Prophylactic (R,S)-Ketamine Is Effective Against Stress-Induced Behaviors in Adolescent but Not Aged Mice.

BACKGROUND: (R,S)-ketamine, an N-methyl-D-aspartate receptor antagonist, is frequently used as an anesthetic and as a rapid-acting antidepressant. We and others have reported that (R,S)-ketamine is prophylactic against stress in adult mice but have yet to test its efficacy in adolescent or aged populations. METHODS: Here, we administered saline or (R,S)-ketamine as a prophylactic at varying doses to adolescent (5-week-old) and aged (24-month-old) 129S6/SvEv mice of both sexes 1 week before a 3-shock contextual fear-conditioning (CFC) stressor. Following CFC, we assessed behavioral despair, avoidance, perseverative behavior, locomotion, and contextual fear discrimination. To assess whether the prophylactic effect could persist into adulthood, adolescent mice were injected with saline or varying doses of (R,S)-ketamine and administered a 3-shock CFC as a stressor 1 month later. Mice were then re-exposed to the aversive context 5 days later and administered behavioral tests as aforementioned. Brains were also processed to quantify Cyclooxygenase 2 expression as a proxy for inflammation to determine whether the prophylactic effects of (R,S)-ketamine were partially due to changes in brain inflammation. RESULTS: Our data indicate that (R,S)-ketamine is prophylactic at sex-specific doses in adolescent but not aged mice. (R,S)-ketamine attenuated learned fear and perseverative behavior in females, reduced behavioral despair in males, and facilitated contextual fear discrimination in both sexes. (R,S)-ketamine reduced Cyclooxygenase 2 expression specifically in ventral Cornu Ammonis region 3 of male mice. CONCLUSIONS: These findings demonstrate that prophylactic (R,S)-ketamine efficacy is sex, dose, and age dependent and will inform future studies investigating (R,S)-ketamine efficacy across the lifespan.

Distal duplication of chromosome 16q22.1q23.1 in a Vietnamese patient with midface hypoplasia and intellectual disability.

The clinical presentation of distal duplications of the long arm of chromosome (chr) 16 is currently not well described. Only one case of microduplication of chr16q22.1 and another involving the chr16q22.1q23.1 region have been reported so far. Here, using array comparative genomic hybridization, we identified a second case of chr16q22.1q23.1 duplication in a Vietnamese boy, who shares significant clinical phenotype with the previously described case. Aside from developmental delay, intellectual disability and midface hypoplasia, our patient also displays a forked tongue, visual impairment and external ptosis. Our report further expands the clinical spectrum associated with duplication of this region.

Undergraduate Medical Education Reform in Viet Nam for a Primary Health Care Workforce.

Strong primary health care (PHC) systems require a robust PHC workforce. Traditionally, medical education takes place in academic medical centres that favour subspecialty care rather than PHC settings. This may undervalue primary care as a career and contribute to a shortage of PHC workers. However, designing undergraduate medical education curricula that incorporate early experiences in clinical care delivery at PHC sites remains a challenge, including in many low- and middle-income countries (LMICs). This paper describes how a collaboration between Harvard Medical School and five medical schools in Vietnam, and in-country collaborations among the Vietnamese medical schools, facilitated curricular innovation and co-creation of coursework relevant to PHC through the development of a Practice of Medicine (POM) course. The collaboration implemented a technical assistance strategy consisting of in-person workshops, focused virtual consultations, on-site 'office hours', site visits and observations to each of the five medical universities, and immersion trips to support the creation and implementation of the POM course. A pilot program was started at a single site and then scaled nationally using local customisation, experience, and expertise utilising a train-the-trainers approach. As a result, five new POM courses have been developed by five Vietnamese institutions. Fifty Vietnamese faculty received training to lead the POM course development, and 228 community-based preceptors have been trained to teach students at PHC sites. A total of 52 new PHC and community-based clinical training sites have been added, and 3,615 students have completed or are currently going through a POM course. This experience can serve as a model for future academic collaborations to support the development of a robust PHC workforce for the 21st century.

"I Wish I Could Die So I Would Not Be in Pain": A Qualitative Study of Palliative Care Needs Among People With Cancer or HIV/AIDS in Vietnam and Their Caregivers.

CONTEXT: Although cancer and HIV/AIDS are common causes of death in Vietnam, limited data exist on their palliative care needs. As palliative care becomes part of Universal Health Coverage, evidence is needed to scale up appropriate care. OBJECTIVES: To elicit from people with cancer or HIV/AIDS in Vietnam, and their caregivers, the specific multidimensional symptoms and concerns that cause serious health-related suffering. METHODS: Semistructured, qualitative, in-depth interviews were conducted with stage III or IV cancer patients, people with HIV/AIDS, and their caregivers at three cancer treatment centers and two HIV/AIDS treatment centers in northern, central, and southern Vietnam. Interviews were analyzed using thematic analysis. RESULTS: Sixty people were interviewed (21 cancer patients, 20 people with HIV/AIDS, 19 caregivers). Pain and other physical symptoms severely impacted their daily lives. Psychological distress-including sadness, depression, worry, and a feeling of having no future-was mentioned frequently, and it was exacerbated by disease progression and by social problems such as financial difficulties and, among people with HIV/AIDS, stigma. Caregivers also suffered physically and psychosocially. Spirituality emerged as a source of strength for patients. Findings highlighted patients' and family caregivers' desire for more information about diagnosis, prognosis, and treatment, a shift toward individual decision-making. CONCLUSION: The findings demonstrate common, multidimensional, and severe suffering among people living with cancer or HIV/AIDS and their caregivers in Vietnam. These qualitative data should guide development of optimum clinical assessment tools and palliative care services for these populations.

Microcephaly primary hereditary (MCPH): Report of novel ASPM variants and prenatal diagnosis in a Vietnamese family.

OBJECTIVE: MCPH (microcephaly primary hereditary) is a group of autosomal recessive developmental disorders with microcephaly present at birth and intellectual disability. Since a second trimester ultrasound is not able to detect subtypes with minimal prenatal presentations, only prenatal diagnosis by genetic testing can confirm these cases and allow for effective genetic counseling, especially a family with a previously affected child. CASE REPORT: A 37-year-old women was pregnant for the third time and had two prior children with profound microcephaly and mental retardation. Targeted panel sequencing identified novel compound heterozygous ASPM pathogenic variants: c.1615_1616del (p. Glu539ArgfsTer15); c.∗293T > A (p. Leu98Ter), which confirmed the diagnosis of MCPH5 (#OMIM 608716). Genetic testing was conducted for family members and applied on prenatal diagnosis. CONCLUSION: This is the first cases of MCPH5 to be reported in Vietnam and the genetic result aided in prenatal diagnosis of a high-risk pregnancy. The study highlights the importance of genetic testing in defining definitive diagnosis which allowed for timely prenatal diagnosis and genetic counseling for the family.

Building the hospital event-based surveillance system in Viet Nam: a qualitative study to identify potential facilitators and barriers for event reporting.

INTRODUCTION: Hospitals are a key source of information for the early identification of emerging disease outbreaks and acute public health events for risk assessment, decision-making and public health response. The objective of this study was to identify potential facilitators and barriers for event reporting from the curative sector to the preventive medicine sector in Viet Nam. METHODS: In 2016, we conducted 18 semi-structured, in-depth interviews, as well as nine focus group discussions, with representatives from the curative and preventive medicine sectors in four provinces. We transcribed the interviews and focus group discussions and used thematic analysis to identify the factors that appeared to affect public health event reporting. RESULTS: We identified five major themes. First, the lack of a legal framework to guide reporting meant hospital staff relied on internal procedures that varied from hospital to hospital, which sometimes delayed reporting. Second, participants stated the importance of an enabling environment, such as leadership support and having focal points for reporting, to facilitate reporting. Third, participants described the potential benefits of reporting, such as support provided during outbreaks and information received about local outbreaks. Fourth, some challenges prohibited timely reporting such as not perceiving reporting to be the task of the curative sector and hesitancy to report without laboratory confirmation. Finally, limited resources and specialist capacities in remote areas hindered timely detection and reporting of unusual events. DISCUSSION: This study identified potential opportunities to promote the detection and reporting of unusual events from health-care workers to the public health sector, and thus to improve the overall health security system in Viet Nam.The influenza virus is a respiratory pathogen that is transmitted through respiratory droplets. 1 During seasonal influenza epidemics, high attack rates cause a significant public health burden. 2 The infection is usually self-limited in young adults but can lead to severe infections in people in high-risk groups, including elderly people (> 65 years old), pregnant women, children aged 6-59 months and adults with chronic illnesses. 3.

Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family.

Leigh syndrome is a rare inherited, heterogeneous and progressive neurometabolic disorder that is mainly caused by specific mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). The present study reported a case of childhood Leigh syndrome with a point mutation at bp 8,993 in the mitochondrial ATPase6 gene. A 21­month­old male child had developed epilepsy, muscular weakness and vomiting, which was accompanied by high fever. Magnetic resonance imaging indicated typical characteristics of Leigh syndrome, including a symmetric abnormal signal in the dorsal medulla oblongata and Sylvian fissure enlargement in association with an abnormal signal in the periventricular white matter and in the putamina and caudate heads. The diagnosis was further supported with genetic tests including polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), sequencing, and quantitative PCR. The patient was found to carry a mitochondrial T8993C (m.T8993C) mutation in peripheral blood with 94.00±1.34% heteroplasmy. Eight of his relatives were also subjected to quantification of the m.T8993C mutation. The percentages of heteroplasmy in samples taken from the grandmother, mother, aunt, cousin 1, and cousin 2 were 16.33±1.67, 66.81±0.85, 71.66±3.22, 87.00±1.79, and 91.24±2.50%, respectively. The mutation was not found in samples taken from the father, the husband of the aunt, or the grandfather of the patient. The obtained data showed that the mutation was maternally inherited and accumulated through generations. Even though the heteroplasmy levels of his mother, aunt, cousin 1, and cousin 2 were relatively high (66.81­91.24%), they remained asymptomatic, indicating that the threshold at which this mutation shows effects is high. To the best of our knowledge, this is the first report of a case of Leigh syndrome in a Vietnamese individual harboring a mtDNA mutation at the 8,993 bp site, and showing a correlation between the heteroplasmy and clinical phenotype. These findings may be useful in helping to improve the clinical diagnosis and treatment of Leigh syndrome.

Screening of common point-mutations and discovery of new T14727C change in mitochondrial genome of Vietnamese encephalomyopathy patients.

Vietnamese patients (106) tentatively diagnosed with encephalomyopathy were screened for the presence of 15 common point mutations in mitochondria using PCR-RFLP. The screened mutations include A3243G, T3271C and T3291C for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS); A8344G and T8356C for Myoclonus Epilepsy and Rag-Red Fibers (MERRF); G11778A, G3460A and T14484C for Leber's Hereditary Optic Neuropathy (LHON); T8993G/C and T9176G for Leigh syndrome; A1555G for deafness syndrome; G4298A, T10010C, T14728C and T14709C for neuromuscular syndrome. As a result, 6 cases of A3243G (5.7%) and 2 cases of T14727C (3.9%) were found. The 6 cases of A3243G mutation were heteroplasmic at different levels (4.23-80.85%). The T14727C change was discovered for the first time in the MTTE gene encoding for tRNA(Glu) and showed homoplasmy. The T14727C change was probably a mutation because it was further confirmed as vertically inherited from the mother and not the result of isolated polymorphism.

Evaluation of Two Techniques for Viral Load Monitoring Using Dried Blood Spot in Routine Practice in Vietnam (French National Agency for AIDS and Hepatitis Research 12338).

Background. Although it is the best method to detect early therapeutic failure, viral load (VL) monitoring is still not widely available in many resource-limited settings because of difficulties in specimen transfer, personnel shortage, and insufficient laboratory infrastructures. Dried blood spot (DBS) use, which was introduced in the latest World Health Organization recommendations, can overcome these difficulties. This evaluation aimed at validating VL measurement in DBS, in a laboratory without previous DBS experience and in routine testing conditions. Methods. Human immunodeficiency virus (HIV)-infected adults were observed in a HIV care site in Hanoi, and each patient provided 2 DBS cards with whole blood spots and 2 plasma samples. Viral load was measured in DBS and in plasma using the COBAS Ampliprep/TaqMan and the Abbott RealTime assays. To correctly identify those with VL ≥ 1000 copies/mL, sensitivity and specificity were estimated. Results. A total of 198 patients were enrolled. With the Roche technique, 51 plasma VL were ≥1000 copies/mL; among these, 28 presented a VL in DBS that was also ≥1000 copies/mL (sensitivity, 54.9; 95% confidence interval [CI], 40.3-68.9). On the other hand, all plasma VL < 1000 copies/mL were also <1000 copies/mL in DBS (specificity, 100; 95% CI, 97.5-100). With the Abbott technique, 45 plasma VL were ≥1000 copies/mL; among these, 42 VL in DBS were also ≥1000 copies/mL (sensitivity, 93.3%; 95% CI, 81.7-98.6); specificity was 94.8 (95% CI, 90.0-97.7). Conclusions. The Abbott RealTime polymerase chain reaction assay provided adequate VL results in DBS, thus allowing DBS use for VL monitoring.

Subclassification of nerve sheath tumors by gene expression profiling.

Nerve sheath tumors are the most common tumors of Neurofibromatosis type 1 (NF1) patients. Dermal neurofibromas develop in nearly all NF1-patients, whereas plexiform neurofibromas are only observed in one-third of the patients. NF1-patients have about a 10% lifetime risk for developing malignant pheripheral nerve sheath tumors (MPNST). The origin of these tumors is thought to be the Schwann cell lacking functional neurofibromin. However, additional genetic alterations are likely to modulate tumor biology and to contribute to individual nerve sheath tumor entities. To gain insight into the molecular events and to determine whether these tumors can be classified according to gene expression profiles, we performed expression analysis applying cDNA array technology. Nine dermal neurofibromas, 7 plexiform neurofibromas, ten MPNST and two MPNST cell cultures were examined. All tumors but 6 sporadic MPNST were obtained from NF1-patients. We detected significant differences in gene expression patterns between neurofibromas and MPNST and between dermal neurofibromas and plexiform neurofibromas. Tumor class prediction agreed in all but one case with histological and clinical classification. NF1-associated and sporadic MPNST could not be distinguished by their gene expression patterns. We present a panel of discriminating genes that may assist subclassification of nerve sheath tumors.