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With the increase of cosmetic injectable hyaluronic acid (HA), there have been more cases with serious complications, including skin necrosis, blindness, and cerebral embolism. Patients who have recovered from HA filler-induced total vision loss are extremely rare. We report a case of a 27-year-old female who developed severe ocular pain on the right side and total vision loss following a 1.0 ml HA filler injection in the nasal dorsum. She arrived at our hospital 4 hours later. Her visual acuity was no light perception (NLP), and she exhibited eyelid ptosis, ophthalmoplegia, and frontal and nasal ecchymosis. She was promptly treated with subcutaneous and retrobulbar hyaluronidase injections, as well as intra-arterial 1500 IU hyaluronidase injections into the right ophthalmic artery with DSA assistance. Her vision improved from NLP to counting fingers at 1.0 meters. Unfortunately, 13 hours later, she felt an intense headache, and her vision again decreased to NLP. We immediately performed an injection of 1500 IU hyaluronidase combined with 8 mg alteplase for intra-arterial thrombolysis (IAT) into the right ophthalmic artery. Her vision improved immediately afterward. After 3 months, her visual acuity had significantly recovered from NLP (admission vision status) to 20/50 (Snellen chart with glasses). Similarly, skin, conjunctival, eye movement, and ptosis symptoms completely recovered. This case demonstrates that reversal of complete blindness due to embolism of the ophthalmic and central retinal arteries could be accomplished through multidisciplinary therapies, especially IAT using fibrinolytic agents combined with hyaluronidase followed by an anticoagulant regimen. Level of evidence VThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

BackgroundNanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant.MethodsWe conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 microgram (mcg), 50 mcg, and 75 mcg doses, aluminum hydroxide adjuvanted). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2 which involved in 560 healthy adults, the primary outcomes are vaccine safety; and anti-S IgG antibody response. Secondary outcomes were surrogate virus neutralization, wild-type SARS-CoV-2 neutralization, and T-cell responses by intracellular staining (ICS) for interferon gamma (IFNg). We performed primary analyses at day 35 and day 42.ResultsFor phase 1 study, no serious adverse events (SAE) were observed for all 60 participants. Most adverse events (AE) were grade 1 and disappeared shortly after injection. For phase 2 study, after randomization, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive placebo. Reactogenicity was absent or mild in the majority of participants and of short duration (mean, ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. There was no statistical difference in antibody responses among dose strengths on Day 42, in terms of anti S-IgG level and neutralizing antibody titer.ConclusionsUp to 42 days, Nanocovax vaccine was safe, well tolerated and induced robust immune responses. We propose using Nanocovax 25 mcg for Phase 3 to evaluate the vaccine efficacy. (Research funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of Vietnam;ClinicalTrials.govnumber,NCT04683484.)

Introduction: Pre-hospital capabilities are minimally developed in Vietnam; therefore, the prognosis of OHCA might differ from that of other countries. The aim of this study was to investigate survival rate from OHCA and potential determinants of the chain of survival following an OHCA in a developing country. Hypothesis: Understanding the country-specific etiologies and the disease risk and prognosis of OHCA are crucial for reducing mortality in Vietnam, as well as in other countries that face challenges in clinical practice owing to limited medical resources. Methods: This is a multi-center prospective observational study of OHCA patients (age>18 years) presenting to the ED of three tertiary hospitals from February 2014 to December 2018. Factors associated with survival following OHCA were collected and compared among types of pre-hospital care transportation and between survival and non-survival to admission. Factors for survival to admission were assessed using logistic regression analysis. Results: Among 590 OHCA patients (male, 74.6%; age, 56.1±17.2 years), we observed low rates of survival to admission (24.2%) and discharge (14.1%). Of total patients, 67.8% occurred at home, 79.4% witnessed by bystanders, 124/555 (22.3%) received bystander CPR, a minority of patients (8.64%) was conveyed by EMS, and 49/152 (32.2%) received pre-hospital defibrillation. Multivariate analysis revealed that past medical history (PMH) of respiratory disease (OR, 3.128; 95% CI, 1.197-8.173), pre-hospital defibrillation (OR, 3.904; 95% CI, 1.540-9.898), pre-hospital advanced airway (OR, 3.441; 95% CI, 1.203-9.844) and ROSC at ED (OR, 2.891; 95% CI, 1.030-8.115) were independent factors for survival to admission. Following OHCA with cardiac etiology, EMS use (OR, 0.203; 95% CI, 0.044-0.935) was also an independent factor for survival to admission. Conclusions: This was a highly selected cohort of OHCA patients presenting to the ED. Many OHCA victims in Vietnam do not come to the ED. PMH of respiratory disease, pre-hospital defibrillation and advanced airway, and ROSC at ED were independent factors predicting survival to admission. EMS use was also an inverse and independent predictor of survival to admission among patients following OHCA with cardiac etiology.

To investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam.We did a multicentre prospective observational study of people ( 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis.Of 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54-9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03-8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33-12.74).Improvements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.Examiner les facteurs associés à la survie après un arrêt cardiaque hors hôpital au Viet Nam.Nous avons mené une étude d'observation prospective multicentrique sur des personnes ( 18 ans) ayant subi un arrêt cardiaque hors hôpital (non traumatique) et admis dans trois hôpitaux tertiaires au Viet Nam entre février 2014 et décembre 2018. Nous avons récolté des données sur les caractéristiques, la gestion et l'issue de ces patients, puis les avons comparés en fonction du moyen de transport vers l'hôpital et de la survie après leur admission. Enfin, nous avons mesuré des facteurs associés à la survie lors de l'admission et de la sortie de l'établissement à l'aide d'une analyse de régression logistique.Sur les 590 patients éligibles ayant subi un arrêt cardiaque hors hôpital, 440 (74,6%) étaient des hommes et l'âge moyen s'élevait à 56,1 ans (écart type: 17.2). Seulement 24,2% (143/590) d'entre eux ont survécu à leur admission à l'hôpital, et 14,1% (83/590) à leur sortie. La plupart des arrêts cardiaques (67,8%; 400/590) ont eu lieu à domicile, 79,4% (444/559) se sont déroulés en présence de passants et 22,3% (124/555) ont fait l'objet d'une réanimation cardiopulmonaire pratiquée par un témoin. À peine 8,6% (51/590) des patients ont été emmenés à l'hôpital par les services médicaux d'urgence, et 32,2% (49/152) ont reçu une défibrillation avant d'arriver à l'hôpital. La défibrillation préhospitalière (odds ratio, OR: 3,90; intervalle de confiance de 95%, IC: 1,54–9,90) et le rétablissement d'une circulation spontanée aux urgences (OR: 2,89; IC de 95%: 1,03–8,12) allaient de pair avec la survie après admission. L'hypothermie thérapeutique administrée durant les soins post-réanimation était liée à un meilleur taux de survie au moment de la sortie (OR: 5,44; IC de 95%: 2,33-12,74).Des aménagements sont requis en matière de services médicaux d'urgence au Viet Nam, notamment pour encourager la pratique de la réanimation cardiopulmonaire auprès de la population, garantir l'accès à des défibrillateurs publics, mais aussi améliorer les soins en ambulance et en post-réanimation.Investigar los factores relacionados con la supervivencia después de un paro cardíaco extrahospitalario en Vietnam.Se realizó un estudio observacional prospectivo multicéntrico de personas (18 años) que sufrieron un paro cardíaco extrahospitalario (no causado por traumatismo) en tres hospitales terciarios de Vietnam entre febrero de 2014 y diciembre de 2018. Se recopilaron los datos sobre las características, el tratamiento y los resultados de los pacientes con paro cardíaco extrahospitalario y se compararon según el tipo de transporte hasta el hospital y la supervivencia hasta el ingreso en el hospital. Se evaluaron los factores de supervivencia hasta el ingreso y el alta hospitalaria mediante un análisis de regresión logística.De las 590 personas que cumplían los requisitos y sufrieron un paro cardíaco extrahospitalario, 440 (74,6 %) eran hombres, cuya edad media era de 56,1 años (desviación estándar: 17,2). Solo el 24,2 % (143/590) de estas personas sobrevivieron al ingreso en el hospital y el 14,1 % (83/590) sobrevivieron al alta hospitalaria. La mayoría de los paros cardíacos (67,8 %; 400/590) ocurrieron en el hogar, el 79,4 % (444/559) fueron presenciados por transeúntes y el 22,3 % (124/555) recibieron reanimación cardiopulmonar por un transeúnte. Solo el 8,6 % (51/590) de las personas fueron trasladadas al hospital por los servicios médicos de emergencia y el 32,2 % (49/152) recibieron desfibrilación prehospitalaria. La desfibrilación prehospitalaria (oportunidad relativa, OR: 3,90; intervalo de confianza del 95 %, IC: 1,54-9,90) y la recuperación de la circulación espontánea en el servicio de urgencias (OR: 2,89; IC del 95 %: 1,03-8,12) se asociaron a la supervivencia hasta el ingreso hospitalario. La hipotermia terapéutica durante la atención posterior a la reanimación se asoció a la supervivencia hasta el alta (OR: 5,44; IC del 95 %: 2,33-12,74).Se necesitan mejoras en los servicios médicos de emergencia de Vietnam, como el aumento de las intervenciones de reanimación cardiopulmonar para transeúntes y de desfibrilación de acceso público, así como el mejoramiento de la atención en las ambulancias y de los cuidados posteriores a la reanimación.الغرض تقصي العوامل المرتبطة بالبقاء على قيد الحياة بعد السكتة القلبية خارج المستشفى في فييت نام. الطريقة قمنا بإجراء دراسة مستقبلية قائمة على الملاحظة متعددة المراكز للأشخاص (الأكبر من 18 عامًا) الذين يعانون من سكتة قلبية خارج المستشفى (ليس بسبب إصابة في الحوادث) في ثلاثة مستشفيات من الدرجة الثالثة في فيتنام، من فبراير/شباط 2014 إلى ديسمبر/كانون أول 2018. قمنا بجمع بيانات عن الخصائص، والإدارة، ونتائج المرضى الذين يعانون من السكتة القلبية خارج المستشفى، ومقارنة هذه البيانات حسب نوع النقل إلى المستشفى والبقاء على قيد الحياة حتى الدخول إلى المستشفى. قمنا بتقييم العوامل المرتبطة بالبقاء على قيد الحياة حتى الدخول إلى المستشفى والخروج منها باستخدام تحليل التحوّف اللوجيستي. النتائج من بين 590 شخصًا مؤهلاً مصابًا بالسكتة القلبية خارج المستشفى، كان 440 (74.6%) منهم من الذكور، وكان متوسط ​​العمر 56.1 عامًا (الانحراف المعياري: 17.2). استمر 24.2% فقط (143/590) من هؤلاء الأشخاص على قيد الحياة حتى الدخول إلى المستشفى، واستمر 14.1% (83/590) على قيد الحياة حتى الخروج من المستشفى. حدثت معظم حالات السكتة القلبية (67.8%؛ 400/590) في المنزل، وحدثت 79.4% (444/559) من الحالات أمام المارة في الشارع، وحصل 22.3% (124/555) من الحالات على الإنعاش القلبي الرئوي من أحد المارة. تم نقل 8.6% فقط (51/590) من الأشخاص إلى المستشفى بواسطة خدمات الطوارئ الطبية، وحصل 32.2% (49/152) على عملية إزالة الرجفان قبل دخول المستشفى. عملية إزالة الرجفان قبل دخول المستشفى (نسبة الاحتمالات: 3.90؛ فاصل الثقة 95%: 1.54 إلى 9.90) وعودة الدورة الدموية التلقائية في قسم الطوارئ (نسبة الاحتمالات: 2.89؛ فاصل الثقة 95%: 1.03 إلى 8.12) ارتبطت بالبقاء على قيد الحياة حتى دخول المستشفى. ارتبط علاج انخفاض حرارة الجسم أثناء الرعاية اللاحقة للإنعاش بالبقاء على قيد الحياة حتى الخروج من المستشفى (نسبة الأرجحية: 5.44؛ فاصل الثقة 95%: 2.33 إلى 12.74). الاستنتاج هناك حاجة إلى تحسينات في الخدمات الطبية الطارئة في فييت نام، مثل زيادة عمليات الإنعاش القلبي الرئوي من جانب المارة، وإمكانية حصول العامة على عملية إزالة الرجفان، وتحسين خدمات الإسعاف والرعاية بعد الإنعاش.研究越南院外心脏骤停存活率的相关因素。.我们针对越南三家三级医院在 2014 年 2 月至 2018 年 12 月期间接收的院外心脏骤停（非创伤引起）患者（18 岁）进行了跨中心前瞻性观察研究。我们收集了与院外心脏骤停患者的特征、诊治情况以及疗效相关的数据，并根据送至医院时采用的交通方式以及存活入院率对这些数据进行了比较。我们使用逻辑回归分析方法评估与存活入院率和存活出院率相关的因素。.590 名参加调查的院外心脏骤停患者中，440 名 (74.6%) 为男性，平均年龄为 56.1 岁（标准偏差：17.2）。这些人中仅 24.2% (143/590) 存活入院，14.1% (83/590) 存活出院。心脏骤停多发生于家中 (67.8%; 400/590)，其中有旁观者目击的情况占 79.4％ (444/559)，旁观者介入实施心肺复苏术的情况占 22.3％ (124/555)。其中仅 8.6% (51/590) 通过紧急医疗服务送至医院，32.2% (49/152) 接受了院前除颤。院前除颤（优势比，OR：3.90；95% 置信区间，CI：1.54–9.90）和急诊室自主循环恢复 (OR: 2.89; 95% CI: 1.03–8.12) 与存活入院率有关。复苏后护理期间的低温疗法与存活出院率相关 (OR: 5.44; 95% CI: 2.33-12.74）。.越南需要提升紧急医疗服务，如增加旁观者介入实施心肺复苏术的比例、普及公众除颤以及改善救护车和复苏后护理服务。.Изучить факторы, связанные с выживанием после внебольничной остановки сердца во Вьетнаме.Авторы провели многоцентровое проспективное обсервационное исследование среди пациентов (старше 18 лет), поступивших с внебольничной остановкой сердца (не связанной с травмой) в три специализированные больницы во Вьетнаме с февраля 2014 г. по декабрь 2018 г. Были собраны данные о характеристиках и результатах лечения пациентов с внебольничной остановкой сердца, которые затем сравнивались по видам транспортировки в больницу и показателям выживаемости до момента госпитализации. Авторы оценили факторы, связанные с выживаемостью при поступлении в больницу и выписке из нее, используя анализ на основании модели логистической регрессии.Из 590 человек с внебольничной остановкой сердца, отвечающих установленным критериям, было 440 (74,6%) мужчин, средний возраст которых составлял 56,1 года (стандартное отклонение: 17,2). Лишь 24,2% (143/590) из указанных пациентов выжили до поступления в больницу, а 14,1% (83/590) выжили до выписки из больницы. Большинство сердечных приступов (67,8%; 400/590) произошли дома, 79,4% (444/559) произошли на глазах у других людей, а 22,3% (124/555) пострадавших была проведена сердечно-легочная реанимация свидетелями происшествия. Только 8,6% (51/590) человек были доставлены в больницу службами скорой медицинской помощи, а 32,2% (49/152) была проведена догоспитальная дефибрилляция. Догоспитальная дефибрилляция (отношение шансов, ОШ: 3,90; 95%-й доверительный интервал, ДИ: 1,54–9,90) и спонтанное восстановление кровообращения в отделении скорой помощи (ОШ: 2,89; 95%-й ДИ: 1,03–8,12) ассоциировались с выживаемостью до госпитализации. Лечение с применением искусственного понижения температуры тела в постреанимационный период ассоциируется с выживанием после выписки (ОШ: 5,44; 95%-й ДИ: 2,33–12,74).Необходимо совершенствовать работу служб неотложной медицинской помощи во Вьетнаме, в частности повысить вероятность оказания сердечно-легочной реанимации свидетелями происшествия и обеспечить общедоступность дефибрилляторов, а также совершенствовать работу машин скорой помощи и лечение в постреанимационный период.

In January 2020, we identified two SARS‐CoV‐2 infections in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS‐CoV‐2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human‐to‐human transmission of SARS‐CoV‐2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient with a mild upper respiratory illness and a brief viral shedding, while the elderly with multi‐morbidity had pneumonia, prolonged viral shedding, and residual lung damage. Evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies. This article is protected by copyright. All rights reserved.

BACKGROUND Little is known about whether there are differences in medication use between older patients of Chinese descent, those of South Asian descent and other Canadian patients after acute ischemic or primary intracerebral hemorrhagic stroke. The aim of this population-based study was to evaluate potential ethnic differences in secondary prevention pharmacotherapy after acute stroke. METHODS Using health administrative data, we conducted a retrospective analysis of all patients aged 66 years or more admitted to hospital with acute stroke in Ontario (1997-2011) and British Columbia (1997-2009). We compared prescriptions filled for statins, warfarin, any antihypertensive agent, the recommended combination of angiotensin-converting-enzyme (ACE) inhibitor and diuretic, and the combination of ACE inhibitor, diuretic and statin within 1 year after ischemic or primary intracerebral hemorrhagic stroke. RESULTS There were 118 362 patients with acute stroke (3430 Chinese, 2075 South Asian and 112 857 other Canadians). Among those with ischemic stroke (n = 108 699), Chinese patients were less likely than other Canadian patients to fill prescriptions for the combination of ACE inhibitor, diuretic and statin (adjusted odds ratio [OR] 0.64 [95% confidence interval (CI) 0.55-0.74]) and, in those with atrial fibrillation, for warfarin (adjusted OR 0.75 [95% CI 0.59-0.95]). There were no differences in filling of prescriptions for antihypertensive therapy overall between the 3 groups. Among patients with intracerebral hemorrhagic stroke (n = 9663), Chinese patients were less likely than other Canadian patients to fill prescriptions for the combination of ACE inhibitor and diuretic (adjusted OR 0.51 [95% CI 0.38-0.69]), and South Asians were more likely than other Canadian patients to fill prescriptions for any antihypertensive agent (adjusted OR 1.73 [95% CI 1.21-2.49]). INTERPRETATION We identified ethnic differences in filling of prescriptions for several secondary prevention medications after acute stroke. The reasons underlying these differences need to be investigated.

Objective: To report an episode of severe diabetic ketoacidosis (DKA) in a type 2 diabetes mellitus (DM) patient with insulin allergy treated by continuous intravenous (IV) regular insulin infusion. Methods: We describe the clinical features, laboratory data, and management of severe DKA in a type 2 DM patient with insulin allergy. Results: A 58-year-old man with type 2 DM initiated subcutaneous insulin administration (SIA) after failure of oral antidiabetic therapies. Symptoms of an allergic reaction then developed, especially distinct at the injection site. Pruritic wheals appeared within 10 minutes of injection and lasted over 24 hours. Both skin prick and intradermal tests were positive with different types of insulin. Two days before admission, he stopped SIA because of allergic symptoms, and then experienced weakness and upper abdominal pain. On admission, his heart rate was 130 beats/min, temperature 37°C, blood pressure 150/90 mmHg, and respiratory rate 28 breaths/min. Blood glucose level was 374.6 mg/dL, pH 6.984, bicarbonate 2.5 mmol/L, lactate 1.5 mmol/L, BUN 24.1 mg/dL, creatinine 1.46 mg/dL, and urinary ketone was 66.48 mg/dL. Over 24 hours, the metabolic acidosis was refractory to IV fluids, bicarbonate and potassium replacement, as well as hemodialysis. Ultimately, he received continuous IV regular insulin infusion at an initial rate of 0.1 units/kg/hour, no further allergic reactions were observed. On the day 5, ketonemia and metabolic acidosis completely resolved. He had transition from IV insulin infusion to SIA on day 14. He was discharged on the day 21 with the treatment of SIA. Three months later, he had a good glycemic control, but has still appeared allergic symptoms at the injection sites of insulin. Conclusion: In this patient, SIA caused an allergic reaction in contrast to continuous IV insulin infusion, for which allergic symptoms did not appear. Thus, identical insulin molecules could behave in markedly different ways depending on the route of injection. Disclosure A.D. Nguyen: None. C.Q. Luong: None. H.C. Chu: None. V.K. Nguyen: None. C.V. Nguyen: None. T.A. Nguyen: None. Q.H. Nguyen: None. T.D. Mai: None. D.V. Nguyen: None. B.Q. Nguyen: None. T.H. Tran: None. N.N. Nguyen: None. S.N. Do: None.

The quantification of changes in gene copy number is critical to our understanding of tumor biology and for the clinical management of cancer patients. DNA fluorescence in situ hybridization is the gold standard method to detect copy number alterations, but it is limited by the number of genes one can quantify simultaneously. To increase the throughput of this informative technique, a fluorescent bar-code system for the unique labeling of dozens of genes and an automated image analysis algorithm that enabled their simultaneous hybridization for the quantification of gene copy numbers were devised. We demonstrate the reliability of this multiplex approach on normal human lymphocytes, metaphase spreads of transformed cell lines, and cultured circulating tumor cells. It also opens the door to the development of gene panels for more comprehensive analysis of copy number changes in tissue, including the study of heterogeneity and of high-throughput clinical assays that could provide rapid quantification of gene copy numbers in samples with limited cellularity, such as circulating tumor cells.

A simple, affordable diagnostic test for pulmonary tuberculosis (TB) is urgently needed to improve detection of active Mycobacterium tuberculosis. Recently, it has been suggested that animal behavior can be used as a biosensor to signal the presence of human disease. For example, the giant African pouched rats can detect tuberculosis by sniffing sputum specimens while trained honeybees respond to three of the volatile organic compounds (VOCs) detected in the breath of TB positive patients by proboscis extension. However, both rats and honeybees require animal housing facilities and professional trainers, which are outside the scope of most disease testing facilities. Here, we report that the innate olfactory behavioral response of the roundworm nematode Caenorhabditis elegans can be used to detect the TB-specific VOCs methyl p-anisate, methyl nicotinate, methyl phenylacetate and o-phenylanisole, in chemotaxis assays. Dauer larvae, a long-lived stress resistant alternative development state of C. elegans in which the animals can survive for extended periods of time in dry conditions with no food, were also demonstrated to detect the VOCs. We propose that exposing naive dauer larvae to TB-related VOCs and recording their response in this behavioral assay could lead to the development of a new method for TB diagnostics using breath as the sample type. Keywords: Tuberculosis, Caenorhabditis elegans, Chemotaxis, Volatile organic compounds, Diagnostics, Odorants

Background: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers the possibility of cure for hematological malignancies, various complications have been described. Capillary leak syndrome (CLS) has been previously observed in HSCT patients. CLS is a rare disease characterized by recurrent episodes of generalized edema and severe hypotension along with hypoproteinemia.Case Report: A 27-year-old Chinese man, diagnosed with refractory acute myeloid leukemia, was treated with a haploidentical stem cell transplant combined with an unrelated umbilical cord blood unit. The patient developed fatal CLS during the 9th day of the conditioning therapy. Conclusion: Since it is difficult to distinguish between CLS and other early complications during allo-HSCT, our report highlights the need for rigorous investigation of identifying CLS and the increasing need of insightful diagnosis to manage any incidence of CLS.

Background Delay discounting refers to the devaluation of a reward given increasing delays to delivery. Similarly, effort discounting refers to the devaluation of a reward given increasing effort required to obtain it. Individuals with substance use disorder show higher rates of delay discounting, exacerbating short-term positive reinforcement at the expense of long-term consequences. This study explores how effort discounting compares to delay discounting behavior among alcohol users as well as how these preferences change between monetary and alcohol rewards. Methods A total of 100 participants completed an online survey through Amazon Mechanical Turk. Participant alcohol use was evaluated using DSM-5 and the Alcohol Use Disorders Identification Test criteria. All participants completed 4 randomized discounting tasks involving delay or effort discounting, in which the reward was money or alcohol. A follow-up experiment (n = 423) added the alcohol purchase task to assess alcohol valuation. Results Individuals with greater alcohol use disorder (AUD) severity discounted future money and alcohol significantly more than those with less AUD. However, individuals meeting more DSM-5 criteria were only willing to perform more effort for alcohol. The follow-up experiment replicated these findings and demonstrated that individuals with greater AUD also showed an increased valuation of alcohol and alcohol value-mediated effort discounting. Conclusions These results suggest that individuals with greater AUD were less willing to wait for money or alcohol. While all participants were willing to work for money regardless of AUD severity, individuals with greater AUD showed increased valuation of alcohol drinks and were willing to exert more effort to obtain alcohol. Together, these results paint a picture of individuals with increased AUD as both more impulsive and willing to work to obtain alcohol, contributing to our understanding of decision making among individuals who abuse substances.

Purpose: Deregulated Myc drives an oncogenic metabolic state, including pseudohypoxic glycolysis, adapted for the constitutive production of biomolecular precursors to feed rapid tumor cell growth. In glioblastoma, Myc facilitates renewal of the tumor-initiating cell reservoir contributing to tumor maintenance. We investigated whether targeting the Myc-driven metabolic state could be a selectively toxic therapeutic strategy for glioblastoma. Experimental Design: The glycolytic dependency of Myc-driven glioblastoma was tested using 13C metabolic flux analysis, glucose-limiting culture assays, and glycolysis inhibitors, including inhibitors of the NAD+ salvage enzyme nicotinamide phosphoribosyl-transferase (NAMPT), in MYC and MYCN shRNA knockdown and lentivirus overexpression systems and in patient-derived glioblastoma tumorspheres with and without MYC/MYCN amplification. The in vivo efficacy of glycolyic inhibition was tested using NAMPT inhibitors in MYCN-amplified patient-derived glioblastoma orthotopic xenograft mouse models. Results: Enforced Myc overexpression increased glucose flux and expression of glycolytic enzymes in glioblastoma cells. Myc and N-Myc knockdown and Myc overexpression systems demonstrated that Myc activity determined sensitivity and resistance to inhibition of glycolysis. Small-molecule inhibitors of glycolysis, particularly NAMPT inhibitors, were selectively toxic to MYC/MYCN–amplified patient-derived glioblastoma tumorspheres. NAMPT inhibitors were potently cytotoxic, inducing apoptosis and significantly extended the survival of mice bearing MYCN-amplified patient-derived glioblastoma orthotopic xenografts. Conclusions: Myc activation in glioblastoma generates a dependency on glycolysis and an addiction to metabolites required for glycolysis. Glycolytic inhibition via NAMPT inhibition represents a novel metabolically targeted therapeutic strategy for MYC or MYCN-amplified glioblastoma and potentially other cancers genetically driven by Myc. Clin Cancer Res; 22(17); 4452–65. ©2016 AACR.

Introduction: Invasive mucinous adenocarcinoma is a unique histologic subtype of lung cancer, and our knowledge of its genetic and clinical characteristics is rapidly evolving. Here, we present next- generation sequencing analysis of nucleotide variant and fusion events along with clinical follow-up in a series of lung mucinous adenocarcinoma. Methods: We collected 72 mucinous adenocarcinomas from the United States and Korea. All had been previously assessed for KRAS and EGFR mutations. For KRAS wild-type cases ( n = 30), we performed deep targeted next-generation sequencing for gene fusions and nucleotide variants and correlated survival and other clinical features. Results: As expected, KRAS mutations were the most common alteration found (63% of cases); however, the distribution of nucleotide position alterations was more similar to that observed in gastrointestinal tumors than other lung tumors. Within the KRAS -negative cases, we found numerous potentially targetable gene fusions and mutations, including CD74-NRG1 , VAMP2-NRG1 , TRIM4-BRAF , TPM3-NTRK1 , and EML4-ALK gene fusions and ERBB2 , BRAF , and PIK3CA mutations. Unexpectedly, we found only two cases with TP53 mutation, which is much lower than observed in lung adenocarcinomas in general. The overall mutation burden was low in histologically confirmed mucinous adenocarcinomas from the public The Cancer Genome Atlas exome data set, regardless of smoking history, suggesting a link between TP53 status and mutation burden in mucinous tumors. There was no significant difference for recurrence-free survival between stage-matched mucinous and nonmucinous adenocarcinomas. It was notable that all recurrence sites were in the lungs for completely resected cases. Conclusions: Our data suggest that mucinous adenocarcinoma is typified by (1) frequent KRAS mutations and a growing list of gene fusions, but rare TP53 mutations, (2) a low mutation burden overall, and (3) a recurrence-free survival similar to stage-matched nonmucinous tumors, with recurrences limited to the lungs.

BACKGROUND/AIMS There are increasing evidences for gastrointestinal motility disorder (GIMD) and gastric stress ulcer induced by noise stress. The present study was to investigate the reversed effect of melatonin on GIMD and gastric stress ulcer induced by noise stress and potential mechanism. METHODS Noise stress was induced on rats, and melatonin (15 mg/kg) was administered to rats by intraperitoneal injection. Differences were assessed in gastric residual rate (GRR), small intestine propulsion rate (SPR), Guth injury score, cortisol, gastrointestinal hormones (calcitonin-gene-related peptide and motilin) and oxidative stress markers (superoxide dismutase and malondialde hyde) in blood plasma as well as gastric mucosa homogenate with or without melatonin. The pathological examination of gastric mucosa was also performed. RESULTS The GRR and SPR were improved by noise stress compared with control (P < 0.05). The pathological examination and Guth injury score revealed gastric stress ulcer. Moreover, the levels of cortisol, motilin and malondialdehyde in blood plasma and ma-londialdehyde in gastric mucosa homogenate were increased by noise stress (P < 0.05). CGRP and superoxide dismutase activ-ity in both of blood plasma and gastric mucosa homogenate were significantly decreased (P< 0.05). Furthermore, melatonin reversed changes in GRR, SPR, pathological examination, Guth injury score, cortisol, motilin, CGRP, superoxide dismutase activity and malondialdehyde (P < 0.05). CONCLUSIONS Melatonin is effective in reversing the GIMD and gastric stress ulcer induced by noise stress. The underlying mechanism may be involved in oxidative stress and gastrointestinal hormones.

This paper introduces temporal confusion network and its application for speech-based soccer event retrieval, where an event is remarked by the announcer's spoken words. A temporal confusion network is a confusion network in which each cluster is marked with temporal information. Since the purpose of soccer event retrieval is to retrieve only the interesting highlights - not the whole video clip, temporal information is crucial in tracking them. By expanding the indexing model from 1-best transcriptions to temporal confusion networks, recall rates for event retrieval can be improved. Experiments are conducted on the first round of World Cup 2010 and the Vietnamese AFF Suzuki-cup 2008 databases. In the best case, an average improvement of 7.1% recall rate is achieved.

Background and purpose— Statins can effectively attenuate focal cerebral ischemic injury. However, the role of statins in modulating permeability of endothelial barrier in ischemia-reperfusion (IR) and the impact of statins withdrawal on endothelial barrier during the acute phase of IR are unclear. Methods— Focal cerebral ischemia (2 hours) was created in adult male Sprague-Dawley rats (240 to 270 g) by middle cerebral artery occlusion (MCAO) using a suture. Rats were randomly treated with vehicle, atorvastatin daily for 7 days before MCAO (pretreatment), 3 days after MCAO (post operative treatment), or both 7 days before and 3 days after MCAO (continuous treatment). Brains were harvested at 24 and 72 hours after reperfusion for assays of brain edema (n=5), BBB leakage (n=5), calculations of occludin and claudin-5 positive vessels (n=5) and expression of occludin, claudin-5 and Phosphoinositide 3-kinase (PI3K)-γ (n=5), respectively. Results— 24 hours after reperfusion, pretreatment with atorvastatin significantly reduced BBB leakage (7.55±0.63ng/g versus 9.38±0.77ng/g; P Conclusions— These results demonstrate that protective effects of atorvastatin against endothelial barrier breakdown may be related to the up-regulation of occludin and claudin-5 and down-regulation of PI3Kγ. However, there are no withdrawal effects of atorvastain on endothelial barrier during the acute phase of IR (72 hours).

Background. The potential role of finasteride in treating androgen related skin disorders was investigated. Methods. Pooled human dermal fibroblasts were used to assess the effect of finasteride on the 5α-reductase activity in skin tissue. Vmax and Km were estimated in the presence of 0, 10, and 200 nM finasteride. Results. Vmax values remain constant near 1.20 pmol/mg protein/h in the presence of increasing concentrations of finasteride; however, apparent Km increases from 0.27 nM at 0 nM finasteride to 0.31 nM and 0.44 nM at 10 nM and 200 nM finasteride, respectively. This suggests that ministered competes with testosterone and has a high affinity for same binding site of the 5α-reductase enzyme. Apparent Ki was estimated at 282 nM, indicating that a high concentration of finasteride is required to significantly suppress the enzyme activity. Conclusions. This study confirms that finasteride inhibits the conversion of testosterone to dihydrotestosterone in human reticular dermal fibroblasts. Finasteride may have therapeutic potential in treating skin disorders influenced by the action of dihydrotestosterone.

background . The biomechanical and viscoelastic properties of the skin enable it to be significantly stretched within a relatively short period of time. This property, called mechanical creep, is exploited in various surgical maneuvers for intraoperative closure of large surgical defects. The recently introduced Miami Suture Tension Adjustment Reel (S.T.A.R.) device permits both the precise sutured attachment of a linear cycled load to approximate the edges of widened surgical defects, and the easy measurement of wound edge tension across the defects. objective . It was our purpose to compare the relative effects of linear load cycling with the S.T.A.R. device, spherical load cycling with balloon expander, and surgical undermining on the closing tension of surgical defects. methods . Surgical wounds were created on the flanks of six pigs and these defects were closed by various methods of repair. The combination of undermining and the S.T.A.R. device was also evaluated. results . The average total decreases in skin closing tension were: undermining, 17.8 ± 0.5%; balloon, 28.5 ± 1.6%; S.T.A.R. device, 36.6 ± 4.8%. conclusions . Our data showed that all three techniques were effective in lowering the tension required to approximate surgically created defects, with the S.T.A.R. device proving to be most effective. Undermining and the S.T.A.R. device also worked synergistically to decrease skin-closing tension.

DTNBP1 (dystrobrevin binding protein 1) is a leading candidate susceptibility gene in schizophrenia and is associated with working memory capacity in normal subjects. In schizophrenia, the encoded protein dystrobrevin-binding protein 1 (dysbindin-1) is often reduced in excitatory cortical limbic synapses. We found that reduced dysbindin-1 in mice yielded deficits in auditory-evoked response adaptation, prepulse inhibition of startle, and evoked γ-activity, similar to patterns in schizophrenia. In contrast to the role of dysbindin-1 in glutamatergic transmission, γ-band abnormalities in schizophrenia are most often attributed to disrupted inhibition and reductions in parvalbumin-positive interneuron (PV cell) activity. To determine the mechanism underlying electrophysiological deficits related to reduced dysbindin-1 and the potential role of PV cells, we examined PV cell immunoreactivity and measured changes in net circuit activity using voltage-sensitive dye imaging. The dominant circuit impact of reduced dysbindin-1 was impaired inhibition, and PV cell immunoreactivity was reduced. Thus, this model provides a link between a validated candidate gene and an auditory endophenotypes. Furthermore, these data implicate reduced fast-phasic inhibition as a common underlying mechanism of schizophrenia-associated intermediate phenotypes.

BACKGROUND AND OBJECTIVE: Oncoprotein Myc is a master transcription factor and plays a crucial role in human cancer pathogenesis and the stem-like phenotype of glioblastoma (GBM). Since dyregulated Myc in cancer drives altered glucose and glutamine metabolism promoting tumor growth, pathways involved in Myc-induced aberrant metabolism could offer therapeutic targets. The coenzyme Nicotinamide Adenine Dinucleotide (NAD+) is essential in redox reactions including glycolysis and the citric acid cycle. We sought to determine whether MYC-amplified GBM, as compared to MYC-non-amplified GBM, utilizes distinct NAD+ biosynthesis pathways and exhibits differential dependence on metabolic pathways that require NAD+. MATERIALS AND METHODS: A total of 11 patient-derived GBM stem-like cell (GSCs) lines established from surgical specimens were used. FISH analysis was performed to determine copy number status of MYC and MYCN. Expression of enzymes involved in NAD+ synthesis [e.g., nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT-1)] was tested with Western blot. NAD+ levels were measured after treating GSCs with FK866, a potent and specific small molecule inhibitor for NAMPT. The effects of pharmacological inhibition of NAMPT on GSC viability were determined by CellTiter Glo cell viability assay. RESULTS: Five (45.5%) GSCs had MYC (1) or MYCN (4) amplification. FK866 depleted NAD+ levels in GSCs. Treatment with FK866 potently inhibited in vitro growth of all the GSCs that harbored MYC/MYCN amplification with IC50 values in a low-nanomolar range (0.7 - 4.6 nM). In contrast, non-amplified GSCs as well as human normal astrocytes showed resistance to FK866. The MYC/MYCN amplified GSCs expressed low or undetectable levels of NAPRT-1, which is involved in the NAD+ synthesis pathway utilizing nicotinic acid. CONCLUSIONS: MYC/MYCN-amplified GSCs, but not non-amplified GSCs, were exquisitely sensitive to NAMPT inhibition. NAMPT may represent a promising therapeutic target for GBM with MYC amplification.

background. Factors associated with the development of squamous cell carcinoma (SCC) of the finger are verruca vulgaris, radiation exposure, burns, and arsenic ingestion, objectives. We wish to further document the relationship between human papillomavirus (HPV) and roentgen exposure to squamous cell carcinoma of the finger. methods. A retrospective study of 32 cases of digital squamous cell carcinoma seen at UCLA Medical Center was performed. results. Ten patients (31%) had histories ofverrucae at the site of the carcinoma. Eight patients (25%) had histories of x-ray therapy to the hand. conclusion. Our study further supports the association of verruca vulgaris and radiation exposure in the development of squamous cell carcinoma of the finger.

Immunohistochemistry and flow cytometry analyses were performed to characterize the specific T cell subpopulations infiltrating basal cell carcinomas (BCC) and to determine their phenotypic response to in vitro expansion with IL-2. Tumor-infiltrating lymphocytes (TIL) within BCC predominantly expressed the CD45RO (activated or "memory") phenotype (65 ± 3%) and the percentage of TIL expressing CD45RO consistently increased when cultured in vitro with IL-2 (85 ± 5%). In comparison, fresh normal peripheral blood lymphocytes predominantly expressed the CD45RA (naive) phenotype (79 ± 4%), but shifted to the expression of CD45RO following in vitro expansion in IL-2 (86 ± 6%). To determine whether IL-2 alone, in the absence of antigen or mitogen, can promote naive lymphocytes to convert from the expression of the CD45RA isoform to the CD45RO isoform, we cultured purified CD45RA + lymphocytes in IL-2. After three weeks in culture, 90% of the lymphocytes expressed exclusively CD45RO. We conclude that tumor-infiltrating lymphocytes from BCC predominantly express CD45RO and that this expression may represent specific antigen stimulation and/or in situ activation by cytokines.

• Background.— Angiolymphoid hyperplasia (ALH) with eosinophilia is a benign rare tumor, characterized by marked proliferation of endothelial cells. The tumors are associated with extensive infiltrate of lymphocytes, histiocytes, and eosinophils, and occur on the head and neck of young adults. A variety of treatments have been attempted with frequent recurrences. We report two cases of ALH with eosinophilia that seemed to be dependent on sex hormones. Observation.— The first case is a patient with ALH that resolved after stopping treatment with birth control pills. Biopsy specimens of the tumor demonstrated increased level of estrogen and progesterone receptors compared with her normal skin. The second case is a patient with a previous lesion of ALH with eosinophilia, who during pregnancy had new lesions develop and whose primary lesion increased in size. All lesions decreased to half their original sizes after pregnancy. Conclusion.— Both of these cases suggest a role for hyperestrogen states with the presence of hormonal receptors. The response to sex hormones could contribute to the pathogenesis of the disease and may offer future alternative treatment modalities. (Arch Dermatol.1992;128:825-828)