and 7 other mutations, which were G34Fs, c.699-1 G>T, V89L, Y128C, N193S, R227Q, and g.5352+15 T>C, in the SRD5A2 gene were detected. There were no clear genotype-phenotype correlations found.

Conclusion: The diagnostic accuracy of urinary Et/An ratio was good in 5ARD2 cases and carriers, and the accuracy was very good if the urinary Et/An ratios of cases and their closed family members were combined. The T/DHT ratio was inaccurate in diagnosing 5ARD2 cases. Six new mutations were detected."

"Nefropati diabetik adalah salah satu komplikasi yang banyak terjadi pada pasien diabetes melitus tipe 2 DM tipe 2 . Salah satu metode untuk mengukur tingkat kerusakan ginjal dan memprediksi perkembangan serta progresivitasnya adalah rasio albumin kreatinin urin UACR . Selain UACR, kolagen tipe IV urin diduga dapat menjadi penanda alternatif yang lebih sensitif. Penelitian ini bertujuan untuk menganalisis UACR, kadar kolagen tipe IV urin, serta mengetahui hubungan keduanya pada pasien DM tipe 2 yang berusia lebih dari 25 tahun di Puskesmas Kecamatan Pasar Minggu dengan desain studi cross sectional dan teknik pengambilan consecutive sampling. Terdapat 3 kelompok sampel, yakni subjek nondiabetes sebagai kontrol n = 10 , pasien DM tipe 2 dengan normoalbuminuria n = 62 , dan pasien DM tipe 2 dengan albuminuria n = 27. Albumin urin diukur secara imunoturbidimetri sedangkan kreatinin urin diukur secara kolorimetri enzimatik. Kadar kolagen tipe IV diukur berdasarkan prinsip sandwich ELISA. Hasil uji beda rerata pada ketiga kelompok menunjukkan terdapat perbedaan bermakna pada nilai UACR p < 0,001 dan kadar kolagen tipe IV urin p < 0,001 . Uji korelasi antara nilai UACR dan kadar kolagen tipe IV menunjukkan adanya hubungan moderat pada kelompok pasien DM tipe 2 r = 0,336; p = 0,001 sehingga dapat disimpulkan bahwa kolagen tipe IV belum cukup kuat untuk dijadikan penanda kerusakan ginjal.

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Diabetic nephropathy DN is one of the most complications that happened in Type 2 Diabetes Mellitus Patients T2DM . Urine albumin creatinine ratio UACR is a gold standard method to assess renal dysfunction levels and predict the development and progression of early DN. Type IV collagen is glomerular basement membrane's component which expected to be an earlier marker for determining renal dysfunction levels.

The aim of this study was to assess UACR, urinary type IV collagen, and correlation both of them in T2DM patients more than 25 years old at Pasar Minggu Community Health Center by cross sectional study and consecutive sampling method. There were 3 sampling groups of this study, nondiabetic subjects as control n 10 , normoalbuminuric patients n 62 , and albuminuric patients n 27 . Urine albumin was measured by immunoturbidimetry, meanwhile urine creatinine was measured by colorimetric enzymatic assay. Urinary type IV collagen was analyzed by sandwich ELISA.

The result of comparing means of the groups showed significant differences on urinary type IV collagen p 0,001 and UACR p 0,001 . The correlation test showed possitive moderate correlation r 0,336 p 0,001 between UACR and urinary type IV collagen in T2DM patients. It might be indicate that urinary type IV collagen was not an accurate biomarker for assessing renal dysfunction."

"Latar belakang Disorders of sex development (DSD) 46,XY adalah kelainan bawaan perkembangan gonad maupun struktur genitalia interna dan eksterna yang berhubungan dengan kromosom 46,XY. Manifestasi klinis DSD yang bervariasi, diagnosis akhir, gender assignment, tata laksana terapi hormon dan pembedahan dapat memberikan dampak pada kualitas hidup dan psikososial. Tujuan Penelitian ini dilakukan untuk mengetahui gambaran spektrum klinis, luaran (diagnosis akhir, gender assignment, pembedahan), kualitas hidup, gangguan psikososial dan faktor-faktor yang memengaruhinya. Metode Studi dilakukan terhadap 122 anak yang berusia kurang dari 18 tahun dengan DSD 46,XY yang berobat ke RSUPN Cipto Mangunkusumo pada 5 tahun terakhir. Pengambilan data sekunder seperti spektrum dan luaran klinis dilakukan mulai Januari hingga Mei 2022. Sebanyak 56 subyek dilakukan wawancara untuk evaluasi kualitas hidup dengan instrumen The Pediatric Quality of Life Inventory (PedsQLTM) dan gangguan psikososial dengan instrumen Strength and Difficulties Questionnaire (SDQ).Hasil Manifestasi klinis terbanyak pada DSD 46,XY adalah hipospadia (97,5%), mikropenis (82,8%), skor EMS < 7 (81,1%), dan skrotum bifidum (75,4%). Sebagian besar individu dengan DSD 46,XY ditetapkan (gender assignment) sebagai lelaki (98,4%), dengan 5,74% subyek yang mengalami perubahan gender assignment dari perempuan. Diagnosis akhir pada DSD 46,XY adalah gangguan maskulinisasi (89,34%), disgenesis gonad (7,38%) dan gangguan sintesis/fungsi androgen (3,28%). Prevalensi gangguan kualitas hidup dan psikososial pada DSD 46,XY rendah. Analisis fungsi domain PedsQLTM dan SDQ menunjukkan 10,71% dan 25,64% subyek mengalami gangguan pada salah satu fungsi kualitas hidup dan/atau salah satu komponen psikososial. Pembedahan pada DSD 46,XY berhubungan dengan fungsi emosi kualitas hidup (p = 0,012) dan psikososial (p = 0,025), sedangkan skor EMS berhubungan dengan fungsi sekolah (p = 0,038).

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Background : Clinical Manifestations, Outcomes, and Quality of Life in Children with 46,XY Disorder of Sex Development (DSD) : Dr. Frida Soesanti, Sp.A(K) DR. Dr. Irfan Wahyudi, Sp.U(K) DR. Dr. Bernie Endyarni Medise, Sp.A(K), MPH Disorders of sex development (DSD) 46,XY is a developmental disorder of gonadal, external, and internal genitalia associated with chromosome 46,XY abnormalities. Varied clinical manifestations, definitive diagnosis, gender assignment, hormone replacement therapy, and surgery may have an impact on the quality of life and psychosocial problems. Objective The study aims to describe clinical manifestations, outcomes (definitive diagnosis, gender assignment, surgery), quality of life, psychosocial problems, and their related factors in children with 46,XY DSD. Methods A study was conducted on 122 subjects below 18 years of age who had been initially diagnosed with 46,XY DSD for the past 5 years (2017-2022) in Cipto Mangunkusumo General Hospital, Jakarta. Secondary data such as clinical manifestations and outcomes were collected from both paper-based and electronic-based medical records from January until May 2022. Fifty-six subjects were able to join telephone interviews assessing their quality of life using The Pediatric Quality of Life Inventory (PedsQLTM) and psychosocial problems using the Strength and Difficulties Questionnaire (SDQ). All data were statistically analyzed with SPSS version 25.0.

Results The most common clinical manifestations in 46,XY DSD were hypospadias (97.5%), micropenis (82.8%), EMS score < 7 (81.1%), and bifid scrotum (75.4%). The majority of the subjects were finally assigned as male (98,4%) with only 5.74% of subjects having gender assignment change from female to male. The definitive diagnosis of DSD 46,XY was undermasculinization disorder (undefined) (89.34%), gonadal dysgenesis (7.38%), and androgen insensitivity syndromes (3.28%). The prevalence of quality of life disorders and psychosocial problems was low. PedsQLTM and SDQ subscale analysis showed that 10.17% and 25.64% of subjects had abnormal scores of quality of life and psychosocial problems, respectively. Surgery was associated with lower emotional function in PedsQLTM (p = 0,012) and its total score (p = 0,023), and emotional component of SDQ (p = 0.025). Scores of EMS were also associated with the school function of PedsQLTM (p = 0.038). Conclusion Surgery is an important factor affecting the emotional function of the quality of life and psychosocial problems; whereas an EMS score < 7 is associated with school function."

"Nefropati diabetik merupakan komplikasi DM tipe 2 yang umumnya ditandai dengan kondisi albuminuria dari hasil penilaian UACR. TGF-β1 urin merupakan faktor pertumbuhan yang banyak dikaitkan dengan patologis dari kerusakan ginjal pada nefropati diabetik. Tujuan dari penelitian ini yaitu untuk mengetahui hubungan nilai UACR dengan kadar TGF-β1 urin pada pasien DM tipe 2. Desain studi pada penelitian ini yaitu cross sectional dimana pengambilan sampel menggunakan teknik consecutive sampling. Sampel yang diperoleh berjumlah 99 subjek penelitian (62 pasien DM normolbuminuria, 27 pasien DM albuminuria, dan 10 subjek non DM sebagai kontrol) di Puskesmas Kecamatan Pasar Minggu. Kadar TGF-β1 urin diukur menggunakan ELISA, sedangkan nilai UACR diperoleh dari hasil uji laboratorium klinik. Hasil dari uji beda rerata pada kadar TGF-β1 urin menunjukkan tidak terdapat perbedaan bermakna (p = 0,790) pada ketiga kelompok sampel. Hasil analisis hubungan kadar TGF-β1 urin dengan nilai UACR pada kelompok DM normoalbuminuria dan albuminuria juga menunjukkan tidak adanya hubungan yang bermakna (r = -0,079; p = 0,462). Hal ini diduga adanya pengaruh tekanan darah dan konsumsi obat antihipertensi yang berpotensi mempengaruhi kadar TGF-β1 urin. Oleh karena itu, dapat disimpulkan bahwa kadar TGF-β1 urin dengan nilai UACR tidak terdapat hubungan yang signifikan pada pasien DM tipe 2.

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Diabetic nephropathy is one of type 2 DM complication that can be detected by UACR (Urine Albumin Creatinine Ratio) as a marker for albuminuria condition. Urinary transforming growth factor β1 (TGF-β1) is a growth factor related to pathology of kidney disease in nepropathy diabetic. The aim of the present study was to know the correlation between TGF-β1 and UACR in type 2 DM patients. Design study was using cross sectional with consecutive sampling method. The study was performed in 99 subjects (62 DM normolbuminuria patients, 27 DM albuminuria patients, and 10 non DM subject as controls) at Pasar Minggu Community Health Center. Urinary TGF-β1 level was measured by ELISA, and UACR was measured in clinical laboratory. The result of mean difference test showed that urinary TGF-β1 level (p = 0,790) difference were not present in three group samples. Analysis correlation urinary TGF-β1 level and UACR in DM normoalbuminuria and albuminuria groups did not show correlation (r = -0,079; p = 0,462), and the result might influenced by blood pressure and received antihypertention medication that potent to reduce urinary TGF-β1 level. In conclusion, urinary TGF-β1 level and UACR did not have significant correlation in type 2 DM patients."

"Hiperglikemia pada pasien diabetes melitus dapat menyebabkan kerusakan selular dan komplikasi. Salah satu komplikasi yang muncul yaitu pada jaringan mikrovaskular dan menyebabkan nefropati diabetik. Nefropati diabetik secara klinis diawali dengan kondisi albuminuria. Selain albuminuria, produksi spesies oksigen reaktif ROS berlebihan melalui NADPH oksidase juga merupakan salah satu patogenesis dari nefropati diabetik. Penelitian ini bertujuan untuk menganalisis aktivitas NADPH Oksidase yang diukur melalui rasio NADP /NADPH serum, dan hubungannya terhadap rasio albumin kreatinin urin. Penelitian dilakukan dengan studi cross sectional dan menggunakan teknik consecutive sampling. Populasi sampel pada penelitian ini adalah 89 orang pasien diabetes melitus tipe 2 usia 39-75 tahun di Puskesmas Kecamatan Pasar Minggu. Sampel penelitian dibagi menjadi 3 kelompok, yaitu kelompok subjek non DM sebagai kontrol n=10 , kelompok normoalbuminuria n=62 dan kelompok albuminuria n=27 . Rasio NADP /NADPH serum dan konsentrasi kreatinin urin diukur menggunakan metode kolorimetri, sedangkan albumin urin diukur dengan metode immunoturbidimetri. Hasil uji beda rata-rata menunjukkan terdapat perbedaan rasio NADP /NADPH serum pada ketiga kelompok.

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Hyperglycemic condition on diabetes mellitus patient can cause a cellular injury and complication. One of those was microvascular complication which lead to diabetic nephropathy. Diabeteic nephropathy defined by proteinuria that preceded by lower degrees of proteinuria or albuminuria condition. Reactive oxygen species derived from NADPH Oxidase also play an important roles in the pathogenesis of diabetic nephropathy. Our study aimed to analyzed the activity of NADPH Oxidase by measuing the NADP NADPH serum ratio, and to find out if there any correlation with the normoalbuminuria and albuminuria condition.

Consecutive method is used in this cross sectional study. Population of this study are 89 type 2 diabetes mellitus patient from ages 39 75 years at Pasar Minggu Community Health Center and 10 non diabetes volunteers served as control. For this purpose we divided the samples into three groups,a group of 10 healthy volunteers, normoalbuminuria group n 62 and and albuminuria group n 27. NADP NADPH serum ratio was analyzed by colorimetric method. Urine albumin creatinine ratio was measured by immunoturbidimetri and enzymatic colorimetric. The NADP NADPH serum ratio and urine albumin creatinine ratio were lower in control subject than in type 2 diabetes melitus patient."

"ABSTRAKHipospadia merupakan salah satu kelainan genitalia paling umum yang ditemukan pada bayi lelaki baru lahir, yang ditandai adanya meatus uretra di ventral dan bentuk abnormal dari kulup penis. Etiologi hipospadia sebagian besar masih belum diketahui, tetapi dilaporkan dipengaruhi oleh faktor genetik dan lingkungan. Salah satu kelainan genetik adalah defek gen steroid 5 alpha-reductase type 2 (SRD5A2). Belum banyak laporan mengenai faktor genetik pada gen SRD5A2 yang melatarbelakangi hipospadia di Indonesia. Teknik PCR-sekuens dilakukan pada ekson 1-5 gen SRD5A2 pada 40 sampel DNA arsip penyandang hipospadia, dan PCR-RFLP pada ekson 1 dan 4 untuk mendeteksi mutasi p.Val89Leu dan p.Arg227Glu. Hasil penelitian mendapatkan 8 mutasi pada gen SRD5A2, yaitu mutasi p.Gly34Fs, p.Arg50His, p.Val89Leu 3 di ekson 1, p.Tyr128Cys di ekson 2, p.Asn193Ser dan p.Arg227Gln di ekson 4, p.Ile253Val di ekson 5, dan c.281+15T>C di intron 1. Studi in silico untuk memprediksi fungsi dan struktur protein adalah possibly dan/atau probably damaging untuk p.Gly34Fs, p.Arg50His, p.Tyr128Cys, p.Asn193Ser, dan p.Arg227Gln, dan benign untuk p.Val89Leu, Ile253Val, dan c.281+15T>C. Mutasi p.Arg50His dan p.Ile253Val merupakan mutasi baru yang belum pernah dilaporkan di populasi lain. Penelitian ini mendapatkan 8 mutasi pada penyandang hipospadia di Indonesia dan 2 diantaranya merupakan mutasi baru. Selain itu penelitian ini berhasil mengembangkan teknik PCR-RFLP untuk mendeteksi substitusi p.Val89Leu dan p.Arg227Glu. Teknik tersebut dapat diterapkan untuk

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ABSTRACT

Hypospadias is one of the most common external genitalia congenital abnormalities found in newborn baby boys, which is characterized by urethral opening, penile curvature, and abnormal distribution of the penis foreskin. The etiology of hypospadia is mostly unknown, but it is believed that hypospadias are caused by genetic and environmental factors. There have not been many reports on variations of steroid 5 alpha-reductase type 2 (SRD5A2) gene underlying hypospadias in Indonesia. The PCR-sequencing technique on exon 1-5 SRD5A2 gene were performed on 40 archived DNA samples from hypospadias cases of aged 0-29 years, and PCR-RFLP on exon 1 and 4 to detect mutation p.Val89Leu and p.Arg227Glu. The sequencing result showed that there were eight different mutations identified in the SRD5A2 gene, p.Gly34Fs, p.Arg50His, p.Val89Leu 3 in exon 1, p.Tyr128Cys in exon 2, p.Asn193Ser dan p.Arg227Gln in exon 4, p.Val89Leu in exon 5, and c.281+15T>C in intron 1. In silico analysis showed 5 mutations predicted to be possibly and/or probably damaging (p.Gly34Fs, p.Arg50His, p.Tyr128Cys, p.Asn193Ser, and p.Arg227Gln) and 3 benign mutations (p.Val89Leu, Ile253Val, and c.281+15T>C). p.Arg50His and p.Ile253Val are new mutations that have never been reported before. This study found 8 mutations obtained from hypospadias patients and successfully developed the PCR-RFLP technique to detect p.Val89Leu and p.Arg227Gln mutations, which can be applied as a starting point for mutation detection in places where the mutations frequently detected and access to sequencing technique is limited."

"Defisiensi enzim 6-pyruvoyl tetrahydropterin synthase PTPS menyebabkan terjadinya hambatan dalam proses biosintesis tetrahydrobiopterin BH4 yang merupakan kofaktor berbagai jenis enzim, termasuk phenylalanine hydroxylase PAH. Enzim PAH tidak dapat diaktivasi tanpa adanya senyawa BH4, sehingga menyebabkan timbulnya penyakit langka yang disebut dengan hyperphenylalaninemia HPA. Penelitian ini dilakukan untuk menganalisis mutasi yang terjadi pada ekson 2 dan 5--6 gen PTS di Indonesia. Analisis mutasi dilakukan pada 3 penderita defisiensi enzim PTPS dan 50 individu normal asal Indonesia. Tahapan analisis mutasi pada penelitian ini diawali dengan melakukan desain primer spesifik dan penentuan suhu annealing optimal dengan menggunakan PCR gradien. Sequencing kemudian dilakukan dengan metode automated Sanger sequencing yang dilanjutkan dengan analisis hasil sequencing untuk mengetahui mutasi yang terdapat pada ekson 2 dan 5--6 gen PTS di Indonesia. Hasil yang didapatkan pada penelitian ini yaitu, tiga mutasi novel pada ekson 2 yaitu c.123G>A, c.127T>G, serta c.155A>T, serta tidak ditemukan mutasi pada ekson 5--6.

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Deficiency of 6 pyruvoyl tetrahydropterin synthase PTPS enzyme can interrupt biosynthesis of tetrahydrobiopterin BH4 , which is a cofactor of various enzymes, including phenylalanine hydroxylase PAH. The PAH enzyme can not be activated in the absence of BH4 compounds, leading to the occurrence of a rare disease called hyperphenylalaninemia HPA. This study was conducted to analyze the mutations that occurred in exon 2 and 5 6 of the PTS gene in Indonesia. The mutation analysis was performed on 3 patients with PTPS enzyme deficiency and 50 normal individuals from Indonesia.

Stages of mutation analysis in this study is began by performing specific primer design and optimal annealing temperature determination using PCR gradient. Sequencing is then performed by automated Sanger sequencing method followed by sequencing analysis to find out the mutations found in exon 2 and 5 6 of the PTS gene in Indonesia. The results obtained in this study are three novel mutations in exon 2 which are c.123G A, c.127T G, and c.155A T, and no mutations found in exon 5 6."

"Disfungsi ginjal adalah salah satu komplikasi kronik pada pasien diabetes melitus tipe 2 DM tipe 2 yang diketahui sebagai nefropati diabetik. Salah satu penanda yang digunakan sebagai pendeteksi kerusakan ginjal adalah rasio albumin kreatinin UACR. Selain UACR, kolagen tipe IV banyak diteliti terkait fungsinya sebagai pendeteksi awal nefropati diabetik. Tujuan penelitian ini adalah untuk menilai perbedaan UACR, kadar kolagen tipe IV urin, serta mengetahui hubungan keduanya pada pasien yang menerima terapi angiotensin-converting enzyme inhibitors ACEI dan angiotensin receptor blockers ARB sebagai kelas yang menghambat perkembangan nefropati diabetik pada pasien DM tipe 2. Penelitian dilakukan dengan menggunakan studi cross sectional dan teknik pengambilan consecutive sampling. Terdapat dua kelompok dalam penelitian ini, pasien dengan terapi ACEI n = 14 dan ARB n = 26. Kolagen tipe IV urin dianalisis dengan menggunakan ELISA kit. Albumin dan kreatinin urin diukur dengan menggunakan metode imunoturbidimetri dan kolorimetri. Kadar kolagen tipe IV urin dihitung dengan normalisasi pengukuran kolagen tipe IV urin dengan kadar kreatinin urin. Pada nilai UACR, rerata kedua kelompok ACEI = 276,61 65,119 g/mg kreatinin urin; ARB = 87,25 24,743 g/mg kreatinin urin menunjukkan perbedaan bermakna p = 0,019, kedua kelompok ACEI = 117,14 37,36 ng/mg kreatinin urin; ARB = 14,19 1,46 ng/mg kreatinin urin juga menunjukkan perbedaan bermakna pada kadar kolagen tipe IV urin p < 0,001. Uji korelasi antara nilai UACR dan kadar kolagen tipe IV urin menunjukkan hubungan moderat pada kedua kelompok penelitian r = 0,489; p = 0,001. Hasil menunjukkan bahwa kelompok ARB memiliki tingkat kolagen tipe IV urin yang lebih rendah dibandingkan dengan ACEI, sehingga terapi dengan ARB kemungkinan dapat menghambat perkembangan nefropati diabetik.

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Renal dysfunction is one of chronic complications in type 2 diabetes mellitus patients T2DM known as diabetic nephropathy DN. Urine albumin creatinine ratio UACR is a widely used test for detection of DN. Beside of UACR, type IV collagen has been studied to its function as an early detection of DN. The aim of this study was to compare differences in UACR, urinary type IV collagen, and their correlation in patients with angiotensin converting enzyme inhibitors ACEI versus angiotensin receptor blockers ARB treatment as classes with respect to delay the development of DN in patients with type 2 diabetes by using cross sectional study and consecutive sampling method. There were 2 groups in this study, patients with ACEI n 14 and ARB therapy n 26. Urinary type IV collagen were analyzed using ELISA kit. Urine albumine and urine creatinine was measured by using immunoturbidimetry and colorimetric method. Urinary type IV collagen levels were calculated by normalizing type iv collagen with urine creatinine levels. Results showed that UACR ACEI 276,61 65,119 g mg urine creatinine ARB 87,25 24,743 g mg urine creatinine showed significant differences p 0.019, urinary type IV collagen ACEI 117,14 37,36 ng mg urine creatinine ARB 14,19 1,46 ng mg urine creatinine showed significant differences p 0.001. Correlation between UACR and urinary type IV collagen presented a moderate correlation in both studied groups r 0.489 p 0.001. The results showed that group with ARB treatment have lower level of urinary type IV collagen compared to groups with ACEI treatment, conclude that ARB more likely to inhibit the development of DN."

"The rapid advances in medicine over the last 50 years have totally changed the outlook for children with disorders of sex development (DSD), but there is still much to learn. This book crystallizes the combined experience of a leading dedicated unit over 25 years in delivering expert medical and surgical care to children with DSD in a holistic environment. It documents the most recent advances in the molecular biology and embryology of sex development, and describes each disorder in detail. The clinical presentation and approach to diagnosis are described both for babies and for children presenting later in childhood or at adolescence. The chapters on management highlight all the latest knowledge and include the shared wisdom of the authors on current controversies, such as the timing of surgical treatment. Finally, the authors describe their short-, medium-, and long-term outcomes, which demonstrate the strengths of holistic team management."

"Human milk oligosaccharides (HMO) adalah karbohidrat yang terdiri dari 3–10 monosakarida dan tidak dapat dicerna oleh manusia. Fungsi HMO adalah prebiotik untuk mikrobiota usus. Metabolit yang dihasilkan mikrobiota adalah asam lemak rantai pendek (short chain fatty acid/SCFA). Sintesis HMO ditentukan oleh enzim fukosiltransferase 2 (FUT2) dan fukosiltransferase 3 (FUT3), yang disandi gen FUT2 dan FUT3. Polimorfisme gen FUT2 menyebabkan perbedaan HMO pada ASI. Ibu dengan kadar 2’fukosillaktosa (2’FL) ≥ 50 mg/L disebut ibu sekretor. Proporsi ibu sekretor bervariasi, karena polimorfisme gen FUT2 berbeda antar ras. Proporsi sekretor di Eropa > 80%, namun belum ada data di Indonesia. Penelitian ini bertujuan menganalisis proporsi sekretor dan polimorfisme gen FUT2, serta profil SCFA berdasarkan pasangan genotipe ibu-bayi. Penelitian menggunakan desain potong lintang, dilakukan di RSIA Bunda selama bulan Desember 2021–Juli 2022. Subjek penelitian adalah ibu berusia minimal 18 tahun, menyusui eksklusif, dan sehat. Ibu dengan ras Kaukasia di atas 2 generasi dieksklusi. Bayi dari ibu yang memenuhi kriteria inklusi automatis menjadi subjek penelitian dan dieksklusi bila bayi pernah mendapat antibiotik. Pemeriksaan HMO dilakukan saat bayi berusia 2–5 minggu, sedangkan SCFA feses bayi saat usia 4 minggu. Sekuensing coding region FUT2 dilakukan pada ibu dan bayi. Sebanyak 120 pasangan ibu-bayi memenuhi kriteria inklusi dengan proporsi ibu fenotipe sekretor 65,8% dan genotipe sekretor 65,8%. Hubungan antara genotipe FUT2 dan kadar 2’FL bermakna. Penelitian ini menemukan varian baru c.851C>G yang bersifat merusak berdasarkan prediksi in silico. Berdasarkan genotipe FUT2, diusulkan nilai ambang baru 2’FL 425,9 mg/L dengan nilai sensitivitas 98,7% dan spesifisitas 100%. Tidak terdapat hubungan antara proporsi relatif asetat, propionat, butirat dan genotipe ibu, genotipe bayi, maupun pasangan genotipe ibu-bayi.

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Human milk oligosaccharides (HMO) are complex carbohydrates consisting of 3–10 monosaccharides which is undigestible to human. HMO acts as a prebiotic for gut microbiota, which produce short chain fatty acid (SCFA). The synthesis of HMO is determined by the activity of fucosyltransferase 2 (FUT2) and fucosyltransferase 3 (FUT3) enzymes, which are encoded by the FUT2 and FUT3 genes. Polymorphisms of the FUT2 gene result in different secretor status. Mothers with 2'-fucosyllactose (2'FL) level of ≥ 50 mg/L are referred to as secretor. The proportion of secretor varies worldwide due to FUT2 polymorphisms among races. The proportion of secretor in Europe is generally > 80%, but there is no data on secretor status in Indonesia. Thus, baseline data about secretor phenotype and genotype status in Indonesia is needed. This study aimed to analyze the proportion of secretor and FUT2 gene polymorphism in Indonesia, as well as the stool SCFA profile based on the mother-infant dyad genotype.

This was a cross-sectional study conducted at Bunda Mother and Child Hospital from December 2021 to July 2022. The study subjects were healthy mothers aged at least 18 years, exclusively breastfeeding. Mothers with Caucasion ancestor from two generations above were excluded. Infants from eligible mothers were automatically included as study subjects but excluded if they had history of antibiotic administration. Breastmilk samples were obtained at infant’s age 2–5 weeks old, while infant’s stool at 4 weeks old. Sequencing of the entire coding region of FUT2 was performed for mothers and infants.

A total of 120 mother-infant dyads met the eligibility criteria. The proportion of secretor mother was 65.8%. Secretor genotypes were found in 65.8% of mothers. There was a significant association between secretor genotype and 2’FL level. A novel variant was identified, c.851C>G, which showed deleterious effect based on in silico analysis. A new threshold value of 425.9 mg/L for 2'FL is proposed, with 98.7% sensitivity and 100% specificity. There was no significant relationship between the relative proportion of acetate, propionate, butyrate, and valerate among the mother-infant’s genotype dyads."