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CMX001, an orally active lipid conjugate of cidofovir, is 50 times more active in vitro against herpes simplex virus (HSV) replication than acyclovir or cidofovir. These studies compared the efficacy of CMX001 to acyclovir in BALB/c mice inoculated intranasally with HSV types 1 or 2. CMX001 was effective in reducing mortality using doses of 5 to 1.25 mg/kg administered orally once daily, even when treatments were delayed 48-72 h post viral inoculation. Organ samples obtained from mice treated with CMX001 had titers 3-5 log(10) plaque-forming units per gram of tissue lower than samples obtained from mice treated with acyclovir, including 5 different regions of the brain. Detectable concentrations of drug-related radioactivity were documented in the central nervous system of mice after oral administration of (14)C-CMX001. These studies indicate that CMX001 penetrates the blood-brain barrier, is a potent inhibitor of HSV replication in disseminated infections and central nervous system infections, and is superior to acyclovir.

Turbidity flows can transport massive amounts of sediment across large distances with dramatic, long-lasting impacts on deep-sea benthic communities. The 2016 Mw 7.8 Kaikōura Earthquake triggered a canyon-flushing event in Kaikōura Canyon, New Zealand, which included significant submarine mass wasting, debris, and turbidity flows. This event provided an excellent opportunity to investigate the effects of large-scale natural disturbance on benthic ecosystems. Benthic meiofauna community structure before and after the event was analysed from a time series of sediment cores collected 10 years and 6 years before, and 10 weeks, 10 months, and 4 years after the disturbance. Immediately after the 2016 event abundances of all meiofauna dramatically decreased. Four years later the meiofauna community had recovered and was no longer distinguishable from the pre-event community. However, the nematode component of the community was similar, but not fully comparable to the pre-event community by 4 years after the disturbance. Community recovery was systematically correlated to changes in the physical characteristics of the habitat caused by the disturbance, using physical and biochemical variables derived from sediment cores, namely: sediment texture, organic matter, and pigment content. While these environmental variables explained relatively little of the overall variability in meiofauna community structure, particle size, food availability and quality were significant components. The minimum threshold time for the meiofauna community to fully recover was estimated to be between 3.9 and 4.7 years, although the predicted recovery time for the nematode community was longer, between 4.6 and 5 years. We consider the management implications of this study in comparison to the few studies of large-scale disturbances in the deep sea, in terms of their relevance to the efficacy of the marine reserve that encompasses Kaikōura Canyon, along with potential implications for our understanding of the impacts of anthropogenic seafloor disturbances, such as seabed mining. [ABSTRACT FROM AUTHOR]

This study investigated the uptake of thallium (Tl) by rice seedlings grown in different soils with varying physiochemical properties and Tl levels to elucidate the key factors governing soil Tl availability and accumulation in rice plants. The bioconcentration factors of Tl in rice roots (2.5–25.6) and shoots (1.5–14.7) indicated high soil Tl availability and efficient uptake and translocation of Tl in rice plants, with significant variations across soil types. Growth suppression and visual toxic symptoms, such as stem buckling, yellowish leaf tips, and withering leaf edges, occurred at low soil Tl levels due to high Tl toxicity. The accumulation of Tl by rice plants was influenced by both soil and plant-related factors. Cation exchange reactions primarily influenced the concentration of Tl in soil solution, with potassium ions (K+) acting as competitors for cation exchange sites with Tl+ ions and effective inhibitors of Tl uptake by rice plants. Increasing soil K content may mitigate soil Tl availability in contaminated soils by reducing soil Tl(I) adsorption and plant uptake. This study elucidates the key mechanisms governing soil Tl bioavailability and highlights potential management strategies to reduce Tl accumulation in crops. [ABSTRACT FROM AUTHOR]

Soil salinization negatively affects rice growth and yield; however, how different sludge sources regulate rice growth and yield under salt stress was rarely investigated. This study evaluated the performance of two salt-tolerant rice cultivars, Chaoyou 1000 and Longliangyou 506, grown in two sediment sources, pond sediment (PS) and river sludge (RS), under salt stress (56 ds m−1 brine irrigation) with conventional soil (CS) used as the control. The results showed that the rice yield under the PS and RS treatments was enhanced by 51.0% and 43.6% as compared with CS, respectively, owing to an improvement in spikelet per panicle, 1000-grain weight, dry matter accumulation, and the chlorophyll content in both rice cultivars. Compared with CS, the total nitrogen accumulation, nitrogen grain production efficiency, nitrogen harvest index, and nitrogen partial productivity under the PS and RS treatments were increased by 18.9–28.9%, 17.0–20.6%, 7.2–16.6%, and 43.8–50.9%, respectively. Moreover, rice grown in PS and RS showed higher activities of nitrogen metabolism-related enzymes (nitrate reductase, glutamine synthetase, and glutamate synthetase) at the heading stage and higher K+ and K+/Na+ contents in the leaves. Overall, a balanced utilization of sediment resources (especially pond sediment) can effectively alleviate salt stress and improve the yield and nitrogen use efficiency in rice. [ABSTRACT FROM AUTHOR]

Five Vietnamese rice varieties, which differ in their basic chemical composition (starch content, amylose content, fiber content) including polished rices and whole grain rices, were chosen for this study. High-fat diet-induced obesity, using these rice, was subjected to in vivo experiments to evaluate the effects of body weight gain, caloric intake, postprandial blood glucose level (PBGL), and glycemic index (GI) in tested mice groups. PBGL peaks appeared at 30th minute after eating, and GI of each experimental group was ranked in order as GN > TL > HR > GM > L Đ and GN > LT > HR > L Đ > GM , respectively, in which, brown rice (LĐ) and germinated brown rice (GM) had low GI. Furthermore, these rice varieties caused the lowest LDL cholesterol and the ratio of LDL/HDL cholesterols in mice. In this study, the higher the amylose and fiber contents were, the lower glycemic index, triglycerides, LDL, and LDL/HDL values were. The golden flower glutinous rice (GN), with low amylose and fiber content, gave worse blood lipid parameters than that of GM and LĐ. Histopathological studies of white adipose and liver tissues showed that LĐ and GM significantly reduced the symptoms of obesity and fatty liver compared with the others, especially compared to GN. The results obtained from this study help patients with overweight, obesity, and type 2 diabetes choose the right rice variety for their daily diet to be able to control their diseases. [ABSTRACT FROM AUTHOR]

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Background: The mean unbound vancomycin fraction and whether the unbound vancomycin level could be predicted from the total vancomycin level are still controversial, especially for patients in different groups, such as intensive care unit (ICU) versus non-ICU patients. Other relevant potential patient characteristics that may predict unbound vancomycin levels have yet to be clearly determined. Methods: We enrolled a relatively large study population and included widely comprehensive potential covariates to evaluate the unbound vancomycin fractions in a cohort of ICU (n=117 samples) and non-ICU patients (n=73 samples) by using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results: The mean unbound vancomycin fraction was 45.80% ± 18.69% (median, 46.01%; range: 2.13– 99.45%) in the samples from the total population. No significant differences in the unbound vancomycin fraction were found between the ICU patients and the non-ICU patients (P=0.359). A significant correlation was established between the unbound and total vancomycin levels. The unbound vancomycin level can be predicted with the following equations: unbound vancomycin level=0.395×total vancomycin level+0.019×total bilirubin level+0.468 (R2=0.771) for the ICU patients and unbound vancomycin level=0.526×total vancomycin level-0.527 (R2=0.749) for the non-ICU patients. Overall, the observed-versus-predicted plots were acceptable. Conclusion: A significant correlation between the total and unbound vancomycin levels was found, and measurement of the unbound vancomycin level seems to have no added value over measurement of the total vancomycin level. The study developed parsimonious equations for predicting the unbound vancomycin level and provides a reference for clinicians to predict the unbound vancomycin level in adult populations. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of overweight and obesity among the worldwide population has been associated with a range of adverse health consequences such as Type 2 diabetes and cardiovascular diseases. The metabolic syndrome (MetS) is a cluster of cardiometabolic abnormalities that occur more commonly in overweight individuals. Time-restricted feeding (TRF) is a dietary approach used for weight loss and overall health. TRF may be an option for those subjects who struggle with extreme restriction diets with foods that generally do not belong to an individual's habits.Objective: The purpose of this study was to determine the effect of TRF on body composition and the association of weight loss with metabolic and cardiovascular risks in obese middle-aged women.Methods: A non-randomized controlled clinical trial was performed over 3 months in obese women (TRF group, n = 20, BMI 32.53 ± 1.13 vs. Control n = 12, BMI 34.55 ± 1.20). The TRF protocol adopted was 16 h without any energy intake followed by 8 h of normal food intake.Main Outcomes and Measures: Anthropometric measurements, body composition, blood biomarkers, cardiovascular risk in 30 years (CVDRisk30y), and quality of life were evaluated at baseline and after the 3 months.Results: TRF was effective in reducing weight (~ 4 kg), BMI, % of body fat (%BF), waist circumference from baseline without changes in blood biomarkers associated with MetS. TRF promoted a reduction in CVDRisk30y (12%) wich was moderately correlated with %BF (r = 0.62, n = 64, p < 0.001) and %MM (r = - 0.74, n = 64, p < 0.001).Conclusions: TRF protocol reduces body weight without changes in biomarkers related to MetS. In addition, the anthropometric evaluation that predicts %BF and %MM could be used as an approach to follow individuals engaged in the TRF regimen since they correlate with cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Histamine release and vasodilation during an allergic reaction can alter the pharmacokinetics of drugs administered via the intranasal (IN) route. The current study evaluated the effects of histamine-induced nasal congestion on epinephrine pharmacokinetics and heart rate changes after IN epinephrine.Methods: Dogs received 5% histamine or saline IN followed by 4 mg epinephrine IN. Nasal restriction pressure, epinephrine concentration, and heart rate were assessed. Maximum concentration (Cmax), area under plasma concentration-time curve from 1 to 90 min (AUC1-90), and time to reach Cmax (Tmax) were measured. Clinical observations were documented.Results: In the 12 dogs in this study, nasal congestion occurred at 5-10 min after IN histamine administration versus no nasal congestion after IN saline. After administration of IN epinephrine, IN histamine-mediated nasal congestion was significantly reduced to baseline levels at 60, 80, and 100 min. There were no significant differences in Cmax and AUC1-90 between histamine and saline groups after IN epinephrine delivery (3.5 vs 1.7 ng/mL, p = 0.06, and 117 vs 59 ng/mL*minutes, p = 0.09, respectively). After receiving IN epinephrine, the histamine group had a significantly lower Tmax versus the saline group (6 vs 70 min, respectively; p = 0.02). Following IN epinephrine administration, the histamine group showed rapidly increased heart rate at 5 min, while there was a delayed increase in heart rate (occurring 30-60 min after administration) in the saline group. Clinical observations included salivation and emesis.Conclusion: IN histamine led to more rapid epinephrine absorption and immediately increased heart rate compared with IN saline. IN epinephrine decreased histamine-induced nasal congestion. [ABSTRACT FROM AUTHOR]

Epinephrine is the standard of care for the treatment of severe allergy and anaphylaxis. Epinephrine is most often administered through the intramuscular (IM) route via autoinjector. The current study aimed to evaluate an alternative method of epinephrine treatment through intranasal (IN) delivery in dogs. The pharmacokinetic (PK) parameters of maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), and area under the plasma concentration‐time curve from 0 to 90 minutes (AUC0–90) were observed after IN epinephrine (2, 3, 4, 5, 10, and 20 mg) and IM epinephrine via autoinjector (0.15 and 0.3 mg) for 90 minutes. Heart rate effects were measured after IN (2 and 5 mg) and IM (0.15 and 0.3 mg) epinephrine administration. IN epinephrine (5 mg) demonstrated significantly greater plasma epinephrine concentration at 1 minute as compared with IM epinephrine (0.3 mg) (1.68 ± 0.65 ng/mL vs 0.21 ± 0.08 ng/mL, P = .03). There were no significant differences in Cmax, Tmax, and AUC0–90 between 2‐mg IN and 0.15‐mg IM epinephrine or between 5‐mg IN and 0.3‐mg IM epinephrine. IN epinephrine reduced heart rate increases, as compared to IM epinephrine. IN and IM epinephrine were both well‐tolerated. Overall, IN epinephrine demonstrated advantages over IM epinephrine, including the rapid increase in plasma epinephrine and lack of increased heart rate over time. [ABSTRACT FROM AUTHOR]

Background: Obesity can significantly reduce health-related quality of life (HRQoL) and may lead to numerous health problems even in youths. This study aimed to investigate whether HRQoL varies among youths with obesity depending on grade of obesity and other factors.Methods: For the Youths with Extreme obesity Study (YES) (2012-2014), a prospective multicenter cohort study, a baseline sample of 431 obese and extremely obese adolescents and young adults (age 14 to 24 years, BMI ≥30 kg/m2) was recruited at four German university medical centers and one job center. Obesity grade groups (OGG) were defined according to BMI (OGG I: 30-34.9 kg/m2, OGG II: 35-39.9 kg/m2, OGG III (extreme obesity): ≥40 kg/m2). HRQoL was measured with the Euroqol-5D-3 L (EQ-5D-3 L), DISABKIDS chronic generic (DCGM-31) and the KINDLR obesity module. Differences between OGGs were assessed with logistic and linear regression models, adjusting for age, sex, and study center in the base model. In a second regression analysis, we included other characteristics to identify possible determinants of HRQoL.Results: Three hundred fifty-two adolescents (mean age: 16.6 (±2.4), mean BMI: 39.1 (±7.5) kg/ m2) with available HRQoL data were analysed. HRQoL of youths in all OGGs was markedly lower than reference values of non-obese adolescents. Adjusting for age and sex, HRQoL of youths in OGG III significantly impaired compared to OGG I. Youths in OGG III were 2.15 times more likely to report problems with mobility in the EQ-5D-3 L than youths in OGG I. A mean difference of 9.7 and 6.6 points between OGG III and I were found for DCGM-31 and KINDL respectively and 5.1 points between OGG II and I for DCGM-31. Including further variables into the regression models, showed that HRQoL measured by DCGM-31 was significantly different between OGGs. Otherwise, female sex and having more than 4 h of daily screen time were also associated with lower HRQoL measured by DCGM-31 and KINDL.Conclusion: HRQoL of adolescents with obesity is reduced, but HRQoL of adolescents with extreme obesity is particularly affected. Larger and longitudinal studies are necessary to understand the relation of extreme obesity and HRQoL, and the impact of other lifestyle or socioeconomic factors.Trial Registration: Clinicaltrials.gov NCT01625325; German Clinical Trials Register (DRKS) DRKS00004172. [ABSTRACT FROM AUTHOR]

Objective: Despite the progress in the treatment of burn injuries, the mortality rate among seriously ill patients still remains high nowadays. The main causes of fatal cases with extensive deep burns are generalized infectious complications, the major of which is sepsis. According to the authors, 25%-85% of those who died of burn injuries in later periods, died from sepsis. The frequency and severity of infectious complications in patients with burn injuries requires an accurate diagnosis of infection that will determine the tactics of therapeutic and surgical treatment of such patients (Di Lonardo A. et al., 1993). However, the clinical diagnosis of wound infection in patients with burn injuries is quite difficult. Materials and methods: The clinical material included 188 patients with burn injuries. The average age of those patients ranged from 20 to 59 years. Men - 98 (52.1%), women - 90 (47.9%). The survey was conducted from April 2014 to July 2016. Results: In our opinion, the strength of NLR (neutrophil-lymphocyte ratio) is the possibility of implementing this parameter simply by using already available biomarkers (neutrophil count and lymphocyte count). Therefore, this ratio is easy to integrate in clinical practice and cost effective. Conclusion: The application of NLR for the diagnosis of sepsis in patients with burn injuries is the option of choice, since its determination requires only a general blood test. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate muscle performance by using isokinetic dynamometer before and at third month of anti-tumor necrosis factor-alpha treatment in ankylosing spondylitis patients. Patients and methods: Thirty ankylosing spondylitis patients (23 males, 7 females; mean age 39.3±8.6 years; range 18 to 45 years) starting on anti- tumor necrosis factor-alpha treatment and 30 healthy controls (23 males, 7 females; mean age 39.1±8.8 years; range 18 to 48 years) with similar age, body mass index, and sex were enrolled. The clinical anthropometric measurements of chest expansion, lumbar Schober test, hand-finger floor distance and visual analog scale-global, C-reactive protein, erythrocyte sedimentation rate, Ankylosing Spondylitis Disease Activity Score-C-reactive protein and Ankylosing Spondylitis Disease Activity Score-erythrocyte sedimentation rate, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index were determined before and at third month of the treatment. Results: There was no statistically significant difference in age, sex and, body mass index between the groups (p>0.05). A statistically significant difference was detected between 60 ̊/second and 180 ̊/second peak torque in angular velocity of flexor and extensor muscles (p<0.05). A significant difference was detected in respect to total work of patients with 180 ̊/second peak torque in angular velocity of flexor and extensor muscles (p<0.05). There was a statistically significant difference between the findings of 60 ̊/second and 180 ̊/second peak torque in angular velocity of flexor and extensor muscles (p<0.05). Isokinetic test results were better at third month after treatment than before treatment. Conclusion: The results of this study showed that both functional limitations and performance and endurance of muscles may be improved with anti-tumor necrosis factor-alpha treatment in ankylosing spondylitis patients. [ABSTRACT FROM AUTHOR]

Aim: To develop NB-201, a nanoemulsion compound, as a novel microbicidal agent against methicillin-resistant Staphylococcus aureus (MRSA) infection, which is a common threat to public health but with limited therapeutic options. Materials & methods: NB-201 was tested in in vitro and in vivo murine and porcine models infected with MRSA. Results: Topical treatment of MRSA-infected wounds with NB-201 significantly decreased bacterial load and had no toxic effects on healthy skin tissues. NB-201 attenuated neutrophil sequestration in MRSA-infected wounds and inhibited epidermal and deep dermal inflammation. The levels of proinflammatory cytokines were reduced in NB-201-treated MRSA-infected wounds. Conclusion: NB-201 can greatly reduce inflammation characteristic of infected wounds and has antimicrobial activity that effectively kills MRSA regardless of the genetic basis of antibiotic resistance. [ABSTRACT FROM AUTHOR]

The study is about the estimation of preconsolidation stress using a correlation method. Disturbance of soil samples can result in the yield point of void ratio-log vertical stress data from oedometer test being unreadable. Therefore, correlations were calculated to estimate preconsolidation stress using effective vertical stress (σ'v0), oedometer modulus (Eoed) from oedometer tests and unloading-reloading modulus (Eur) from triaxial tests. Profile of stress history: Overconsolidation ratio (OCR), overconsolidation difference (OCD) and overconsolidation gradient (OCG) were determined in Kiscelli Clay based on new equations. An additional new parameter, ratio of mechanical preloading component of overconsolidation is defined and analysed. [ABSTRACT FROM AUTHOR]

Context: Delayed-onset muscle soreness (DOMS) is a common muscle pain that many people experience and is often used as a model of acute muscle pain. Researchers have reported the effects of various interventions on DOMS, but different DOMS assessment protocols used in these studies make it difficult to compare the effects. Objective: To investigate DOMS characteristics after elbow- flexor eccentric exercise to establish a standardized DOMS assessment protocol. Design: Descriptive laboratory study. Setting: Research laboratory. Patients or Other Participants: Ten healthy, untrained men (21-39 years). Intervention(s): Participants performed 10 sets of 6 maximal isokinetic eccentric contractions of the elbow flexors. Main Outcome Measure(s): Indirect muscle-damage markers were maximal voluntary isometric contraction torque, range of motion, and serum creatine kinase activity. Muscle pain was assessed before exercise, immediately postexercise, and 1 to 5 days postexercise using (1) a visual analog scale (VAS), (2) a category ratio-10 scale (CR-10) when applying static pressure and palpation at different sites (3, 9, and 15 cm above the elbow crease), and (3) pressure-pain thresholds (PPTs) at 50 sites (pain mapping). Results: Maximal voluntary isometric contraction and range of motion decreased and creatine kinase activity increased postexercise, indicating muscle damage. Palpation induced greater pain than static pressure, and longitudinal and transverse palpations induced greater pain than circular palpation (P < .05). The PPT was lower in the medial region before exercise, but the pain-sensitive regions shifted to the central and distal regions of the biceps brachii at 1 to 3 days postexercise (P, .05). The VAS was correlated with the CR-10 scale (r = 0.91, P < .05) but not with the PPT (r = -0.28, P = .45). Conclusions: The way in which muscles are assessed affects the pain level score. This finding suggests that pain level and pain threshold cannot be used interchangeably and that the central and distal regions of the biceps brachii should be included in DOMS assessment using the VAS, CR-10 scale, and PPT after elbow-flexor eccentric exercise. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are a vital component of the innate immune system of all eukaryotic organisms and many of these peptides have potent antifungal activity. They have potential application in the control of fungal pathogens that are a serious threat to both human health and food security. Development of antifungal peptides as therapeutics requires an understanding of their mechanism of action on fungal cells. To date, most research on antimicrobial peptides has focused on their activity against bacteria. Several antimicrobial peptides specifically target fungal cells and are not active against bacteria. Others with broader specificity often have different mechanisms of action against bacteria and fungi. This review focuses on the mechanism of action of naturally occurring antifungal peptides from a diverse range of sources including plants, mammals, amphibians, insects, crabs, spiders, and fungi. While antimicrobial peptides were originally proposed to act via membrane permeabilization, the mechanism of antifungal activity for these peptides is generally more complex and often involves entry of the peptide into the cell. [ABSTRACT FROM AUTHOR]

The cell cycle is an important process during seed development in plants and its progression is driven by a number of core regulators such as the cyclins. Currently, however, little is known regarding the role of the cyclins in embryo and endosperm development in cereals. In our current study, we show that the knockdown of Orysa;CycB1;1 in rice results in the production of abnormal seeds, which at maturity contain only an enlarged embryo. It was further found that a delayed and abnormal cellularization occurred in the endosperm in these knockdown seeds which eventually became abortive. Moreover, the observed development of the enlarged embryo was also morphologically abnormal and found to be caused by an enlarged cell size rather than an increased cell number. Expression analysis showed that Orysa;CycB1;1 transcripts were localized in the endosperm and embryo. Genome-wide transcriptional profiling further indicated that a large number of genes are responsible for the phenotype of the enlarged embryo. The results of the knockdown of Orysa;CycB1;1 via an endosperm or an embryo-specific promoter also suggest that the enlarged embryo may be correlated to the abortive endosperm. Our results suggest that Orysa;CycB1;1 expression is critical for endosperm formation via the regulation of mitotic division, and that the endosperm plays an important role in maintenance of embryo development in rice. [ABSTRACT FROM AUTHOR]