Perawatan Gigitan Terbuka Anteroposterior Tipe Skeletal dengan Teknik Straightwire

Gigitan terbuka merupakan maloklusi yang bercirikan tidak terdapatnya tutup menutup gigi rahang atas dan bawah, dapat terjadi pada regio anterior maupun posterior dan dapat melibatkan dental maupun skeletal. Maloklusi ini memerlukan ketelitian dalam penentuan diagnosis dan perawatan untuk mendapatkan hasil perawatan yang baik dan kestabilan jangka panjang. Tujuan penulisan studi kasus ini adalah untuk menginformasikan manajemen pasien dengan gigitan terbuka tipe skeletal. Pasien pria berumur 19 tahun datang ke Klinik Ortodonsia FKG UGM dengan keluhan utama gigi depan yang tidak rata dan tidak dapat digunakan untuk menggigit. Pemeriksaan klinis menunjukkan pasien memiliki kebiasaan menelan dengan menjulurkan lidah. Pemeriksaan model studi menunjukkan maloklusi Angle kelas I dengan gigitan terbuka anterior dari regio premolar kedua kanan ke kiri sebesar 10,7 mm disertai malposisi gigi individual dan pergeseran garis tengah rahang bawah ke kiri. Pemeriksaan sefalometri menunjukkan relasi skeletal kelas II dengan retrusif bimaksila, rotasi mandibula searah jarum jam dan gigitan terbuka skeletal. Pasien menolak tindakan bedah ortognatik sehingga dilakukan perawatan ortodontik kamuflase. Perawatan diawali dengan latihan miofungsional untuk melatih cara penelanan yang benar dilanjutkan dengan perawatan ortodontik teknik straightwire dengan pencabutan empat gigi molar pertama. Penutupan gigitan terbuka menggunakan elastic box anterior. Hasil evaluasi menunjukkanpengurangan besar gigitan terbuka dari 10,7 mm menjadi 1,25 mm. Kesimpulannya elastic box anterior dapat digunakan untuk mengoreksi gigitan terbuka yang etiologinya melibatkan intrusi gigi anterior. Skeletal Anteroposterior Open Bite Treatment with Straight Wire Technique. Open bite is a malocclusion with characteristic no overlapping between maxillar and mandibular teeth. This malocclusion may occur in anterior or posterior region and involved dental or skeletal. This malocclusion needed precise diagnosis and treatment to get a good treatment result and long term stability. The aim of this case report was to inform management of patient with skeletal open bite. A 19 years old male came to orthodontic clinic Faculty of Dentistry Gadjah Mada University with the chief complaint anterior crowding, and anterior teeth cannot be used to bite. Clinical finding showed patient had tongue thrusting habit. Study model analysis showed class I Angle malocclusion with 10.7 mm anterior open bite from right second premolar to left second premolar, with individual teeth malposition and mandibular midline shifting to the left. Cephalometric finding showed class II skeletal relationship with bimaxillar retrusive, clockwise mandibular rotation and skeletal open bite. This patient refused orthognatic surgery, so he received camouflage orthodontic treatment. This treatment was started with monofunctional exercise to correct the swallowing action then continued with straight wire orthodontic treatment with four first molar extractions. Anterior box elastic was used to close the bite. Evaluation result showed open bite was decreased from 10.7 mm to 1.25 mm. The conclusion was anterior box elastic could be used in open bite correction that involved anterior teeth intrusion as an etiology

ATAMM enhancement and multiprocessor performance evaluation

ATAMM (Algorithm To Architecture Mapping Model) enhancement and multiprocessor performance evaluation is discussed. The following topics are included: the ATAMM model; ATAMM enhancement; ADM (Advanced Development Model) implementation of ATAMM; and ATAMM support tools

Long-term Outcome of Round Window Vibrant SoundBridge Implantation in Extensive Ossicular Chain Defects

To evaluate retrospectively the long-term safety and efficacy of the first 50 patients, all suffering from severe ossicular chain defects and with moderate to severe mixed hearing loss, who received the Vibrant SoundBridge with the floating mass transducer located on the round window membrane. To evaluate differences in outcome versus etiology and age of the patient population. Patients eligible for implantation of the floating mass transducer on the round window membrane ranged in age from 2 months to 74 years with a moderate to severe conductive or mixed hearing loss from different etiologies. For each adult patient, preoperative versus postoperative bone and air conduction thresholds, air-bone gaps, and speech understanding scores were evaluated at 24-month follow-up. At 60-month follow-up, data were available from 33 patients. Preoperative and postoperative freefield auditory brainstem responses were studied in infants and children. Intraoperative and short- and long-term postoperative complications are presented. There were significant improvements in speech perception and pure-tone audiometry in adults and auditory brainstem response thresholds in infants immediately after surgery and at follow-up examinations (12 to 71 months). No significant complications or device extrusions were observed in the present series. Infants, children, and adults with moderate to severe conductive or mixed hearing loss obtained substantial benefit from implantation of the floating mass transducer on the round window membrane regardless of the etiology of hearing loss and previous surgery

UJI DIAGNOSTIK KRITERIA AMSEL DIBANDINGKAN DENGAN KRITERIA NUGENT DALAM SKRINING INFEKSI BAKTERIAL VAGINOSIS PADA KEHAMILAN

Latar Belakang: Diagnosis dini infeksi bakterial vaginosis (BV) pada ibu hamil menjadi sangat penting untuk dilakukan mengingat komplikasi yang sangat berbahaya bagi kesehatan ibu dan janin. Saat ini ada dua metode pemeriksaan infeksi bakterial vaginosis yang sering digunakan dalam praktik klinik yaitu Kriteria Amsel dan Kriteria Nugent. Penelitian ini dilakukan untuk membandingkan kemampuan diagnostik kriteria Amsel dengan kriteria Nugent sebagai metode skrining. Metode: Dua puluh dua ibu hamil yang datang ke klinik ibu dan anak di Rumah Sakit RSUP Dr. Kariadi, Puskesmas Halmahera dan Puskesmas Ngesrep Semarang menjadi populasi dalam penelitian ini. Diagnosis infeksi bakterial vaginosis dilakukan dengan kriteria Amsel dan Kriteria Nugent. Nilai duga positif, nilai duga negatif, sensitivitas, dan spesifisitas didapatkan dengan membandingkan kriteria Amsel dengan kriteria Nugent sebagai baku emas. Hasil : Prevalensi infeksi bakterial vaginosis pada populasi 54,54%. Sebagai perbandingan, kriteria Amsel mempunyai sensitivitas 78,57%, spesifisitas 87,50%, PPV 91,67%, dan NPV 70%. Kesimpulan: Kriteria Amsel merupakan metode pemeriksaan paling mudah dan murah yang dapat dilakukan oleh klinisi, namun pemeriksaan ini belum reliabel. Diperlukan studi lebih lanjut mengenai parameter klinis dan mikrobiologi untuk membuat kriteria ini menjadi lebih sensitif sementara tetap mempertahankan spesifisitasnya. Kata Kunci : Kriteria Nugent, Kriteria Amsel, Bakterial vaginosi

Nicotinamide Phosphoribosyltransferase (NAMPT) as a Therapeutic Target in BRAF-Mutated Metastatic Melanoma

Background: One of the effects of oncogenic signaling is metabolic reprogramming of tumor cells to support anabolic growth, opening the way to therapeutic targeting of metabolic pathways. Methods: We studied NAD biosynthesis in BRAF inhibitor (BRAFi)-resistant (BiR) melanoma cell lines. Data in cell lines were confirmed by immunohistochemistry in biopsies from 17 patients with metastatic melanoma (MM) before and after the acquisition of resistance to BRAFi. Therapeutic potential of NAD biosynthesis inhibitors was determined by in vitro monitoring cell growth and death and in mouse xenograft models. Mice (n=6-10 mice/group) were treated with nicotinamide phosphoribosyltranferase inhibitor (NAMPTi), BRAFi, or their combination, and tumor growth and survival were analyzed. All statistical tests were two-sided. Results: BiR cells had higher NAD levels compared with their BRAFi-sensitive counterparts (P < .001 and P = .001 for M14 and A375, respectively) and with normal melanocytes (P<.001), achieved through transcriptional upregulation of the enzyme NAMPT, which became the master regulator of NAD synthesis. Conversely, treatment with BRAFi or MEK inhibitors decreased NAMPT expression and cellular NAD levels. Robust NAMPT upregulation was documented in tissue biopsies from MM patients after development of resistance to BRAFi (P < .001). Treatment of melanoma cells with NAMPTi depleted NAD and ATP, depolarized mitochondrial membrane, and led to reactive oxygen species production, blocking cells in the G2/M phase and inducing apoptosis. Treatment of BiR xenografts with NAMPTi improved mouse survival (median survival of vehicletreated mice was 52 days vs 100 days for NAMPTi-treated ones in M14/BiR, while in A375/BiR median survival of vehicletreated mice was 23.5 days vs 43 days for NAMPTi-treated ones, P < .001). Conclusions: BiR melanoma cells overexpress NAMPT, which acts as a connecting element between BRAF oncogenic signaling and metabolism, becoming an actionable target for this subset of MM patients

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

Timing of sentinel node biopsy independently predicts disease-free and overall survival in clinical stage I-II melanoma patients: A multicentre study of the Italian Melanoma Intergroup (IMI)

Background: Sentinel lymph node biopsy (SNB) still remains a key procedure to appropriately stage melanoma patients and to select those who are candidate to novel treatments with immunotherapy and targeted therapy in the adjuvant setting. The impact of timing of SNB on disease-free survival (DFS) and overall survival (OS) is still unclear. Material and methods: The study was conducted at 6 Italian Melanoma Intergroup (IMI) centres and included 8953 consecutive clinical stage I-II melanoma patients who were diagnosed, treated, and followed up between November 1997 and March 2018. All patients were prospectively included in dedicated IMI database. Multivariable Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to DFS and OS. Results: Considering the whole population, at multivariable analysis, after adjusting for age, gender, Breslow thickness, site, ulceration, and the SNB status, a delay in the timing of SNB was associated with a better DFS (adjusted hazard ratio [aHR, delayed versus early SNB] 0.98, 95% confidence interval [CI] 0.97\u20130.99, p < 0.001) and OS (aHR 0.98, 95% CI 0.97\u20130.99, p = 0.001). Specifically, in patients with a negative SNB status, a beneficial impact of delayed SNB (i.e. at least 32 days after primary excision) was confirmed for DFS (aHR 0.70, 95%CI 0.63\u20130.79, p < 0.001) and OS (aHR 0.69, 95%CI 0.61\u20130.78, p < 0.001), whereas in those with a positive SNB status, DFS (aHR 0.96, 95%CI 0.84\u20131.09, p = 0.534) and OS (aHR 0.94 95%CI 0.81\u20131.08, p = 0.374) were not significantly different in patients with early or delayed SNB. Conclusions: Our study does not support a strict time interval for SNB. These results may be useful for national guidelines, for counselling patients and reducing the number of high urgency referrals

Adjuvant nivolumab for stage III/IV melanoma: Evaluation of safety outcomes and association with recurrence-free survival

Background Several therapeutic options are now available in the adjuvant melanoma setting, mandating an understanding of their benefit €'risk profiles in order to make informed treatment decisions. Herein we characterize adjuvant nivolumab select (immune-related) treatment-related adverse events (TRAEs) and evaluate possible associations between safety and recurrence-free survival (RFS) in the phase III CheckMate 238 trial. Methods Patients with resected stage IIIB-C or IV melanoma received nivolumab 3 mg/kg every 2 weeks (n=452) or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n=453) for up to 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. First-occurrence and all-occurrence select TRAEs were analyzed within discrete time intervals: from 0 to 3 months of treatment, from &gt;3-12 months of treatment, and from the last dose (regardless of early or per-protocol treatment discontinuation) to 100 days after the last dose. Possible associations between select TRAEs and RFS were investigated post randomization in 3-month landmark analyses and in Cox model analyses (including a time-varying covariate of select TRAE), within and between treatment groups. Results From the first nivolumab dose to 100 days after the last dose, first-occurrence select TRAEs were reported in 67.7% (306/452) of patients. First-occurrence select TRAEs were reported most frequently from 0 to 3 months (48.0%), during which the most common were pruritus (15.5%) and diarrhea (15.3%). Most select TRAEs resolved within 6 months. There was no clear association between the occurrence (or not) of select TRAEs and RFS by landmark analysis or by Cox model analysis within treatment arms or comparing nivolumab to the ipilimumab comparator arm. Conclusion Results of this safety analysis of nivolumab in adjuvant melanoma were consistent with its established safety profile. In the discrete time intervals evaluated, most first-occurrence TRAEs occurred early during treatment and resolved. No association between RFS and select TRAEs was evident. Trial registration number NCT02388906

Health-related quality of life impact of cobimetinib in combination with vemurafenib in patients with advanced or metastatic BRAFV600 mutation-positive melanoma

Background: In the coBRIM study, cobimetinib plus vemurafenib (C+V) significantly improved survival outcomes vs placebo and vemurafenib (P+V) in patients with advanced/metastatic BRAF(V600)-mutated melanoma. An analysis of health-related quality of life (HRQOL) from coBRIM is reported.Methods: Patients completing the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline and &gt;= 1 time point thereafter constituted the analysis population. Change from baseline &gt;= 10 points was considered clinically meaningful.Results: Mean baseline scores for all QLQ-C30 domains were similar between arms. Most on-treatment scores for QLQ-C30 domains were also comparable between arms. A transient deterioration in role function in cycle 1 day 15 (C1D15; -14.7 points) in the P+V arm and improvement in insomnia in the C+V arm at C2D15 (-12.4 points) was observed. Among patients who experienced a &gt;= 10-point change from baseline (responders), between-group differences were greatest for insomnia (16%), social functioning (10%), fatigue (9%) and pain (7%), all favouring C+V. Diarrhoea, photosensitivity reaction, pyrexia, and rash did not meaningfully affect global health status (GHS). Serous retinopathy was associated with a transient decrease in GHS at C1D15 assessment.Conclusions: In patients with advanced/metastatic BRAFV600-mutated melanoma, treatment with C+V maintained HRQOL compared with P+V, with superior efficacy