Life table parameters of Amblyseius largoensis, Amblyseius swirskii and Proprioseiopsis lenis (Acari: Phytoseiidae) fed on eggs and larvae of Frankliniella occidentalis.

The immature development and reproduction of the predatory mites Amblyseius largoensis (Muma), Proprioseiopsis lenis (Corpuz and Rimando), and Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae) were investigated using both thrips eggs and first instars of the western flower thrips, Frankliniella occidentalis Pergande, as prey in a controlled laboratory environment at 25 °C and 60% relative humidity. When provided with thrips eggs as food, A. largoensis exhibited a notably shorter immature development period for both males (7.05 days) and females (6.51 days) as compared with A. swirskii (8.05 and 7.19 days, respectively) and P. lenis (8.10 days and 7.05 days, respectively). Amblyseius largoensis also displayed a higher oviposition rate (2.19 eggs/female/day) than A. swirskii and P. lenis (1.79 and 1.78 eggs/female/day, respectively). Moreover, it exhibited the highest fecundity (25.34 eggs/female), followed by P. lenis (24.23 eggs/female) and A. swirskii (22.86 eggs/female). These variations led to A. largoensis having the highest intrinsic rate of increase (rm) at 0.209, followed by A. swirskii at 0.188, and P. lenis at 0.165. However, when the predatory mites were provided with first instars of F. occidentalis, A. swirskii demonstrated a faster immature development period for both males (7.67 days) and females (7.59 days) as compared with P. lenis (9.00 days and 7.86 days, respectively) and A. largoensis (8.47 days and 8.61 days, respectively). While the oviposition rates of P. lenis (1.92 eggs/female/day) and A. swirskii (1.90 eggs/female/day) were similar when feeding on this prey, A. largoensis produced fewer eggs (1.83 eggs/female/day). Further, A. swirskii exhibited the highest fecundity (31.93 eggs/female), followed by A. largoensis (25.71 eggs/female) and P. lenis (23 eggs/female). Consequently, the intrinsic rate of increase (rm) on thrips first instars was highest in A. swirskii (0.190), followed by A. largoensis (0.186), and P. lenis (0.176). In summary, our findings indicate that in terms of life history parameters A. largoensis performs optimally when feeding on thrips eggs, whereas A. swirskii performs best when preying on the mobile first instars of the thrips. These insights into the dietary preferences and reproductive capabilities of the studied predatory mite species have important implications for their potential use as biological control agents against F. occidentalis in agricultural settings.

Adaptation of an arthropod predator to a challenging environment is associated with a loss of a genome-wide plastic transcriptional response.

BACKGROUND: Structural and chemical plant defence traits may reduce the efficacy of biological control agents in integrated pest management. Breeding programmes have shown arthropod predators' potential to acclimate to challenging host plants. However, whether and how these predators adapt to novel plant environments remain unclear. Using the predatory mite Phytoseiulus persimilis - herbivorous mite Tetranychus urticae system in an experimental evolution setup, we studied the adaptation mechanisms to tomato and cucumber, plants that possess a distinct repertoire of defensive traits. RESULTS: Experimental evolution experiments on whole plants revealed that allowing P. persimilis to adapt to tomatoes led to an ~100% larger population size. Independent feeding assays showed that tomato- and cucumber-adapted prey reduced predator fecundity. The deleterious effect of ingesting low-quality prey persisted after adaptation of the predator to both cucumber and tomato. We demonstrated that jasmonic acid (JA)-dependent defences reduce prey quality by evaluating predator performance on prey fed on JA defence-deficient tomato plants. Transcriptomic profiling of the replicated P. persimilis lines showed that long-term propagation on tomato and cucumber plants produces distinctive gene-expression levels. Predator adaptation to tomatoes results in the loss of a large transcriptional response, in which predicted cuticle-building rather than detoxification pathways are affected. CONCLUSION: We showed that the adaptation of predatory arthropods to a novel, challenging plant does not necessarily occur via the prey, but rather through the physical environment of the plant. We provided first insights into the underlying molecular mechanisms. © 2023 Society of Chemical Industry.

Standardised patient study to assess tuberculosis case detection within the private pharmacy sector in Vietnam.

BACKGROUND: Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB. METHODS: A cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs' referral. RESULTS: In total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan. CONCLUSIONS: Few SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings.

The phenylpropanoid pathway inhibitor piperonylic acid induces broad-spectrum pest and disease resistance in plants.

Although many phenylpropanoid pathway-derived molecules act as physical and chemical barriers to pests and pathogens, comparatively little is known about their role in regulating plant immunity. To explore this research field, we transiently perturbed the phenylpropanoid pathway through application of the CINNAMIC ACID-4-HYDROXYLASE (C4H) inhibitor piperonylic acid (PA). Using bioassays involving diverse pests and pathogens, we show that transient C4H inhibition triggers systemic, broad-spectrum resistance in higher plants without affecting growth. PA treatment enhances tomato (Solanum lycopersicum) resistance in field and laboratory conditions, thereby illustrating the potential of phenylpropanoid pathway perturbation in crop protection. At the molecular level, transcriptome and metabolome analyses reveal that transient C4H inhibition in tomato reprograms phenylpropanoid and flavonoid metabolism, systemically induces immune signalling and pathogenesis-related genes, and locally affects reactive oxygen species metabolism. Furthermore, C4H inhibition primes cell wall modification and phenolic compound accumulation in response to root-knot nematode infection. Although PA treatment induces local accumulation of the phytohormone salicylic acid, the PA resistance phenotype is preserved in tomato plants expressing the salicylic acid-degrading NahG construct. Together, our results demonstrate that transient phenylpropanoid pathway perturbation is a conserved inducer of plant resistance and thus highlight the crucial regulatory role of this pathway in plant immunity.

Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone.

The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chromatin accessibility and histone modification level, that can be partially recapitulated in an orthogonal cell line system by the introduction of H3.3-G34W. These epigenetic alterations affect mainly heterochromatic and bivalent regions and provide possible explanations for the genomic instability, as well as the osteolytic phenotype of GCTB. The mutation occurs in differentiating mesenchymal stem cells and associates with an impaired osteogenic differentiation. We propose that the observed epigenetic alterations reflect distinct differentiation stages of H3.3 WT and H3.3 MUT stromal cells and add to H3.3-G34W-associated changes.

Molecular typing of conjunctivitis-causing adenoviruses in Hanoi, Vietnam from 2017 to 2019 and complete genome analysis of the most prevalent type (HAdV-8).

Adenoviral conjunctivitis is a common epidemic worldwide. In Vietnam, up to 80,000 patients are infected with adenoviral conjunctivitis annually. However, there are few investigations on the pathogenic adenoviruses that cause conjunctivitis. In total, 120 eye-swab samples were collected from patients with viral conjunctivitis symptoms in Hanoi, Vietnam from 2017 to 2019. Human adenoviruse (HAdV) was detected in 67 samples (55.83%) using polymerase chain reaction amplification of at least one of three HAdV-specific marker genes (hexon, penton, and fiber). Of the 67 HAdV samples, 46 samples could be analyzed by all three marker genes. DNA sequence analysis and phylogenetic tree building based on the three marker genes from the 46 HAdV samples revealed five different HAdV types associated with conjunctivitis in Hanoi, including HAdV-3 (4.3%), HAdV-4 (2.2%), HAdV-8 (89.1%), HAdV-37 (2.2%), and a potential recombinant type between types HAdV-8 and HAdV-3 (2.2%). This showed that HAdV-8 was the most common type identified in Hanoi. Complete genome analysis of HAdV-8 isolated from a Vietnamese patient (VN2017) using Sanger sequencing revealed 34 unique nucleotide changes, indicating that the adenovirus continuously accumulates new mutations. Hence, continuous surveillance of HAdV-8 changes in Vietnam is necessary in the future.

Implementing the mobile continuing medical education (mCME) project in Vietnam: making it work and sharing lessons learned.

BACKGROUND: Mobile technology is a novel approach for delivering continuing medical education (CME), with numerous advantages including lower costs and the ability to reach larger numbers than traditional in-person CME workshops. METHODS: From May 2015 to May 2017, we conducted two randomized controlled trials in a phased approach to evaluate the effectiveness of a mobile CME (mCME) approach for two cadres of health professionals in Vietnam. The first randomized controlled trial (RCT) tested the use of an SMS-based educational intervention among Community-Based Physician's Assistants; while feasible and acceptable, this intervention failed to improve medical knowledge among participants. Given the failure of the first RCT, and drawing on qualitative work conducted with participants at the conclusion of the trial, various modifications were employed in the second RCT conducted among HIV specialist physicians in Vietnam. Version 2.0 of the mCME intervention did lead to significant improvement in medical knowledge among intervention participants. Here, we discuss in detail the development of an mCME platform and the experiential "lessons learned" during two phases of implementation. RESULTS: Numerous lessons were learned during implementation, including the importance of: (I) mixed methods approaches; (II) an underlying theoretical framework for behavior change projects; (III) expertise in software programming; (IV) aligning educational content to a well-defined participant population; and (V) engaging and motivating adult learners. We also discuss the critical importance of projects with local ownership and investment that are relevant to local problems. CONCLUSIONS: mHealth approaches for continued healthcare training and education is increasingly relevant in many low-resource settings, the lessons learned here will be valuable to other organizations looking to scale-up similar mHealth-type educational programmes.

Motivating HIV Providers in Vietnam to Learn: A Mixed-Methods Analysis of a Mobile Health Continuing Medical Education Intervention.

BACKGROUND: The Mobile Continuing Medical Education Project (mCME V.2.0) was a randomized controlled trial designed to test the efficacy of a text messaging (short message service [SMS])-based distance learning program in Vietnam that included daily quiz questions, links to readings and online courses, and performance feedback. The trial resulted in significant increases in self-study behaviors and higher examination scores for intervention versus control participants. OBJECTIVE: The objective of this mixed-methods study was to conduct qualitative and quantitative investigations to understand participants' views of the intervention. We also developed an explanatory framework for future trial replication. METHODS: At the endline examination, all intervention participants completed a survey on their perspectives of mCME and self-study behaviors. We convened focus group discussions to assess their experiences with the intervention and attitudes toward continuing medical education. RESULTS: A total of 48 HIV specialists in the intervention group completed the endline survey, and 30 participated in the focus group discussions. Survey and focus group data suggested that most clinicians liked the daily quizzes, citing them as convenient mechanisms to convey information in a relevant manner. A total of 43 of the 48 (90%) participants reported that the daily quizzes provided motivation to study for continuing medical education purposes. Additionally, 83% (40/48) of intervention participants expressed that they were better prepared to care for patients with HIV in their communities, compared with 67% (32/48) at baseline. Participation in the online coursework component was low (only 32/48, 67% of intervention participants ever accessed the courses), but most of those who did participate thought the lectures were engaging (26/32, 81%) and relevant (29/32, 91%). Focus group discussions revealed that various factors influenced the clinicians' decision to engage in higher learning, or "lateral learning," including the participant's availability to study, professional relevance of the topic area, and feedback. These variables serve as modifying factors that fit within an adapted version of the health belief model, which can explain behavior change in this context. CONCLUSIONS: Qualitative and quantitative endline data suggested that mCME V.2.0 was highly acceptable. Participant behaviors during the trial fit within the health belief model and can explain the intervention's impact on improving self-study behaviors. The mCME platform is an evidence-based approach with the potential for adoption at a national scale as a method for promoting continuing medical education. TRIAL REGISTRATION: ClinicalTrials.gov NCT02381743; https://clinicaltrials.gov/ct2/show/NCT02381743.

An open database of productivity in Vietnam's social sciences and humanities for public use.

This study presents a description of an open database on scientific output of Vietnamese researchers in social sciences and humanities, one that corrects for the shortcomings in current research publication databases such as data duplication, slow update, and a substantial cost of doing science. Here, using scientists' self-reports, open online sources and cross-checking with Scopus database, we introduce a manual system and its semi-automated version of the database on the profiles of 657 Vietnamese researchers in social sciences and humanities who have published in Scopus-indexed journals from 2008 to 2018. The final system also records 973 foreign co-authors, 1,289 papers, and 789 affiliations. The data collection method, highly applicable for other sources, could be replicated in other developing countries while its content be used in cross-section, multivariate, and network data analyses. The open database is expected to help Vietnam revamp its research capacity and meet the public demand for greater transparency in science management.

mCME project V.2.0: randomised controlled trial of a revised SMS-based continuing medical education intervention among HIV clinicians in Vietnam.

BACKGROUND: Continuing medical education (CME) is indispensable, but costs are a barrier. We tested the effectiveness of a novel mHealth intervention (mCME V.2.0) promoting CME among Vietnamese HIV clinicians. METHODS: We enrolled HIV clinicians from three provinces near Hanoi. The 6-month intervention consisted of (1) daily short message service multiple-choice quiz questions, (2) daily linked readings, (3) links to online CME courses and (4) feedback messages describing the performance of the participant relative to the group. Control participants had equal access to the online CME courses. Our primary endpoint was utilisation of the online CME courses; secondary endpoints were self-study behaviour, performance on a standardised medical exam and job satisfaction. RESULTS: From 121 total HIV clinicians in the three provinces, 106 (87.6%) enrolled, and 48/53 intervention (90%) and 47/53 control (89%) participants completed the endline evaluations. Compared with controls, intervention participants were more likely to use the CME courses (risk ratio (RR) 2.3, 95% CI 1.4 to 3.8, accounting for 83% of course use (P<0.001)). Intervention participants increased self-study behaviours over controls in terms of use of medical textbooks (P<0.01), consulting with colleagues (P<0.01), searching on the internet (P<0.001), using specialist websites (P=0.02), consulting the Vietnam HIV/AIDS treatment guidelines (P=0.02) and searching the scientific literature (P=0.09). Intervention participants outperformed controls on the exam (+23% vs +12% score gains, P=0.05) and had higher job satisfaction. CONCLUSION: The mCME V.2.0 intervention improved self-study behaviour, medical knowledge and job satisfaction. This approach has potential for expansion in Vietnam and similar settings. TRIAL REGISTRATION NUMBER: NCT02381743.

The mCME Project: A Randomized Controlled Trial of an SMS-Based Continuing Medical Education Intervention for Improving Medical Knowledge among Vietnamese Community Based Physicians' Assistants.

BACKGROUND: Community health workers (CHWs) provide critical services to underserved populations in low and middle-income countries, but maintaining CHW's clinical knowledge through formal continuing medical education (CME) activities is challenging and rarely occurs. We tested whether a Short Message Service (SMS)-based mobile CME (mCME) intervention could improve medical knowledge among a cadre of Vietnamese CHWs (Community Based Physician's Assistants-CBPAs) who are the leading providers of primary medical care for rural underserved populations. METHODS: The mCME Project was a three arm randomized controlled trial. Group 1 served as controls while Groups 2 and 3 experienced two models of the mCME intervention. Group 2 (passive model) participants received a daily SMS bullet point, and were required to reply to the text to acknowledge receipt; Group 3 (interactive model) participants received an SMS in multiple choice question format addressing the same thematic area as Group 2, entering an answer (A, B, C or D) in their response. The server provided feedback immediately informing the participant whether the answer was correct. Effectiveness was based on standardized examination scores measured at baseline and endline (six months later). Secondary outcomes included job satisfaction and self-efficacy. RESULTS: 638 CBPAs were enrolled, randomized, and tested at baseline, with 592 returning at endline (93.7%). Baseline scores were similar across all three groups. Over the next six months, participation of Groups 2 and 3 remained high; they responded to >75% of messages. Group 3 participants answered 43% of the daily SMS questions correctly, but their performance did not improve over time. At endline, the CBPAs reported high satisfaction with the mCME intervention, and deemed the SMS messages highly relevant. However, endline exam scores did not increase over baseline, and did not differ between the three groups. Job satisfaction and self-efficacy scores also did not improve. Average times spent on self-study per week did not increase, and the kinds of knowledge resources used by the CBPAs did not differ between the three groups; textbooks, while widely available, were seldom used. CONCLUSIONS: The SMS-based mCME intervention, while feasible and acceptable, did not result in increased medical knowledge. We hypothesize that this was because the intervention failed to stimulate lateral learning. For an intervention of this kind to be effective, it will be essential to find more effective ways to couple SMS as a stimulus to promote increased self-study behaviors. TRIAL REGISTRATION: ClinicalTrials.gov NCT02381743.

Long-term treatment with fasudil improves bleomycin-induced pulmonary fibrosis and pulmonary hypertension via inhibition of Smad2/3 phosphorylation.

Pulmonary hypertension (PH) associated with pulmonary fibrosis (PF) considerably worsens prognosis of interstitial lung diseases (ILD). RhoA/Rho-kinases (ROCK) pathway is implicated in high pulmonary vascular tone and pulmonary fibrosis but the effect of ROCK inhibitors on PH associated with PF is not known. We therefore aimed to determine whether long-term treatment with fasudil, a selective ROCK inhibitor, could attenuate PF and PH induced by bleomycin in mice. Male C57BL/6 mice received a single dose of intratracheal bleomycin (3.3 U/kg) to induce PF. Treatment with fasudil (30 mg kg(-1) day(-1)) was given intraperitoneally for 7, 14 or 21 days until mice underwent hemodynamic measurements. Right ventricular systolic pressure (RVSP) and RV/(LV + S) ratio were assessed. Lung inflammatory cells profiles, including macrophages, neutrophils, lymphocytes B and lymphocytes T were assessed by immunohistochemistry. Lung fibrosis was evaluated by histological and biochemical methods. Pulmonary arteriole muscularization and medial wall thickness (MWT) were evaluated by immunohistochemical staining for α-SMA. Bleomycin induced severe PF and PH in mice, associated with an increased RhoA/ROCK activity in the lung. Fasudil reduced lung inflammation and lung collagen content, and attenuated the increased RVSP, RV hypertrophy, and pulmonary vascular remodeling in bleomycin-intoxicated mice. Fasudil inhibited the increased activity of RhoA/ROCK pathway, and partly altered bleomycin-associated activation of TGF-ß1/Smad pathway, via inhibition of Smad2/3 phosphorylation. The efficacy of long-term treatment with fasudil suggests that the blockade of RhoA/ROCK pathway may be a promising therapy for patients with ILD-associated PH.

New features in the treatment of androgen-independent prostate cancer.

Prostate cancer develops from clones that are already present as early as thirty-five years of age, when circulating concentrations of androgens are high. The progression of the disease is low and the cancer is diagnosed at a more advanced age. Prostate cancer evolves from an androgen dependant stage to stage where it escapes from all anti-androgenic treatments. The patient usually dies within two years following the diagnosis of advanced cancer. Therefore, it is of great interest to develop new therapies for androgen independent prostate cancer. The androgen independent evolution of prostate cancer is a complex phenomenon at the cellular and molecular levels. It includes an increased sensitivity to growth factors, the control of proliferation pathways, apoptotic and survival pathways as well as the control of angiogenesis. Epidemiological studies have also suggested that certain vitamins or phyto-oestrogens could protect against prostate cancer development. The present review attempts to present an overview of the fundamental research in cellular signalling which could be interesting as target for the treatment of androgen independent prostate cancer. Also the potential interest of non-androgenic steroids was reviewed for the same goal.

Prostatic androgen repressed message-1 (PARM-1) may play a role in prostatic cell immortalisation.

BACKGROUND: Prostatic androgen-repressed message-1 (PARM-1) has been cloned from the prostate. The transcript of the PARM-1 gene is overexpressed during regression of the prostate after androgen withdrawal. The regulation of PARM-1 by androgens is limited to this organ. We have studied the effects of PARM-1 overexpression in malignant prostate cells. METHODS: The PARM-1 cDNA was introduced into the rat cancer cell line MAT LyLu along with a doxycycline-dependent regulator. RESULTS: Maximal expression of PARM-1 (fivefold induction) was achieved by incubating the cells with 2 microM doxycycline for 48 hr. A study investigating the effect of PARM-1 overexpression on the transcription of 588 genes has shown that the TLP1 gene (encoding rat telomerase protein component 1) was the most up-regulated (fourfold). In addition, a dose-dependent increase in telomerase activity was observed in cells overexpressing PARM-1. In vivo, the androgen-deprived prostate showed an increased TLP1 level and increased telomerase activity. CONCLUSIONS: Increased telomerase activity is often associated with the immortalisation of cancer cell lines, particularly prostatic ones. This could mean that PARM-1 is involved, via increased telomerase activity, in a survival program enabling certain prostatic cells to resist apoptosis, thus conferring a selective advantage to pre-cancerous or cancerous cells.