Burden of depressive disorders in Vietnam from 1990 to 2019: A secondary analysis of the Global Burden of Disease Study 2019.

Depressive disorders are among the leading causes of disability globally. However, information on the burden of depressive disorders in Vietnam is limited. We aimed to analyse the burden of depressive disorders in Vietnam from 1990 to 2019. Using data from the Global Burden of Disease Study 2019, prevalence and disability-adjusted life-years (DALYs) were used as indicators to analyse the burden of depressive disorders by age and sex. In 2019 in Vietnam, depressive disorders comprised 2629.1 thousand (95% uncertainty interval (UI): 2233.3-3155.9) estimated cases and 380.6 thousand (95% UI: 258.9-533.8) estimated DALYs. The crude prevalence rate of depressive disorders was higher among females than among males. The DALYs of depressive disorder accounted for a higher percentage of the total all-cause DALYs in the 10-64-year age group than in other age groups. Major depressive disorder was the largest contributor to the burden of depressive disorders. From 1990 to 2019, the crude prevalence and DALY rates per 100 000 population due to depressive disorders increased significantly, whereas age-standardised rates of prevalence and DALYs decreased significantly; the respective average annual percent changes were 0.88% (95% confidence interval: 0.87 to 0.89), 0.68% (0.66 to 0.70), -0.20% (-0.21 to -0.19), and -0.27% (-0.28 to -0.25). Although the age-standardised prevalence rate was lower than that seen globally, depressive disorders were considerable mental health issues in Vietnam. This study will help governments and policymakers to establish appropriate strategies to reduce the burden of these disorders by identifying the priority areas and individuals.

Review on the Significant Interactions between Ultrafine Gas Bubbles and Biological Systems.

Having sizes comparable with living cells and high abundance, ultrafine bubbles (UBs) are prone to inevitable interactions with different types of cells and facilitate alterations in physiological properties. The interactions of four typical cell types (e.g., bacterial, fungal, plant, and mammalian cells) with UBs have been studied over recent years. For bacterial cells, UBs have been utilized in creating the capillary force to tear down biofilms. The release of high amounts of heat, pressure, and free radicals during bubble rupture is also found to affect bacterial cell growth. Similarly, the bubble gas core identity plays an important role in the development of fungal cells. By the proposed mechanism of attachment of UBs on hydrophobin proteins in the fungal cell wall, oxygen and ozone gas-filled ultrafine bubbles can either promote or hinder the cell growth rate. On the other hand, reactive oxygen species (ROS) formation and mass transfer facilitation are two means of indirect interactions between UBs and plant cells. Likewise, the use of different gas cores in generating bubbles can produce different physical effects on these cells, for example, hydrogen gas for antioxidation against infections and oxygen for oxidation of toxic metal ions. For mammalian cells, the importance of investigating their interactions with UBs lies in the bubbles' action on cell viability as membrane poration for drug delivery can greatly affect cells' survival. UBs have been utilized and tested in forming the pores by different methods, ranging from bubble oscillation and microstream generation through acoustic cavitation to bubble implosion.

Yeast vacuolar enzymes as novel hatching inhibitors for aquatic organisms, Daphnia magna and Danio rerio eggs.

Concerns over the spread of non-native species in aquatic environments have led to the need for effective methods to prevent and control their spread while protecting native species. This study investigated the potential of yeast vacuolar enzymes as a natural hatching inhibitor for controlling aquatic organisms. Hatching experiments with Daphnia magna eggs demonstrated that exposure to yeast vacuole enzymes inhibited hatching in a concentration-dependent manner, suggesting their potential as an effective inhibitor of egg hatching in aquatic organisms. Interestingly, the protease used for comparative purposes did not inhibit hatching, but instead increased the mortality of hatched D. magna. Additionally, chorionic changes were observed in non-hatched D. magna eggs and zebrafish eggs exposed to yeast vacuole enzymes, suggesting that the enzyme can alter the chorion and interfere with hatching. These findings suggest that yeast vacuolar enzymes may be a promising and natural management tool for controlling the spread of harmful aquatic organisms, and further research is warranted to explore their potential for species-specific control.

Impacts of the COVID-19 pandemic on access to healthcare among people with disabilities: evidence from six low- and middle-income countries.

BACKGROUND: The pandemic has placed considerable strain on health systems, especially in low- and middle-income countries (LMICs), leading to reductions in the availability of routine health services. Emerging evidence suggests that people with disabilities have encountered marked challenges in accessing healthcare services and supports in the context of the pandemic. Further research is needed to explore specific barriers to accessing healthcare during the pandemic, and any strategies that promoted continued access to health services in LMICs where the vast majority of people with disabilities live. METHODS: Qualitative in-depth interviews were conducted with persons with disabilities in Ghana, Zimbabwe, Viet Nam, Türkiye (Syrian refugees), Bangladesh, and India as part of a larger project exploring the experiences of people with disabilities during the COVID-19 pandemic and their inclusion in government response activities. Data were analysed using thematic analysis. RESULTS: This research found that people with disabilities in six countries - representing a diverse geographic spread, with different health systems and COVID-19 responses - all experienced additional difficulties accessing healthcare during the pandemic. Key barriers to accessing healthcare during the pandemic included changes in availability of services due to systems restructuring, difficulty affording care due to the economic impacts of the pandemic, fear of contracting coronavirus, and a lack of human support to enable care-seeking. CONCLUSION: These barriers ultimately led to decreased utilisation of services which, in turn, negatively impacted their health and wellbeing. However, we also found that certain factors, including active and engaged Organisations of Persons with Disabilities (OPDs) and Non-Governmental Organizations (NGOs) played a role in reducing some of the impact of pandemic-related healthcare access barriers.

Selective detection of HBV pre-genomic RNA in chronic hepatitis B patients using a novel RT-PCR assay.

In chronic hepatitis B (CHB) patients, quantification of HBV pgRNA in plasma has the potential to provide information on disease prognosis and liver injury or histopathology. However, current methods for detecting HBV pgRNA present technical difficulties due to the co-existence of HBV DNA in plasma samples. We have successfully established a novel one-step RT-PCR assay that allows selective quantification of HBV pgRNA. Two cohorts of participants were recruited for assay validation, including treatment-naïve patients with CHB and HBeAg-positive CHB patients who were treated with Tenofovir and monitored for 6 months to assess the predictive value of baseline HBV RNA for HBeAg seroclearance. Statistical analysis was performed using MedCalc version 20.019 software. The novel selective one-step RT-PCR assay for detecting HBV pgRNA was validated with a limit of detection of 100 copies/mL. The assay was able to selectively measure HBV pgRNA even in the presence of excess HBV rcDNA. In treatment-naïve CHB patients, HBV pgRNA levels were significantly lower than HBV DNA concentration. Serum HBV DNA levels and HBeAg status were positively associated with HBV pgRNA. Baseline serum HBV pgRNA levels were found to be strong predictors of HBeAg seroclearance after 6 months of Tenofovir treatment. The study presents a novel RT-PCR assay that allows accurate measurement of plasma HBV pgRNA in chronic hepatitis B patients, even in the presence of excess HBV DNA. The assay is highly selective and represents a significant advancement with potential for further breakthroughs in understanding the clinical significance of HBV pgRNA.

Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan: An Observational Analysis.

Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies.

Situation Awareness-Oriented Dashboard in ICUs in Support of Resource Management in Time of Pandemics.

In a pediatric intensive care unit (PICU) of 32 beds, clinicians manage resources 24 hours a day, 7 days a week, from a large-screen dashboard implemented in 2017. This resource management dashboard efficiently replaces the handwriting information displayed on a whiteboard, offering a synthetic view of the bed's layout and specific information on staff and equipment at bedside. However, in 2020 when COVID-19 hit, the resource management dashboard showed several limitations. Mainly, its visualization offered to the clinicians limited situation awareness (SA) to perceive, understand and predict the impacts on resource management and decision-making of an unusual flow of patients affected by the most severe form of coronavirus. To identify the SA requirements during a pandemic, we conducted goal-oriented interviews with 11 clinicians working in ICUs. The result is the design of an SA-oriented dashboard with 22 key indicators (KIs): 1 on the admission capacity, 15 at bedside and 6 displayed as statistics in the central area. We conducted a usability evaluation of the SA-oriented dashboard compared to the resource management dashboard with 6 clinicians. The results showed five usability improvements of the SA-oriented dashboard and five limitations. Our work contributes to new knowledge on the clinicians' SA requirements to support resource management and decision-making in ICUs in times of pandemics.

MicroRNA-profiling of miR-371~373- and miR-302/367-clusters in serum and cerebrospinal fluid identify patients with intracranial germ cell tumors.

PURPOSE: Intracranial germ cell tumors (iGCT) comprise germinoma and non-germinoma. Their diagnosis predominantly relies on biopsy as only one-fifth of patients present with elevated biomarkers (AFP/ß-HCG) in serum or cerebrospinal fluid (CSF). MicroRNAs (miR/miRNA) have emerged as non-invasive biomarkers in extracranial GCT and may potentially facilitate non-invasive diagnosis in iGCT. METHODS: We analyzed eight miRNAs in serum and CSF from the miR-371~373- and miR-302/367-clusters and four miRNAs differentially expressed in iGCT tissue (miR-142-5p/miR-146a-5p/miR-335-5p/miR-654-3p) from eight iGCT patients (age 10-33 years) and 12 control subjects by pre-amplified RT-qPCR. MiR-30b-5p (serum) and miR-204-5p (CSF) acted as reference genes. ΔCt-values were expressed as [Formula: see text] after standardization against controls. RESULTS: Between iGCT and control patients' serum ΔCt-values of miR-371a-3p (p = 0.0159), miR-372-3p (p= 0.0095, miR-367 (p = 0.0190), miR-302a (p = 0.0381) and miR-302d-3p (p = 0.0159) differed significantly. Discriminatory pattern in CSF was similar to serum as miR-371a (p = 0.0286), miR-372-3p (p = 0.0028), miR-367-3p (p = 0.0167) and miR-302d-3p (p = 0.0061) distinguished between patients and controls. Abundant [Formula: see text] levels of each of these miRNAs were found across all serum and CSF samples including biomarker-negative patients. CONCLUSION: With the largest data set so far, we underline the suitability of miR-371a, miR-372, miR-367 and miR-302d in serum and CSF for diagnosis of iGCT, particularly in biomarker-negative germinoma. Diagnosis of iGCT by miRNA analysis is a feasible and valid approach, particularly as serum can be readily obtained by a less invasive procedure. MiRNA analysis may discriminate iGCT from other tumors with similar radiological findings and may allow to monitor response to therapy as well as early relapse during follow-up.

Combined Effects of Soil Silicon and Host Plant Resistance on Planthoppers, Blast and Bacterial Blight in Tropical Rice.

Soil silicon enhances rice defenses against a range of biotic stresses. However, the magnitude of these effects can depend on the nature of the rice variety. We conducted a series of greenhouse experiments to examine the effects of silicon on planthoppers (Nilaparvata lugens [BPH] and Sogatella furcifera [WBPH]), a leafhopper (Nephotettix virescens [GLH]), blast disease (Magnaporthe grisea) and bacterial blight (Xanthomonas oryzae) in susceptible and resistant rice. We added powdered silica gel (SiO2) to paddy soil at equivalent to 0.25, 1.0, and 4.0 t ha-1. Added silicon reduced BPH nymph settling, but the effect was negligible under high nitrogen. In a choice experiment, BPH egg-laying was lower than untreated controls under all silicon treatments regardless of nitrogen or variety, whereas, in a no-choice experiment, silicon reduced egg-laying on the susceptible but not the resistant (BPH32 gene) variety. Stronger effects in choice experiments suggest that silicon mainly enhanced antixenosis defenses. We found no effects of silicon on WBPH or GLH. Silicon reduced blast damage to susceptible and resistant (Piz, Piz-5 and Pi9 genes) rice. Silicon reduced damage from a virulent strain of bacterial blight but had little effect on a less virulent strain in susceptible and resistant (Xa4, Xa7 and Xa4 + Xa7 genes) varieties. When combined with resistance, silicon had an additive effect in reducing biomass losses to plants infested with bacterial blight (resistance up to 50%; silicon 20%). We discuss how silicon-containing soil amendments can be combined with host resistance to reduce biotic stresses in rice.

Crucial Role of Surfactants in Improving the Extraction Efficiency of ß-Amyrin from Dischidia major Using Ultrasound-Assisted Extraction Coupled with Gas Bubble Flotation.

Ultrasound-assisted extraction coupled with gas bubble flotation was developed as a green method for extracting ß-amyrin fromDischidia major. The solvent system was water:ethanol (9:1). To improve the adsorption of ß-amyrin onto the air/liquid interface during flotation, surfactants were employed; however, the positive effect was only observed with cationic surfactants. High-performance liquid chromatography with spectrophotometric detection (HPLC-PDA) was, for the first time, applied to quantify the ß-amyrin content in D. major and its extracts. With the assistance of surfactants, the foam layer collected from flotation showed high selectivity toward ß-amyrin. The product content was notably increased after surfactants had been removed from the solution.

Cost of Delivering Tetanus Toxoid and Tetanus-Diphtheria Vaccination in Vietnam and the Budget Impact of Proposed Changes to the Schedule.

INTRODUCTION: In 2017, aligned with global World Health Organization tetanus guidelines, Vietnam prepared evidence to support a recommendation to introduce the tetanus-diphtheria (Td) vaccine into routine immunization. This study aimed to provide evidence on the costs and budgetary impact of the potential replacement of the tetanus-toxoid (TT) vaccine with the Td vaccine, considering different possible delivery strategies. METHOD: We used an activity-based ingredients costing approach to estimate the 2017 program costs of providing TT vaccination to girls aged 15-16 years and conducting Td campaigns in outbreak areas. We performed a budget impact analysis for 2018-2025 using the cost per dose estimates based on the current delivery of these vaccines. We assumed complete cessation of TT vaccination of girls aged 15-16 years and a transition period where Td outbreak control campaigns would still occur. Td vaccine was assumed to be provided to children aged 7 years using either facility- or school-based delivery or combined facility- and school-based delivery. RESULTS: The delivery cost per dose for current TT vaccination for girls aged 15-16 years was US$1.49 for school-based delivery, US$1.76 for facility-based delivery, and US$3.86 for delivery via outreach. Td vaccination through campaigns was estimated to cost US$3.56/dose. During 2018-2025, replacing the TT vaccine for girls aged 15-16 years with the Td vaccine for children aged 7 years is estimated to save US$4.61 million in immunization delivery costs if a school-based delivery strategy is used or US$1.04 million if facility-based delivery is used. CONCLUSION: Compared to the current plan, delivery of Td routine vaccination via a school-based strategy was the most cost saving. These results were used in late 2019 to support the delivery of Td vaccination using a school-based delivery strategy for children aged 7 years in 30 Northern provinces in Vietnam.

Key Factors Influencing Use of Immunization Cost Evidence in Country Planning and Budgeting Processes: Experiences From Indonesia, Tanzania, and Vietnam.

In many low- and middle-income countries, planning cycles and policy decisions are not always informed by cost evidence, even where relevant and recent cost evidence is available. The Immunization Costing Action Network (ICAN) project was a research and learning community designed to strengthen country capacity to generate immunization cost evidence and to understand and improve the evidence-to-policy linkages for the evidence. We identified key factors that increase the likelihood that health policy makers will use evidence for policy making or planning, which shaped the development of a 6-step evidence to policy and practice (EPP) facilitated process. ICAN used the EPP process in Indonesia, Tanzania, and Vietnam from 2016-2019. The experience resulted in several insights regarding country priorities related to cost evidence and factors that determine uptake. Cost evidence is more likely to be used if it answers a specific policy question prioritized by the immunization program, while the use case is less clear and urgent for routine planning and program management. Nonhealth ministries and subnational stakeholders can provide important perspectives to inform the research and its usability. The use case for evidence should be revisited periodically as divergences from formal planning cycles are common and new policy windows open. Ensuring evidence is available at the right time is critical, even if this requires a sacrifice between rigor and speed. Engaging a small group of stakeholders, rather than an individual, to champion the research may be more effective, and the research has greater legitimacy if it is produced by multidisciplinary country teams. Evidence and messages should be tailored for and packaged targeting different audiences. Going forward, continued support is necessary to bridge the divide between those who generate cost evidence and those who translate evidence for policy and planning decisions.

Do health preferences differ among Asian populations? A comparison of EQ-5D-5L discrete choice experiments data from 11 Asian studies.

INTRODUCTION: Many countries have established their own EQ-5D value sets proceeding on the basis that health preferences differ among countries/populations. So far, published studies focused on comparing value set using TTO data. This study aims to compare the health preferences among 11 Asian populations using the DCE data collected in their EQ-5D-5L valuation studies. METHODS: In the EQ-VT protocol, 196 pairs of EQ-5D-5L health states were valued by a general population sample using DCE method for all studies. DCE data were obtained from the study PI. To understand how the health preferences are different/similar with each other, the following analyses were done: (1) the statistical difference between the coefficients; (2) the relative importance of the five EQ-5D dimensions; (3) the relative importance of the response levels. RESULTS: The number of statistically differed coefficients between two studies ranged from 2 to 16 (mean: 9.3), out of 20 main effects coefficients. For the relative importance, there is not a universal preference pattern that fits all studies, but with some common characteristics, e.g. mobility is considered the most important; the relative importance of levels are approximately 20% for level 2, 30% for level 3, 70% for level 4 for all studies. DISCUSSION: Following a standardized study protocol, there are still considerable differences in the modeling and relative importance results in the EQ-5D-5L DCE data among 11 Asian studies. These findings advocate the use of local value set for calculating health state utility.

"You're a 'high-risk' customer": A qualitative study of women's experiences of receiving information from health professionals regarding health problems or complications in pregnancy.

BACKGROUND: Experiencing complications in pregnancy is stressful for women and can impact on fetal and maternal outcomes. Supportive encounters with health professionals can reduce the worry women experience. Further research is needed to understand women's perspectives on communicating with their healthcare providers about their concerns. AIM: This study explored women's experiences of receiving information about pregnancy complications from healthcare providers and their interactions with multiple professionals and services during pregnancy. METHODS: This was a qualitative interpretive study. Semi-structured interviews were conducted with 20 women experiencing pregnancy complications recruited from antenatal services at two hospitals in Sydney. Inductive thematic analysis was used to analyse the data. FINDINGS: Women had a range of reactions to their diagnoses, including concern for their baby, for themselves and for their labour. Most women reported that communication with healthcare providers was distressing, they were not listened to and staff used insensitive, abrupt language. Women were also distressed by delays in education, receiving contradictory information and having to repeatedly share their stories with different health professionals. In some cases, this damaged the therapeutic relationship and reduced trust towards healthcare providers. Midwives were generally preferred over doctors because they had a more woman-centred approach. CONCLUSION: To improve women's experiences of care for pregnancy complications, it is critical to improve the communication skills of maternity service providers. Women's need for information, resources and support can best be provided by continuity of care with a named health professional, for example, a midwife working within an integrated multidisciplinary antenatal service model.

Health-related quality of life among breast cancer patients compared to cancer survivors and age-matched women in the general population in Vietnam.

PURPOSE: This study compared the health-related quality of life (HRQoL) of breast cancer (BC) patients, survivors, and age-matched women from the general population in Vietnam to address the paucity of HRQoL research and contribute to the robust assessment of BC screening and care in Vietnam. METHODS: The standardised EQ-5D-5L instrument was incorporated in an online survey and a hospital-based face-to-face survey, and together with data from the Vietnam EQ-5D-5L norms study. χ2 tests assessed EQ-5D health profile associations and a Tobit regression model investigated the association between overall health status (EQ-VAS/utility scores) and sociodemographic and clinical characteristics. RESULTS: A total of 309 participants (107 patients undergoing treatment and 202 survivors who had completed treatment) provided usable responses. The dimensions that affected mostly the HRQoL of women with BC were pain/discomfort and anxiety/depression. Current patients and survivors differed significantly regarding HRQoL dimensions of mobility, self-care, usual activities, and anxiety/depression. Their health utilities were 0.74 and 0.84, respectively, compared with 0.91 for age-matched Vietnamese women in the general population (p < 0.001). Treatment status (survivor vs patient), younger age, higher monthly household income, and higher education levels were associated with higher health utility. CONCLUSIONS: The results point to unmet needs in mental health support and well-being and for attention to be given to the development of a biopsychosocial system of cancer diagnosis, treatment, and care. The results will also inform future assessments of the comparative value for money of interventions intended to impact on breast cancer in Vietnam.

Reference data among general population and known-groups validity among hypertensive population of the EQ-5D-5L in Vietnam.

PURPOSE: This study aims to provide EQ-5D-5L population norms among the general population in Vietnam and to test EQ-5D-5L' construction validity among people living with hypertension there. METHODS: Descriptive statistics of the five dimensions and five levels, EQ-VAS and EQ-5D-5L indexes were categorised into gender and age groups for the EQ-5D-5L population norms. Known-groups testing was set for lower EQ-5D-5L outcomes among people who were aware of their hypertensive status, females, people with more comorbidities, less education, older ages, and higher body mass indexes. Level of confident interval was 95%. RESULTS: The mean EQ-VAS and EQ-5D-5L indexes were 81.10 (SD: 13.35) and 0.94 (SD: 0.09) among the general population. The EQ-5D-5L outcomes were better among younger people, males, people with more education, employees, and single people. Respondents reported fewer problems with self-care and usual activities and tend to have problems at higher levels across older ages. The known-group testing showed statistically significant results. The mean EQ-VAS and EQ-5D-5L indexes of people in the diagnosed hypertensive group (71.48 and 0.94, respectively) were statistically significantly smaller than they were in the non-hypertensive and undiagnosed hypertensive group (76.65 and 0.97; 76.95 and 0.96 accordingly). Statistically significant associations of lower EQ-5D-5L indexes and EQ-VAS were found among people diagnosed for hypertension, people suffering from an incremental comorbidity, and obese people. CONCLUSION: This study has provided EQ-5D-5L population norms for the general population and evidence for known-groups validity of the EQ-5D-5L instrument among hypertensive people in Vietnam.

Novel propargylamine-based inhibitors of cholinesterases and monoamine oxidases: Synthesis, biological evaluation and docking study.

A combination of several pharmacophores in one molecule has been successfully used for multi-target-directed ligands (MTDL) design. New propargylamine substituted derivatives combined with salicylic and cinnamic scaffolds were designed and synthesized as potential cholinesterases and monoamine oxidases (MAOs) inhibitors. They were evaluated invitro for inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE) using Ellman's method. All the compounds act as dual inhibitors. Most of the derivatives are stronger inhibitors of AChE, the best activity showed 5-bromo-N-(prop-2-yn-1-yl)salicylamide 1e (IC50 = 8.05 µM). Carbamates (4-bromo-2-[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2d and 2,4-dibromo-6-[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2e were selective and the most active for BuChE (25.10 and 26.09 µM). 4-Bromo-2-[(prop-2-yn-1-ylimino)methyl]phenol 4a was the most potent inhibitor of MAOs (IC50 of 3.95 and ≈10 µM for MAO-B and MAO-A, respectively) along with a balanced inhibition of both cholinesterases being a real MTDL. The mechanism of action was proposed, and binding modes of the hits were studied by molecular docking on human enzymes. Some of the derivatives also exhibited antioxidant properties. Insilico prediction of physicochemical parameters affirm that the molecules would be active after oral administration and able to reach brain tissue.

Cyclisation strategies for stabilising peptides with irregular conformations.

Cyclisation is a common synthetic strategy for enhancing the therapeutic potential of peptide-based molecules. While there are extensive studies on peptide cyclisation for reinforcing regular secondary structures such as α-helices and ß-sheets, there are remarkably few reports of cyclising peptides which adopt irregular conformations in their bioactive target-bound state. In this review, we highlight examples where cyclisation techniques have been successful in stabilising irregular conformations, then discuss how the design of cyclic constraints for irregularly structured peptides can be informed by existing ß-strand stabilisation approaches, new computational design techniques, and structural principles extracted from cyclic peptide library screening hits. Through this analysis, we demonstrate how existing peptide cyclisation techniques can be adapted to address the synthetic design challenge of stabilising irregularly structured binding motifs.

Nonsense-mediated mRNA decay does not restrict influenza A virus propagation.

Nonsense-mediated mRNA decay (NMD) was identified as a process to degrade flawed cellular messenger RNA (mRNA). Within the last decades it was also shown that NMD carries virus-restricting capacities and thus could be considered a part of the cellular antiviral system. As this was shown to affect primarily positive-sense single stranded RNA ((+)ssRNA) viruses there is only scarce knowledge if this also applies to negative-sense single stranded RNA ((-)ssRNA) viruses. Influenza A viruses (IAVs) harbour a segmented (-)ssRNA genome. During their replication IAVs produce numerous RNA transcripts and simultaneously impair cellular transcription and translation. The viral mRNAs hold several molecular patterns which can elicit NMD and in turn would lead to their degradation. This, in consequence, may mitigate viral propagation. Thus, we examined if a knockdown or a pharmacological inhibition of NMD key components may influence IAV replication. Additionally, we performed similar experiments with respiratory syncytial virus (RSV), another (-)ssRNA virus, but with a non-segmented genome. Although it seemed that a knockdown of up-frameshift protein 1 (UPF1), the central NMD factor, slightly increased viral mRNA and protein levels, no significant alteration of viral replication could be observed, implying that the NMD machinery may not have restricting capacities against (-)ssRNA viruses.

Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase.

Based on the broad spectrum of biological activity of hydrazide-hydrazones, trifluoromethyl compounds, and clinical usage of cholinesterase inhibitors, we investigated hydrazones obtained from 4-(trifluoromethyl)benzohydrazide and various benzaldehydes or aliphatic ketones as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). They were evaluated using Ellman's spectrophotometric method. The hydrazide-hydrazones produced a dual inhibition of both cholinesterase enzymes with IC50 values of 46.8-137.7 µM and 19.1-881.1 µM for AChE and BuChE, respectively. The majority of the compounds were stronger inhibitors of AChE; four of them (2-bromobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, cyclohexanone, and camphor-based 2o, 2p, 3c, and 3d, respectively) produced a balanced inhibition of the enzymes and only 2-chloro/trifluoromethyl benzylidene derivatives 2d and 2q were found to be more potent inhibitors of BuChE. 4-(Trifluoromethyl)-N'-[4-(trifluoromethyl)benzylidene]benzohydrazide 2l produced the strongest inhibition of AChE via mixed-type inhibition determined experimentally. Structure-activity relationships were identified. The compounds fit physicochemical space for targeting central nervous systems with no apparent cytotoxicity for eukaryotic cell line together. The study provides new insights into this CF3-hydrazide-hydrazone scaffold.