Household-Contact Investigation for Detection of Tuberculosis in Vietnam.

BACKGROUND: Active case finding is a top priority for the global control of tuberculosis, but robust evidence for its effectiveness in high-prevalence settings is lacking. We sought to evaluate the effectiveness of household-contact investigation, as compared with standard, passive measures alone, in Vietnam. METHODS: We performed a cluster-randomized, controlled trial at clinics in 70 districts (local government areas with an average population of approximately 500,000 in urban areas and 100,000 in rural areas) in eight provinces of Vietnam. Health workers at each district clinic or hospital were assigned to perform either household-contact intervention plus standard passive case finding (intervention group) or passive case finding alone (control group). In the intervention districts, household contacts of patients with positive results for tuberculosis on sputum smear microscopy (smear-positive tuberculosis) were invited for clinical assessment and chest radiography at baseline and at 6, 12, and 24 months. The primary outcome was the cumulative incidence of registered cases of tuberculosis among household contacts of patients with tuberculosis during a 2-year period. RESULTS: In 70 selected districts, we enrolled 25,707 household contacts of 10,964 patients who had smear-positive pulmonary tuberculosis. In the 36 districts that were included in the intervention group, 180 of 10,069 contacts were registered as having tuberculosis (1788 cases per 100,000 population), as compared with 110 of 15,638 contacts (703 per 100,000) in the control group (relative risk of the primary outcome in the intervention group, 2.5; 95% confidence interval [CI], 2.0 to 3.2; P<0.001); the relative risk of smear-positive disease among household contacts in the intervention group was 6.4 (95% CI, 4.5 to 9.0; P<0.001). CONCLUSIONS: Household-contact investigation plus standard passive case finding was more effective than standard passive case finding alone for the detection of tuberculosis in a high-prevalence setting at 2 years. (Funded by the Australian National Health and Medical Research Council; ACT2 Australian New Zealand Clinical Trials Registry number, ACTRN12610000600044 .).

Src Kinase Is Biphosphorylated at Y416/Y527 and Activates the CUB-Domain Containing Protein 1/Protein Kinase C δ Pathway in a Subset of Triple-Negative Breast Cancers.

Targeted therapeutics are needed for triple-negative breast cancer (TNBC). In this study, we investigated the activation of Src family of cytoplasmic tyrosine kinases (SFKs) and two SFK substrates-CUB-domain containing protein 1 (CDCP1) and protein kinase C δ (PKCδ)-in 56 formalin-fixed, paraffin-embedded (FFPE) TNBCs. Expression of SFK phosphorylated at Y416 (SFK_pY416+) in tumor cells was strongly associated with phosphorylation of CDCP1 and PKCδ (CDCP1_ pY743+ and PKCδ_pY311+), as assessed by immunohistochemistry, indicating increased SFK activity in situ. To enable biochemical analysis, protein extraction from FFPE tissue was optimized. Cleaved CDCP1 isoform (70 kDa) was expressed to a varying degree in all samples but only phosphorylated in TNBC tumor cells that expressed SFK_pY416. Interestingly, active SFK was found to be biphosphorylated (SFK_pY416+/pY527+). Biphosphorylated active SFK was observed more frequently in forkhead box protein A1 (FOXA1)- TNBCs. In addition, in SFK_pY416- samples, FOXA1+ TNBC tended to be SFK_pY527+ (classic inactive SFK), and FOXA1- TNBC tended to be SFK_pY527- (SFK poised for activation). Strong SFK_pY416 staining was also observed in tumor-infiltrating lymphocytes in a subset of TNBCs with high tumor-infiltrating lymphocyte content. This report will facilitate protein biochemical analysis of FFPE tumor samples and justifies the development of therapies targeting the SFK/CDCP1/PKCδ pathway for TNBC treatment.

The extrachromosomal elements of the Naegleria genus: How little we know.

There are currently 47 characterized species in the Naegleria genus of free-living amoebae. Each amoeba has thousands of extrachromosomal elements that are closed circular structures comprised of a single ribosomal DNA (rDNA) copy and a large non-rDNA sequence. Despite the presence of putative open reading frames and introns, ribosomal RNA is the only established transcript. A single origin of DNA replication (ori) has been mapped within the non-rDNA sequence for one species (N. gruberi), a finding that strongly indicates that these episomes replicate independently of the cell's chromosomal DNA component. This article reviews that which has been published about these interesting DNA elements and by analyzing available sequence data, discusses the possibility that different phylogenetically related clusters of Naegleria species individually conserve ori structures and suggests where the rRNA promoter and termination sites may be located.

Effect of penetration enhancer with novel corneal cross-linking using recombinant human decoron in porcine eyes.

The aim of the study was to investigate the effectiveness of exogenous recombinant human decoron and an accompanying penetration-enhancing solution in stiffening ex-vivo porcine corneas both transepithelially and after de-epithelialization. Eight porcine paired eyes were treated transepithelially: one eye with a pre-treatment solution (Pre-Tx), penetration enhancing solution (PE), and decoron while the fellow eye was treated by the same protocol but without decoron. A second group included 4 de-epithelialized pairs treated identically. The final group included 4 de-epithelialized pairs with one eye treated with Pre-Tx, PE, and decoron while the fellow eye was treated without PE. Uniaxial tensile testing was used to compare the corneal stiffness between the different treatment conditions. Residual tissue underwent immunohistochemistry analysis to evaluate the depth of penetration of decoron into the corneal stroma. There was no stiffening effect exhibited among corneas treated transepithelially with decoron compared to control (P > 0.05) and poor stromal penetration was exhibited on tissue analysis. Among de-epithelialized corneas, there was a significant stiffening effect seen in those treated with decoron at 3%, 4%, 5%, & 6% strain (P < 0.05) compared to control. Among de-epithelialized corneas there was also a significant stiffening effect seen in those treated with the PE and decoron at 4%, 5%, & 6% strain (P < 0.05) with improved stromal penetration confirmed by immunohistochemistry, versus without PE. De-epithelialization is necessary for effective stromal penetration of decoron. Depth of penetration and subsequent corneal stiffening may be improved with a penetration enhancing solution. Compared to riboflavin, decoron requires shorter treatment time and spares UV light exposure.

Biomechanical contribution of the sclera to dynamic corneal response in air-puff induced deformation in human donor eyes.

This study was conducted to evaluate the impact of varying scleral material properties on the biomechanical response of the cornea under air-puff induced deformation. Twenty pairs of human donor eyes were obtained for this study. One eye from each pair had its sclera stiffened using 4% glutaraldehyde, while the fellow eye served as control for uniaxial strip testing. The whole globes were mounted in a rigid holder and intraocular pressure (IOP) was set using a saline column. Dynamic corneal response parameters were measured before and after scleral stiffening using the CorVis ST, a dynamic Scheimpflug analyzer. IOP was set to 10, 20, 30, and 40 mmHg, with at least 3 examinations performed at each pressure step. Uniaxial tensile testing data were fit to a neo-Hookean model to estimate the Young's modulus of treated and untreated sclera. Scleral Young's modulus was found to be significantly correlated with several response parameters, including Highest Concavity Deformation Amplitude, Peak Distance, Highest Concavity Radius, and Stiffness Parameter-Highest Concavity (SP-HC). There were significant increases in SP-HC after scleral stiffening at multiple levels of IOP, while no significant difference was observed in the corneal Stiffness Parameter - Applanation 1 (SP-A1) at any level of IOP. Scleral mechanical properties significantly influenced the corneal deformation response to an air-puff. The stiffer the sclera, the greater the constraining effect on corneal deformation resulting in lower displaced amplitude. This may have important clinical implications and suggests that both corneal and scleral material properties contribute to the observed corneal response in air-puff induced deformation.

Diversity and Distribution of Rice Blast (Pyricularia oryzae Cavara) Races in Vietnam.

A total of 239 isolates of blast (Pyricularia oryzae Cavara) collected from northern and central Vietnam showed a wide variation in pathogenicity based on the reaction patterns to 25 differential varieties (DVs) harboring 23 resistance genes and susceptible cultivar Lijiangxintuanheigu (LTH). The frequencies of isolates virulent toward DVs for Pish, Pik-m, Pi1, Pik-h, Pik, Pik-p, Pi7(t), Pi9(t), Piz-5, Pita-2, and Pita were low, but they were high for DVs for Pib, Pit, Pia, Pii, Pi3, Pi5(t), Pik-s, Piz, Piz-t, Pi12(t), Pi19(t), and Pi20(t). Isolates were classified into three cluster groups Ia, Ib, and II based on reaction patterns to DVs and LTH. The frequencies of isolates virulent toward 11 DVs for Pik-m, Pi1, Pik-h, Pik, Pik-p, Pi7(t), Pi9(t), Piz, Piz-5, Pita-2, and Pita in cluster II and DV for Piz-t were higher and lower than those of Ia and Ib, respectively. The frequencies to DVs for Pii, Pi3, Pi5(t), and Piz-t were different between clusters Ia and Ib. Clusters Ia and Ib were distributed with similar frequencies in the northeast, north central, and south central coast regions, but the frequencies among three cluster groups in the Red River Delta and northwest regions were different. This means that the blast races in these two regions were different from the others. Overall, the blast isolates were categorized into 153 races. Among them, 26 were selected as a set of standard differential blast isolates for characterizing 23 resistance genes and developing a differential system in Vietnam.

Post-treatment Mortality Among Patients With Tuberculosis: A Prospective Cohort Study of 10 964 Patients in Vietnam.

BACKGROUND: Tuberculosis is the leading infectious cause of death. Steep reductions in tuberculosis-related mortality are required to realize the World Health Organization's "End Tuberculosis Strategy." However, accurate mortality estimates are lacking in many countries, particularly following discharge from care. This study aimed to establish the mortality rate among patients with pulmonary tuberculosis in Vietnam and to quantify the excess mortality in this population. METHODS: We conducted a prospective cohort study among adult patients treated for smear-positive pulmonary tuberculosis in 70 clinics across Vietnam. People living in the same households were recruited as controls. Participants were re-interviewed and their survival was established at least 2 years after their treatment with an 8-month standardized regimen. The presence of relapse was established by linking identifying data on patients and controls to clinic registries. Verbal autopsies were performed. The cumulative mortality among patients was compared to that among a control population, adjusting for age and gender. RESULTS: We enrolled 10964 patients and 25707 household controls. Among enrolled tuberculosis patients, 9% of patients died within a median follow-up period of 2.9 years: 342 (3.1%) during treatment and 637 (5.8%) after discharge. The standardized mortality ratio was 4.0 (95% confidence interval 3.7-4.2) among patients with tuberculosis, compared to the control population. Tuberculosis was the likely cause of death for 44.7% of these deceased patients. CONCLUSIONS: Patients treated for tuberculosis had a markedly elevated risk of death, particularly in the post-treatment period. Interventions to reduce tuberculosis mortality must enhance the early detection of drug-resistance, improve treatment effectiveness, and address non-communicable diseases.

The utility of optical coherence tomography for diagnosis of basal cell carcinoma: a quantitative review.

BACKGROUND: Optical coherence tomography (OCT) is a noninvasive near-infrared light imaging technology that can be utilized to diagnose basal cell carcinomas (BCCs) based on specific morphological features. OBJECTIVES: To conduct a quantitative review using tumour-level data from published studies to assess: (i) the in vivo diagnostic accuracy of different OCT systems; (ii) correlation between OCT features and histopathological diagnosis; and (iii) factors that impact the accuracy of tumour depth estimation. METHODS: Primary tumour-level data were extracted from published studies on the use of time-domain (TD-OCT), frequency-domain (FD-OCT) and high-definition (HD-OCT) systems for diagnosis of BCCs. Quality assessment was performed using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool. Sensitivity and specificity for diagnosis of BCC, prevalence of morphological features and correlation of tumour depth between OCT and histopathology were analysed. RESULTS: In total, 901 BCCs from 31 studies were included. The sensitivity and specificity were 89·3% and 60·3% overall, and were highest for FD-OCT (93·7% and 61·4%, respectively). The most prevalent morphological features were lobular pattern (80·2%, 315 of 393 tumours) and hyper-reflective peritumoral stroma (51·7%, 203 of 393). Concordance between OCT and histopathological tumour depth categories was moderate (Pearson coefficient 0·48); it was highest for tumours < 1 mm and those on the extremities. The overall bias was 0·075 mm with an agreement range from -0·88 to 1·03 mm. HD-OCT and FD-OCT were superior to TD-OCT at identifying morphological features, but not at tumour depth estimation. CONCLUSIONS: OCT is a viable tool for in vivo diagnosis of BCCs. FD-OCT and HD-OCT outperformed TD-OCT in diagnostic accuracy and detection of morphological features, but not tumour depth estimation.

Short communication: Microlearning courses are effective at increasing the feelings of confidence and accuracy in the work of dairy personnel.

Optimization of work processes and personnel compliance becomes progressively essential to ensure high process and product quality on dairy farms with an increasingly nonfamily work force. Standard operating procedures (SOP) are important to minimize variation. In addition to having a set of protocols and SOP, regular training of employees is indispensable to reduce procedural drift. A total of 243 farm owners, employees, and veterinarians from 35 farms were invited to take 3 microlearning lessons for colostrum management and provide feedback in an embedded survey. The overall response rate was 48%, and almost all participants accessed the SOP within the course (i.e., 92, 90, and 96% in the first, second, and third course, respectively). Overall, 59% (22/37) launched the course in their leisure time and 80% stated that they were convinced to work more accurately after having taken the course. Most employees underestimated the time spent in the course (76%), accessed background information (89%), or provided feedback (55%). These observations are indicative of high engagement. Overall, 78% of employees felt more confident in correct task completion after the training.

Immunization in Vietnam.

Since the Expanded Program on Immunization was proposed by the World Health Organization in 1981, it has been promptly adopted by Vietnam as one of the country's national priority programs. In 1986, Vietnam achieved some remarkable goals, including polio-free status and the elimination of neonatal tetanus. At the same time, however, barriers and difficulties have also emerged. This article aims to provide an overview of both achievements and barriers to the implementation of the program and proposes some solutions.

Genetic relationships among Vietnamese local pigs investigated using genome-wide SNP markers.

Vietnam is one of the most important countries for pig domestication, and a total of 26 local breeds have been reported. In the present study, genetic relationships among the various pig breeds were investigated using 90 samples collected from local pigs (15 breeds) in 15 distantly separated, distinct areas of the country and six samples from Landrace pigs in Hanoi as an out-group of a common Western breed. All samples were genotyped using the Illumina Porcine SNP60 v2 Genotyping BeadChip. We used 15 160-15 217 SNPs that showed a high degree of polymorphism in the Vietnamese breeds for identifying genetic relationships among the Vietnamese breeds. Principal components analysis showed that most pigs indigenous to Vietnam formed clusters correlated with their original geographic locations. Some Vietnamese breeds formed a cluster that was genetically related to the Western breed Landrace, suggesting the possibility of crossbreeding. These findings will be useful for the conservation and management of Vietnamese local pig breeds.

Quasiballistic quantum transport through Ge/Si core/shell nanowires.

We study signatures of ballistic quantum transport of holes through Ge/Si core/shell nanowires at low temperatures. We observe Fabry-Pérot interference patterns as well as conductance plateaus at integer multiples of 2e 2/h at zero magnetic field. Magnetic field evolution of these plateaus reveals relatively large effective Landé g-factors. Ballistic effects are observed in nanowires with silicon shell thickness of 1-3 nm, but not in bare germanium wires. These findings inform the future development of spin and topological quantum devices which rely on ballistic sub-band-resolved transport.

Remodeling of abdominal aortic branch perfusion after thoracic endovascular aortic repair for aortic dissections.

OBJECTIVE: The fate of the abdominal aorta and its branches after thoracic endovascular aortic repair for aortic dissection (TEVAR-AD) has not been studied. The objective of this study was to describe the midterm changes in abdominal aortic branch perfusion after TEVAR-AD. METHODS: A retrospective analysis of TEVAR-AD at a single institution from December 1, 2008, to March 31, 2015, was performed. Computed tomography angiography (CTA) images were reviewed to characterize the perfusion pattern changes of the celiac, superior mesenteric, inferior mesenteric, bilateral renal, and common iliac arteries. Risk factors associated with branch interventions were identified. RESULTS: During the study period, 68 patients underwent TEVAR-AD, 46 of whom had pre-TEVAR and post-TEVAR CTA images available for review. For post-TEVAR CTA, the most recent scans were selected for analysis. The mean period between CTA studies was 371 days. Indications for TEVAR-AD were persistent pain (41%), malperfusion (15%), rupture (6%), and aneurysmal degeneration (33%). Twenty-five patients (54%) were treated during the acute phase (<14 days). All patients had dissections extending to the paravisceral aorta. Of the 304 abdominal aortic branches analyzed, 8 required intervention (2.6%). Branch events requiring intervention included malperfusion (two) and aneurysms involving the branches (three). No intervention was performed for one asymptomatic inferior mesenteric artery occlusion. Of the remaining 295 branches, changes in perfusion patterns were observed in 16 (5.4%). Twelve branches (75%) demonstrated an increased true lumen contribution to perfusion. Four branches (25%) had increased false lumen contribution, without clinical evidence of malperfusion. Patients requiring branch interventions were more likely to have severe chronic kidney disease (P = .012) and more extensive aortic zone coverage during TEVAR (P = .003). On multivariable Cox proportional hazards analysis, coverage of four or more zones during TEVAR-AD was associated with branch intervention (odds ratio, 6.44; 95% confidence interval, 1.01-40.8). The estimated intervention-free patency of the abdominal aortic branches was 89% at 5 years. CONCLUSIONS: Perfusion patterns of abdominal aortic branches remain largely stable after TEVAR-AD. The need for branch intervention is rare and associated with extensive aortic coverage.

Vibrio cholerae O1 El Tor from southern Vietnam in 2010 was molecularly distinct from that present from 1999 to 2004.

The Vibrio cholerae O1 (VCO1) El Tor biotype appeared during the seventh cholera pandemic starting in 1961, and new variants of this biotype have been identified since the early 1990s. This pandemic has affected Vietnam, and a large outbreak was reported in southern Vietnam in 2010. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analyses (MLVA) were used to screen 34 VCO1 isolates from the southern Vietnam 2010 outbreak (23 patients, five contact persons, and six environmental isolates) to determine if it was genetically distinct from 18 isolates from outbreaks in southern Vietnam from 1999 to 2004, and two isolates from northern Vietnam (2008). Twenty-seven MLVA types and seven PFGE patterns were identified. Both analyses showed that the 2008 and 2010 isolates were distinctly clustered and separated from the 1999-2004 isolates.

Efficacy of trabectedin in malignant solitary fibrous tumors: a retrospective analysis from the French Sarcoma Group.

BACKGROUND: Advanced malignant solitary fibrous tumors (SFTs) are rare soft-tissue sarcomas with a poor prognosis. Several treatment options have been reported, but with uncertain rates of efficacy. Our aim is to describe the activity of trabectedin in a retrospective, multi-center French series of patients with SFTs. METHODS: Patients were mainly identified through the French RetrospectYon database and were treated between January 2008 and May 2013. Trabectedin was administered at an initial dose of 1.5 mg/m(2), q3 weeks. The best tumor response was assessed according to the Response Evaluation Criteria In Solid Tumors 1.1. The Kaplan-Meier method was used to estimate median progression-free survival (PFS) and overall survival (OS). The growth-modulation index (GMI) was defined as the ratio between the time to progression with trabectedin (TTPn) and the TTP with the immediately prior line of treatment (TTPn-1). RESULTS: Eleven patients treated with trabectedin for advanced SFT were identified. Trabectedin had been used as second-line treatment in 8 patients (72.7 %) and as at least third-line therapy in a further 3 (27.3 %). The best RECIST response was a partial response (PR) in one patient (9.1 %) and stable disease (SD) in eight patients (72.7 %). Disease-control rate (DCR = PR + SD) was 81.8 %. After a median follow-up of 29.2 months, the median PFS was 11.6 months (95 % CI = 2.0; 15.2 months) and the median OS was 22.3 months (95 % CI = 9.1 months; not reached). The median GMI was 1.49 (range: 0.11-4.12). CONCLUSION: Trabectedin is a very promising treatment for advanced SFTs. Further investigations are needed.

Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial.

BACKGROUND: Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. PATIENTS AND METHODS: Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. RESULTS: Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09-0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). CONCLUSIONS: Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit-risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted.

Transition to adult care in adolescent obesity: a systematic review and why it is a neglected topic.

Transition in pediatric health care involves the purposeful, planned movement of patients from pediatric to adult services. Following the significant increases in long-term survival of chronic childhood diseases in the 1980s, transition has taken on an increasing importance in the management of these chronic diseases. In Australia, there is a conspicuous lack of programs/guidelines for transitioning adolescents with obesity. The authors sought to determine if this is an international phenomenon that should be addressed. This study aimed to identify what formal transition services or guidelines exist internationally for adolescents with overweight/obesity. Two systematic reviews of the published and 'gray' literature were implemented via searches of relevant databases, search engines and websites. The primary review eligibility criteria were documents published between 1982 and 2012 including any aspect of transitioning adolescents with overweight/obesity from pediatric to adult weight management services. The secondary review included current clinical practice guidelines/statements on pediatric obesity management published between 1992 and 2012, and transition recommendations contained within. Non-English language documents were excluded. Relevant text from eligible documents was systematically identified and extracted, and a qualitative synthesis of the data was prepared. Overall, 2272 unique records were identified from the literature searches. Three eligible articles were identified by the primary review. The secondary review identified 24 eligible guidelines/statements. In total, six of the identified documents contained information on transition in adolescent obesity-the most detailed documents provided only a brief statement recommending that transition from pediatric to adult weight management services should take place. In conclusion, internationally there is an absence of published intervention programs/policies, and brevity of clinical guidance and expert opinion, on the transition of adolescents with obesity making this a priority research area. Consideration is given to the reasons why transition in adolescent obesity is a neglected topic.