Development and Characterization of a Hydrogel Containing Curcumin-Loaded Nanoemulsion for Enhanced In Vitro Antibacteria and In Vivo Wound Healing.

Curcumin (CUR) is a natural compound extracted from turmeric (Curcuma longa L.) used to cure acne, wound healing, etc. Its disadvantages, such as poor solubility and permeability, limit its efficacy. Nanoemulsion (NE)-based drug delivery systems have gained popularity due to their advantages. This study aimed to optimize a CUR-NE-based gel and evaluate its physicochemical and biological properties. A NE was prepared using the catastrophic phase inversion method and optimized using the Design Expert 12.0 software. The CUR-NE gel was characterized in terms of visual appearance, pH, drug release, antibacterial and wound healing effects. The optimal formulation contained CUR, Capryol 90 (oil), Labrasol:Cremophor RH40 (1:1) (surfactants), propylene glycol (co-surfactant), and water. The NE had a droplet size of 22.87 nm and a polydispersity index of 0.348. The obtained CUR-NE gel had a soft, smooth texture and a pH of 5.34 ± 0.05. The in vitro release of CUR from the NE-based gel was higher than that from a commercial gel with nanosized CUR (21.68 ± 1.25 µg/cm2, 13.62 ± 1.63 µg/cm2 after 10 h, respectively). The CUR-NE gel accelerated in vitro antibacterial and in vivo wound healing activities as compared to other CUR-loaded gels. The CUR-NE gel has potential for transdermal applications.

Spatiotemporal Patterns of Anthrax, Vietnam, 1990-2015.

Anthrax is a priority zoonosis for control in Vietnam. The geographic distribution of anthrax remains to be defined, challenging our ability to target areas for control. We analyzed human anthrax cases in Vietnam to obtain anthrax incidence at the national and provincial level. Nationally, the trendline for cases remained at ≈61 cases/year throughout the 26 years of available data, indicating control efforts are not effectively reducing disease burden over time. Most anthrax cases occurred in the Northern Midlands and Mountainous regions, and the provinces of Lai Chau, Dien Bien, Lao Cai, Ha Giang, Cao Bang, and Son La experienced some of the highest incidence rates. Based on spatial Bayes smoothed maps, every region of Vietnam experienced human anthrax cases during the study period. Clarifying the distribution of anthrax in Vietnam will enable us to better identify risk areas for improved surveillance, rapid clinical care, and livestock vaccination campaigns.

The effects of gelled konjac glucomannan fibre on appetite and energy intake in healthy individuals: a randomised cross-over trial.

Konjac glucomannan (KGM) is a viscous dietary fibre that can form a solid, low-energy gel when hydrated and is commonly consumed in a noodle form (KGM-gel). Increased meal viscosity from gel-forming fibres have been associated with prolonged satiety, but no studies to date have evaluated this effect with KGM-gel. Thus, our objective was to evaluate subsequent food intake and satiety of KGM-gel noodles when replacing a high-carbohydrate preload, in a dose-response manner. Utilising a randomised, controlled, cross-over design, sixteen healthy individuals (twelve females/four males; age: 26·0 (sd 11·8) years; BMI: 23·1 (sd 3·2) kg/m2) received 325 ml volume-matched preloads of three KGM-gel noodle substitution levels: (i) all pasta with no KGM-gel (1849 kJ (442 kcal), control), half pasta and half KGM-gel (1084 kJ (259 kcal), 50-KGM) or no pasta and all KGM-gel (322 kJ (77 kcal), 100-KGM). Satiety was assessed over 90 min followed by an ad libitum dessert. Compared with control, cumulative energy intake was 47 % (-1761 kJ (-421 kcal)) and 23 % (-841 kJ (-201 kcal)) lower for 100-KGM and 50-KGM, respectively (both P<0·001), but no differences in subsequent energy intake was observed. Ratings of hunger were 31 % higher (P=0·03) for 100-KGM when compared with control, and were 19 % lower (P=0·04) for fullness and 28 % higher (P=0·04) for prospective consumption when comparing 100-KGM to 50-KGM. Palatability was similar across all treatments. Replacement of a high-carbohydrate preload with low-energy KGM-gel noodles did not promote additional food intake despite large differences in energy. The energy deficit incurred from partial KGM-gel substitution may have relevance in weight loss regimens, and should be further evaluated beyond the healthy population.

Development of electrosprayed artesunate-loaded core-shell nanoparticles.

OBJECTIVE: Artesunate (ART) is proven to have potential anti-proliferative activities, but its instability and poor aqueous solubility limit its application as an anti-cancer drug. The present study was undertaken to develop coaxial electrospraying as a novel technique for fabricating nanoscale drug delivery systems of ART as the core-shell nanostructures. METHODS: The core-shell nanoparticles (NPs) were fabricated with coaxial electrospraying and the formation mechanisms of NPs were examined. The physical solid state and drug-polymer interactions of NPs were characterized by X-ray powder diffraction (XRPD) and Fourier transform infrared (FTIR) spectroscopy. The effects of materials and electrospraying process on the particle size and surface morphology of NPs were investigated by scanning electron microscopy (SEM). The drug release from NPs was determined in vitro by a dialysis method. RESULTS: The ART/poly(lactic-co-glycolic) acid (PLGA) chitosan (CS) NPs exhibited the mean particle size of 303 ± 93 nm and relatively high entrapment efficiency (80.5%). The release pattern showed an initial rapid release within two hours followed by very slow extended release. The release pattern approached the Korsmeyer-Peppas model. CONCLUSIONS: The present results suggest that the core-shell NPs containing PLGA and CS have a potential as carriers in the anticancer drug therapy of ART.

Integration of comprehensive 3D microCT and signaling analysis reveals differential regulatory mechanisms of craniofacial bone development.

Growth factor signaling regulates tissue-tissue interactions to control organogenesis and tissue homeostasis. Specifically, transforming growth factor beta (TGFß) signaling plays a crucial role in the development of cranial neural crest (CNC) cell-derived bone, and loss of Tgfbr2 in CNC cells results in craniofacial skeletal malformations. Our recent studies indicate that non-canonical TGFß signaling is activated whereas canonical TGFß signaling is compromised in the absence of Tgfbr2 (in Tgfbr2(fl/fl);Wnt1-Cre mice). A haploinsufficiency of Tgfbr1 (aka Alk5) (Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+)) largely rescues craniofacial deformities in Tgfbr2 mutant mice by reducing ectopic non-canonical TGFß signaling. However, the relative involvement of canonical and non-canonical TGFß signaling in regulating specific craniofacial bone formation remains unclear. We compared the size and volume of CNC-derived craniofacial bones (frontal bone, premaxilla, maxilla, palatine bone, and mandible) from E18.5 control, Tgfbr2(fl/fl);Wnt1-Cre, and Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+)mice. By analyzing three dimensional (3D) micro-computed tomography (microCT) images, we found that different craniofacial bones were restored to different degrees in Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+) mice. Our study provides comprehensive information on anatomical landmarks and the size and volume of each craniofacial bone, as well as insights into the extent that canonical and non-canonical TGFß signaling cascades contribute to the formation of each CNC-derived bone. Our data will serve as an important resource for developmental biologists who are interested in craniofacial morphogenesis.

The effect of oat ß-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for CVD risk reduction: a systematic review and meta-analysis of randomised-controlled trials.

Oats are a rich source of ß-glucan, a viscous, soluble fibre recognised for its cholesterol-lowering properties, and are associated with reduced risk of CVD. Our objective was to conduct a systematic review and meta-analysis of randomised-controlled trials (RCT) investigating the cholesterol-lowering potential of oat ß-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for the risk reduction of CVD. MEDLINE, Embase, CINAHL and Cochrane CENTRAL were searched. We included RCT of ≥3 weeks of follow-up, assessing the effect of diets enriched with oat ß-glucan compared with controlled diets on LDL-cholesterol, non-HDL-cholesterol or apoB. Two independent reviewers extracted data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences with 95 % CI. Heterogeneity was assessed by the Cochran's Q statistic and quantified by the I 2-statistic. In total, fifty-eight trials (n 3974) were included. A median dose of 3·5 g/d of oat ß-glucan significantly lowered LDL-cholesterol (-0·19; 95 % CI -0·23, -0·14 mmol/l, P<0·00001), non-HDL-cholesterol (-0·20; 95 % CI -0·26, -0·15 mmol/l, P<0·00001) and apoB (-0·03; 95 % CI -0·05, -0·02 g/l, P<0·0001) compared with control interventions. There was evidence for considerable unexplained heterogeneity in the analysis of LDL-cholesterol (I 2=79 %) and non-HDL-cholesterol (I 2=99 %). Pooled analyses showed that oat ß-glucan has a lowering effect on LDL-cholesterol, non-HDL-cholesterol and apoB. Inclusion of oat-containing foods may be a strategy for achieving targets in CVD reduction.

Correlation Between Vestibular Disorders and Superior Semicircular Dehiscence on High-resolution Computed Tomography at Tam Anh Ho Chi Minh General Hospital.

Objective: Superior semicircular canal dehiscence (SSCD) is a pathologic condition within the inner ear characterized by various vestibular manifestations. Numerous studies have reported an incidence rate of SSCD ranging from 3.6% to 9% in the general population. The objective of this medical study was to evaluate the prevalence of superior SSCD and investigate its correlation with vestibular symptoms among patients who underwent high-resolution computed tomography (HRCT) scans. To the best of our knowledge, there is limited research and awareness regarding SSCD in Vietnam. In addition, the secondary aim of our investigation is to assess the prevalence of SSCD in Vietnam and compare it with findings from previous studies worldwide. Methods: This retrospective study was conducted at Tam Anh Ho Chi Minh General Hospital from March 2022 to February 2024. Medical records and HRCT scans of the patients were collected. Patients were categorized into two groups: those with and without vestibular disorders. SSCD was defined as the absence of bone overlying the superior semicircular canal facing toward the dura of the middle cranial fossa. Statistical analysis was performed to determine the correlation between vestibular symptoms and the presence of SSCD. Results: A total of 362 patients (including 151 men and 211 women) were recruited. The prevalence of SSCD was 10.2% according to the HRCT scan results. The study found that 18.33% of patients with vestibular disorders had SSCD on HRCT scans, whereas only 6.2% of patients without vestibular disorders exhibited SSCD, indicating a significant association (p-value <0.001). Conclusions: These findings highlight the importance of considering SSCD as a potential etiology in patients presenting with vestibular symptoms and emphasize the diagnostic utility of HRCT.

Statins suppress cell-to-cell propagation of α-synuclein by lowering cholesterol.

Cell-to-cell propagation of protein aggregates has been implicated in the progression of neurodegenerative diseases. However, the underlying mechanism and modulators of this process are not fully understood. Here, we screened a small-molecule library in a search for agents that suppress the propagation of α-synuclein and mutant huntingtin (mHtt). These screens yielded several molecules, some of which were effective against both α-synuclein and mHtt. Among these molecules, we focused on simvastatin and pravastatin. Simvastatin administration in a transgenic model of synucleinopathy effectively ameliorated behavioral deficits and α-synuclein accumulation, whereas pravastatin had no effect. Because only simvastatin enters the brain effectively, these results suggest that inhibition of brain cholesterol synthesis is important in simvastatin effects. In cultured cells, accumulation of intracellular cholesterol, induced by genetic ablation of the NPC1 gene or by pharmacological treatment with U18666A, increased α-synuclein aggregation and secretion. In contrast, lowering cholesterol using methyl-ß-cyclodextrin or statins reversed α-synuclein aggregation and secretion in NPC1-knockout cells. Consistent with these observations, feeding a high-fat diet aggravated α-synuclein pathology and behavioral deficits in the preformed fibril-injected mouse model, an effect that was also reversed by simvastatin administration. These results suggest that statins suppress propagation of protein aggregates by lowering cholesterol in the brain.

Incidence and Spatial distribution of Human and Livestock Anthrax in Cao Bang Province, Vietnam (2004-2020).

Specific knowledge on the distribution of anthrax, a zoonosis caused by Bacillus anthracis, in Southeast Asia, including Vietnam, remains limited. In this study, we describe disease incidence and spatial distribution of human and livestock anthrax using spatially smoothed cumulative incidence from 2004 to 2020 in Cao Bang province, Vietnam. We employed the zonal statistics routine a geographic information system (GIS) using QGIS, and spatial rate smoothing using spatial Bayes smoothing in GeoDa. Results showed higher incidence of livestock anthrax compared with human anthrax. We also identified co-occurrence of anthrax in humans and livestock in northwestern districts and the province center. Livestock anthrax vaccine coverage was <6% and not equally distributed among the districts of Cao Bang province. We provide implications for future studies and recommend improving disease surveillance and response through data sharing between human and animal health sectors.

Endovascular management of severe lower gastrointestinal bleeding from angiodysplasia in the cecum: A case report.

Gastrointestinal angiodysplasias (GIADs) are rare disorder but can cause noticeable issue clinically. Their clinical characteristics can range from being an asymptomatic incidental finding to causing life-threatening bleeding. Many modalities are applied for treating bleeding GIADs include endoscopic therapies, angiography with embolization, surgical resection, and pharmacologic therapy. However, since patients with GIADs are often aged and have many comorbidities, endoscopic therapies may not be the best initial option. Angiography is suitable method for hemodynamically unstable patients with active bleeding, patients with an unknown active bleeding source, and patients who are poor surgical candidates. Angiography not only diagnose the bleeding point but also provide therapeutic endovascular intervention at the same time. We report a case of endovascular management of severe lower gastrointestinal bleeding from a GIAD in the cecum using a mixture of n-butyl cyanoacrylate and lipiodol to embolize the bleeding source. Clinical symptoms improved without prominent complications.

Formulation and characterization of hydroxyethyl cellulose-based gel containing metronidazole-loaded solid lipid nanoparticles for buccal mucosal drug delivery.

Local delivery of drug is a promising strategy to manage periodontitis characterized by chronic inflammation of the soft tissue surrounding the teeth. An optimized system should prolong the drug retention time and exhibit controlled drug permeation through the buccal mucosal layer. This study was aimed to develop hydroxyethyl cellulose (HEC)-based gel containing metronidazole (MTZ) loaded in solid lipid nanoparticles (SLNs), and to enhance the antimicrobial activity of MTZ. SLNs were prepared using a combination method of solvent evaporation and hot homogenization. The results showed that the fabricated SLNs, comprising of Precirol (2.93%, w/v), Tween 80 (1.8%, w/v), and the drug:lipid ratio of 19.3% (w/w), were approximately 200 nm in size, with a narrow distribution. The HEC (3%, w/w)-based gel formed a smooth, homogeneous structure and had preferable mechanical and rheological properties. Moreover, the MTZ-loaded SLNs-based HEC gel (equivalent to 1% of MTZ, w/w) exhibited a sustained in vitro drug release pattern, optimal ex vivo permeability, and enhanced in vitro antimicrobial activity after 24 h of treatment. These findings indicate the potential of the MTZ-loaded SLNs-based HEC formulation for local drug delivery at the buccal mucosa in managing periodontal disease.

Asymmetric impact of exchange rate on trade between Vietnam and each of EU-27 countries and the UK: evidence from nonlinear ARDL and the role of vehicle currency.

The relationship between exchange rate and trade balance has been spotlighted in the past several decades and thus examined by manifold research. The findings, however, lack of consensus despite the intensive efforts in investigating the role of exchange rate as an important determinant of trade balance in various countries. Although the existing papers are abundant, most of them neglect the role of vehicle currency. Besides, few articles are dedicated to Vietnam, and none has inspected the exchange rate-trade balance nexus between Vietnam and the EU. This study is the first to scrutinize how bilateral exchange rates, together with vehicle currency exchange rate, asymmetrically impact Vietnam's bilateral trade balance with respect to EU-27 countries and the UK. The NARDL estimation results strongly acknowledge the importance of USD as vehicle currency when more significant short-run and long-run coefficients are found. Accordingly, this article can provide some useful implications for policy-makers, especially when Vietnam was first labelled currency manipulator by the USA in December 2020. Particularly, USD/VND movement can affect not only Vietnam-USA but also Vietnam-EU and Vietnam-UK trade balance. In addition, VND appreciation against USD seems beneficial to Vietnam's bilateral trade with the EU plus the UK.

Optimization of Ultrasound-Assisted Extraction of Flavonoids from Celastrus hindsii Leaves Using Response Surface Methodology and Evaluation of Their Antioxidant and Antitumor Activities.

Celastrus hindsii is a potential source of flavonoids with biological activities. This study aimed to develop an ultrasound-assisted technique for extracting flavonoids from leaves of C. hindsii. Response surface methodology was employed to optimize the extraction conditions for maximizing the total flavonoid content (TFC). A maximum TFC of 23.6 mg QE/g was obtained under the extraction conditions of ultrasonic power of 130 W, extraction temperature of 40°C, extraction time of 29 min, and ethanol concentration of 65%. The flavonoid-rich extracts were then studied for their antioxidant and anticancer activities. The results showed that the C. hindsii leaf extract exhibited potent radical scavenging activities against DPPH (IC50 of 164.85 µg/mL) and ABTS (IC50 of 89.05 µg/mL). The extract also significantly inhibited the growth of 3 cancer cell lines MCF7, A549, and HeLa with the IC50 values of 88.1 µg/mL, 120.4 µg/mL, and 118.4 µg/mL, respectively. Notably, the extract had no cytotoxicity effect on HK2 normal kidney cell line. This study suggests that flavonoid-rich extract is a promising antioxidant and anticancer agent and that ultrasound-assisted extraction is an efficient method for extracting flavonoids from C. hindsii leaves.

Effect of soluble-viscous dietary fibre on coronary heart disease risk score across 3 population health categories: data from randomized, double-blind, placebo-controlled trials.

We applied the Framingham risk equation in healthy, metabolic syndrome, and diabetes populations, following treatment with viscous fibre from konjac-based blend (KBB). KBB yielded reduction in estimated risk score by 16% (1.04 ± 0.03 vs. 0.87 ± 0.04, p < 0.01) in type 2 diabetes, 24% (1.08 ± 0.01 vs. 0.82 ± 0.02, p < 0.01) in metabolic syndrome, and 25% (1.09 ± 0.05 vs. 0.82 ± 0.06, p < 0.01) in healthy individuals. Drivers for decreased risk were improvements in blood cholesterol and systolic blood pressure. The composite coronary heart disease risk across populations was reduced 22% (p < 0.01). Novelty Viscous fibre from konjac-xanthan reduced 10-year relative coronary heart disease using Framingham Risk Score across the glycemic status spectrum.

A novel injectable pH-temperature sensitive hydrogel containing chitosan-insulin electrosprayed nanosphere composite for an insulin delivery system in type I diabetes treatment.

A novel insulin composite delivery system was prepared and characterized. The composite consisted of a pH- and temperature-sensitive hydrogel, which is an oligomer serine-b-poly(lactide)-b-poly(ethylene glycol)-b-poly(lactide)-b-oligomer serine (OS-PLA-PEG-PLA-OS) pentablock copolymer, as matrix and chitosan-insulin electrosprayed nanospheres (CIN) as constituent materials. The properties of the OS-PLA-PEG-PLA-OS pentablock copolymer and the chitosan-insulin nanoparticles were characterized. The chitosan-insulin nanospheres uniformly distributed in the matrix had a reinforcing effect on the mechanical properties and prolonged the degradation time of the hydrogel depot under body conditions. The composite solutions accommodating different concentrations of the chitosan-insulin nanospheres were subcutaneously injected into induced diabetic BALB/c mice to study the in vivo insulin-release profile. The result showed that insulin concentrations in blood plasma were maintained at a steady-state level. Furthermore, the bio-properties of the insulin were retained and it showed a blood glucose level reducing effect for more than 60 hours after injection to a streptozotocin (STZ)-induced diabetic mouse model. The results suggested that this injectable pH-temperature sensitive hydrogel containing chitosan-insulin electrosprayed nanosphere composites has promising potential applications for type 1 diabetes treatment.

Modeling α-Synuclein Propagation with Preformed Fibril Injections.

The aggregation of α-synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Postmortem analyses of α-syn pathology, especially that of PD, have suggested that aggregates progressively spread from a few discrete locations to wider brain regions. The neuron-to-neuron propagation of α-syn has been suggested to be the underlying mechanism by which aggregates spread throughout the brain. Many cellular and animal models has been created to study cell-to-cell propagation. Recently, it has been shown that a single injection of preformed fibrils (PFFs) made of recombinant α-syn proteins into various tissues and organs of many different animal species results in widespread α-syn pathology in the central nervous system (CNS). These PFF models have been extensively used to study the mechanism by which aggregates spread throughout the brain. Here, we review what we have learned from PFF models, describe the nature of PFFs and the neuropathological features, neurophysiological characteristics, and behavioral outcomes of the models.

Effect of high-carbohydrate or high-monounsaturated fatty acid diets on blood pressure: a systematic review and meta-analysis of randomized controlled trials.

Context: Current dietary guidelines for cardiovascular disease risk management recommend restricting intake of saturated fatty acids (SFAs). However, the optimal macronutrient profile, in the context of a low-SFA diet, remains controversial. The blood-pressure effect of replacing SFAs in diets with monounsaturated fatty acids (MUFAs) compared with carbohydrate has not been quantified to date. Objective: To synthesize the evidence for the effect of substituting a high-carbohydrate (high-CHO) diet for a high-monounsaturated fatty acid (high-MUFA) diet on blood pressure, a systematic review and meta-analysis of randomized clinical trials in a population without health restrictions was conducted. Data Sources: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Clinical Trials were searched through June 7, 2017. Randomized controlled trials of > 3 weeks duration that assessed the effect of high-MUFA diets in isocaloric substitution for high-CHO diets on systolic blood pressure (SBP) and diastolic blood pressure (DBP) were included. Data Extraction: Data were pooled using the generic-inverse variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by Cochran Q statistic and quantified by the I2 statistic. The quality of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Fourteen trials (n = 980 participants) were included in the analysis. Comparatively, the high-MUFA diets in isocaloric substitution for high-CHO diets did not demonstrate a greater reduction in blood pressure (SBP: MD, -0.08 mmHg [95%CI, -1.01 to 0.84], P = 0.86; DBP: MD = 0.01 mmHg [95%CI, -0.73 to 0.75], P = 0.98). The overall quality of the evidence was assessed as moderate. Conclusions: In the context of low SFAs, high-MUFA diets in isocaloric substitution for high-CHO diets did not affect blood pressure in individuals with and without hypertension. Large-scale trials achieving higher MUFA targets are required to support these findings. ClinicalTrials.gov ID: NCT02626325.

Should Viscous Fiber Supplements Be Considered in Diabetes Control? Results From a Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Evidence from randomized controlled trials (RCTs) suggests that viscous dietary fiber may offer beneficial effects on glycemic control and, thus, an improved cardiovascular disease risk profile. Our purpose was to conduct a systematic review and meta-analysis of RCTs to synthesize the therapeutic effect of viscous fiber supplementation on glycemic control in type 2 diabetes. RESEARCH DESIGN AND METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through 15 June 2018. We included RCTs ≥3 weeks in duration that assessed the effects of viscous fiber on markers of glycemic control in type 2 diabetes. Two independent reviewers extracted data. Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I 2 statistic). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall certainty of the evidence. RESULTS: We identified 28 eligible trial comparisons (n = 1,394). Viscous fiber at a median dose of ∼13.1 g/day significantly reduced HbA1c (MD -0.58% [95% CI -0.88, -0.28]; P = 0.0002), fasting blood glucose (MD -0.82 mmol/L [95% CI -1.32, -0.31]; P = 0.001), and HOMA-insulin resistance (IR) (MD -1.89 [95% CI -3.45, -0.33]; P = 0.02) compared with control and in addition to standard of care. The certainty of evidence was graded moderate for HbA1c, fasting glucose, fasting insulin, and HOMA-IR and low for fructosamine. CONCLUSIONS: Viscous fiber supplements improve conventional markers of glycemic control beyond usual care and should be considered in the management of type 2 diabetes.

Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms.

FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.

Clinical evidence on dietary supplementation with chia seed (Salvia hispanica L.): a systematic review and meta-analysis.

Context: Chia seed is a popular dietary supplement, taken mainly for its high content of alpha-linolenic acid, vegetable protein, and dietary fiber, yet information about its clinical effects is lacking. Objective: This review aims to summarize the clinical evidence regarding the use of chia seed for a wide variety of health conditions. Data Sources: A number of databases, including PubMed and Embase, were searched systematically. Study Selection: Randomized controlled trials that assessed the clinical effects of chia seed consumption in human participants were included. The quality of trials was assessed using the Cochrane Risk of Bias Tool. Data Extraction: Data on study design, blinding status, characteristics of participants, chia seed intervention, comparator, clinical assessment, duration of intake, interval of assessment, and study funding status were extracted. Meta-analysis was performed. Results: Twelve trials were included. Participants included healthy persons, athletes, diabetic patients, and individuals with metabolic syndrome. Pooling of results showed no significant differences except for the following findings of subgroup analysis at higher doses of chia seed: (1) lower postprandial blood glucose level (mean difference [MD] of -33.95 incremental area under the curve [iAUC] [mmol/L × 2 h] [95%CI, -61.85, -6.05] and -51.60 iAUC [mmol/L × 2 h] [95%CI, -79.64, -23.56] at medium doses and high doses, respectively); (2) lower high-density lipoprotein in serum (MD of -0.10 mmol/L [95%CI, -0.20, -0.01]); and (3) lower diastolic blood pressure (MD of -7.14 mmHg [95%CI, -11.08, -3.19]). The quality of all evidence assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was low or very low. All trials employed only surrogate markers as outcomes. Conclusions: Future trials with improved methodological quality, well-described clinical events, and validated surrogate markers as outcomes are needed to support the potential health benefits of chia seed consumption. Systematic Review Registration: PROSPERO registration no. CRD42015029990.