Using an In-Sample Addition of Medronic Acid for the Analysis of Purine- and Pyrimidine-Related Derivatives and Its Application in the Study of Lung Adenocarcinoma A549 Cell Lines by LC-MS/MS.

Intracellular purine- and pyrimidine-related derivatives are vital molecules for preserving genetic information and are essential for cellular bioenergetics and signal transduction. This study developed a practical liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying intracellular purine- and pyrimidine-related derivatives. To solve the distorted peak shape related to di- and triphosphate nucleotides, in-sample addition of medronic acid and ammonium phosphate was performed. Using the BEH-amide column, the results showed that adding 0.5 mM medronic acid to the sample significantly improved the peak shape without causing an obvious ion suppressive effect. Method validation confirmed that the coefficients of determination (R2) values for linearity evaluation were above 0.94 for all analytes. The intraday and interday accuracies ranged from 85.1 to 128.4%, with the precision below 16.6%. The validated method was successfully applied in characterizing the alterations of purine- and pyrimidine-related derivatives in the A549 cell line with perturbed mitochondrial fission or blockade of the electron transport chain. Collectively, this study demonstrates that the strategy of in-sample medronic acid addition is effective in improving the quantification of intracellular purine- and pyrimidine-related derivatives. We believe that our proposed platform can facilitate the development of novel drugs targeting purine and pyrimidine metabolism in the future.

The effect of research on life satisfaction in middle-aged and older adults: physical disability and physical activity as a parallel and serial mediation analysis.

BACKGROUND AND OBJECTIVE: Maintaining the life satisfaction of frail middle-aged and older adults when they experience physical disability, lower activity status, or complex conditions that are related to each other is now an urgent issue. Therefore, the purpose of this study was to provide evidence for the impact of frailty in middle-aged and older adults on life satisfaction under the simultaneous occurrence and correlation of physical disability and physical activity status. METHODS: Data from the 2015 Taiwan Longitudinal Study in Ageing (TLSA) were analyzed by PROCESS in SPSS to explore three different mediation models (N = 4,421). The first was a parallel mediation model for exploring life satisfaction in middle-aged and older adults with frailty through physical disability or physical activity. The second was a serial mediation model for examining physical disability and physical activity in causal chains linked with a specific direction of flow and to test all combinations. The third was a moderated mediation model for testing whether the indirect effect of frailty status on life satisfaction through physical disability or physical activity was moderated by age stratification. RESULTS: Physical disability and physical activity partially mediated the relationship between frailty status and life satisfaction (IEOVERALL = -0.196, 95% CI: -0.255 to -0.139). The causal path with the highest indirect effect was found to be that between frailty and physical disability; increased frailty led to higher physical disability, which in turn affected physical activity, leading to lower life satisfaction (IE = 0.013, 95% CI: 0.008 to 0.019). The different stratifications by age significantly increased the mediating effect of physical activity (Index of Moderated Mediation = -0.107, SE = 0.052, 95% CI: -0.208 to -0.005) but did not reduce the mediating effect of physical disability. CONCLUSION: This study provides evidence that physical activity and physical disability influence the development of frailty. It also has a significant impact on the life satisfaction of middle-aged and older adults.

[Research Progress of Regulatory T Cells in the Pathogenesis of Multiple Myeloma --Review].

The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.

Codon usage bias in chloroplast genes implicate adaptive evolution of four ginger species.

Codon usage bias (CUB) refers to different codons exhibiting varying frequencies of usage in the genome. Studying CUB is crucial for understanding genome structure, function, and evolutionary processes. Herein, we investigated the codon usage patterns and influencing factors of protein-coding genes in the chloroplast genomes of four sister genera (monophyletic Roscoea and Cautleya, and monophyletic Pommereschea and Rhynchanthus) from the Zingiberaceae family with contrasting habitats in southwestern China. These genera exhibit distinct habitats, providing a unique opportunity to explore the adaptive evolution of codon usage. We conducted a comprehensive analysis of nucleotide composition and codon usage on protein-coding genes in the chloroplast genomes. The study focused on understanding the relationship between codon usage and environmental adaptation, with a particular emphasis on genes associated with photosynthesis. Nucleotide composition analysis revealed that the overall G/C content of the coding genes was ˂ 48%, indicating an enrichment of A/T bases. Additionally, synonymous and optimal codons were biased toward ending with A/U bases. Natural selection is the primary factor influencing CUB characteristics, particularly photosynthesis-associated genes. We observed differential gene expressions related to light adaptation among sister genera inhabiting different environments. Certain codons were favored under specific conditions, possibly contributing to gene expression regulation in particular environments. This study provides insights into the adaptive evolution of these sister genera by analyzing CUB and offers theoretical assistance for understanding gene expression and regulation. In addition, the data support the relationship between RNA editing and CUB, and the findings shed light on potential research directions for investigating adaptive evolution.

A Green Approach for High Oxidation Resistance, Flexible Transparent Conductive Films Based on Reduced Graphene Oxide and Copper Nanowires.

Copper nanowires (CuNWs)-based thin film is one of the potential alternatives to tin-doped indium oxide (ITO) in terms of transparent conductive films (TCFs). However, the severe problem of atmospheric oxidation restricts their practical applications. In this work, we develop a simple approach to fabricate highly stable TCFs through the dip-coating method using reduced graphene oxide (rGO) and CuNWs as the primary materials. Compared with previous works using toxic reduction agents, herein, the CuNWs are synthesized via a green aqueous process using glucose and lactic acid as the reductants, and rGO is prepared through the modified Hummers' method followed by a hydrogen-annealing process to form hydrogen-annealing-reduced graphene oxide (h-rGO). In the rGO/CuNWs films, the dip-coated graphene oxide layer can increase the adhesion of the CuNWs on the substrate, and the fabricated h-rGO/CuNWs can exhibit high atmospheric oxidation resistance and excellent flexibility. The sheet resistance of the h-rGO/CuNWs film only increased from 25.1 to 42.2 Ω/sq after exposure to ambient atmosphere for 30 days and remained almost unchanged after the dynamic bending test for 2500 cycles at a constant radius of 5.3 mm. The h-rGO/CuNWs TCF can be not only fabricated via a route with a superior inexpensive and safe method but also possessed competitive optoelectronic properties with high electrical stability and flexibility, demonstrating great opportunities for future optoelectronic applications.

Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson disease (PD), but fecal levels of SCFAs in patients with PD are reduced. Simultaneous assessments of fecal and plasma SCFA levels, and their interrelationships with the PD disease process, are scarce. We aimed to compare fecal and plasma levels of different SCFA subtypes in patients with PD and healthy controls to delineate their interrelations and link to gut microbiota changes and clinical severity of PD. METHODS: A cohort of 96 patients with PD and 85 controls were recruited from National Taiwan University Hospital. Fecal and plasma concentrations of SCFAs were measured using chromatography and mass spectrometry. Gut microbiota was analyzed using metagenomic shotgun sequencing. Body mass index and medical comorbidities were evaluated and dietary information was obtained using a food frequency questionnaire. To assess motor and cognitive impairment, we used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examination (MMSE). RESULTS: Compared with controls, patients with PD had lower fecal but higher plasma concentrations of acetate, propionate, and butyrate. After adjustment for age, sex, disease duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concentrations (ρ = 0.26, p = 0.042) in patients with PD. MMSE scores negatively correlated with plasma levels of butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for confounders. SCFAs-producing gut bacteria correlated positively with fecal levels of SCFAs in healthy controls but revealed no association in patients with PD. In the PD patient group, the abundance of proinflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, especially propionic acid. DISCUSSION: Reductions in fecal SCFAs but increased plasma SCFAs were observed in patients with PD and corelated to specific gut microbiota changes and the clinical severity of PD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that gut metabolite SCFAs distinguish between patients with PD and controls and are associated with disease severity in patients with PD.

The Mediation Effect of Health Literacy on Social Support with Exchange and Depression in Community-Dwelling Middle-Aged and Older People in Taiwan.

The proportion of the world's population that are over 60 years old is increasing rapidly. The physical and mental health of older people is affected by depression. Health literacy is a major determinant of health and healthcare for the aging; middle-aged and older people with high health literacy are more likely to maintain a healthy lifestyle, and control or manage their chronic diseases. Therefore, this study explored the relationship between health literacy, social support with exchange, and depression, in middle-aged and older adults in the community, using data from the 2015 Taiwan Longitudinal Study on Aging (TLSA) database. Of the 7636 participants, 1481 (19.4%) were middle-aged or older persons with depression symptoms. We found age, gender, and education level to be significantly related to health literacy status, social support with exchange, and depression. Health literacy was positively correlated with depression and social exchange in social support with exchange, whereas the emotional support component of social support with exchange was negatively correlated with depression. Regression-based process analysis was used to verify the mediation effect of health literacy. Our results indicated that when health literacy was entered into the regression model (a × b path), the effect of social exchange on depression was insignificant (c' = -0.01, p = 0.84), indicating a complete mediation effect. These findings suggest that improving health literacy may offset the impact of social support with exchange on depression, and lead to the mitigation of depression in middle-aged and older people in Taiwanese communities.

Short-course daily isoniazid and rifapentine for latent tuberculosis infection in people living with HIV who received coformulated bictegravir/emtricitabine/tenofovir alafenamide.

INTRODUCTION: Short-course preventive therapy with 1-month course of daily administration of isoniazid (300-mg) plus rifapentine (600-mg) (1HP) and 3-month course of weekly administration of isoniazid (900-mg) plus rifapentine (900-mg) (3HP) has higher completion rates than 9-month course of daily isoniazid (9H) for individuals with latent tuberculosis infection (LTBI). We aimed to evaluate the effect, safety and tolerability of 1HP in people living with HIV (PLWH) and LTBI who received coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). METHODS: PLWH testing positive by interferon-gamma release assay and having received BIC/FTC/TAF for >2 weeks with plasma HIV RNA load (PVL) <200 copies/ml were enrolled. BIC trough plasma concentrations and cytokine profiles were determined before the first dose (day 1/baseline), 24 h after the 14th (day 15) and 28th (day 29) doses of 1HP. PVL were determined on days 15 and 29 of 1HP and every 3 months subsequently after discontinuation of 1HP. RESULTS: From November 2019 to December 2020, 48 PLWH with LTBI were enrolled. One participant (2.1%) discontinued 1HP on day 15 due to fever and generalized rashes with PVL of 72 copies/ml, which was <50 copies/ml in three subsequent determinations while on BIC/FTC/TAF over the 12 months of follow-up. The percentages of BIC trough plasma concentrations above the protein-adjusted 95% effective concentration (paEC95 = 162 ng/ml) were 56.3% and 37.0% on days 15 and 29, respectively. The percentage of PVL <200 copies/ml was 91.7% on day 15, 97.8% on day 29 and 100% at both months 3 and 6. After a median observation of 52 weeks (interquartile range, 51-55), all participants continued BIC/FTC/TAF with a median PVL of 20 copies/ml (range 20-331). Except for the participant who discontinued 1HP because of allergic reactions, none of the participants had relevant symptoms or increases of the cytokine levels assessed between baseline and days 15 and 29 of 1HP. CONCLUSIONS: BIC/FTC/TAF in combination with 1HP was well tolerated with a high completion rate. BIC trough plasma concentrations were significantly decreased with concurrent use of 1HP among PLWH with LTBI. While transient viral blips were observed during 1HP without causing subsequent treatment failure, such combination should be applied with caution.

The Efficacy of Chitosan Hemostatic Pad on Hemostatic Function in Patients Undergoing Cardiac Catheterization: A Systematic Review and Meta-Analysis.

BACKGROUND: Chitin is a nitrogen-containing polysaccharide that can promote wound healing and stop bleeding. This paper investigates the effects of the addition of a chitin hemostatic patch on the time to arterial hemostasis, bleeding time, and reduction of the risk of bleeding and hematoma in patients undergoing cardiac catheterization. METHODS: Databases were searched for published clinical studies. The subjects were patients who received cardiac catheterization and had a chitin hemostatic patch added at the site of arterial puncture, while the control group received routine hemostatic treatment. The research quality was evaluated using the Cochrane risk-of-bias tool, version 2.0, and the meta-analysis was carried out using RevMan software. RESULTS: After searching literature databases, five randomized controlled trials were retrieved and included in the meta-analysis. The results showed that adding a chitin hemostatic patch could shorten the time to arterial hemostasis in patients, who received cardiac catheterization (Std. Mean Difference, -0.58; P < .001). In the subgroup analysis, the grouped effect of the chitin hemostatic patch on the bleeding time showed that the bleeding time was not significantly shortened after adding a chitin hemostatic patch in patients in the experimental group (RR, 0.78). At the same time, this measure did not significantly reduce the risk of arterial bleeding (RR, 0.49) or hematoma (RR, 0.73). CONCLUSIONS: The results of the meta-analysis showed that adding a chitin hemostatic patch at the site of arterial puncture in patients undergoing cardiac catheterization significantly reduced the time to hemostasis, but did not significantly reduce the incidence of bleeding and hematoma.

Acute HIV infection with presentations mimicking acalculous cholecystitis: A case report.

RATIONALE: Acute retroviral syndrome is the symptomatic presentation of acute human immunodeficiency virus (HIV) infection, which often manifests as a self-limited infectious mononucleosis-like syndrome and occurs 2 to 6 weeks after exposure to HIV. Atypical manifestations including hepatitis, meningitis, or hemophagocytic lymphohistiocytosis have been reported. However, manifestations of acute acalculous cholecystitis during acute HIV infection are rarely reported. PATIENT CONCERNS: A 30-year-old man with nausea and loose stools, followed by fever and abdominal pain at the right upper quadrant for 10 days. DIAGNOSIS: Acute retroviral syndrome, complicated with acute acalculous cholecystitis. INTERVENTIONS: Percutaneous transhepatic gallbladder drainage was performed and treatment with co-formulated bictegravir/emtricitabine/tenofovir alafenamide was initiated upon HIV diagnosis. OUTCOMES: The patient's symptoms improved after the drainage. The levels of liver enzyme including aspartate transaminase alanine aminotransferase decreased to a level within normal limits 1 month after initiation of antiretroviral therapy. CONCLUSION: Acalculous cholecystitis in combination with acute hepatitis could be manifestations of acute HIV infection. For individuals at risk of acquiring HIV infection who present with manifestations of acute acalculous cholecystitis, HIV testing should be considered.

Spiritual well-being of patients with chronic renal failure: A cross-sectional study.

AIMS: The study aimed to investigate the relationship among physical symptom distress, sleep quality, depression and spiritual well-being of patients with chronic renal failure (CRF) and analyse the predictors of the spiritual well-being. DESIGN: A cross-sectional study. METHODS: A total of 188 patients were selected. The collection tools were the Physical Symptom Distress Scale, the Chinese version of PSQI, the Geriatric Depression Scale and the Spiritual Well-Being Scale. Hierarchical regression analysis was conducted using SPSS 20.0. RESULTS: Patients with different treatments exhibited significantly different physical symptom distress. Furthermore, spiritual well-being was significantly negatively correlated with physical symptom distress, poor sleep disturbances and depression. After controlling for the variables, sleep quality and haemodialysis treatment were the key predictors of spiritual well-being. CONCLUSION: To achieve holistic caregiving for patients' physiological, psychological and spiritual health, Nurses should evaluate patients' symptom distress and depression when providing care for these patients to enhance their spiritual well-being.

Life satisfaction and emotional distress in people living with type 2 diabetes mellitus: The mediating effect of cognitive function.

AIMS AND OBJECTIVES: To explore the relationships among emotional distress, cognitive function and life satisfaction in people living with type 2 diabetes mellitus (T2DM), and to verify the mediating role of cognitive function. BACKGROUND: People with T2DM face cognitive decline caused by age and disease complications. Emotional distress will reduce their life satisfaction, and cognitive function will also affect the life satisfaction, but whether cognitive function mediates the effect of emotional distress on life satisfaction has not been verified. DESIGN: A cross-sectional study. METHODS: A total of 200 people living with T2DM in the community by convenience sampling were enrolled from November-December 2018. Data collection involved a demographic and disease characteristic questionnaire, Problem Areas in Diabetes Scale, Subjective and Objective Cognitive Function Evaluation and Life Satisfaction Questionnaire. Data analysis included descriptive statistics and structural equation modelling. This report followed the STROBE guideline. RESULTS: The emotional distress and subjective memory complaints of cognitive function had a significant positive correlation, while both emotional distress and cognitive function showed significant negative correlations with life satisfaction. In addition, cognitive function completely mediated the relationship between emotional distress and life satisfaction. CONCLUSION: The cognitive function played a mediating role in life satisfaction and explains how emotional distress affects life satisfaction of people with T2DM. Therefore, it is suggested that diabetes nurses should early identify the decline of cognitive function, and to intervene at an early stage. RELEVANCE TO CLINICAL PRACTICE: This study provides opinions on the mediating factors of cognitive function. Coping strategies and supporting resources to help the T2DM people to improve their life satisfaction are suggested.

Development of an Automated Optical Inspection System for Rapidly and Precisely Measuring Dimensions of Embedded Microchannel Structures in Transparent Bonded Chips.

This study aimed to develop an automated optical inspection (AOI) system that can rapidly and precisely measure the dimensions of microchannels embedded inside a transparent polymeric substrate, and can eventually be used on the production line of a factory. The AOI system is constructed based on Snell's law. The concept holds that, when light travels through two transparent media (air and the microfluidic chip transparent material), by capturing the parallel refracted light from a light source that went through the microchannel using a camera with a telecentric lens, the image can be analyzed using formulas derived from Snell's law to measure the dimensions of the microchannel cross-section. Through the NI LabVIEW 2018 SP1 programming interface, we programmed this system to automatically analyze the captured image and acquire all the needed data. The system then processes these data using custom-developed formulas to calculate the height and width measurements of the microchannel cross-sections and presents the results on the human-machine interface (HMI). In this study, a single and straight microchannel with a cross-sectional area of 300 µm × 300 µm and length of 44 mm was micromachined and sealed with another polymeric substrate by a solvent bonding method for experimentations. With this system, 45 cross-sectional areas along the straight microchannel were measured within 20 s, and experiment results showed that the average measured error was less than 2%.

Impact of high plasma concentrations of linezolid in Taiwanese adult patients- therapeutic drug monitoring in improving adverse drug reactions.

BACKGROUND: Previous studies have shown that the development of thrombocytopenia was associated with the elevated plasma concentration of linezolid, but little is known about the relationship between other uncommon adverse drug reactions (ADRs) and plasma concentration. The appropriate dosing adjustment has remained controversial. This prospective observational study was conducted to investigate the association between the plasma concentration of linezolid, ADRs, and clinical outcomes. METHODS: Adult patients on linezolid treatment undergoing at least one therapeutic drug monitoring (TDM) were enrolled. The association between linezolid concentrations and ADRs was examined by multivariate Cox regression model. Predictors of linezolid concentrations was determined by linear regression model. The cut-off point of linezolid concentration and the effect of dosing adjustments based on TDM was also explored. RESULTS: Of 50 patients enrolled in the study, plasma concentrations were 1.5-3 times higher than what was described in the prescribing information. The median minimum concentration (Cmin) was significantly higher in patients with thrombocytopenia compared to patients without thrombocytopenia (13.0 vs. 7.2 µg/mL, P = 0.0273), and a higher median maximum concentration was also observed in patients with lactic acidosis (33.0 vs. 27.5 µg/mL, P = 0.0420). The Cmin was elevated in patients with advanced age and severely impaired renal function. Dosing adjustment tailored by early TDM with the upper limit of Cmin 9 µg/mL may improve platelet counts. CONCLUSION: Elevated linezolid concentrations were associated with thrombocytopenia and lactic acidosis. TDM-guided dosing adjustment could be considered as a pragmatic way to mitigate thrombocytopenia.

Using the PCI-IS Method to Simultaneously Estimate Blood Volume and Quantify Nonvitamin K Antagonist Oral Anticoagulant Concentrations in Dried Blood Spots.

Nonvitamin K antagonist oral anticoagulants (NOACs) have emerged as the preferred choice for the treatment of atrial fibrillation (AF). The establishment of a therapeutic range to minimize bleeding and thrombosis is important for personalized treatment of NOACs. The importance of dried blood spots (DBSs) has increased in medical care. An efficient and effective DBS analytical method could facilitate the concentration management of NOACs. The postcolumn infused internal standard (PCI-IS) method was applied to estimate spot volume and quantify dabigatran, rivaroxaban, and apixaban concentrations on DBS cards. The extraction solvent contented 0.1% formic acid and 70% ACN with a successive extraction procedure. Paired DBS and plasma samples from patients undergoing NOAC therapy (n = 269) were used to calculate conversion factors. [13C6]-Rivaroxaban was selected as the PCI-IS. The quantification accuracy for the three NOACs was within 88.9-104.3%. The RSDs of the repeatability and intermediate precision were below 10%. The obtained conversion factors of DBS to plasma concentrations of dabigatran, apixaban, and rivaroxaban were 1.81, 1.59, and 1.31, respectively. Bland-Altman analysis showed that the % differences between predicted and measured plasma concentrations were within a bias of ±20%. The result showed that PCI-IS was an accurate and efficient LC-MS/MS method to simultaneously estimate blood volume and NOAC concentrations on DBS cards. The stability results revealed that the DBS sampling strategy could improve compound stability. The developed method offers a new strategy for the therapeutic drug monitoring of NOACs and may improve the safe use of these drugs.

Effectiveness of half-a-tablet efavirenz plus 2 nucleos(t)ide reverse-transcriptase inhibitors as maintenance therapy with the guidance of therapeutic drug monitoring among virologically suppressed HIV-positive patients: A prospective study.

BACKGROUND: Optimal efavirenz (EFV) dose that minimizes adverse effects while maintaining efficacy has yet to be elucidated. With a therapeutic drug monitoring (TDM)-guided strategy, we assessed the effectiveness of half-a-tablet EFV plus 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) in HIV-infected Taiwanese who had achieved viral suppression with full-dose (600 mg) EFV. METHODS: HIV-infected adults receiving EFV-containing regimens who had plasma mid-dose EFV concentration (C12) ≥2.0 mg/L and had plasma HIV RNA load (PVL) <200 copies/mL were enrolled in this single-arm, open-label study by reducing EFV to half-a-tablet daily. The primary endpoint was PVL <50 copies/ml in an intention-to-treat (ITT) population at week 48. The secondary endpoints were the plasma EFV C12, the proportion of patients with plasma EFV C12 <1.0 mg/L, PVL <50 copies/ml at week 96 and week 144. RESULTS: Between April 2013 and September 2016, 203 patients (93.6% male; median age, 39.0 years) were enrolled. The median EFV C12 before switch was 2.80 mg/L (interquartile range (IQR), 2.41-3.73), which decreased to 1.59 mg/L (IQR, 1.23-2.03) after switch with a reduction of 47.4% (IQR, 38.3-55.5%). In ITT analysis, 93.6%, 92.3% and 87.3% of the patients achieved PVL <50 copies/ml at weeks 48, 96 and 144, respectively. More than 70% of the patients reported alleviation of EFV-associated adverse effects following the switch. CONCLUSION: Under the guidance of TDM, switch to half-a-tablet EFV plus 2 NRTIs is effective in maintaining viral suppression in HIV-infected Taiwanese with EFV C12 ≥ 2.0 mg/L.

Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI.

Weekly rifapentine and isoniazid therapy (known as 3HP) for latent tuberculosis infection (LTBI) is increasingly used, but systemic drug reactions (SDR) remain a major concern. Methods: We prospectively recruited two LTBI cohorts who received the 3HP regimen. In the single-nucleotide polymorphism (SNP) cohort, we collected clinical information of SDRs and examined the NAT2, CYP2E1, and AADAC SNPs. In the pharmacokinetic (PK) cohort, we measured plasma drug and metabolite levels at 6 and 24 h after 3HP administration. The generalised estimating equation model was used to identify the factors associated with SDRs. Candidate SNPs predicting SDRs were validated in the PK cohort. A total of 177 participants were recruited into the SNP cohort and 129 into the PK cohort, with 14 (8%) and 13 (10%) in these two cohorts developing SDRs, respectively. In the SNP cohort, NAT2 rs1041983 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 7.00 [2.03-24.1]) and CYP2E1 rs2070673 (AA vs. TT+TA, OR [95% CI]: 3.50 [1.02-12.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 h after 3HP administration (OR [95% CI]: 1.61 [1.15-2.25]) was associated with SDRs. Additionally, the association between the NAT2 SNP and SDRs was validated in the PK cohort (rs1041983 TT vs. CC+CT, OR [95% CI]: 4.43 [1.30-15.1]). Conclusions: Isoniazid played a role in the development of 3HP-related SDRs. This could provide insight for further design of a more optimal regimen for latent TB infection.

Evaluation and Optimization of Sample Handling Methods for Quantification of Short-Chain Fatty Acids in Human Fecal Samples by GC-MS.

The gut microbiota has attracted a great deal of interest in recent years due to its association with many diseases. Short-chain fatty acids (SCFAs), the end products of dietary fiber fermentation by the intestinal microbiota, are among the most frequently discussed gut metabolites. As the sample handling method greatly affects the integrity of data, this study investigated the most important parameters that affect the bias of SCFA comparisons in human fecal studies. An accurate gas chromatography-mass spectrometry (GC-MS) method was first established and validated for quantifying six SCFAs, including acetic, propionic, butyric, isobutyric, isovaleric, and valeric acids. To remove interfering species, we used butanol to extract SCFAs from acidified fecal suspensions. The validated quantification method was then applied to evaluate fecal sample handling protocols. We found that lyophilization of fecal samples can not only minimize bias due to the water content but also provide better stability of SCFAs. Six SCFAs were stable and that their recoveries were higher than 90% after lyophilization. Lyophilization of a large fecal sample is extremely time-consuming, and 1 g of fecal sample is suggested for lyophilization to minimize sampling bias. The interindividual difference was significantly higher than the intra-individual difference when using 1 g of fecal sample to study SCFAs. Finally, an effective protocol from sample collection to GC-MS analysis was proposed. As SCFAs have been shown to play an important role in health maintenance and disease development, the proposed protocol is anticipated to be applicable to clinical studies to delineate the biological functions of each SCFA.

Identification of potential sphingomyelin markers for the estimation of hematocrit in dried blood spots via a lipidomic strategy.

The dried blood spot (DBS) strategy is a convenient and minimally invasive approach to blood sampling. Due to its various advantages, this sampling technique has drawn significant attention in recent years. Hematocrit (HCT)-associated bias is one of the main obstacles that hinder wider DBS application in clinical practice. An accurate HCT estimation method could help calibrate HCT-associated bias and improve the quantification accuracy. This study used a lipidomics profiling strategy to identify HCT estimation markers using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), which provided advantages including the potential for the simultaneous measurements of target drug and HCT values. Three sphingomyelins (SMs), specifically SM 44:1, SM 44:2, and SM 44:3, were identified as potential HCT estimation markers. The proposed estimation markers were applied to 54 DBS samples collected from two sets of patients. The analytical results revealed that the estimation errors for all of the HCT values were less than 20%, which demonstrated the feasibility of using the proposed markers to estimate the HCT values for the DBS samples. We suggest that the proposed HCT markers could provide a new strategy for HCT estimation with higher convenience using an LC-ESI-MS platform, which could contribute to wider DBS applications in clinical practice. We also demonstrated that lipidomics is a promising strategy for the discovery of HCT estimation markers in DBS samples.