Influence of Potentially Inappropriate Medication Use on Older Australians' Admission to Emergency Department Short Stay.

Older people in the emergency department (ED) often pose complex medical challenges, with a significant prevalence of polypharmacy and potentially inappropriate medicines (PIMs) in Australia. A retrospective analysis of 200 consecutive patients aged over 65 years admitted to the emergency short stay unit (ESSU) aimed to identify polypharmacy (five or more regular medications), assess PIM prevalence, and explore the link between pre-admission PIMs and ESSU admissions. STOPP/START version 2 criteria were used for the PIM assessment, with an expert panel categorizing associated risks. Polypharmacy was observed in 161 patients (80.5%), who were older (mean age 82 versus 76 years) and took more regular medications (median 9 versus 3). One hundred and eighty-five (92.5%) patients had at least one PIM, 81 patients (40.5%) had STOPP PIMs, and 177 patients (88.5%) had START omissions. Polypharmacy significantly correlated with STOPP PIM (OR 4.8; 95%CI: 1.90-12.1), and for each additional medication the adjusted odds of having a STOPP PIM increased by 1.20 (95%CI: 1.11-1.28). Nineteen admissions (9.5%) were attributed to one or more PIMs (total 21 PIMs). Of these PIMs, the expert panel rated eight (38%) as high risk, five (24%) as moderate risk, and eight (38%) as low risk for causing hospital admission. The most common PIMs were benzodiazepines, accounting for 14 cases (73.6%). Older ESSU-admitted patients commonly presented with polypharmacy and PIMs, potentially contributing to their admission.

Isolation and Characterization of Novel Huperzine-Producing Endophytic Fungi from Lycopodiaceae Species.

Huperzine A (HupA) is an important drug for treating Alzheimer's disease (AD) and is primarily extracted from the Huperzia serrata (Lycopodiaceae). Failures in the chemical synthesis of Hup and in vitro culture have put H. serrata in danger of extinction, and there is a need for an extensive investigation of Hup from alternative perspectives. The aim of this study is to identify endophytic fungi that produce high Hup or simultaneously produce many types of Hup and have high genetic stability derived from other Lycopodiaceae species as a source of materials for natural Hup production. In this work, Hup-producing endophytic fungi were isolated from three species: Lycopodium clavatum, Phlegmariurus squarrosus, and P. phlegmaria. Of these, L. clavatum and P. squarrosus were confirmed as novel sources of Hup-producing fungi. Based on morphological characteristics and nuclear ribosomal DNA ITS sequences, four endophytic fungi Colletotrichum siamense THG1-17, Epicoccum sorghinum THG01-18, Phoma sp. TKH3-2, and Phyllosticta sp. THG2-27 were firstly isolated from these Lycopodiaceae plants, which were capable of simultaneously producing both HupA and HupB, as evidenced by high-performance liquid chromatography analysis. The four strains showed stability in Hup yield over 50 generations of culture with an in vitro storage period of 3 months. These isolated fungi will provide a new source of materials for further research to develop drugs containing HupA as well as HupB for AD treatment in the future.

Insulin autoimmune syndrome: not just one but two different diseases with therapeutic implications.

Summary: We present a young woman with treatment resistant insulin autoimmune syndrome (IAS) with a protracted course. Her serum insulin level was 6945 pmol/l (<160), C-peptide 4042 pmol/L (<1480), anti-insulin antibodies 5305 U/mL (<0.4) were monoclonal IgG kappa. After 12 h of fasting, her blood glucose fell to 1.2 mmol/L. Post-meal blood glucose peaked at 12.2 mmol/L with reactive hypoglycaemia below 2 mmol/L. Frequent meals and continuous blood glucose monitoring were helpful, but further treatments advocated in the literature with prednisolone, rituximab, plasmapheresis, cyclophosphamide and ciclosporin were without beneficial effect. Based on this case and a review of the literature, we propose that IAS is not one but two different diseases with different therapeutic strategies. The first disease, polyclonal IAS, predominates in Asia and is characterized by polyclonal anti-insulin antibodies, association with certain HLA genotypes and other autoimmune conditions, medications and viral infections possibly triggering the disease, a possible female predominance among young patients and a tendency towards spontaneous remission. The other disease, monoclonal IAS, predominates in Caucasians. Typical features are monoclonal anti-insulin antibodies, only weak HLA association, no drug predisposition, no sex difference, rare remission and conventional therapy often being without any clinical effect. We suggest that monoclonal IAS with IgG or IgA anti-insulin antibodies should receive therapy targeting plasma cells rather than lymphocytes. Learning points: IAS may be considered as two separate diseases, polyclonal and monoclonal. The presence of either polyclonal or monoclonal antibodies should determine the choice of treatment for IAS. In polyclonal IAS, discontinuation of a triggering medication and treatment of triggering conditions should be the backbone of therapy. Monoclonal IAS should receive treatment targeting plasma cells.

Myocarditis Following Inactivated SARS-CoV-2 Vaccine (Vero Cell) in an Adult Female in Vietnam: A Case Report.

During the Coronavirus disease 2019 (COVID-19) pandemic, vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has proven to be an important measure to help control disease spread and improve patient outcome. There are four distinct vaccine categories: inactivated viral vaccines, messenger RNA (mRNA) vaccines, adenovirus vector-based vaccines, and adjuvanted protein vaccines. In 2021, increased cases of myocarditis and pericarditis were reported after mRNA and adenovirus vector-based COVID-19 vaccination. A similar reporting pattern has not been observed after receipt of inactivated virus vaccines. Here, we present a case of clinically suspected acute myocarditis in a 26-year-old female, occurring 11 days after the administration of Sinopharm Vero Cell, an inactivated virus COVID-19 vaccine. This event led to acute heart failure, with marked clinical resolution observed within 34 days.

Safe and effective profile of the VSTENT bioresorbable polymer sirolimus-eluting stent in the treatment of patients with de novo coronary artery lesions: a prospective, cohort, multicenter study.

Background: The drug-eluting stent was a significant stride forward in the development of enhanced therapeutic therapy for coronary intervention, with three generations of increased advancement. VSTENT is a newly developed stent manufactured in Vietnam that aims to provide coronary artery patients with a safe, effective, and cost-efficient option. The purpose of this trial was to determine the efficacy and safety of a new bioresorbable polymer sirolimus-eluting stent called VSTENT. Methods: This is a prospective, cohort, multicenter research in 5 centers of Vietnam. A prespecified subgroup received intravascular ultrasound (IVUS) or optical coherence tomography (OCT) imaging. We determined procedure success and complications during index hospitalization. We monitored all participants for a year. Six-month and 12-month rates of major cardiovascular events were reported. All patients had coronary angiography after 6 months to detect late lumen loss (LLL). Prespecified patients also had IVUS or OCT performed. Results: The rate of device success was 100% (95% CI: 98.3-100%; P<0.001). Major cardiovascular events were 4.7% (95% CI: 1.9-9.4%; P<0.001). The LLL over quantitative coronary angiography (QCA) was 0.08±0.19 mm (95% CI: 0.05-0.10; P<0.001) in the in-stent segment and 0.07±0.31 mm (95% CI: 0.03-0.11; P=0.002) in 5 mm within the two ends of the stent segment. The LLL recorded by IVUS and OCT at 6 months was 0.12±0.35 mm (95% CI: 0.01-0.22; P=0.028) and 0.15±0.24 mm (95% CI: 0.02-0.28; P=0.024), respectively. Conclusions: This study's device success rates were perfect. IVUS and OCT findings on LLL were favorable at 6-month follow-up. One-year follow-up showed low in-stent restenosis (ISR) and target lesion revascularization (TLR) rates, reflecting few significant cardiovascular events. VSTENT's safety and efficacy make it a promising percutaneous intervention option in developing nations.

Enhanced podophyllotoxin production of endophyte Fusarium proliferatum TQN5T by host extract and phenylalanine.

Fermentation technology using endophytes is considered a potential alternative approach for producing pharmaceutical compounds like podophyllotoxin (PTOX). In this study, fungus TQN5T (VCCM 44284) was selected from endophytic fungi isolated from Dysosma versipellis in Vietnam for PTOX production through TLC. The presence of PTOX in TQN5T was further confirmed by HPLC. Molecular identification indicated TQN5T as Fusarium proliferatum with 99.43% identity. This result was asserted by morphological characteristics such as white cottony, filamentous colony, layer and branched mycelium, and clear hyphae septa. Cytotoxic assay indicated both biomass extract and culture filtrate of TQN5T presented strong cytotoxicity on LU-1 and HepG2 with IC50 of 0.11, 0.20, 0.041, and 0071, respectively, implying anti-cancer compounds were accumulated in the mycelium and secreted into the medium. Further, the production of PTOX in TQN5T was investigated in the fermentation condition supplemented with 10 µg/ml of host plant extract or phenylalanine as elicitors. The results revealed a significantly higher amount of PTOX in the PDB + PE and PDB + PA at all studied time points in comparison with PDB (control). Especially, after 168 h of culture, PTOX content in the PDB with plant extract reached the peak with 314 µg/g DW which is 10% higher than the best yield of PTOX in previous studies, denoting F. proliferatum TQN5T as a promising PTOX producer. This is the first study on enhancing the PTOX production in endophytic fungi by supplementing phenylalanine-a precursor for PTOX biosynthesis in plants into fermented media, suggesting a common PTOX biosynthetic pathway between host plant and endophytes. KEY POINTS: • Fusarium proliferatum TQN5T was proven for PTOX production. • Both mycelia extract and spent broth extract of Fusarium proliferatum TQN5T presented strong cytotoxicity on cancer cell lines LU-1 and HepG2. • The supplementation of 10 µg/ml host plant extract and phenylalanine into fermentation media of F. proliferatum TQN5T improved the yield of PTOX.

Mid-term safe and effective profile of the Magmaris scaffold in percutaneous coronary intervention: a prospective, single-center study.

Introduction: Significant advances have been made in the diagnosis and treatment of coronary artery disease over the years. New generations of scaffolds containing novel material and eluting drug have produced one of the most significant advancements in coronary intervention. The newest generation would be Magmaris with a magnesium frame and a sirolimus cover. Methods: From July 2018 to August 2020, 58 patients treated with Magmaris at the University Medical Center Ho Chi Minh City were enrolled in this study. Results: A total of 60 lesions were stented, 60.3% of which were left anterior descending (LAD) lesions. There was no in-hospital event. Within 1 year after discharge, we noted one myocardial infarction event that required target-lesion revascularization, one stroke event, one non-target-lesion revascularization patient, two target-vessel revascularization patients, and one in-stent thrombosis. Among them, one myocardial infarction occurrence, one non-target-lesion revascularization, and one in-stent thrombosis event were recorded within the first 30 days after discharge. Conclusion: In conclusion, the Magmaris scaffold is a safe and effective option for structural procedures performed with imaging device support, particularly intravascular ultrasound.

Side effects following first dose of COVID-19 vaccination in Ho Chi Minh City, Vietnam.

Vaccines are strongly recommended globally as an effective measure to prevent serious illness from and spread of COVID-19. Concerns about safety following vaccination continue to be the most common reason that people do not accept the vaccine. This retrospective study was carried out on 4341 people who received the first dose of ChAdOx1 nCoV-19, BBIBP-CorV, or mRNA-1273 vaccine at Jio Health Clinic in Ho Chi Minh City, Vietnam. Post-injection side effects were either reported by participants or actively collected by health care staff by means of telemedicine. Local side effects were reported by 35.5% of all individuals, with pain being the most common symptom (33.3%). Systemic side effects were reported by 44.2% of individuals, with fever (25.3%) and fatigue (21.4%) being the most common. Age ≤60 years, female gender, and ChAdOx1 nCoV-19 were significant independent risk factors for both local and systemic side effects, while a history of allergy was significant as a risk factor for local side effects. A total of 43 individuals (1.0%) reported concerning symptoms of rare severe complications, which were addressed and treated by physicians via Jio Health app.

Damage assessment of suspension footbridge using vibration measurement data combined with a hybrid bee-genetic algorithm.

Optimization algorithms (OAs) are a vital tool to deal with complex problems, and the improvement of OA is inseparable from practical strategies and mechanisms. Among the OAs, Bee Algorithm (BA) is an intelligent algorithm with a simple mechanism and easy implementation, in which effectiveness has been proven when handling optimization problems. Nevertheless, BA still has some fundamental drawbacks, which can hinder its effectiveness and accuracy. Therefore, this paper proposes a novel approach to tackle the shortcomings of BA by combining it with Genetic Algorithm (GA). The main intention is to combine the strengths of both optimization techniques, which are the exploitative search ability of BA and the robustness with the crossover and mutation capacity of GA. An investigation of a real-life suspension footbridge is considered to validate the effectiveness of the proposed method. A baseline Finite Element model of the bridge is constructed based on vibration measurement data and model updating, which is used to generate different hypothetical damage scenarios. The proposed HBGA is tested against BA, GA, and PSO to showcase its effectiveness in detecting damage for each scenario. The results show that the proposed algorithm is effective in dealing with the damage assessment problems of SHM.

Isolation and Cytotoxic Potency of Endophytic Fungi Associated with Dysosma difformis, a Study for the Novel Resources of Podophyllotoxin.

Endophytic fungi are promising sources for the production of podophyllotoxin-an important anticancer compound, replacing depleted medical plants. In this study, the endophytes associated with Dysosma difformis-an ethnomedicinal plant species were isolated to explore novel sources of podophyllotoxin. Fifty-three endophytic fungi were isolated and identified by morphological observation and ITS-based rDNA sequencing, assigning them to 27 genera in 3 divisions. Fusarium was found the most prevalent genus with a colonization frequency of 11.11%, followed by Trametes (9.26%) and Penicillium (7.41%). Phylogenetic trees were constructed for the endophytic fungi community in two collection sites, Ha Giang and Lai Chau, revealing the adaptation of the species to the specific tissues and habitats. Cytotoxic activity of endophytic fungal extracts was investigated on cancer cell lines such as SK-LU-1, HL-60, and HepG2, demonstrating strong anti-cancer activity of six isolates belonging to Penicillium, Trametes, Purpureocillium, Aspergillus, and Ganoderma with IC50 value of lower than 10 µg/mL. The presence of podophyllotoxin was indicated in Penicillium, Trametes, Aspergillus and for the first time in Purpureocillium and Ganoderma via high-performance liquid chromatography, which implied them as a potential source of this anti-cancer compound.

COVID-19 impacts, opportunities and challenges for wildlife farms in Binh Duong and Ba Ria Vung Tau, Vietnam.

The wildlife trade is a major cause of species loss and can trigger disease transmission. While the COVID-19 pandemic sparked public interest in eliminating the wildlife trade, a better understanding is needed of the economic repercussions of COVID-19 on those who rely on wildlife farming for their livelihoods. Using the case studies of Ba Ria Vung Tau and Binh Duong provinces in Vietnam - a country seen as Asia's wildlife trade hotspot - this paper explores COVID-19's impacts on wildlife farms and their owners. Understanding these impacts is important, both in order to design appropriate interventions to support local people in mitigating COVID-19's impacts as well as to inform effective policymaking around wildlife conservation in Vietnam. In this study, we adopted mixed research methods (including a literature and policy review, stakeholder consultation with government agencies and NGOs engaged in designing and monitoring wildlife conservation policies, a wildlife farming household survey, and research validation workshop) to understand the status of Vietnamese wildlife farms, as well as the impacts of COVID-19, and any opportunities and challenges for wildlife conservation and management in Vietnam. Our paper shows that, across the two studied provinces, numbers of wildlife farms and farmed wildlife animals have both declined since the pandemic, with declining market demand and wildlife farm owners experiencing difficulties accessing markets due to travel restrictions. Although this affected wildlife-related income, this represented less than 30 % of families' overall income on average, and thus households were able to maintain their livelihoods through other sources. Most wildlife is raised as an additional food source for farming families and plays an important role in the diets of surveyed households. Findings also highlighted that most surveyed households' post-pandemic recovery strategies involved expanding their wildlife farms in scope and scale; these households perceived a stable domestic market and high prices for wildlife products in future. Our study found several opportunities for sustainable wildlife farming practices, including greater political commitment, an increasing number of wildlife conservation policies, and stronger law enforcement mechanisms. Challenges remain, however; including an unclear and inconsistent policy framework, the presence of an illegal market, and wildlife farm owners' limited knowledge and understanding of wildlife policies. Our paper also shows a lack of comprehensive data and understanding around actual wildlife transactions during the pandemic, leading to challenges in confirming whether COVID-19 had any real impact on wildlife trade. Further research is required to address this knowledge gap.

Identification of Modifiable Risk Factors of Exacerbations Chronic Respiratory Diseases with Airways Obstruction, in Vietnam.

OBJECTIVES: to determine modifiable risk factors of exacerbations in chronic respiratory diseases with airways obstruction (i.e., asthma and COPD) in southern Vietnam. METHODS: an environmental and health-related behavioural questionnaire was submitted to patients with both chronic respiratory symptoms and airways obstruction. An exacerbation was defined as any acute worsening in clinical symptoms requiring a change in treatment, in a patient receiving prophylactic therapy. RESULTS: 235 patients were evaluated, including 131 (56%) chronic obstructive pulmonary disease (COPD) and 104 (44%) asthmatics. There were 75% males and 69% smokers. Occupational exposure accounted for 66%, mainly among construction and industry workers. Smoking was associated with more severe airways obstruction. Respiratory exacerbations were reported in 56/235 patients (24%). The risk of exacerbation was increased in patients with a lower education level, exposure to occupational pollutants, cumulative smoking ≥ 20 pack year, housing space < 10 m2, and poorly ventilated housing. Based on multivariate analysis, the risk of exacerbation remained significantly higher among patients with occupational exposure and low housing space per person. CONCLUSIONS: besides smoking cessation, more supportive policies, including improvement of occupational environment and housing design for better ventilation, are needed to prevent the severity of chronic respiratory diseases in Vietnam.

Horizontal transfer of a plasmid possessing mcr-1 marked with a single nucleotide mutation between Escherichia coli isolates from community residents.

OBJECTIVES: The widespread dissemination of phenotypic colistin-resistant (COR) bacteria in the community threatens public health. The horizontal gene transfer of the mobile colistin resistance gene via plasmids is thought to be one of the main mechanisms for dissemination. However, genotypic evidence to prove this in community settings is limited. This study used genome analysis to demonstrate the direct horizontal colistin resistance gene transfer via plasmids in isolates from the community. RESULTS: A total of 19 isolates of COR Escherichia coli from stool specimens of 23 residents from seven households in the Vietnamese community were assessed in this study. The whole-genome sequence data of isolates were acquired using a combination of DNBSEQ short-reads and Nanopore long-read sequencing. Analysis of genomic data was performed using online tools such as Geneious. Analysis of the genomic information of COR E. coli isolates revealed that the isolates from two residents of different households had a similar IncP1 plasmid possessing mcr-1.1, marked with a single nucleotide mutation at the same position. The study provided direct evidence to prove that mcr was horizontally transmitted among bacteria in community residents.

Minimal residual disease-guided stop and start of venetoclax plus ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (HOVON141/VISION): primary analysis of an open-label, randomised, phase 2 trial.

BACKGROUND: Targeted time-limited treatment options are needed for patients with relapsed or refractory chronic lymphocytic leukaemia. The aim of this study was to investigate the efficacy of minimal residual disease (MRD)-guided, time-limited ibrutinib plus venetoclax treatment in this patient group. METHODS: HOVON141/VISION was an open-label, randomised, phase 2 trial conducted in 47 hospitals in Belgium, Denmark, Finland, the Netherlands, Norway, and Sweden. Eligible participants were aged 18 years or older with previously treated chronic lymphocytic leukaemia with or without TP53 aberrations; had not been exposed to Bruton tyrosine-kinase inhibitors or BCL2 inhibitors; had a creatinine clearance rate of 30 mL/min or more; and required treatment according to International Workshop on Chronic Lymphocytic Leukemia 2018 criteria. Participants with undetectable MRD (<10-4; less than one chronic lymphocytic leukaemia cell per 10 000 leukocytes) in peripheral blood and bone marrow after 15 28-day cycles of oral ibrutinib (420 mg once daily) plus oral venetoclax (weekly ramp-up 20 mg, 50 mg, 100 mg, 200 mg, up to 400 mg once daily) were randomly assigned (1:2) to ibrutinib maintenance or treatment cessation. Patients who were MRD positive continued to receive ibrutinib monotherapy. Patients who became MRD (>10-2) during observation reinitiated treatment with ibrutinib plus venetoclax. The primary endpoint was progression-free survival at 12 months after random assignment in the treatment cessation group. Progression-free survival was analysed in the intention-to-treat population. All patients who received at least one dose of study drug were included in the safety assessment. The study is registered at ClinicalTrials.gov, NCT03226301, and is active but not recruiting. FINDINGS: Between July 12, 2017, and Jan 21, 2019, 230 patients were enrolled, 225 of whom were eligible. 188 (84%) of 225 completed treatment with ibrutinib plus venetoclax and were tested for MRD at cycle 15. After cycle 15, 78 (35%) patients had undetectable MRD and 72 (32%) were randomly assigned to a treatment group (24 to ibrutinib maintenance and 48 to treatment cessation). The remaining 153 patients were not randomly assigned and continued with ibrutinib monotherapy. Median follow-up of 208 patients still alive and not lost to follow-up at data cutoff on June 22, 2021, was 34·4 months (IQR 30·6-37·9). Progression-free survival after 12 months in the treatment cessation group was 98% (95% CI 89-100). Infections (in 130 [58%] of 225 patients), neutropenia (in 91 [40%] patients), and gastrointestinal adverse events (in 53 [24%] patients) were the most frequently reported; no new safety signals were detected. Serious adverse events were reported in 46 (40%) of 116 patients who were not randomly assigned and who continued ibrutinib maintenance after cycle 15, eight (33%) of 24 patients in the ibrutinib maintenance group, and four (8%) of 48 patients in the treatment cessation group. One patient who was not randomly assigned had a fatal adverse event (bleeding) deemed possibly related to ibrutinib. INTERPRETATION: These data point to a favourable benefit-risk profile of MRD-guided, time-limited treatment with ibrutinib plus venetoclax for patients with relapsed or refractory chronic lymphocytic leukaemia, suggesting that MRD-guided cessation and reinitiation is feasible in this patient population. FUNDING: AbbVie and Janssen.

Insulin Resistance in Gestational Diabetes Mellitus and Its Association With Anthropometric Fetal Indices.

Background: In pregnant women with gestational diabetes mellitus (GDM), insulin resistance (IR) increases the risk of developing manifest type 2 diabetes mellitus and is associated with complications in both mother and fetus. Objectives: This research aimed to evaluate the associations between IR evaluated by 3 indices (namely updated homeostasis model assessment model (HOMA2), QUICKI, and McAuley's index) and the diabetes risk factors and the fetal growth indices in Vietnamese women with GDM. Methods: A cross-sectional descriptive study was conducted on 370 women with GDM and 40 healthy pregnant women from January 2015 to May 2019. IR was calculated by HOMA2 (HOMA2-IR), QUICKI, and McAuley's index. Fetal anthropometric measurements were assessed via ultrasound which was performed and interpreted by ultrasound experts. Results: In the simple regression analysis, McAuley's index illustrated had statistically significant correlations to the highest number of risk factors of diabetes mellitus compared with HOMA2-IR and QUICKI indices. Moreover, McAuley's index correlated statistically significantly to the highest number of fetal ultrasound measurements factors such as including biparietal diameter (BPD) (r = -0.271, P < .001), head circumference (HC) (r = -0.225, P < .001), abdominal circumference (AC) (r = -0.214, P < .001), femur length (FL) (r = -0.231, P < .001), estimated fetal weight (EFW) (r = -0.239, P < .001) and fetal estimated age (r = -0.299, P < .001). In the multivariable analysis, the McAuley's index contributed the greatest to AC (Standardized B of -0.656, P < .001). Conclusion: The McAuley's index was significantly associated with a higher number of more risk factors for diabetes mellitus as well as fetal ultrasound sonography findings measurements than compared with HOMA2-IR and QUICKI indices.

Understanding the epidemiology, clinical characteristics, knowledge and barriers to treatment and prevention of malaria among returning international laborers in northern Vietnam: a mixed-methods study.

BACKGROUND: With the decline in local malaria transmission in Vietnam as a result of the National Malaria Control Program (NMCP) elimination activities, a greater focus on the importation and potential reintroduction of transmission are essential to support malaria elimination objectives. METHODS: We conducted a multi-method assessment of the demographics, epidemiology, and clinical characteristics of imported malaria among international laborers returning from African or Southeast Asian countries to Vietnam. Firstly, we conducted a retrospective review of hospital records of patients from January 2014 to December 2016. Secondly, we conducted a mixed-methods prospective study for malaria patients admitted to the study sites from January 2017 to May 2018 using a structured survey with blood sample collection for PCR analysis and in-depth interviews. Data triangulation of the qualitative and quantitative data was used during analysis. RESULTS: International laborers were young (median age 33.0 years IQR 28.0-39.5 years), predominantly male (92%) adults returning mostly from the African continent (84%) who stayed abroad for prolonged periods (median time 13.5 months; IQR 6.0-331.5 months) and were involved in occupations that exposed them to a higher risk of malaria infection. Epidemiological trends were also similar amongst study strands and included the importation of Plasmodium falciparum primarily from African countries and P. vivax from Southeast Asian countries. Of 11 P. malariae and P. ovale infections across two study strands, 10 were imported from the African continent. Participants in the qualitative arm demonstrated limited knowledge about malaria prior to travelling abroad, but reported knowledge transformation through personal or co-worker's experience while abroad. Interestingly, those who had a greater understanding of the severity of malaria presented to the hospital for treatment sooner than those who did not; median of 3 days (IQR 2.0-7.0 days) versus 5 days (IQR 4.0-9.5 days) respectively. CONCLUSION: To address the challenges to malaria elimination raised by a growing Vietnamese international labor force, consideration should be given to appropriately targeted interventions and malaria prevention strategies that cover key stages of migration including pre-departure education and awareness, in-country prevention and prophylaxis, and malaria screening upon return.

A Case of Rebound Inflammation in a 38-Year-Old Man with Severe COVID-19 Pneumonia Following Cessation of Dexamethasone Therapy.

BACKGROUND Since the initial COVID-19 cases in 2019, the pandemic has expanded globally. Clinical data showed that dexamethasone treatment at a dose of 6 mg daily for up to 10 days in hospitalized patients with COVID-19 who were receiving respiratory support decreased 28-day mortality in COVID-19 patients. Recent reports, on the other hand, have indicated that both steroid resistance and rebound events occur. We report a case of rebound inflammation after the termination of dexamethasone medication in a 38-year-old man with severe COVID-19 pneumonia, which improved after the reintroduction of dexamethasone. CASE REPORT A 38-year-old male patient with no past medical history of note presented with new onset of dyspnea. He was subsequently diagnosed with severe coronavirus disease 2019 (COVID-19). Initially, the patient was clinically improved following a 3-day course of 16 mg of dexamethasone daily. Shortly after discontinuing corticosteroids, the patient's clinical condition deteriorated, necessitating increased oxygen support. Following the reintroduction of corticosteroids, the patient gradually improved and responded favorably in terms of respiratory function, symptoms, and imaging, after which he was successfully discharged. CONCLUSIONS This case exemplifies the previously observed rebound effects of discontinuing dexamethasone medication in individuals with severe COVID-19 pneumonia. The timing and length of dexamethasone medication should be tailored to the individual patient. In addition, monitoring lung function should be part of the gradual withdrawal of dexamethasone to avoid rebound lung inflammation and the long-term effects of increasing lung fibrosis.

Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety.

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC50 values of 3.4-37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC50 value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (-7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11.

Diabetic Peripheral Neuropathy Associated with Cardiovascular Risk Factors and Glucagon-Like Peptide-1 Concentrations Among Newly Diagnosed Patients with Type 2 Diabetes Mellitus.

PURPOSE: This study was aimed at the prevalence, cardiovascular risk factors of diabetic peripheral neuropathy (DPN), and the relationship between DPN and fasting glucagon-like peptide-1 (fGLP-1) concentrations in newly diagnosed patients with type 2 diabetes mellitus (nT2D). METHODS: A cross-sectional descriptive study was conducted from 2015 to 2020 with a population of 473 nT2D. Screening for DPN was based on the United Kingdom screening test. fGLP-1 was measured by enzyme-linked immunosorbent assay. RESULTS: The prevalence of DPN was 26.6%, in which mild grade was 17.3%, moderate grade was 8.2% and severe grade was 1.1% in total. Age (OR = 1.73, 95% CI 1.12-2.67, p = 0.012), smoking (OR = 1.64, 95% CI 1.03-2.62, p = 0.037), poor control HbA1c (OR = 2.66, 95% CI 1.23-5.76, p = 0.01), 24-h urinary albumin (24hUA) (OR = 2.49, 95% CI 1.26-4.94, p = 0.007), and diabetic retinopathy (OR = 3.17, 95% CI 1.46-6.89, p = 0.002) significantly increased the risk for DPN. In multivariate logistic regression analysis, hypertension (OR = 2.96, 95% CI 1.16-7.55, p = 0.023), triglyceride (OR = 1.50, 95% CI 1.11-2.03, p = 0.009), albumin (OR = 0.85, 95% CI 0.75-0.95, p = 0.005), and fGLP-1 (OR = 0.79, 95% CI 0.67-0.93, p = 0.005) correlated with DPN. The fGLP-1 concentrations were reduced significantly in DPN (p < 0.001). In particular, male patients with DPN had a significantly lower fGLP-1 levels than those without DPN (p < 0.001). CONCLUSION: The prevalence of DPN among nT2D was 26.6%. Age, smoking, hypertension, HbA1c control, triglyceride, albumin, 24hUA, diabetic retinopathy were the associated risk factors of DPN, and fGLP-1 was negatively correlated with DPN (OR = 0.79, 95% CI 0.67-0.93, p = 0.005).

Biosynthesis of Tasikamides via Pathway Coupling and Diazonium-Mediated Hydrazone Formation.

Naturally occurring hydrazones are rare despite the ubiquitous usage of synthetic hydrazones in the preparation of organic compounds and functional materials. In this study, we discovered a family of novel microbial metabolites (tasikamides) that share a unique cyclic pentapeptide scaffold. Surprisingly, tasikamides A-C (1-3) contain a hydrazone group (C═N─N) that joins the cyclic peptide scaffold to an alkyl 5-hydroxylanthranilate (AHA) moiety. We discovered that the biosynthesis of 1-3 requires two discrete gene clusters, with one encoding a nonribosomal peptide synthetase (NRPS) pathway for assembling the cyclic peptide scaffold and another encoding the AHA-synthesizing pathway. The AHA gene cluster encodes three ancillary enzymes that catalyze the diazotization of AHA to yield an aryl diazonium species (diazo-AHA). The electrophilic diazo-AHA undergoes nonenzymatic Japp-Klingemann coupling with a ß-keto aldehyde-containing cyclic peptide precursor to furnish the hydrazone group and yield 1-3. The studies together unraveled a novel mechanism whereby specialized metabolites are formed by the coupling of two biosynthetic pathways via an unprecedented in vivo Japp-Klingemann reaction. The findings raise the prospect of exploiting the arylamine-diazotizing enzymes (AAD) for the in vivo synthesis of aryl compounds and modification of biological macromolecules.