Two-stage preparation of highly mesoporous carbon for super-adsorption of paracetamol and tetracycline in water: Important contribution of pore filling and π-π interaction.

This study aimed to develop an extremely highly porous activated carbon derived from soybean curd residues (SCB-AC) through two-step pyrolyzing coupled with KOH activating process and then apply it for removing paracetamol (PRC) and tetracycline (TCH) from water. The optimal conditions for chemical activation were 800 °C and the ratio of KOH to material (4/1; wt./wt.). SCB-AC adsorbents (before and after adsorption) were characterized by Brunauer-Emmet-Teller (BET) analyser, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy, and Raman spectroscopy. Adsorption kinetics, isotherm, and thermodynamics were concluded under batch experiments. The effects of pH (2-10) and NaCl (0-1 M) on adsorption processes were investigated. Reusable properties of laden SCB-AC were evaluated by studying desorption and cycles of adsorption/desorption. Results indicated that SCB-AC exhibited a large specific surface area (3306 m2/g) and high total pore volume (2.307 cm3/g), with mesoporous volume accounting for 86.9%. Its porosity characteristics (average pore width: 2.725 nm) are very appropriate for adsorbing two pharmaceuticals through pore-filling mechanism. Adsorption processes were less affected by the parameters: pH, NaCl, and water matrixes. The kinetics for adsorbing PRC reached a faster equilibrium than that for TCH. The Langmuir maximum adsorption capacity of SCB-AC (pHeq 7.0 and 25 °C) was 1235 mg/g (for adsorbing TCH) and 646 mg/g (PRC). Pore filling (confirmed by BET analyser) and π-π interaction (confirmed by FTIR and Raman spectroscopy) were dominant adsorption mechanisms. Those mechanisms were physisorption (ΔH° = 13.71 and -21.04 kJ/mol for adsorbing TCH and PRC, respectively). SCB-AC can serve as an outstanding material for removing pharmaceuticals from water.

Serial electrocardiogram recordings revealed a high prevalence of QT interval prolongation in patients with tuberculosis receiving fluoroquinolones.

BACKGROUND: Fluoroquinolones, crucial components of treatment regimens for drug-resistant tuberculosis (TB), are associated with QT interval prolongation and risks of fatal cardiac arrhythmias. However, few studies have explored dynamic changes in the QT interval in patients receiving QT-prolonging agents. METHODS: This prospective cohort study recruited hospitalized patients with TB who received fluoroquinolones. The study investigated the variability of the QT interval by using serial electrocardiograms (ECGs) recorded four times daily. This study analyzed the accuracy of intermittent and single-lead ECG monitoring in detecting QT interval prolongation. RESULTS: This study included 32 patients. The mean age was 68.6 ± 13.2 years. The results revealed mild-to-moderate and severe QT interval prolongation in 13 (41%) and 5 (16%) patients, respectively. The incremental yields in sensitivity of one to four daily ECG recordings were 61.0%, 26.1%, 5.6%, and 7.3% in detecting mild-to-moderate QT interval prolongation, and 66.7%, 20.0%, 6.7%, and 6.7% in detecting severe QT interval prolongation. The sensitivity levels of lead II and V5 ECGs in detecting mild-to-moderate and severe QT interval prolongation exceeded 80%, and their specificity levels exceeded 95%. CONCLUSION: This study revealed a high prevalence of QT interval prolongation in older patients with TB who receive fluoroquinolones, particularly those with multiple cardiovascular risk factors. Sparsely intermittent ECG monitoring, the prevailing strategy in active drug safety monitoring programs, is inadequate owing to multifactorial and circadian QT interval variability. Additional studies performing serial ECG monitoring are warranted to enhance the understanding of dynamic QT interval changes in patients receiving QT-prolonging anti-TB agents.

Agrobacterium-mediated cassava transformation for the Asian elite variety KU50.

KEY MESSAGE: Cassava genetic transformation has mostly been reported for African cassava varieties, but not for Asian varieties. This is the first report of cassava transformation in Asian elite varieties using friable embryogenic calli. Agrobacterium-mediated cassava transformation via friable embryogenic calli (FEC) has enabled the robust production of transgenic cassava. So far, mostly the model cassava variety 60444 and African varieties have been transformed because of their good production and regeneration from embryogenic tissues. It is important to develop transformation methods for elite Asian cassava varieties to meet the changing needs in one of the world's major cassava production areas. However, a suitable transformation method for the Asian elite variety Kasetsart 50 (KU50) has not been developed. Here, we report a transformation method for KU50, the cultivar with the highest planting area in Thailand and Vietnam. In cassava transformation, the preparation of FEC as the target tissue for transgene integration is a key step. FEC induction from KU50 was improved by using media with reduced nutrients and excess vitamin B1, and somatic embryo and plant regeneration optimized by manipulation of naphthalene acetic acid (NAA), and benzylamino purine (BAP). The transformation efficiency for KU50 was 22%, approximately half that of 60444 at 45%. Transcriptome analysis indicated that the expression of genes related to cell-wall loosening was upregulated in FEC from KU50 compared with 60444, indicating that cell-wall production and assembly were disproportionate in the Asian variety. The transformation system for KU50 reported here will contribute to the molecular breeding of cassava plants for Asian farmers using transgenic and genome-editing technologies.

Field transcriptome analysis reveals a molecular mechanism for cassava-flowering in a mountainous environment in Southeast Asia.

KEY MESSAGE: The field survey in this article showed in 'KU50', a popular variety and late-branching type of cassava in Southeast Asia, that flowering rarely occurs in normal-field conditions in Southeast Asia but is strongly induced in the dry season in the mountainous region. Flowering time is correlated with the expression patterns of MeFT1 and homologs of Arabidopsis GI, PHYA, and NF-Ys. Cassava (Manihot esculenta Crantz) is a tropical crop that is propagated vegetatively rather than sexually by seed. Flowering rarely occurs in the erect-type variety grown in Southeast Asia, but it is known that cassava produces flowers every year in mountainous regions. Data pertaining to the effect of environmental factors on flowering time and gene expression in cassava, however, is limited. The aim of the present study was to determine the kinds of environmental conditions that regulate flowering time in cassava and the underlying molecular mechanisms. The flowering status of KU50, a popular variety in Southeast Asia and late-branching type of cassava, was monitored in six fields in Vietnam and Cambodia. At non-flowering and flowering field locations in North Vietnam, the two FLOWERING LOCUS T (FT)-like genes, MeFT1 and MeFT2, were characterized by qPCR, and the pattern of expression of flowering-related genes and genes responsive to environmental signals were analyzed by using RNA sequencing data from time-series samples. Results indicate that cassava flowering was induced in the dry season in the mountain region, and that flowering time was correlated with the expression of MeFT1, and homologs of Arabidopsis GI, PHYA, and NF-Ys. Based upon these data, we hypothesize that floral induction in cassava is triggered by some conditions present in the mountain regions during the dry season.

Fish species composition, diversity, and migration in the Mekong Delta: a study in the Cua Tieu River, Vietnam.

Southern Vietnam, particularly the Mekong Delta, is popular in inland fish species diversity. In this study, fish species diversity across six stations from the estuary to the upstream of Cua Tieu River, which is situated in the Tien Giang province in Southern Vietnam, has been studied from January 2018 to June 2020. Altogether, 2088 specimens were collected and classified, and these belonged to 115 species, 98 genera, and 54 families of 15 orders that were recognized and identified. The names of species, genera, families, and orders are cited. In the total of 115 species, the Perch-like order (Perciformes) is the most diverse group, with 50 species (consist of 43.48% of total species). The catfish order (Siluriformes) is the second-most diverse group, consisting of 19 species (16.52% of total species). The carp order (Cypriniformes) consists of 8 species (6.96%), and the herring order (Clupeiformes) consists of 7 species (6.09%). Three orders of fishes, needle fish order (Beloniformes), Spiny eel order (Synbranchiformes), and flounder order (Pleuronectiformes), consist of 6 species (5.22%), and other orders consist of 1-3 species (0.87-2.61%). Among the 115 species recorded, 4 species were classified as vulnerable (VU) in the Red Data Book of Viet Nam (2007) (which is 3.48% of the total species collected). These are Elops saurus, Anodontostoma chacunda, Datnioides polota, and Toxotes chatareus. According to the IUCN Red list (2020), 1 species is endangered (EN) (0.87%), 1 species is vulnerable (VU) (0.87%), 3 species of fish are near threatened (NT) (2.61%), 6 species are data deficient (DD) (5.22%), and 58 species are least concern (LC) (50.43%). The result also recorded 41 fish as migratory species (26 freshwater species and 15 marine species), which is 35.65% of total species collected. Some migratory species are important and endemic species of the Mekong River, such as Bagarius yarrelli, Boesemania microlepis, Yasuhikotakia modesta, Cyclocheilos enoplos, Pangasianodon hypophthalmus, Pangasius conchophilus, Pangasius krempfi, Pangasius pleurotaenia, Phalacronotus bleekeri.

Impact of a dam construction on the intertidal environment and free-living nematodes in the Ba Lai, Mekong Estuaries, Vietnam.

The impact of high siltation and accumulation of organic and waste material in the intertidal of the dammed Ba Lai River in Vietnam as part of the Mekong estuarine system was investigated by means of marine free-living nematodes. Nutrients content (nitrate, ammonium, total phosphorus, total nitrogen), total suspended solids, total organic carbon, coliform, bacteria E. coli, pH, dissolved oxygen, total dissolved solids, methane and hydrogen sulfide concentration, and the nematode communities were characterized in sediment at selected stations along the river above and below the dam. Our results found elevated methane concentrations at the upstream side of the dam while hydrogen sulfide concentrations found to be highest in the downstream side of the dam. Furthermore, methane and hydrogen sulfide concentrations were correlated to nematode community characteristics such as trophic composition densities and genera composition. There was a clear difference between the communities above and below the dam. The discontinuous nematode community distribution indicated that the Ba Lai River is impacted by dam construction. Potentially the high deposition and eutrophication could turn the area into a methane-rich area related to predicted impact on nematodes.

Blood pressure screening results from May Measurement Month 2019 in Vietnam.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative to raise awareness of high BP and act as a temporary solution to the lack of screening programmes worldwide. We aimed to screen for hypertension and cardiovascular risk factors in people aged ≥18 years in the community, thereby defining the proportion of subjects with elevated BP and assess the awareness and the effectiveness of its treatment. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. From May 2019 to June 2019, through 10 cities/provinces in Vietnam, 25 887 individuals with mean age 48.7 (SD ±17.7) years were screened. After multiple imputations, 8758 (33.8%) had hypertension. Of individuals not receiving antihypertensive medication, 3025 (15.0%) were hypertensive. Of individuals receiving antihypertensive medication, 2800 (48.8%) had uncontrolled BP. Raised BP [systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg] was also associated with additional risk factors including smoking, alcohol intake, previous hypertension in pregnancy, and obesity. May Measurement Month 2019 was the most extensive BP screening campaign ever undertaken in Vietnam. Undiagnosed and uncontrolled hypertension in Vietnam remains a substantial health problem. Local campaigns applying standardized methods such as MMM 2019 will be beneficial to screen for the significant number of individuals with raised BP and increase the awareness of hypertension.

10-pm-order mechanical displacement measurements using heterodyne interferometry.

In this paper, we present 10-pm-order mechanical displacement measurements using heterodyne interferometry. The measuring system includes a single-path heterodyne interferometer and a phase meter based on a phase-locked loop (PLL). It is not easy to measure a mechanical displacement of 10 pm or less owing to electronics and environmental noises in the interferometer. To solve this problem, the improvement of the noise floor is required for the phase meter. A PLL algorithm, which is programmed on a field-programmable gate array module, is used for efficient noise reduction of the phase meter. The interferometer combined with a stiff piezoelectric flexure stage is placed in a vacuum chamber. The measurement comparisons and the noise floor evaluations are performed between air and vacuum to evaluate effects from their environments. The interferometer has two spatially separated beams with different frequencies and two balanced optical arms. The measurement results demonstrate that the system combined with the above components is capable of measuring mechanical displacements of 11 pm in air and vacuum. A noise floor of 0.2 pm/Hz between 50 Hz and 100 Hz can be obtained in vacuum. In this paper, the setup of the interferometer, the signal processing of the PLL, experiments, and results are discussed.

May Measurement Month 2018: an analysis of blood pressure screening results from Vietnam.

Vietnam in the Asia Pacific region has a high hypertension (HTN) prevalence. The May Measurement Month (MMM) program was enthusiastically responded to in Vietnam by launching and deploying it across the whole country from 2017. The aims of the MMM 2018 program in Vietnam were to screen at least 15 000 people aged 18 and over across the country; to inform participants of the risks associated with HTN; and thereby define the proportion of subjects with elevated blood pressure (BP) and assess the awareness and the effectiveness of its treatment. An opportunistic cross-sectional survey of volunteers aged ≥ 18 was carried out in May 2018. Blood pressure measurement, the definition of HTN, and statistical analysis followed the standard MMM protocol. From May 2018 to June 2018, through 10 cities/provinces in Vietnam, 17 332 individuals with mean age 47.0 ± 17.9 years were screened during MMM18. After multiple imputation, 5260 (30.3%) had HTN. Of individuals not receiving antihypertensive medication, 1956 (13.9%) were hypertensive. Of patients receiving antihypertensive medication, 1540 (46.6%) had uncontrolled BP. Those who had HTN also displayed many additional risk factors similarly to MMM 2017 including smoking, alcohol, overweight-obesity, and diabetes. In conclusion, MMM 2018 campaign is a continuation program of MMM 2017 that has promoted the strength of the BP screening survey in the community in Vietnam, which hopefully will influence on awareness of disease prevention in this century. The next steps of the program will have special innovations on how to reduce the frequency of focusing on variable risk factors to change the overall picture of HTN in Vietnam.

Optimal control of a fractional order model for granular SEIR epidemic with uncertainty.

In this study, we present a general formulation for the optimal control problem to a class of fuzzy fractional differential systems relating to SIR and SEIR epidemic models. In particular, we investigate these epidemic models in the uncertain environment of fuzzy numbers with the rate of change expressed by granular Caputo fuzzy fractional derivatives of order ß ∈ (0, 1]. Firstly, the existence and uniqueness of solution to the abstract fractional differential systems with fuzzy parameters and initial data are proved. Next, the optimal control problem for this fractional system is proposed and a necessary condition for the optimality is obtained. Finally, some examples of the fractional SIR and SEIR models are presented and tested with real data extracted from COVID-19 pandemic in Italy and South Korea.

Blood pressure screening during the May Measurement Month 2017 programme in Vietnam-South-East Asia and Australasia.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. Our aim was to screen for hypertension (HTN) and cardiovascular risk factors in people aged ≥18 years in the community, thereby define the proportion of subjects with elevated BP and assess the awareness and the effectiveness of its treatment. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of HTN and statistical analysis followed the standard MMM protocol. From May 2017 to June 2017, through 10 cities/provinces in Vietnam, 10 993 individuals with mean age 49.1 ± 16.2 years were screened during MMM17. After multiple imputation, 3154 (28.7%) had HTN. Of individuals not receiving antihypertensive medication, 1509 (16.1%) were hypertensive. Of individuals receiving antihypertensive medication, 620 (37.7%) had uncontrolled BP. Raised BP was also associated with additional risk factors including smoking, alcohol, overweight-obesity, and diabetes. May Measurement Month 17 was the largest BP screening campaign ever undertaken in Vietnam. Undiagnosed and uncontrolled HTN in Vietnam remains a substantial health problem. Local campaigns applying standardized methods such as MMM17, will be highly useful to screen for the significant number of individuals with raised BP and increase the awareness of HTN.

Positive regulatory role of strigolactone in plant responses to drought and salt stress.

This report provides direct evidence that strigolactone (SL) positively regulates drought and high salinity responses in Arabidopsis. Both SL-deficient and SL-response [more axillary growth (max)] mutants exhibited hypersensitivity to drought and salt stress, which was associated with shoot- rather than root-related traits. Exogenous SL treatment rescued the drought-sensitive phenotype of the SL-deficient mutants but not of the SL-response mutant, and enhanced drought tolerance of WT plants, confirming the role of SL as a positive regulator in stress response. In agreement with the drought-sensitive phenotype, max mutants exhibited increased leaf stomatal density relative to WT and slower abscisic acid (ABA)-induced stomatal closure. Compared with WT, the max mutants exhibited increased leaf water loss rate during dehydration and decreased ABA responsiveness during germination and postgermination. Collectively, these results indicate that cross-talk between SL and ABA plays an important role in integrating stress signals to regulate stomatal development and function. Additionally, a comparative microarray analysis of the leaves of the SL-response max2 mutant and WT plants under normal and dehydrative conditions revealed an SL-mediated network controlling plant responses to stress via many stress- and/or ABA-responsive and cytokinin metabolism-related genes. Our results demonstrate that plants integrate multiple hormone-response pathways for adaptation to environmental stress. Based on our results, genetic modulation of SL content/response could be applied as a potential approach to reduce the negative impact of abiotic stress on crop productivity.

Evaluation of Luminex xTAG Gastrointestinal Pathogen Panel Assay for Detection of Multiple Diarrheal Pathogens in Fecal Samples in Vietnam.

Diarrheal disease is a complex syndrome that remains a leading cause of global childhood morbidity and mortality. The diagnosis of enteric pathogens in a timely and precise manner is important for making treatment decisions and informing public health policy, but accurate diagnosis is a major challenge in industrializing countries. Multiplex molecular diagnostic techniques may represent a significant improvement over classical approaches. We evaluated the Luminex xTAG gastrointestinal pathogen panel (GPP) assay for the detection of common enteric bacterial and viral pathogens in Vietnam. Microbiological culture and real-time PCR were used as gold standards. The tests were performed on 479 stool samples collected from people admitted to the hospital for diarrheal disease throughout Vietnam. Sensitivity and specificity were calculated for the xTAG GPP for the seven principal diarrheal etiologies. The sensitivity and specificity for the xTAG GPP were >88% for Shigellaspp.,Campylobacterspp., rotavirus, norovirus genotype 1/2 (GI/GII), and adenovirus compared to those of microbiological culture and/or real-time PCR. However, the specificity was low (∼60%) for Salmonella species. Additionally, a number of important pathogens that are not identified in routine hospital procedures in this setting, such as Cryptosporidiumspp. and Clostridium difficile, were detected with the GPP. The use of the Luminex xTAG GPP for the detection of enteric pathogens in settings, like Vietnam, would dramatically improve the diagnostic accuracy and capacity of hospital laboratories, allowing for timely and appropriate therapy decisions and a wider understanding of the epidemiology of pathogens associated with severe diarrheal disease in low-resource settings.

Tracking the establishment of local endemic populations of an emergent enteric pathogen.

Shigella sonnei is a human-adapted pathogen that is emerging globally as the dominant agent of bacterial dysentery. To investigate local establishment, we sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data show that S. sonnei was introduced into Vietnam in the 1980s and has undergone localized clonal expansion, punctuated by genomic fixation events through periodic selective sweeps. We uncover geographical spread, spatially restricted frontier populations, and convergent evolution through local gene pool sampling. This work provides a unique, high-resolution insight into the microevolution of a pioneering human pathogen during its establishment in a new host population.

Pancreatic polypeptide is recognized by two hydrophobic domains of the human Y4 receptor binding pocket.

Structural characterization of the human Y4 receptor (hY4R) interaction with human pancreatic polypeptide (hPP) is crucial, not only for understanding its biological function but also for testing treatment strategies for obesity that target this interaction. Here, the interaction of receptor mutants with pancreatic polypeptide analogs was studied through double-cycle mutagenesis. To guide mutagenesis and interpret results, a three-dimensional comparative model of the hY4R-hPP complex was constructed based on all available class A G protein-coupled receptor crystal structures and refined using experimental data. Our study reveals that residues of the hPP and the hY4R form a complex network consisting of ionic interactions, hydrophobic interactions, and hydrogen binding. Residues Tyr(2.64), Asp(2.68), Asn(6.55), Asn(7.32), and Phe(7.35) of Y4R are found to be important in receptor activation by hPP. Specifically, Tyr(2.64) interacts with Tyr(27) of hPP through hydrophobic contacts. Asn(7.32) is affected by modifications on position Arg(33) of hPP, suggesting a hydrogen bond between these two residues. Likewise, we find that Phe(7.35) is affected by modifications of hPP at positions 33 and 36, indicating interactions between these three amino acids. Taken together, we demonstrate that the top of transmembrane helix 2 (TM2) and the top of transmembrane helices 6 and 7 (TM6-TM7) form the core of the peptide binding pocket. These findings will contribute to the rational design of ligands that bind the receptor more effectively to produce an enhanced agonistic or antagonistic effect.

Population-level antibody estimates to novel influenza A/H7N9.

There are no contemporary data available describing human immunity to novel influenza A/H7N9. Using 1723 prospectively collected serum samples in southern Vietnam, we tested for antibodies to 5 avian influenza virus antigens, using a protein microarray. General-population antibody titers against subtype H7 virus are higher than antibody titers against subtype H5 and lower than titers against H9. The highest titers were observed for human influenza virus subtypes. Titers to avian influenza virus antigens increased with age and with geometric mean antibody titer to human influenza virus antigens. There were no titer differences between the urban and the rural location in our study.

Important role of pore-filling mechanism in separating naproxen from water by micro-mesoporous carbonaceous material.

Commercial micro-mesoporous carbonaceous material (MCM; 56.8% mesopores) was applied for investigating the removal phenomenon of naproxen drug in aqueous solutions through batch adsorption experiments. Results demonstrated that the adsorption capacity of MCM to naproxen was slightly affected by different pHeq (2.0-11) and ionic strength (0-1 M NaCl). Adsorption kinetics, isotherms, thermodynamics, and mechanisms were evaluated at pH 7.0. Adsorption kinetics indicated the rate constants for adsorption (0.2 × 10-3  L/(mg × min) and desorption (0.076/min) and the adsorption equilibrium constant (2.6 × 10-3  L/mg). Adsorption isotherm showed that MCM exhibited a high-affinity adsorption capacity to naproxen (even at low concentrations) and its Langmuir maximum adsorption capacity (Qmax ) was 252.7 mg/g at 25°C. Adsorption thermodynamics proved that the adsorption process was endothermic and physisorption (ΔH° = 9.66 kJ/mol). The analysis result of pore size distribution demonstrated that the internal pore structure of MCM was appropriate for adsorbing naproxen molecules. Pore-filing mechanism (pore diffusion phenomenon) was confirmed by a considerable decrease in BET-surface area (585 m2 /g) and total pore volume (0.417 cm3 /g) of MCM after adsorbing naproxen (~1000 mg/L and pH 7.0) at 5 min (341 and 0.256), 60 min (191 and 0.205), 120 min (183 and 0.193), 360 min (144 and 0.175), and 24 h (71.6 m2 /g and 0.123 cm3 /g, respectively). The pore diffusion occurred rapidly (even at the initial adsorption period of 5 min). The FTIR technique was applied to identify the existence of C-H···π and n-π interaction. π-π interaction (evaluated through ID /IG ratio and C=C band) played a minor contribution in adsorption mechanisms. The ID /IG ratio (determined by the Raman technique) of MCM before adsorption (1.195) was similar to that after adsorption (1.190), and the wavenumber (C=C band; its FTIR spectrum) slightly shifted from 1638 to 1634 cm-1 after adsorption. A decrease in the Qmax value of MCM from 249 to 217 (H2 O2 -oxidized MCM) or to 224 mg/g (HNO3 -oxidized MCM) confirmed the presence of π-π interaction. Electrostatic attraction was a minor contribution. MCM can serve as a promising material for removing naproxen from water environment through a pore-filling mechanism. PRACTITIONER POINTS: Pore-filling mechanism was proposed by comparing textural properties of MCM before and after adsorbing naproxen. C-H···π and n-π interactions were identified via FTIR technique. π-π interaction was observed by FTIR and Raman techniques. Oxidation of MCM with HNO3 or H2 O2 was a helpful method to explore π-π interaction. Electrostatic attraction was explained through studies: effects of pH and NaCl along with desorption.

ROBIN: a randomised, double-masked, placebo-controlled Phase IIa study of the AOC3 inhibitor BI 1467335 in diabetic retinopathy.

OBJECTIVE: To evaluate the safety and efficacy of BI 1467335 in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: ROBIN is a Phase IIa, double-masked, randomised, placebo-controlled study (NCT03238963). Patients with NPDR and without centre-involved diabetic macular oedema were included; all had a best corrected visual acuity letter score of ≥70 Early Treatment Diabetic Retinopathy Study letters in the study eye at screening. Patients received oral BI 1467335 10 mg or placebo once daily for 12 weeks. Post-treatment follow-up was 12 weeks. The primary endpoint was the proportion of patients over the 24 weeks with ocular adverse events (AEs). Secondary endpoints were the proportion of patients with ≥2-step improvement from baseline in DRSS severity level at Week 12 and the proportion of patients with non-ocular AEs at 24 weeks. RESULTS: Seventy-nine patients entered the study (BI 1467335, n = 40; placebo, n = 39). The proportion of patients with ocular AEs over 24 weeks was greater in the BI 1467335 versus the placebo group (35.0% vs 23.1%, respectively). Treatment-related AEs were reported for similar numbers of patients in the placebo and BI 1467335 group (7.7% vs 7.5%, respectively). At Week 12, 5.7% (n = 2) of patients in the BI 1467335 group had a 2-step improvement in DRSS severity level from baseline, compared with 0% in the placebo group. CONCLUSIONS: BI 1467335 was well tolerated by patients with NPDR. There was a high variability in DRSS levels for individual patients over time, with no clear efficacy signal.

Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy.

BACKGROUND: This analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti-vascular endothelial growth factor (VEGF) monotherapy. METHODS: Post hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-naïve nAMD patients. READ-3 enrolled treatment-naïve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0 mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0 mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12. MAIN OUTCOME MEASURE: association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA). RESULTS: In both trials (HARBOR, N = 36; READ-3, N = 137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (-2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of -9.0 (-22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters. CONCLUSIONS: Higher IL-6 AH concentrations may predict suboptimal visual responses to anti-VEGF monotherapy in patients with nAMD/DMO.

Osteoclast microRNA Profiling in Rheumatoid Arthritis to Capture the Erosive Factor.

In rheumatoid arthritis (RA), only a subset of patients develop irreversible bone destruction. Our aim was to identify a microRNA (miR)-based osteoclast-related signature predictive of erosiveness in RA. Seventy-six adults with erosive (E) or nonerosive (NE) seropositive RA and 43 sex- and age-matched healthy controls were recruited. Twenty-five miRs from peripheral blood mononuclear cell (PBMC)-derived osteoclasts selected from RNA-Seq (discovery cohort) were assessed by qPCR (replication cohort), as were 33 target genes (direct targets or associated with regulated pathways). The top five miRs found differentially expressed in RA osteoclasts were either decreased (hsa-miR-34a-3p, 365b-3p, 374a-3p, and 511-3p [E versus NE]) or increased (hsa-miR-193b-3p [E versus controls]). In vitro, inhibition of miR-34a-3p had an impact on osteoclast bone resorption. An integrative network analysis of miRs and their targets highlighted correlations between mRNA and miR expression, both negative (CD38, CD80, SIRT1) and positive (MITF), and differential gene expression between NE versus E (GXYLT1, MITF) or versus controls (CD38, KLF4). Machine-learning models were used to evaluate the value of miRs and target genes, in combination with clinical data, to predict erosion. One model, including a set of miRs (predominantly 365b-3p) combined with rheumatoid factor titer, provided 70% accuracy (area under the curve [AUC] 0.66). Adding genes directly targeted or belonging to related pathways improved the predictive power of the model for the erosive phenotype (78% accuracy, AUC 0.85). This proof-of-concept study indicates that identification of RA subjects at risk of erosions may be improved by studying miR expression in PBMC-derived osteoclasts, suggesting novel approaches toward personalized treatment. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.