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Global myocardial work (GMW) is an emerging method to characterize left ventricle (LV) function with potential advantages over both ejection fraction and global longitudinal strain (GLS). We aimed to determine the feasibility and reproducibility for echocardiographic-derived GMW in a healthy pediatric population; establish normal reference values; and investigate the influence of age, gender, and other clinical factor on normal reference ranges. We prospectively enrolled 212 individuals (median age of 9 years; interquartile range, 6 to 12 years, 112 female). Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were measured from LV pressure–strain loops. Quantification of GMW was performed using a GE Vivid E95 system and available software package (Echopac V.203, GE). The mean LV EF was 64 ± 3% with GLS of -21.3 ± 1.5%. GWI was 1688 ± 219 mmHg% with mean GWE of 96.5 ± 1.4%. The GCW was 1959 ± 207 mmHg%, and the mean GWW of 61.1 ± 30.9 mmHg%. No significant difference was found in MW indices across age group and gender (p > 0.05 for all). There were significant correlations between both GWI and GCW with GLS and systolic blood pressure (p < 0.001), but not with GWE and GWW. Linear regression model revealed that GWI and GCW were more closely correlated with systolic blood pressure than GLS. LV MW indices had good intra-observer and inter-observer reproducibility. This study establishes both the feasibility and reference ranges for non-invasive echocardiographic indices of GMW in healthy children. Myocardial work appears to be a complementary modality to assess LV performance in children. [ABSTRACT FROM AUTHOR]

Background: Lipopolysaccharide‐responsive and beige‐like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000–1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals. Methods: We report a 16‐year‐old Vietnamese, male patient with recurrent CVID symptoms including chronic diarrhea, interstitial pneumonia, cutaneous granulomatous lesions, hepatosplenomegaly, and finger clubbing. Immunological analyses and whole exome sequencing (WES) were performed to investigate phenotypic and genotypic features. Results: Immunological analyses revealed hypogammaglobulinemia and low ratios of CD4+/CD8+ T cells. Two novel compound heterozygous stop‐gain mutation in LRBA were identified: c.1933C > T (p.R645X) and c.949C > T (p.R317X). Sanger sequencing confirmed the segregation of these variants from the intact parents. The abolished LRBA protein expression was shown by immunoblot analysis. Subsequent treatment potentially saves the child from the same immune thrombocytopenia which led to his brother's untimely death; likely caused by the same LRBA mutations. Conclusion: This first report of LRBA deficiency in Vietnam expands our knowledge of the diverse phenotypes and genotypes driving CVID. Finally, the utilization of WES shows great promise as an effective diagnostic for CVID in our setting. [ABSTRACT FROM AUTHOR]

Purpose: While increased suicidal tendencies among cancer patients have been well documented, this study aims to examine suicide rates and factors associated with suicide specifically in patients with colorectal cancer (CRC).Methods: Patients diagnosed with CRC between the years of 1988-2010 were selected from the Surveillance, Epidemiology, and End Result (SEER) database. Comparisons with the general population were done using the National Center for Disease Control registry.Results: One thousand three hundred eighty-one suicides among 884,529 patients were identified, with a standardized mortality ratio (SMR) of 1.53 (95% CI, 1.13-1.33) compared to the general population. No statistically significant difference in suicide rate was found with respect to age, marital status, socio-economic status, surgical intervention, histologic subtype, or stage at diagnosis. Within the CRC population, Whites were significantly more likely to commit suicide than non-Whites (OR, 2.28; 95% CI, 1.89-2.75; P < 0.001), and males were significantly more likely than females (OR, 5.635; 95% CI, 4.85-6.54; P < 0.001). Most suicides occurred in patients with distal lesions in the sigmoid/rectosigmoid junction (P < 0.001). SMRs for CRC patients were 4.24 for females (95% CI, 3.69-4.86), 1.35 for males (95% CI, 1.28-1.43), 0.38 for African-Americans (95% CI, 0.28-0.52), 1.77 for Whites (95% CI, 1.68-1.87), and 0.90 for other races (95% CI, 0.72-1.12).Conclusion: Identification of risk factors associated with suicide among patients with CRC is an important step in developing screening strategies and management of psychosocial stressors. These results could be helpful in formulating a comprehensive suicide risk scoring system for screening all cancer patients. [ABSTRACT FROM AUTHOR]

Freezing of gait (FoG) is common in Parkinsonian gait and strongly relates to falls. Current clinical FoG assessments are patients’ self-report diaries and experts’ manual video analysis. Both are subjective and yield moderate reliability. Existing detection algorithms have been predominantly designed in subject-dependent settings. In this paper, we aim to develop an automated FoG detector for subject independent. After extracting highly relevant features, we apply anomaly detection techniques to detect FoG events. Specifically, feature selection is performed using correlation and clusterability metrics. From a list of 244 feature candidates, 36 candidates were selected using saliency and robustness criteria. We develop an anomaly score detector with adaptive thresholding to identify FoG events. Then, using accuracy metrics, we reduce the feature list to seven candidates. Our novel multichannel freezing index was the most selective across all window sizes, achieving sensitivity (specificity) of \text96\% ( \text79\%). On the other hand, freezing index from the vertical axis was the best choice for a single input, achieving sensitivity (specificity) of \text94\% ( \text84\%) for ankle and \text89\% (\text94\%) for back sensors. Our subject-independent method is not only significantly more accurate than those previously reported, but also uses a much smaller window (e.g., \text3\,\texts versus \text7.5\,\texts ) and/or lower tolerance (e.g., \text0.4\,\texts versus \text2\,\texts). [ABSTRACT FROM PUBLISHER]

Goal: Respiratory artefact removal for the forced oscillation technique can be treated as an anomaly detection problem. Manual removal is currently considered the gold standard, but this approach is laborious and subjective. Most existing automated techniques used simple statistics and/or rejected anomalous data points. Unfortunately, simple statistics are insensitive to numerous artefacts, leading to low reproducibility of results. Furthermore, rejecting anomalous data points causes an imbalance between the inspiratory and expiratory contributions. Methods: From a machine learning perspective, such methods are unsupervised and can be considered simple feature extraction. We hypothesize that supervised techniques can be used to find improved features that are more discriminative and more highly correlated with the desired output. Features thus found are then used for anomaly detection by applying quartile thresholding, which rejects complete breaths if one of its features is out of range. The thresholds are determined by both saliency and performance metrics rather than qualitative assumptions as in previous works. Results: Feature ranking indicates that our new landmark features are among the highest scoring candidates regardless of age across saliency criteria. F1-scores, receiver operating characteristic, and variability of the mean resistance metrics show that the proposed scheme outperforms previous simple feature extraction approaches. Our subject-independent detector, 1IQR-SU, demonstrated approval rates of \text80.6% for adults and \text98% for children, higher than existing methods. Conclusion: Our new features are more relevant. Our removal is objective and comparable to the manual method. Significance: This is a critical work to automate forced oscillation technique quality control. [ABSTRACT FROM AUTHOR]

Nowadays, when the zero-waste strategy is an inevitable component of the circular economy, the reuse of waste, including dredged sludges, has drawn the attention of many researchers. This study evaluated four kinds of bio-wastes (corn core powder, rice husk powder, sugarcane bagasse powder, and peanut shell powders) and two kinds of construction wastes (autoclaved aerated concrete-AAC and pavement stone) in enhancing the dewaterability of dredged sludge from the lake, in which the sludges would then be reused for brick production. The results showed that the moisture contents decreased from 62 ± 0.14% to 57 ± 1.89% after mixing and then to 35 ± 8.31% after compressing for the construction waste-blended sludge. Among the bio-wastes, the sugarcane bagasse additive performed the best at a mixing ratio of 1:3 by weight and rice husk powder worked best at a mixing ratio of 1:5 by weight. The organic matter was increased up to 80% when the bio-wastes were added, while it was decreased to 5% for the case of construction wastes. The optimum percentage of sludge in the mixture to meet all the oxide contents in the brick and energy saving shall be about 30%. The results have revealed a potentially green route for brick production with lake sediment and bio-waste/construction wastes. Implications: It is the first time the reuse of agro-wastes/construction waste was evaluated to mix with lake sediment to partly replace clay for brick production; Among the bio-wastes, the sugarcane bagasse additive performed the best at a mixing ratio of 1:3 by weight; Moisture contents decreased from 62 ± 0.14% to 57 ± 1.89% after mixing and then to 35 ± 8.31% after compressing for the blended sludge; The optimum percentage of mixed sludge, possibly replaced the clay in brick production, considering oxide contents and energy saving shall be up to 30%. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the potential of pure β-galactosidase and β-glucosidase for hydrolyzing isoflavone glycosides to aglycones in soy milk. Both pure β-galactosidase and β-glucosidase were added at various concentrations (0.5, 1.0, 2.0 and 4.0 U/mL) to soy milk made from 4% soy protein isolate and incubated at 37C for up to 240 min. Isoflavones were quantified using high-performance liquid chromatography. The isoflavone contents of soy milk before and after autoclaving were also compared. β-Glucosidase and β-galactosidase were both able to hydrolyze the β-glucosidic linkages in isoflavone glycosides. A range of 43.3 to 77.2% of the total isoflavone glycosides was hydrolyzed at various β-galactosidase concentrations. The β-glucosidase hydrolyzed isoflavone glycosides more efficiently than β-galactosidase. At the most diluted β-glucosidase concentration (0.5 U/mL), 86.6% of isoflavone glycosides were hydrolyzed to aglycones at 240 min. PRACTICAL APPLICATIONS Isoflavone glycosides, which are mainly found in the bean family, are the inactive forms of isoflavones. However, aglycones, which are the nonsugar component of a glycoside molecule that results from hydrolysis of the isoflavone glycosides, are the biologically active forms. Because of their similarity to female hormone, they are considered a “natural way” to relieve the menopausal symptoms as they prevent certain cancers and improve bone health. Only a small amount of the total isoflavones, however, exists in the aglycone forms in nature. A novel method to produce aglycones from natural isoflavones is highly important. β-Glucosidase has been claimed to be the only enzyme which is able to hydrolyze isoflavone glycosides to aglycones. However, other enzymes could hydrolyze isoflavone glycosides more efficiently and could be easier to produce. This paper investigates the ability of β-galactosidase to biotransform isoflavone glycosides to aglycones, as the source of the enzyme is abundant. [ABSTRACT FROM AUTHOR]

Abstract: Four probiotic bacteria, Lactobacillus acidophilus 4461, L. acidophilus 4962, Lactobacillus casei 290 and L. casei 2607, were used for fermentation of soymilk (SM) prepared from soy protein isolate (SPI) supplemented with skim milk powder (SMP) (SSM). Soymilk and reconstituted skim milk (RSM) were used as controls. Lactose utilization in SSM by these probiotic organisms ranged from 14.97 to 18.15mg/ml, compared to 14.12–16.06mg/ml for RSM. The pH in SSM dropped to 4.07–4.29 compared to 6.15–6.36 for SM and 4.10–4.96 for RSM. The microbial viable counts were also significantly enhanced by up to 0.98logCFU/ml by the supplementation of SMP to SM. The biotransformation level of isoflavone glycosides (IG) to isoflavone aglycones (IA) in SSM ranged from 81.4% to 85.1%, which was 13.9–19.0% higher than that for SM, after 24h of incubation. Most of IG in SSM was completely converted to IA, except malonyl glycitin and malonyl genistin. At the end of the incubation, IA comprised up to 76.8% of total isoflavones in SSM. [Copyright &y& Elsevier]

The article presents a comparative genomic analysis of mycobacteriophage Tweety, a newly isolated phage of Mycobacterium smegmatis. Isolation of Tweety genome from a soil sample from the Oakland district of Pittsburgh, Pennsylvania revealed significant similarity of Tweety to other mycobariophages such as Che8, PMC and Llij. New integration-proficient plasmid vectors was developed to illustrate the general utility of mycobacteriophage studies for mycobacterial genetics. It was concluded that the construction efficiently transform both fast- and slow-growing mycobacteria through plasmid integration at a chromosomal locus containing a tRNALys gene.

Provides information on a study on the effects of life-long caloric restriction on diastolic and systolic cardiac function in situ using Doppler techniques in female hybrid mice. Methodology; Results of the study; Discussion on systolic function.

The Phan Si Pan uplift area of NW Vietnam is a part of the Archean to Paleoproterozoic Yangtze Block (SW China) that was displaced along the Ailaoshan-Red River Fault shear zone and adjacent structures (i.e., Song Da zone). The region is of interest as it is at the forefront of the debate regarding the extrusion of SE Asia during the Early Paleogene. Two Cenozoic silicic plutonic complexes of contrasting composition intruded the basement rocks of the Phan Si Pan uplift area. The Ban Xeo granite is ferroan (A-type), alkalic and yielded a zircon weighted-mean 206Pb/238U age of 49 ± 0.9 Ma. The major and trace element compositions of the Ban Xeo granite are similar to the spatially associated Late Permian Muong Hum granites. The εNd (t) values (−2.5 to −1.4), 87Sr/86Sr initial ratios (0.70793, 0.70989, and 0.75341), and zircon εHf (t) values (−1.1 to +3.0) indicate that the Ban Xeo granite is likely derived by differentiation of a mafic parental magma that had EMII-like mantle source characteristics. The younger Ye Yen Sun (YYS) granite is magnesian, alkali-calcic to calc-alkalic, and yielded zircon U–Pb weighted-mean ages of 35.3 ± 0.5 to 34.1 ± 0.4 Ma. The YYS granites have 87Sr/86Sr initial ratios of 0.70636 to 0.70860, εNd (t) values from −8.7 to −2.6, and zircons εHf (t) values from −9.3 to +0.6 which indicate a crustal origin. The YYS dioritic rocks range from syeno-diorite to granodiorite, and have similar Sr (87Sr/86Sr = 0.70627) and εNd (t) (−3.8) values as the YYS granites. However, the zircon Hf isotopes (εHf (t) = +0.3 to +3.2) of the syeno-diorite are slightly more chondritic than the granites and indicates that the parental magma was likely derived from a mantle source. Rhyolite–MELTS modeling results show that the YYS granites were likely generated by fractionation of a parental magma similar in composition to the granodiorite. Furthermore, the YYS syeno-diorites may be representative of a cumulate rock that developed during the early stages of emplacement or crystallization. The parental magma of YYS igneous rocks likely formed by partial melting of mafic Mesoproterozoic juvenile rocks (lower crust/uppermost mantle) by heat from the upwelling lithospheric mantle during a period of crustal relaxation. The formation of the Ban Xeo granites and Ye Yen Sun igneous rocks are likely related to lateral melt migration along the eastern edge of the India-Asia collision zone. It is possible that repeated episodes of Cenozoic magmatism was pivotal in the development and initiation of fault movement of the Ailaoshan-Red River shear zone. Unlabelled Image • Eocene peralkaline granites were derived from an EMII mantle source. • The Early Oligocene YYS granites crystallized from a granodioritic parental magma. • The YYS syeno-diorites likely accumulated from the primary granodioritic melt. • Multiple Cenozoic magmatic events may have contributed to the ASRR movement. [ABSTRACT FROM AUTHOR]

Mitral valve prolapse (MVP) is the most common valvar dysfunction in children. There is emerging evidence that MVP is not always a benign entity, hence identification of underlying mechanisms is pertinent to clinical management. Our group previously identified a ventricular contraction abnormality named end-systolic basal eversion (ESBE) in adults that contributed to MVP. The aim of this study was to evaluate regional circumferential strain in pediatric patients with MVP and ESBE compared to normal controls. Left ventricular circumferential strain was assessed in 16 pediatric patients referred for clinical echocardiographic examination with MVP and ESBE (MVP group) and compared to age-gender-matched healthy subjects. ESBE has been previously described as late systolic bileaflet mitral valve prolapse, papillary traction, and concomitant late systolic outward movement of the basal inferior myocardium. The mean age of the MVP group was 13.8 ± 4.6 year and 75% were female. All patients with MVP and controls had qualitatively normal systolic cardiac function. The MVP group had significantly lower regional strain values for 11/16 of the segments including all 6 basal segments. Importantly, the basal inferior (− 17.02 ± 8.32% vs. − 26.10 ± 3.18, p = 0.001) and basal inferolateral (− 19.53 ± 9.76 vs. − 26.10 ± 3.18, p = 0.03) had the lowest strain values compared to the average of all other segments suggesting weaker contraction in the basal inferior segments. Pediatric patients with MVP and ESBE are subject to a similar left ventricular mechanical dysfunction previously described in adults. ESBE was evident by decreased basal circumferential strain values. These findings denoted weaker contraction which is believed to propagate the late systolic outward movement of the basal ventricular myocardium. [ABSTRACT FROM AUTHOR]

High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1–10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15–3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75–2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use among HIV-infected patients. [ABSTRACT FROM AUTHOR]

In this study, soy protein isolate (SPI) (4%, v/w) was supplemented to the yogurt mix to increase the amount of biologically active isoflavone in yogurt (SY). The control yogurt was without any SPI supplementation (USY). The supplementation significantly ( P < 0.05) increased the lactose metabolism by the yogurt starter including Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 (Lb 11842) and Streptococcus thermophilus ST 1342 (ST 1342) during the fermentation process by 4.7%. The starter produced more acetic acid and less lactic acid in SY than that in USY and altered the ratio of lactic and acetic acid during the entire storage period. The viability of both Lb 11842 and ST 1342 in SY was significantly ( P < 0.05) lower than that in USY from 14 d of the storage period, however, their concentration still remained high (8.11 to 8.84 log CFU/g). The starter transformed 72.8% of total inactive isoflavone glycosides (IG) to active isoflavone aglycones (IA), increasing the IA content from 1.35 to 15.01 mg/100 g sample. During the storage period, IA concentration slowly rose from 15.02 to 15.51 mg/100 g sample. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between molecular arrangement and surface tension of water mixtures with methanol and ethanol. It has been found that the molecular structure of interfacial zone was deterministically correlated to alcohol concentration. From the water dipole moment, an interfacial boundary was defined. The boundary then was used to calculate the water and alcohols in the interfacial zone, which was then used to calculate the surface tension. The prediction from simulated data closely followed the experimental data. The analysis revives the relevance of the molecular arrangement, which had been the main focus in the early 20th century, in quantification of surface energy. The results can supplement the current thermodynamic analysis to correctly predict the surface adsorption. [ABSTRACT FROM AUTHOR]

To investigate the effect of growth hormone and insulin-like growth factor 1 deficiency on the aging mouse arterial system, we compared the hemodynamics in young (4 months) and old (30 months) growth hormone–releasing hormone receptor null dwarf (Little) mice and their wild-type littermates. Young Little mice had significantly lower peak and mean aortic velocity and significantly higher aortic impedance than young wild-type mice. However, unlike the wild-type mice, there were no significant changes in arterial function with age in the Little mice. Aortic pulse wave velocity estimated using characteristic impedance increased with age in the wild-type mice, but it changed minimally in the Little mouse. We therefore conclude that arterial function in Little mice expresses a premature aging phenotype at young age and may neither enhance nor reduce their longevity. [ABSTRACT FROM PUBLISHER]

Suppression of immune responses by regulatory T cells (Tregs) is thought to limit late stages of pathogen-specific immunity as a means of minimizing associated tissue damage. We examined a role for Tregs during mucosal herpes simplex virus infection in mice, and observed an accelerated fatal infection with increased viral loads in the mucosa and central nervous system after ablation of Tregs. Although augmented interferon production was detected in the draining Lymph nodes (dLNs) in Treg-deprived mice, it was profoundly reduced at the infection site. This was associated with a delay in the arrival of natural killer cells, dendritic cells, and T cells to the site of infection and a sharp increase in proinflammatory chemokine levels in the dLNs. Our results suggest that Tregs facilitate early protective responses to Local viral infection by allowing a timely entry of immune cells into infected tissue. [ABSTRACT FROM AUTHOR]

Measurement of aortic input impedance in mice: effects of age on aortic stiffness. Am J Physiol Heart Circ Physiol 285: H1464-H1470, 2003. First published May 29, 2003; 10.1152/ajpheart.00004.2003.—Mice are used with increasing frequency as models of human cardiovascular diseases, but significant gaps exist in our knowledge of vascular function in the aging mouse. We determined aortic input impedance spectra, pulse wave velocity, and augmentation index in adult (8-mo-old) and old (29-mo-old) mice to determine whether arterial stiffening occurred with age m mice as it does in humans. Pressure and blood velocity signals measured simultaneously from the same location in the ascending aorta were used re determine input impedance spectra (0-10 harmonics). The first minimum of the impedance modulus occurred at the second harmonic m adult mice but shifted to the fourth harmonic in old mice. Characteristic impedance (average of 2nd-10th harmonic) was 57% higher in old mice: 471 ± 62 vs. 299 ± 10 (SE) dyn·s·cm[sup -3] (P< 0.05). Pulse pressure and augmentation index, determined from the aortic pressure signals, were also higher in old mice: 42±2.2 vs. 29 ± 4.9 mmHg (P < 0.05) and 37±5 vs. 14 ± 2% (P < 0.005). Aortic pulse wave velocity measured from the timing of upstrokes of the Doppler velocity signals was 45% higher in old mice: 416 ± 22 vs. 286 ± 14 cm/s (n = 3, P < 0.01). These results reproduce age-related findings reported in humans and confirm that mice may be used as models of age-related vascular stiffening. [ABSTRACT FROM AUTHOR]

Aims Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is causally linked to AF pathogenesis in obesity remains elusive. We recently demonstrated that the constitutive activation of the 'NACHT, LRR, and PYD Domains-containing Protein 3' (NLRP3) inflammasome promotes AF susceptibility. In this study, we hypothesized that the NLRP3 inflammasome is a key driver of obesity-induced AF. Methods and results Western blotting was performed to determine the level of NLRP3 inflammasome activation in atrial tissues of obese patients, sheep, and diet-induced obese (DIO) mice. The increased body weight in patients, sheep, and mice was associated with enhanced NLRP3-inflammasome activation. To determine whether NLRP3 contributes to the obesity-induced atrial arrhythmogenesis, wild-type (WT) and NLRP3 homozygous knockout (NLRP3−/−) mice were subjected to high-fat-diet (HFD) or normal chow (NC) for 10 weeks. Relative to NC-fed WT mice, HFD-fed WT mice were more susceptible to pacing-induced AF with longer AF duration. In contrast, HFD-fed NLRP3−/− mice were resistant to pacing-induced AF. Optical mapping in DIO mice revealed an arrhythmogenic substrate characterized by abbreviated refractoriness and action potential duration (APD), two key determinants of reentry-promoting electrical remodeling. Upregulation of ultra-rapid delayed-rectifier K+-channel (Kv1.5) contributed to the shortening of atrial refractoriness. Increased profibrotic signaling and fibrosis along with abnormal Ca2+ release from sarcoplasmic reticulum (SR) accompanied atrial arrhythmogenesis in DIO mice. Conversely, genetic ablation of Nlrp3 (NLRP3−/−) in HFD-fed mice prevented the increases in Kv1.5 and the evolution of electrical remodeling, the upregulation of profibrotic genes, and abnormal SR Ca2+ release in DIO mice. Conclusion These results demonstrate that the atrial NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmogenesis and establishes a mechanistic link between obesity-induced AF and NLRP3-inflammasome activation. [ABSTRACT FROM AUTHOR]

The maximum value of the first derivative of the invasively measured left ventricular (LV) pressure (+ dP/dtmax or P′) is often used to quantify LV contractility, which in mice is limited to a single terminal study. Thus, determination of P′ in mouse longitudinal/serial studies requires a group of mice at each desired time point resulting in "pseudo" serial measurements. Alternatively, a noninvasive surrogate for P′ will allow for repeated measurements on the same group of mice, thereby minimizing physiological variability and requiring fewer animals. In this study we evaluated aortic acceleration and other parameters of aortic flow velocity as noninvasive indices of LV contractility in mice. We simultaneously measured LV pressure invasively with an intravascular pressure catheter and aortic flow velocity noninvasively with a pulsed Doppler probe in mice, at baseline and after the administration of the positive inotrope, dobutamine. Regression analysis of P′ versus peak aortic velocity (vp), peak velocity squared/rise time (vp2/T), peak (+ dvp/dt or v′p) and mean (+ dvm/dt or v′m) aortic acceleration showed a high degree of association (P′ versus: vp, r2 = 0.77; vp2/T, r2 = 0.86; v′p, r2 = 0.80; and v′m, r2 = 0.89). The results suggest that mean or peak aortic acceleration or the other parameters may be used as a noninvasive index of LV contractility. [ABSTRACT FROM AUTHOR]

Introduction: HIV viral load (VL) testing is recommended by the WHO as the preferred method for monitoring patients on antiretroviral therapy (ART). However, evidence that routine VL (RVL) monitoring improves clinical outcomes is lacking. Methods: We conducted a prospective, randomized controlled trial of RVL monitoring every six months versus a targeted VL (TVL) strategy (routine CD4 plus VL testing if clinical or immunological failure) in patients starting ART between April 2011 and April 2014 at Bach Mai Hospital in Hanoi. Six hundred and forty‐seven subjects were randomized to RVL (n = 305) or TVL monitoring (n = 342) and followed up for three years. Primary endpoints were death or WHO clinical Stage 4 events between six and thirty‐six months of ART and rate of virological suppression at three years. Results: Overall, 37.1% of subjects were female, median age was 33.4 years (IQR: 29.5 to 38.6), and 47% had a CD4 count ≤100 cells/mm3 at time of ART initiation. Approximately 44% of study events (death, LTFU, withdrawal, or Stage 4 event) and 68% of deaths occurred within the first six months of ART. Among patients on ART at six months, death or Stage 4 event occurred in 3.6% of RVL and 3.9% of TVL (p = 0.823). Survival analysis showed no significant difference between the groups (p = 0.825). Viral suppression at 36 months of ART was 97.2% in RVL and 98.9% in TVL (p = 0.206) at a threshold of 400 copies/mL and was 98.0% in RVL and 98.9% in TVL (p = 0.488) at 1000 copies/mL. In ITT analysis, 20.7% in RVL and 21.9% in TVL (p = 0.693) were unsuppressed at 1000 copies/mL. Conclusions: We found no significant difference in rates of death or Stage 4 events and virological failure in patients with RVL monitoring compared to those monitored with a TVL strategy after three years of follow‐up. Viral suppression rates were high overall and there were few study events among patients alive and on ART after six months, limiting the study's power to detect a difference among study arms. Nonetheless, these data suggest that the choice of VL monitoring strategy may have less impact on patient outcomes compared to efforts to reduce early mortality and improve ART retention. [ABSTRACT FROM AUTHOR]

Abstract Purpose Low trauma rib fracture (hereinafter, rib fracture) is common in the elderly, but its risk factors and mortality consequence are rarely studied. We sought to define the epidemiology of rib fracture and the association between rib fracture and postfracture mortality. Methods The study was part of the Dubbo Osteoporosis Epidemiology Study, which was designed as a population-based prospective study, and consisted of 2041 women and men (aged ≥ 60). The incidence of rib fracture was ascertained from X-ray reports. Bone mineral density (BMD) was measured by DXA (GE-Lunar). The time-dependent Cox model was used to access the relationship between rib fracture and mortality. Results During the median follow-up of 13 years, 59 men and 78 women had sustained a rib fracture, making the annual incidence of 4.8/1000 person-years. Each SD (0.15 g/cm2) lower in femoral neck BMD was associated with ~2-fold increase in the hazard of fracture (hazard ratio [HR] 1.9; 95% CI, 1.4 to 2.6 in men; and HR 2.1; 95% CI, 1.6 to 2.8 in women). Among those with a rib fracture, the incidence of subsequent fractures was 10.2/100 person-years. Compared with those without a fracture, the risk of mortality among those with a fracture was increased by ~7.8-fold (95% CI, 2.7 to 22.5) in men and 4.9-fold (95% CI 2.0 to 11.8) in women within the first year postfracture. Conclusions A rib fracture signifies an increased risk of subsequent fractures and mortality. The increased risk of mortality during the first 2.5 years postfracture suggests a window of opportunity for treatment. Highlights • Rib fracture is common in the elderly, accounting for 7% of all fragility fractures. • Risk factors for rib fracture were old age, osteoporosis, prior fracture and fall. • An existing rib fracture signifies a greater risk of subsequent fractures and death. [ABSTRACT FROM AUTHOR]

The use of dried blood spot (DBS) specimens for HIV viral load (VL) monitoring is recommended to support the roll-out of routine VL monitoring in low and middle income countries (LMICs). To better understand the use of DBS for VL monitoring, we evaluated two DBS testing methods, Roche TaqMan® Free Virus Evolution protocol (DBS-FVE) and Roche TaqMan® SPEX protocol (DBS-SPEX)) in patients receiving ART at an HIV clinic in Hanoi, Vietnam. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each DBS testing method at the thresholds of 1000 and 5000 copies/ml compared to plasma VL. At a threshold of 1000 copies/ml, sensitivity, specificity, PPV and NPV of the DBS-SPEX method were 98.8% (95% CI: 93.3%-100%), 74.3% (95% CI: 70.8%-77.5%), 31.5% (95% CI: 25.8%-37.6%), and 99.8% (95% CI: 98.9%-100%), respectively. Increasing the VL threshold value to 5000 copies/ml improved specificity (97.9% CI: 96.6%-98.9%) and PPV (83.9% CI: 74.5%-90.9%). Using the DBS-FVE method, at the threshold of 1000 copies/ml and with a correction factor of +0.3 log copies/ml, sensitivity was 95.1% (87.8%-98.6%) and specificity was 98.8% (97.7%-99.5%). Sensitivity decreased at the threshold of 5000 copies/ml (65.8%, 95% CI: 54.3%-76.1%). With a correction factor of +0.7 log copies/ml, the sensitivity was 96.3% (89.6%-99.2%) and specificity was 98.2% (96.9%-99.1%) at the threshold of 1000 copies/ml. We found that the Roche DBS-FVE method, with a +0.7 log copies/ml correction factor, performed well with sensitivity and specificity greater than 96% at a VL threshold of 1000 copies/m. These findings add to the growing body of evidence supporting the use of DBS VL testing for ART monitoring. Future research should evaluate the association between VL results by DBS and clinical outcome measures such as HIV drug resistance, morbidity, and mortality. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Abstract: Mycobacteriophages are viruses that infect mycobacterial hosts. Expansion of a collection of sequenced phage genomes to a total of 60—all infecting a common bacterial host—provides further insight into their diversity and evolution. Of the 60 phage genomes, 55 can be grouped into nine clusters according to their nucleotide sequence similarities, 5 of which can be further divided into subclusters; 5 genomes do not cluster with other phages. The sequence diversity between genomes within a cluster varies greatly; for example, the 6 genomes in Cluster D share more than 97.5% average nucleotide similarity with one another. In contrast, similarity between the 2 genomes in Cluster I is barely detectable by diagonal plot analysis. In total, 6858 predicted open-reading frames have been grouped into 1523 phamilies (phams) of related sequences, 46% of which possess only a single member. Only 18.8% of the phams have sequence similarity to non-mycobacteriophage database entries, and fewer than 10% of all phams can be assigned functions based on database searching or synteny. Genome clustering facilitates the identification of genes that are in greatest genetic flux and are more likely to have been exchanged horizontally in relatively recent evolutionary time. Although mycobacteriophage genes exhibit a smaller average size than genes of their host (205 residues compared with 315), phage genes in higher flux average only 100 amino acids, suggesting that the primary units of genetic exchange correspond to single protein domains. [Copyright &y& Elsevier]

Abstract: The small size, high heart rate and small tissue displacement of a mouse require small sensors that are capable of high spatial and temporal tissue displacement resolutions and multichannel data acquisition systems with high sampling rates for simultaneous measurement of high fidelity signals. We developed and evaluated an ultrasound-based mouse vascular research system (MVRS) that can be used to characterize vascular physiology in normal, transgenic, surgically altered and disease models of mice. The system consists of multiple 10/20MHz ultrasound transducers, analog electronics for Doppler displacement and velocity measurement, signal acquisition and processing electronics and personal computer based software for real-time and off-line analysis. In vitro testing of the system showed that it is capable of measuring tissue displacement as low as 0.1μm and tissue velocity (μm/s) starting from 0. The system can measure blood velocities up to 9m/s (with 10MHz Doppler at a PRF of 125kHz) and has a temporal resolution of 0.1 milliseconds. Ex vivo tracking of an excised mouse carotid artery wall using our Doppler technique and a video pixel tracking technique showed high correlation (R2 =0.99). The system can be used to measure diameter changes, augmentation index, impedance spectra, pulse wave velocity, characteristic impedance, forward and backward waves, reflection coefficients, coronary flow reserve and cardiac motion in murine models. The system will facilitate the study of mouse vascular mechanics and arterial abnormalities resulting in significant impact on the evaluation and screening of vascular disease in mice. (E-mail: areddy@bcm.edu) [Copyright &y& Elsevier]

We have developed a high-frequency, high-resolution Doppler spectrum analyzer (DSPW) and compared its performance against an adapted clinical Medasonics spectrum analyzer (MSA) and a zero-crossing interval histogram (ZCIH) used previously by us to evaluate cardiovascular physiology in mice. The aortic velocity (means ± SE: 92.7 ± 2.5 versus 82.2 ± 1.8 cm/s) and aortic acceleration (8194 ± 319 versus 5178 ± 191 cm/s²) determined by the DSPW were significantly higher compared to those by the MSA. Aortic ejection time was shorter (48.3± 0.9 versus 64.6 ± 1.8 ms) and the isovolumic relaxation was longer (17.6 ± 0.6 versus 13.5 ±0.6 ms) when determined by the DSPW because it generates shorter temporal widths in the velocity spectra when compared to the MSA. These data indicate that the performance of the DSPW in evaluating cardiovascular physiology was better than that of the MSA. There were no significant differences between the aortic pulse wave velocity determined by using the ZCIH (391 ± 16 cm/s) and the DSPW (394± 20 cm/s). Besides monitoring cardiac function, we have used the DSPW for studying peripheral vascular physiology in normal, transgenic, and surgical models of mice. Several applications such as the detection of high stenotic jet velocities (>4 m/s), vortex shedding frequencies (250 Hz), and subtle changes in wave shapes in peripheral vessels which could not obtained with clinical Doppler systems are now made possible with the DSPW. [ABSTRACT FROM AUTHOR]

The placement of a ligature to constrict the transverse aorta has become a standard procedure to induce cardiac hypertrophy in mice. Apart from cardiac response, there are adaptive changes in the proximal and distal arterial system that function to maintain adequate peripheral perfusion. The purpose of this study was to characterize the peripheral vascular response by measuring the carotid blood flow using noninvasive Doppler methods, and to investigate the effect of aging on the adequacy and timing of the response after aortic banding in mice. Five 16-month-old and 9 4-month-old male B6D2F1 mice underwent transverse aortic banding. Blood flow velocity was measured with Doppler in the right and left carotid arteries (RCA and LCA) before, 1 day after, and 7 days after, banding. Pulsatility index defined as (peak - minimum)/mean velocity was used to estimate local compliance and distal arterial resistance. The RCA/LCA mean velocity ratio was lower and pulsatility index ratio was higher at 1 day after banding in older mice. However, at 7 days, the RCA/LCA mean velocity ratio and pulsatility index ratio were similar between the 2 age groups. Our data indicate that there is an age-related delay in the development of vascular adaptations in carotid arteries after aortic banding. Older mice take a longer time for adaptation to establish adequate and equal mean flow velocity in the carotid arteries. [ABSTRACT FROM AUTHOR]

The placement of a ligature to constrict the transverse aorta has become a standard procedure to induce cardiac hypertrophy in mice. Apart from cardiac response, there are adaptive changes in the proximal and distal arterial system that function to maintain adequate peripheral perfusion. The purpose of this study was to characterize the peripheral vascular response by measuring the carotid blood flow using noninvasive Doppler methods, and to investigate the effect of aging on the adequacy and timing of the response after aortic banding in mice. Five 16-month-old and 9 4-month-old male B6D2F1 mice underwent transverse aortic banding. Blood flow velocity was measured with Doppler in the right and left carotid arteries (RCA and LCA) before, I day after, and 7 days after, banding. Pulsatility index defined as (peak -- minimum)/mean velocity was used to estimate local compliance and distal arterial resistance. The RCA/LCA mean velocity ratio was lower and pulsatility index ratio was higher at 1 day after banding in older mice. However, at 7 days, the RCA/LCA mean velocity ratio and pulsatility index ratio were similar between the 2 age groups. Our data indicate that there is an age-related delay in the development of vascular adaptations in carotid arteries after aortic banding. Older mice take a longer time for adaptation to establish adequate and equal mean flow velocity in the carotid arteries. [ABSTRACT FROM AUTHOR]

This study was conducted to assess the removal of arsenic (As) and heavy metals from mining wastewater by the combination of adsorption, using modified iron-ore drainage sludge, and horizontal-subsurface-flow constructed wetland with common reed (Phragmites australis). The pilot-scale experiment with a constant flow rate of 5 m3/day was operated for four months using real wastewater from a Pb–Zn mine in northern Vietnam. Atomic absorption spectroscopy was used for elemental analysis in wastewater and plant. X-ray diffraction (XRD), surface charge measurements (by a particle charge detector (PCD)), Fourier-transform infrared (FTIR), and surface area Brunauer–Emmet–Teller (BET) measurements were performed to determine the characteristics of the adsorbent. The results showed that the average removals of As, Mn, Cd, Zn, and Pb by the combined system with limestone substrate during four months were 80.3%, 96.9%, 79.6%, 52.9%, and 38.7%, respectively. The use of another constructed wetland substrate, laterite, demonstrated better removal efficiency of As than limestone. The concentrations of As and heavy metals in the effluent were lower than the limits established by the QCVN 40:2011/BTNMT for industrial wastewater, which indicated the feasibility of combining adsorption and constructed wetland for the treatment of mining wastewater. [ABSTRACT FROM AUTHOR]

Introduction: Multiple comorbidities among HIV‐positive individuals may increase the potential for polypharmacy causing drug‐to‐drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age‐associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age‐associated comorbidities on therapeutic outcomes of cART in HIV‐positive adults in Asian countries. Methods: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in‐line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure. Results: The incidence of virologic failure was 7.72/100 person‐years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age‐related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person‐years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities. Conclusions: In our Asia regional cohort, age‐associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response. [ABSTRACT FROM AUTHOR]