A multi-center comparison of surgical techniques for corpus Callosotomy in pediatric drug-resistant epilepsy.

OBJECTIVES: Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug-resistant epilepsy (DRE). The invasive nature of the procedure contributes to underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi-institutional epilepsy surgery database to characterize the use of CC across participating centers. METHODS: Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0-18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically. RESULTS: Eighty-three patients undergoing 85 CC procedures at 14 participating epilepsy centers met inclusion criteria. Mean age at seizure onset was 2.3 years (0-9.4); mean age for Phase I evaluation and surgical intervention were 9.45 (.1-20) and 10.46 (.2-20.6) years, respectively. Generalized seizure types were the most common (59%). Complete CC was performed in 88%. The majority of CC procedures (57%) were via open craniotomy, followed by laser interstitial thermal therapy (LiTT) (20%) and mini-craniotomy/endoscopic (mc/e) (22%). Mean operative times were significantly longer for LiTT, whereas mean estimated blood loss was greater in open cases. Complications occurred in 11 cases (13%) and differed significantly between surgical techniques (p < .001). There was no statistically significant difference in length of postoperative stay across approaches. Mean follow-up was 12.8 months (range 1-39). Favorable Engel outcomes were experienced by 37 (78.7%) of the patients who underwent craniotomy, 10 (58.8%) with LiTT, and 12 (63.2%) with mc/e; these differences were not statistically significant. SIGNIFICANCE: CC is an effective surgical modality for children with DRE. Regardless of surgical modality, complication rates are acceptable and seizure outcomes generally favorable. Newer, less-invasive, surgical approaches may lead to increased adoption of this efficacious therapeutic option for pediatric DRE.

Serious game as oral histology learning strategy for undergraduate dental students; crossover randomized controlled trial.

BACKGROUND: Oral histology is perceived by dental students as a challenging subject and often struggle to recognize the long-term relevance of understanding the cells and tissues at the microscopic level. Serious games have been reported to have a positive effect on student cognitive skills and learning motivation. However, there is still a limited amount of research supporting the effectiveness of serious games as a learning method in dentistry. The present study aimed to evaluate the impact of serious game of HistoRM as a complementary learning strategy for oral histology. METHODS: The study design was a crossover randomized controlled trial. A total of 74 first year dental students of Universitas Indonesia participated in the study and divided into 2 groups. Study intervention included HistoRM game for 3 days followed by a combination of HistoRM and script-based handouts for another 4 days. The groups represented different intervention sequences. Evaluation was performed using pre-test, post-test on day 3 and 7 and a questionnaire. RESULTS: The data showed significant improvement of student cognitive skills (p < 0.001) and it was influenced by the number of game missions completed. Students who completed the whole 15 missions have a higher day-7 post-tests scores (p = 0.03). Perception of dental students on HistoRM was positive in all domains tested, the learning content, games and learning experience domains. Immediate feedback given after each gameplay helped the students understand the subject matters. CONCLUSION: Serious game of HistoRM effectively improved students' understanding of oral histology learning outcome and provided more interesting learning experiences. This innovative learning can be recommended as a complementary learning strategy of oral histology for dental students.

Epilepsy surgery in children with genetic etiologies: A prospective evaluation of current practices and outcomes.

OBJECTIVE: This study assesses current practices and outcomes of epilepsy surgery in children with a genetic etiology. It explores the pre-surgical workup, types of surgeries, and post-surgical outcomes in a broad array of disorders. METHODS: Patients ≤18 years who completed epilepsy surgery and had a known genetic etiology prior to surgical intervention were extrapolated from the Pediatric Epilepsy Research Consortium (PERC) surgery database, across 18 US centers. Data were assessed univariably by neuroimaging and EEG results, genetic group (structural gene, other gene, chromosomal), and curative intent. Outcomes were based on a modified International League Against Epilepsy (ILAE) outcome score. RESULTS: Of 81 children with genetic epilepsy, 72 % had daily seizures when referred for surgery evaluation, which occurred a median of 2.2 years (IQR 0.3, 5.2) after developing drug resistance. Following surgery, 68 % of subjects had >50 % seizure reduction, with 33 % achieving seizure freedom [median follow-up 11 months (IQR 6, 17). Seizure freedom was most common in the monogenic structural group, but significant palliation was present across all groups. Presence of a single EEG focus was associated with a greater likelihood of seizure freedom (p=0.02). SIGNIFICANCE: There are meaningful seizure reductions following epilepsy surgery in the majority of children with a genetic etiology, even in the absence of a single structural lesion and across a broad spectrum of genetic causes. These findings highlight the need for expedited referral for epilepsy surgery and support of a broadened view of which children may benefit from epilepsy surgery, even when the intent is palliative.

Surgical evaluation in children <3 years of age with drug-resistant epilepsy: Patient characteristics, diagnostic utilization, and potential for treatment delays.

OBJECTIVE: Drug-resistant epilepsy (DRE) occurs at higher rates in children <3 years old. Epilepsy surgery is effective, but rarely utilized in young children despite developmental benefits of early seizure freedom. The present study aims to identify unique patient characteristics and evaluation strategies in children <3 years old who undergo epilepsy surgery evaluation as a means to assess contributors and potential solutions to health care disparities in this group. METHODS: The Pediatric Epilepsy Research Consortium Epilepsy Surgery Database, a multicentered, cross-sectional collaboration of 21 US pediatric epilepsy centers, collects prospective data on children <18 years of age referred for epilepsy surgery evaluation. We compared patient characteristics, diagnostic utilization, and surgical treatment between children <3 years old and those older undergoing initial presurgical evaluation. We evaluated patient characteristics leading to delayed referral (>1 year) after DRE diagnosis in the very young. RESULTS: The cohort included 437 children, of whom 71 (16%) were <3 years of age at referral. Children evaluated before the age of 3 years more commonly had abnormal neurological examinations (p = .002) and daily seizures (p = .001). At least one ancillary test was used in 44% of evaluations. Fifty-nine percent were seizure-free following surgery (n = 34), with 35% undergoing limited focal resections. Children with delayed referrals more often had focal aware (p < .001) seizures and recommendation for palliative surgeries (p < .001). SIGNIFICANCE: There are relatively few studies of epilepsy surgery in the very young. Surgery is effective, but may be disproportionally offered to those with severe presentations. Relatively low utilization of ancillary testing may contribute to reduced surgical therapy for those without evident lesions on magnetic resonance imaging. Despite this, a sizeable portion of patients have favorable outcome after focal epilepsy surgery resections.

Spatiotemporal distribution and age of seizure onset in a pediatric epilepsy surgery cohort with cortical dysplasia.

OBJECTIVE: Focal Cortical Dysplasias (CD) are a common etiology of refractory pediatric epilepsy and are amenable to epilepsy surgery. We investigated the association of lesion volume and location to age of seizure onset among children with CD who underwent epilepsy surgery. METHODS: A retrospective study of epilepsy surgery patients with pathologically-confirmed CD. Regions of interest (ROI) determined preoperative lesion volumes on 1.5 T and 3 T T2 and SPGR MRIs, and location in 7 distributed neural networks. Descriptive and inferential statistics were used. RESULTS: Fifty-five patients were identified: 35 girls (56.5 %). Median age of seizure onset: 19.0 months (range 0.02 months - 16.0 years). Median age of surgery: 7.8 years (range 2.89 months - 24.45 years). CD were frontal (n = 21, 38 %); temporal (n = 15, 27 %); parietal (n = 10, 18 %); occipital (n = 3, 5%); multilobar (n = 6, 11 %). Frontal FCD had seizure onset < 1-year-old (P = 0.10); temporal lobe CD seizure onset was more likely > 5-years-old (P= 0.06). Median lesion volume for CD was 23.23 cm3 (range: 1.87-591.73 cm3). Larger CD lesions were associated with earlier epilepsy (P = 0.01, r = -0.16). We did not find that lesions proximal to early maturing cortical regions were associated with earlier seizure onset. We found an association with CD location in the default mode network (DMN) and age onset < 5years old (P = 0.03). Age of seizure onset was negatively correlated with percent of CD overlapping motor cortex (P = 0.001, r =-0.794) but not with CD overlap of the visual cortex (P = 0.35). There was no effect of CD type on age of epilepsy onset. SIGNIFICANCE: Larger CD lesions are associated with earlier onset epilepsy. CD most commonly occurs within the DMN and Limbic network, and DMN is associated with seizure onset before 5-years-old. Percent of CD overlapping motor cortex correlates with earlier seizure onset. These observations may reflect patterns of brain maturation or regional differences in clinical expression of seizures.

Density of tobacco advertising around schools.

BACKGROUND: Indonesia has the second highest smoking prevalence among adult males in the world, with over 61.4 million current smokers. However, there is no national regulation on outdoor tobacco advertising.OBJECTIVE: >To assess the density of outdoor tobacco advertising around schools in Semarang City, Indonesia.METHODS: We conducted geospatial analyses using buffer and hotspot analyses based on advertising and school data in ArcMap 10.6. We statistically tested the significance of different densities, including between 100 m and 100-300-m buffers from schools using Stata 15.1.RESULTS: We found a total of 3453 tobacco advertisements, of which 3026 (87%) were at least medium in size (1.3 m x l.9 m), and 2556 (74%) were within 300 m of schools. We also found hotspots with a 45% higher density of adverts within 100 m of schools (compared to within 100-300 m). A total of 378 schools (39%) were in these advertising hotspots.CONCLUSION: There was high density of outdoor tobacco advertising, with significant clusters in close proximity to schools in Semarang City. The policy implications of this are discussed.

Measure thrice, cut twice: On the benefit of reoperation for failed pediatric epilepsy surgery.

OBJECTIVE: To determine whether clinical outcomes are improved after repeat surgery for medically refractory epilepsy in children. METHODS: This is a single-center retrospective cohort analysis of all patients who received repeat resective surgery for ongoing seizures from 2000-2017. From a total of 251 consecutive individual epilepsy surgical patients for focal resection, 53 patients met study inclusion criteria and had adequate follow-up documented. RESULTS: Median age of seizure-onset was 2.0-years-old (IQR 0.3-5.5 years). The median age at first epilepsy surgery was 6.3-years-old (IQR 2.9-9.2 years) and at second epilepsy surgery was 8.4-years-old (IQR 4.7-12.6 years). Overall, 53 % (n = 28) of this series achieved Engel Class I (seizure freedom); with improved seizure control (Engel Class I-II) in 83 % (n = 44) of the cohort. 64 % (n = 34) had one reoperation; 26 % (n = 14) had two; and 9% (n = 5) had three. Pathology: 58 % (n = 31) had focal cortical dysplasia; 13 % (n = 10) tumor; 9% (n = 5) encephalitis; 6% (n = 3) gliosis; 4% (n = 2) mesial temporal sclerosis; and 2% (n = 1) hemimegalencephaly. Tumor pathology was associated with increased chance (p = 0.01) for seizure freedom (90 % of tumor patients had Engel Class I outcome). MTS had worse outcome with both patients having ongoing seizures (Engel II-IV). There were 6 patients who developed post-operative hemiparesis; one was unplanned but resolved. SIGNIFICANCE: Reoperation for pediatric epilepsy surgery can lead to seizure freedom in many cases and improved seizure control in most cases. Reoperation for brain tumor pathology is associated with a high rate of seizure freedom.

Prognostic Significance of Acute Kidney Injury Following Emergency Laparotomy: A Prospective Observational Cohort Study.

AIMS: Post-operative acute kidney injury (AKI) is a common and independent mortality risk factor carrying high clinical and economic cost. This study aimed to establish the incidence of AKI in patients undergoing emergency laparotomy (EL), to determine patients' risk profile and consequent mortality. METHODS: Consecutive 239 patients of median age 68 (IQR 51-76) years, undergoing EL in a UK tertiary hospital, were studied. Primary outcome measure was AKI and in-hospital operative mortality. RESULTS: Ninety-five patients (39.7%) developed AKI, which was associated with in-hospital mortality in 32 patients (33.7%) compared with 7 patients (4.9%) without AKI. AKI occurred in 81.1% of all mortalities, but none occurred when AKI resolved within 48 h of EL. AKI was associated with chronic kidney disease, age, serum lactate, white cell count, pre-EL systolic blood pressure and tachycardia (p < 0.010). Median length of hospital stay in AKI survivors was 15 days compared with 11 days in the absence of AKI (p < 0.001). On multivariable analysis, only AKI at 48 h post-EL was significantly and independently associated with mortality [HR 10.895, 95% CI 3.152-37.659, p < 0.001]. CONCLUSION: Peri-operative AKI after EL was common and associated with a more than sixfold significant greater mortality. Pre-operative risk profile assessment and prompt protocol-driven intervention should minimise AKI and reduce EL mortality.

The role of Indonesian patients' health behaviors in delaying the diagnosis of nasopharyngeal carcinoma.

BACKGROUND: With an estimated 13,000 newly diagnosed patients per year, nasopharyngeal carcinoma (NPC) is one of the most common types of cancer in males in Indonesia. Moreover, most patients are diagnosed at an advanced stage of the disease. This study aimed to explore the health behaviors of patients diagnosed with NPC and the possible causes of patient delay in NPC diagnosis. METHODS: A qualitative research method was used to gain better insight into patient behaviors. Twelve patients were interviewed using semi-structured interview guidelines. All interviews were recorded, transcribed verbatim and analyzed according to a standard content analysis framework. RESULTS: Most patients had limited knowledge regarding NPC and its causes. Fifty percent of the patients had a delay of six months from the onset of symptoms to diagnosis. The main reason for this delay was the lack of awareness among the patients, which was influenced by their environment, economic status, family, culture, and religion. The perceived barriers to seeking medical help included direct non-medical costs not covered by health insurance, complex and time-consuming insurance and referral systems, and negative experiences in the past. Health insurance did motivate people to seek medical help. CONCLUSION: This study provides additional insight into patients' motivations to delay seeking medical help and can facilitate the design of NPC education programs. To improve awareness of the abovementioned causes for delay, community-based education programs are highly warranted and should focus on the recognition of NPC symptoms and possible solutions to overcome the main barriers at an earlier disease stage.

The Southwest UK Burns Network (SWUK) experience of electronic cigarette explosions and review of literature.

INTRODUCTION: Since the introduction of e-cigarettes to the UK market in 2007 their popularity amongst young adults has significantly increased. These lithium-ion powered devices remain unregulated by the Standards Agency and as a result burns centres across the world have seen an increasing number of patients presenting with significant burns, resulting from poor quality batteries that appear to be liable to explode when over-heated, over-charged or incorrectly stored. METHODS: Retrospective and perspective review of all e-cigarette related burns presenting to the Southwest Burns Network; South Wales Burns Centre (Morriston Hospital) or to Bristol burns centre (Southmead Hospital) between Oct 15-July 16, followed by a review of available literature performed and eligible papers identified using PRISMA 2009 Checklist. RESULTS: South Wales Burns Centre (Morriston Hospital) (N=5), Bristol burns centre (Southmead Hospital) (N=7). 92% of injuries were seen in male patients with a mean age of 34.58 (±12.7). The mean TSBA sustained 2.54% of mixed depth, most common anatomical area is the thigh 83% (n=10) with a mean 23.1(±5) days to heal with conservative management. The literature search yielded 3 case series (Colaianni et al., 2016; Kumetz et al., 2016; Nicoll et al., 2016) [8,9,12] and 4 case reports (Jablow and Sexton, 2015; Harrison and Hicklin, 2016; Walsh et al., 2016; Shastry and Langdorf, 2016) [6,7,10,11]. We compare our findings with the published studies. CONCLUSION: The import and sale of e-cigarettes remains unrestricted. This increases the risk of devices being available in the UK market that do not meet the British Standard Specification, potentially increasing their risk of causing fire and exploding. Consumers should be made aware of this risk, and advised of adequate charging and storage procedures. In case lithium ion compounds leak following a breach in the battery, first aid with mineral oil use is advocated to avoid a further chemical reaction.

AN INCREASE IN RISK FACTORS FOR CARDIOVASCULAR DISEASE IN YOGYAKARTA, INDONESIA: A COMPARISON OF TWO CROSS-SECTIONAL SURVEYS.

This paper aims to describe changes in risk factors for cardiovascular disease (CVD) over a five year period in urban Indonesia. In 2004 (n = 3,205) and 2009 (n = 2,467) we conducted cross-sectional surveys of residents in Yogjakarta City, Indonesia evaluating risk factors for CVD. Smoking habits, fruit and vegetable intake, physical activity, blood pressure, weight, and height were recorded. The results of these 2 surveys conducted 5 years apart were then compared. The risk for having a CVD event was also calculated. Behavioral CVD risk factors were more common among men. The predicted risk of having a CVD event increased from 8.4% to 11.3% among men between 2004 and 2009. Effective measures need to be taken to change these behaviors among men in Yogyakarta, Indonesia.

Chitosan as a potential osteogenic factor compared with dexamethasone in cultured macaque dental pulp stromal cells.

Chitosan, a natural biopolymer derived from chitin, is considered a promising scaffold material for bone tissue engineering. The ability of chitosan to promote the osteogenic differentiation of dental pulp stromal/stem cells (DPSCs) is unknown. We have evaluated the potential of chitosan to induce the osteogenic differentiation of macaque DPSCs in comparison with that of dexamethasone. DPSCs were cultured in mineralizing medium supplemented with 5 or 10 µg/ml chitosan or with 1 or 10 nM dexamethasone. The metabolic activity of DPSCs was measured by MTT assay. Their osteogenic differentiation was determined by the number of transcripts of RUNX2, alkaline phosphatase (ALP), and COL1A1 by using real-time polymerase chain reaction, by alizarin red staining for mineral deposition, and by the ALP activity released into the medium for their ability to support biomineralizaton. Addition of chitosan to the mineralizing medium significantly increased DPSCs metabolism after 7 and 14 days of culture (P ≤ 0.0001). Chitosan at 5 µg/ml also significantly enhanced RUNX2 and ALP mRNA but not COL1A1 mRNA; chitosan tended to increase the release of ALP hydrolytic enzyme activity into the medium during the first week. Dexamethasone upregulated the osteogenic markers tested. Mineral deposition was similar in the chitosan and dexamethasone groups and was not statistically different from that of the mineralizing control group. Thus, the potential of chitosan to stimulate DPSCs proliferation and early osteogenic differentiation is comparable with that of dexamethasone, but mineralization remains unaffected by chitosan treatment. In addition to its role as a three-dimensional scaffold for osteogenic cells in vivo, chitosan might also stimulate DPSCs proliferation and early osteogenic differentiation in vitro.

Chitosan exerts anticancer activity through induction of apoptosis and cell cycle arrest in oral cancer cells.

Chitosan, a multipurpose biomaterial, has been shown to exert effects against several types of cancer including oral cancer. However, the mechanisms underlying the anticancer activities of chitosan on oral squamous cell carcinoma (SCC) cells remain largely unknown. The present study aimed to compare the effects of low-molecular-weight chitosan (LMWC) and cisplatin on oral SCC Ca9-22 and non-cancer keratinocyte HaCaT cell lines. Cell viability and cell cycle profiles were measured by MTT assay and laser scanning cytometry, respectively. Apoptosis was examined by TUNEL assay and electron microscopy, followed by analysis of caspase activity. LMWC exhibited cytotoxic effects on Ca9-22, but not HaCaT cells, whereas cisplatin induced apoptosis in both types of cells. Exposure of Ca9-22 cells to LMWC led to G1/S cell cycle arrest and an increase of TUNEL-positive cells accompanied by an early apoptotic cell morphology and subtle increases of caspase activity. Short-term LMWC exposure was less cytotoxic to HaCaT cells than to Ca9-22 cells, and anticancer activity was exerted through induction of apoptosis and cell cycle arrest, suggesting that LMWC could be a promising natural anticancer agent with fewer side effects on normal cells.

Compliance with the minimum dataset of the British Orthodontic Society/British Association of Oral and Maxillofacial Surgeons for record keeping for orthognathic patients: retrospective comparative multicentre audit.

Accurate and timely collection of clinical records is of utmost importance in planning, evaluating, and auditing orthognathic operations. The minimum dataset guidelines of the British Orthodontic Society (BOS) and the British Association of Oral and Maxillofacial Surgeons (BAOMS) were published in an attempt to standardise the collection of clinical records of patients having orthognathic operations. This multicentre retrospective audit aimed to assess and compare compliance with the guidelines in 3 maxillofacial units over a 1-year period. A total of 105 cases were reviewed. Compliance varied. Documentation of altered sensation was consistently poor and too many unnecessary radiographs were taken. There may be a need to circulate the guidelines again to increase awareness and reduce variability between centres.

Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice.

Nitric oxide (NO) and peroxynitrite, which are produced by activated microglia, are responsible for accelerated neurodegeneration in cathepsin D-deficient (CD-/-) mice. To elucidate the mechanisms by which microglia are initially activated in CD-/- mice, we analyzed the possible relationship between lysosomal storage and microglial activation. In CD-/- mice, the microglial NO-generating activity that was closely associated with the induction of inducible NO synthase and the cationic amino acid transporter-2 (CAT-2) coincided well with the lysosomal storage of subunit c of mitochondrial F0F1ATPase and the formation of ceroid/lipofuscin. Furthermore, activated microglia, which are often accumulating subunit c and ceroid/lipofuscin, showed proliferation activity and an activation of p38 mitogen-activated protein (MAP) kinase. In the primary cultured microglia, pepstatin A was found to enhance the generation of NO and superoxide anion radicals. In these pepstatin A-treated microglia, both an increased generation of the intracellular reactive oxygen species (ROS) and an activation of p38 MAP kinase were observed. These results suggest that the ceroid/lipofuscin which form in microglia activate the p38 MAP kinase cascade through the increased intracellular generation of ROS in CD-/- mice. The activated p38 MAP kinase cascade then promotes the expression of iNOS and CAT-2, thereby inducing the overproduction of NO.