Hubungan Asupan Protein, Seng, Zat Besi, Dan Riwayat Penyakit Infeksi Dengan Z-score Tb/u Pada Balita

Latar Belakang : Masalah gizi yang paling banyak ditemukan pada anak di Indonesia adalah stunting, Indikator untuk menilai stunting berdasarkan pada Indeks Tinggi Badan menurut Umur (TB/U) dengan ambang batas (Z-score) <-2 Standart Deviasi (SD). Several micronutrients are required for adequate growth among children. However, it has been unclear as to which nutrient deficiencies contribute most often to growth faltering in populations at risk for poor nutrition and poor growth. Inadequate intakes of dietary energy and protein and frequent infections are well-known causes of growth retardation (3–5). However, the role of specific micronutrient deficiencies in the etiology of growth retardation has gained attention more recently (6–8). Tujuan : Mengetahui hubungan antara asupan protein, seng, zat besi, dan penyakit infeksi terhadap indeks z-score TB/U pada Balita usia 24-59 bulan.Metode : Penelitian observasional dengan pendekatan cross sectional di Kelurahan Jangli Semarang, jumlah sampel 61 Balita usia 24-59 bulan, dipilih dengan simple random sampling. Data yang dikumpulkan meliputi: identitas sampel, berat badan, tinggi badan, riwayat asupan makan, dan riwayat penyakit infeksi. Berat badan diukur menggunakan timbangan digital dan tinggi badan diukur menggunakan microtoise. Asupan protein, seng, zat besi, dan riwayat penyakit infeksi diperoleh dari food frequency questionairre semi-kuantitatif. Data dianalisis dengan uji analisis depskripsi, analisis bivariate menggunakan uji Chi Square, Pearson, dan Spearman.Hasil : Sebanyak 36,1 subjek mengalami stunting. Rerata z-score TB/U -1,25 ± 1,2. Rerata asupan protein, seng, dan zat besi subjek berturut-turut 34.8 ± 13 g, 5.2 ± 2.5 mg, 8.2 ± 6.5 mg dengan sebagian besar tingkat kecukupan protein, seng, dan zat besi subjek adalah cukup. Sebanyak 29.1% subjek memiliki riwayat infeksi. Terdapat hubungan antara protein dan penyakit infeksi dengan z-score TB/U pada Balita. Tidak terdapat hubungan antara asupan seng, dan zat besi dengan z-score TB/U pada Balita. Simpulan : Terdapat hubungan antara asupan protein dan riwayat penyakit infeksi terhadap indeks z-score TB/U pada Balita

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Generating and screening haploid transposon mutant libraries.

<p><b>A.</b> The piggyBac transposon used for mutagenesis. The transposon cargo contains splice acceptors that disrupt transcription, but gene trapping is not directly selected for. PuroΔTK, is a positive-negative selection marker: puromycin can be used to select for integrations, and FIAU to select for loss of the transposon <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061520#pone.0061520-Chen1" target="_blank">[30]</a>. <b>B.</b> Outline of the mutagenesis and screening process. A detailed protocol is provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061520#pone.0061520.s002" target="_blank">Protocol S1</a>. <b>C.</b> The mutant pool remains predominantly haploid, as shown by propidium iodide staining of fixed cells from library H3L1. <b>D.</b> Determining drug concentration for screening. Olaparib was used at a concentration that kills >2.5×10⁵ wild type haploid cells (4 µM). <b>E.</b> Scheme for further analysis of clones of interest by transposon reversion.</p

Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells.

We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 mutant clones. Random barcode sequences were inserted into the transposon vector to allow the number of cells bearing each insertion to be measured by amplifying and sequencing the barcodes. These barcodes were associated with their integration sites by inverse PCR. We exposed these libraries to commonly used cancer drugs and profiled changes in barcode abundance by Ion Torrent sequencing in order to identify mutations that conferred sensitivity. Drugs tested included conventional chemotherapeutics as well as targeted inhibitors of topoisomerases, poly(ADP-ribose) polymerase (PARP), Hsp90 and WEE1

Reversion analysis of <i>Parp1</i> mutants.

<p><b>A.</b> Schemes used for isolation of revertants from the D5 (intron one) <i>Parp1</i> mutant ES cells. <b>B.</b> Three FIAU-resistant clones isolated after transfection of clone D5 with PB transposase (Rev1–3, grey and black) have regained sensitivity to olaparib similar to wild type cells (green). <i>Brca2</i>-deficient ES cells <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061520#pone.0061520-Farmer1" target="_blank">[8]</a>, which are sensitive to PARP inhibition, are shown for comparison. Error bars show SEM, <i>n = </i>5. ***, <i>P</i><0.001; comparison shown for D5Rev1 and <i>Parp1</i> mutant. <b>C.</b> Dose response curve for BMN 673 for three clones isolated using the G418 selection scheme. <i>n = 5</i>; ***, <i>P</i><0.001; comparison shown for G418 R2 and <i>Parp1</i> mutant. <b>D.</b> The G418 resistant clone that remains PARP inhibitor resistant (clone R1) is still a <i>Parp1</i> mutant. Lysates from the indicated cells were probed with anti-PARP followed by anti-β-tubulin. <b>E.</b> Clone G418 R1 still contains the original <i>Parp1</i> insertion. DNA from the indicated cells (same order as above) was analysed for the presence of the transposon-genome junction by PCR using the primers shown in <b>A</b>. <b>F.</b> Most clones isolated from the screen have a diploid DNA content. Three out of nine tested had a mixture of haploid and diploid cells similar to D2 (top, this clone also has the intron 1 <i>Parp1</i> insertion); all others were fully diploid including clone D5 (bottom).</p