Skin-Interfaced Wearable Sweat Sensors for Precision Medicine.

Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, materials science, and electrochemistry have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extraction and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clinical value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines state-of-the-art technologies and research that strive to bridge these gaps. The physiology of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Additionally, design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extraction to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.

Mobile Health Intervention Contents and Their Effects on the Healthcare of Patients with Left Ventricular Assist Devices: An Integrative Review.

Self-care in daily life is important for patients with a left ventricular assist device. Mobile health interventions that use an application, the cloud, or telemonitoring enable active health management. This study reviewed the literature on the contents of mobile health interventions for patients with left ventricular assist devices and their effects. We searched four electronic databases (CINAHL, Cochrane Library, EMBASE, and MEDLINE) and reference lists in May 2022. The search terms consisted of "heart-assist devices" and "residence characteristics," combined with "mobile applications," "telemonitoring," "medical informatics applications," "cell*," "app*," "smartphone," and "cloud." In total, seven studies were included in the review. Mobile health interventions included (1) self-management contents and (2) interactions between patient and healthcare providers. The mobile health device and patient's health management were evaluated as a measure of the effect. This review provides a unique understanding for leveraging mobile health interventions as an effective approach to improve healthcare among patients with left ventricular assist devices. Future mobile health intervention strategies targeting these patients should fully consider the patient's perspective. Furthermore, they should be designed and applied to help with long-term health management, accompanied by an evaluation of their effectiveness on self-care improvement.

Safety, Tolerability, Pharmacokinetics, and Metabolism of Telacebec (Q203) for the Treatment of Tuberculosis: a Randomized, Placebo-Controlled, Multiple Ascending Dose Phase 1B Trial.

A phase 1b, randomized, placebo-controlled, double-blind, multiple ascending dose study (NCT02858973) was conducted to assess the safety, tolerability, and pharmacokinetics of the new antituberculosis agent telacebec (Q203). A total of 47 healthy adult subjects entered the study; 36 received telacebec, and 11 received placebo. Telacebec at doses of 20, 50, 100, 160, 250, and 320 mg was orally administered once daily with a standard meal for 14 days. Multiple oral doses of telacebec up to 320 mg daily for 14 days appeared to be safe and well tolerated by healthy adult subjects in this study. There were no deaths, serious adverse events, or subject discontinuations due to adverse events. Following oral doses of telacebec, the overall extent (AUCτ) and peak (Cmax) exposures of telacebec increased from 538.94 to 10,098.47 ng·h/mL and from 76.43 to 1502.33 ng/mL, respectively, with increasing telacebec doses from 20 mg to 320 mg. A steady state was achieved for plasma telacebec by day 12, and there was 1.9- to 3.1-fold accumulation in the extent of telacebec exposure after daily doses for 14 days. Analysis of plasma samples from the participants indicated that telacebec was the primary circulating entity with no significant metabolites. Three potential metabolites of telacebec have been identified, which may be relatively minimal compared to the parent drug. Consistent with findings from preclinical and previous single-dose clinical studies, these results also support the potential of telacebec for further development as a safe and effective agent for the treatment of tuberculosis.

Parents' lived experiences of losing adolescent children in the Korean Ferry Sewol disaster: Lessons through a qualitative meta-synthesis.

This study meta-synthesized qualitative studies on the parents' experiences of losing their adolescent children due to the human-made disaster, Ferry Sewol disaster in Korea, 2014. Five Korean and five international electronic databases were searched. Twenty-one studies were selected and critically appraised. Thematic analysis was employed. Four themes (with 10 subthemes) were derived: screaming in excruciating pain at the unbelievable deaths of children, family love evolving amidst pain and deepening into higher value, relationships collapsed and reformed while experiencing various social perspectives, and transitioning from a life of holding on to a life of progress. Bereaved parents experience psychological, physical, social pain for a long time, but gradually tried not to waste their children's death, forming new values and life goals. There is pressing need to devise sustained recovery strategies that account for distinct characteristics and needs of affected population groups.

Is HOXA5 a Novel Prognostic Biomarker for Uterine Corpus Endometrioid Adenocarcinoma?

Endometrial cancer (EC) is one of the most pervasive malignancies in females worldwide. HOXA5 is a member of the homeobox (HOX) family and encodes the HOXA5 protein. HOXA5 is associated with various cancers; however, its association with EC remains unclear. This study aimed to determine the association between HOXA5 gene expression and the prognosis of endometrioid adenocarcinoma, a subtype of EC (EAEC). Microarray data of HOXA5 were collected from the Gene Expression Omnibus datasets, consisting of 79 samples from GSE17025 and 20 samples from GSE29981. RNA-sequencing, clinical, and survival data on EC were obtained from The Cancer Genome Atlas cohort. Survival analysis revealed that HOXA5 overexpression was associated with poor overall survival in patients with EAEC (p = 0.044, HR = 1.832, 95% CI = 1.006-3.334). Cox regression analysis revealed that HOXA5 was an independent risk factor for poor prognosis in EAEC. The overexpression of HOXA5 was associated with a higher histological grade of EAEC, and it was also associated with TP53 mutation or the high copy number of EC. Our findings suggest the potential of HOXA5 as a novel biomarker for predicting poor survival outcomes in patients with EAEC.

Consumer Involvement in Psychiatric Nursing Education: An Analysis of South Korean Students' Experiences.

This study examined the experiences of South Korean nursing students in a psychiatric nursing class with consumer involvement. Data on 98 nursing students were collected in June 2021 and analysed using content analysis of participants' journals. Our qualitative study design adheres to the COREQ checklist for qualitative studies. Four main categories and subcategories were identified: (1) reflection, (2) learning, (3) preparation for the future, and (4) requirements. The findings demonstrated that applying consumer involvement to psychiatric nursing education is an innovative and effective strategy to correct negative prejudices among nursing students against people with mental illness.

Challenges Experienced by Family Caregivers of Individuals With Severe Mental Illness During the COVID-19 Pandemic: An Integrative Review.

Family caregivers of individuals with severe mental illness (SMI) faced increasing challenges during the coronavirus disease 2019 (COVID-19) pandemic; however, empirical evidence on the general challenges they experienced is lacking. Thus, the purpose of the current integrative review was to explore family caregivers' challenges during the COVID-19 pandemic. A total of nine relevant studies were included. Family caregivers experienced greater care burdens, physical and mental health problems, and limited access to health care services due to the pandemic. It is necessary to develop mental health policies and appropriate interventions to help individuals with mental illness and their family caregivers in the event of future crises. [Journal of Psychosocial Nursing and Mental Health Services, 61(7), 21-28.].

Safety, Tolerability, and Pharmacokinetics of Telacebec (Q203), a New Antituberculosis Agent, in Healthy Subjects.

Telacebec (Q203) is a potent drug candidate under clinical development for the treatment of drug-naïve and drug-resistant tuberculosis. The first-in-human randomized, placebo-controlled, double-blind, dose-escalation Phase 1A trial (Q203-TB-PI-US001) was conducted to evaluate the safety, tolerability, and pharmacokinetics of telacebec. A total of 56 normal, healthy, male and female subjects (42 active and 14 placebo) were enrolled in the study. The doses of telacebec were 10 mg (Cohort 1), 30 mg (Cohort 2), 50 mg (Cohort 3), 100 mg (Cohort 4), 200 mg (Cohort 5), 400 mg (Cohort 6), and 800 mg (Cohort 7) in a fasted state. Subjects participating in Cohort 4 were also enrolled in Cohort 8 to investigate the food effect on the pharmacokinetics of telacebec after a high-fat meal. In all subjects dosed with telacebec (10 to 800 mg), telacebec was well tolerated and did not lead to any significant or serious adverse events. Following a single oral administration of telacebec (10 to 800 mg), telacebec plasma concentration reached the maximal plasma concentration (Cmax) in average 2.0 to 3.5 h and showed multi-exponential decline thereafter. The area under the plasma concentration versus time curve (AUC) was approximately dose-proportional. A significant increase in plasma concentrations was observed in the fed condition compared with the fasted condition with the geometric mean ratio of 3.93 for Cmax. Moderate delay in Tmax (4.5 h) was also observed in the fed condition. These results, combined with the demonstrated activity against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis, support further investigation of telacebec for the treatment of tuberculosis.

Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis.

Nafamostat, a synthetic serine protease inhibitor, has been used for the treatment of inflammatory diseases such as pancreatitis. Recently, an increasing number of studies have shown the promising antiviral effects of nafamostat for the treatment of coronavirus disease-19 (COVID-19). This study aimed to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and to characterize the pharmacokinetics of nafamostat in rats. Nafamostat in the rat plasma was extracted by solid phase extraction, and 13C6-nafamostat was used as an internal standard. The quantification limit of nafamostat in the rat plasma was 0.5 ng/mL. The LC-MS/MS method was fully validated and applied to characterize the pharmacokinetics of nafamostat in rats. Following intravenous injection (2 mg/kg), nafamostat in the plasma showed a multiexponential decline with an average elimination half-life (t1/2) of 1.39 h. Following oral administration of nafamostat solutions (20 mg/kg) in 10% dimethyl sulfoxide (DMSO) and in 10% DMSO with 10% Tween 80, nafamostat was rapidly absorbed, and the average oral bioavailability was 0.95% and 1.59%, respectively. The LC-MS/MS method and the pharmacokinetic information of nafamostat could be helpful for the further preclinical and clinical studies of nafamostat.

Frontline nurses' caring experiences in COVID-19 units: A qualitative study.

AIM: Exploring nurses' caring and communication experiences in COVID-19 units. BACKGROUND: Frontline nurses play a critical role in providing 24-h bedside nursing care to COVID-19 patients. An in-depth understanding of frontline nurses' lived experiences is necessary to establish appropriate nursing strategies during crises, such as the COVID-19 pandemic. METHODS: Qualitative descriptive design with content analysis. RESULTS: Fifteen nurses were interviewed, and three themes were identified: central role of therapeutic communication, compassion that deepens naturally and expansion of professionalism in nursing. CONCLUSION: The nurses proactively provided care for COVID-19 patients, and they acknowledged and accepted their roles in protecting the lives and ensuring the health of their patients daily. The nurses' experiences in COVID-19 units served as an opportunity for ruminating and rediscovering the meaning of nursing. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital policymakers and nurse managers should strive to resolve the communication-related challenges faced by nurses. Standardizing and implementing effective communication strategies should be considered in nursing management.

Role of soft-gel substrates on bouncing-merging transition in drop impact on a liquid film.

Liquid droplets impacting on liquid films is common in many industrial and natural processes. It is crucial to understand the impact of droplets on a liquid film resting on soft deformable substrates in some of the applications including 3D printing of engineering structures, prosthetic implants and tissue engineering. By recognizing the practical relevance of soft-substrates, we present an experimental investigation to assess the role of deformable substrates on bouncing-to-merging transition in droplet impact on the liquid film. First, we prepared polyacrylamide (PAAm) soft-gel substrates with various "softness" (i.e., Young's modulus) by modulating the concentration of a crosslinker, N,N-methylene-bis-acrylamide (BIS). We found that the Young's modulus of PAAm initially increases with the concentration of crosslinker, and subsequently becomes almost constant due to inhomogeneity of crosslinking. Next, through the experiments of droplet impact on the liquid film resting on soft substrates with different Young's moduli, we observe that the early merging and corresponding bouncing-to-merging transitional boundaries remain unaffected by the "softness" since such merging occurs further away from the substrate. However, the late merging, which appears during the retraction process of the deformed droplet, occurs relatively close to the substrate, and hence is found to be significantly affected by its "softness". A scaling analysis is presented to quantify the role of change in Young's modulus of the substrate on late merging, which is supported by the experimental data.

3D-Printed Gastroretentive Sustained Release Drug Delivery System by Applying Design of Experiment Approach.

This study aimed to develop a novel oral drug delivery system for gastroretentive sustained drug release by using a capsular device. A capsular device that can control drug release rates from the inner immediate release (IR) tablet while floating in the gastric fluid was fabricated and printed by a fused deposition modeling 3D printer. A commercial IR tablet of baclofen was inserted into the capsular device. The structure of the capsular device was optimized by applying a design of experiment approach to achieve sustained release of a drug while maintaining sufficient buoyancy. The 2-level factorial design was used to identify the optimal sustained release with three control factors: size, number, and height of drug-releasing holes of the capsular device. The drug delivery system was buoyant for more than 24 h and the average time to reach 80% dissolution (T80) was 1.7-6.7 h by varying the control factors. The effects of the different control factors on the response factor, T80, were predicted by using the equation of best fit. Finally, drug delivery systems with predetermined release rates were prepared with a mean prediction error ≤ 15.3%. This approach holds great promise to develop various controlled release drug delivery systems.

Reduced variability in tacrolimus pharmacokinetics following intramuscular injection compared to oral administration in cynomolgus monkeys: Investigating optimal dosing regimens.

Tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. However, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. Therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (IM) injection and to determine the optimal IM dosing regimens in primate models. Six male cynomolgus monkeys (Macaca fascicularis) were used in the study. Doses of 0.1 mg/kg and 5 mg were administered via IM injection and oral administration, respectively, once to determine single-dose pharmacokinetics and once daily for 5 days to determine multiple-dose pharmacokinetics. According to pharmacokinetic model estimates, the inter- and intra-individual variabilities in bioavailability following IM injection were remarkably reduced compared with those following oral administration. Monte Carlo simulations revealed that Cpeak, Ctrough and AUC would also have less variability following IM injection compared with oral administration. In this study, we found that the pharmacokinetic characteristics of tacrolimus were more constant following IM injection compared with oral administration. These results suggest that IM injection can be an alternative route of administration fin non-human primate model studies.

Supervising pharmacists' opinions about pharmacy technicians as immunizers.

OBJECTIVES: To determine the opinions of pharmacists who supervise immunizing pharmacy technicians regarding initial trust of immunizing technicians, perceived quality of the training program, need for additional on-the-job training, frequency of technician utilization, and recommendations for other pharmacists who are considering implementation of an immunizing technician. SETTING: Albertsons pharmacies located in the state of Idaho in May 2017. PRACTICE DESCRIPTION AND INNOVATION: Qualitative descriptive study of semistructured key informant interviews with Idaho pharmacists who currently supervise a pharmacy technician trained to administer immunizations. EVALUATION: Informant interviews were recorded, transcribed, and coded to evaluate key themes. RESULTS: Nineteen individual pharmacist interviews were conducted at different Albertsons pharmacy locations in the state of Idaho. Pharmacists in this study felt that their immunizing technicians were properly trained to administer immunizations, capable of giving immunizations, and empowered by their new role within the pharmacy. Participants expressed challenges with initial comfort in allowing a technician to immunize, support of this new advanced technician role, and additional on-the-job training for individual technicians. Findings also included a pharmacist-perceived increase in vaccination rates and recommendation for other technicians to be trained to administer immunizations. CONCLUSION: Community pharmacists who supervise pharmacy technicians trained to administer immunizations were receptive to this new advanced technician role. Pharmacists' opinions revealed that working with newly trained immunizing pharmacy technicians has not only positively affected the morale of their team, but can help to increase the number of vaccinations given by the pharmacy. Understanding pharmacist perceptions about technicians as immunizers may lead to regulation changes and adoption of this advanced technician role.

Liquid Chromatography-Tandem Mass Spectrometry of Desoxo-Narchinol a and Its Pharmacokinetics and Oral Bioavailability in Rats and Mice.

Desoxo-narchinol A is one of the major active constituents from Nardostachys jatamansi, which has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidant, and anticonvulsant activity. A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of desoxo-narchinol A in two different biological matrices, i.e., rat plasma and mouse plasma, using sildenafil as an internal standard (IS). The method involved simple protein precipitation with acetonitrile and the analyte was separated by gradient elution using 100% acetonitrile and 0.1% formic acid in water as a mobile phase. The MS detection was performed with a turbo electrospray in positive ion mode. The lower limit of quantification was 10 ng/mL in both rat and mouse plasma. Intra- and inter-day accuracies were in the ranges of 97.23-104.54% in the rat plasma and 95.90-110.11% in the mouse plasma. The precisions were within 8.65% and 6.46% in the rat and mouse plasma, respectively. The method was applied to examine the pharmacokinetics of desoxo-narchinol A, and the oral bioavailability of desoxo-narchinol A was 18.1% in rats and 28.4% in mice. The present results may be useful for further preclinical and clinical studies of desoxo-narchinol A.

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells.

Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

Effects of Phytochemical P-Glycoprotein Modulators on the Pharmacokinetics and Tissue Distribution of Doxorubicin in Mice.

Pungent spice constituents such as piperine, capsaicin and [6]-gingerol consumed via daily diet or traditional Chinese medicine, have been reported to possess various pharmacological activities. These dietary phytochemicals have also been reported to inhibit P-glycoprotein (P-gp) in vitro and act as an alternative to synthetic P-gp modulators. However, the in vivo effects on P-gp inhibition are currently unknown. This study aimed to test the hypothesis that phytochemical P-gp inhibitors, i.e., piperine, capsaicin and [6]-gingerol, modulate the in vivo tissue distribution of doxorubicin, a representative P-gp substrate. Mice were divided into four groups and each group was pretreated with intraperitoneal injections of control vehicle, piperine, capsaicin, or [6]-gingerol and doxorubicin (1 mg/kg) was administered via the penile vein. The concentrations of the phytochemicals and doxorubicin in the plasma and tissues were determined by LC-MS/MS. The overall plasma concentration-time profiles of doxorubicin were not significantly affected by piperine, capsaicin, or [6]-gingerol. In contrast, doxorubicin accumulation was observed in tissues pretreated with piperine or capsaicin. The tissue to plasma partition coefficients, Kp, for the liver and kidney were higher in the piperine-pretreated group, while the Kp for kidney, brain and liver were higher in the capsaicin-pretreated group. [6]-Gingerol did not affect doxorubicin tissue distribution. The data demonstrated that the phytochemicals modulated doxorubicin tissue distribution, which suggested their potential to induce food-drug interactions and act as a strategy for the delivery of P-gp substrate drugs to target tissues and tumors.

Development of a Physiologically Relevant Population Pharmacokinetic in Vitro-in Vivo Correlation Approach for Designing Extended-Release Oral Dosage Formulation.

Establishing a level A in vitro-in vivo correlation (IVIVC) for a drug with complex absorption kinetics is challenging. The objective of the present study was to develop an IVIVC approach based on population pharmacokinetic (POP-PK) modeling that incorporated physiologically relevant absorption kinetics. To prepare three extended release (ER) tablets of loxoprofen, three types of hydroxypropyl methylcellulose (HPMC 100, 4000, and 15000 cps) were used as drug release modifiers, while lactose and magnesium stearate were used as the diluent and lubricant, respectively. An in vitro dissolution test in various pH conditions showed that loxoprofen dissolution was faster at higher pH. The in vivo pharmacokinetics of loxoprofen was assessed following oral administration of the different loxoprofen formulations to Beagle dogs (n = 22 in total). Secondary peaks or shoulders were observed in many of the individual plasma concentration vs time profiles after ER tablet administration, which may result from secondary absorption in the intestine due to a dissolution rate increase under intestinal pH compared to that observed at stomach pH. In addition, in vivo oral bioavailability was found to decrease with prolonged drug dissolution, indicating site-specific absorption. Based on the in vitro dissolution and in vivo absorption data, a POP-PK IVIVC model was developed using S-ADAPT software. pH-dependent biphasic dissolution kinetics, described using modified Michaelis-Menten kinetics with varying Vmax, and site-specific absorption, modeled using a changeable absorbed fraction parameter, were applied to the POP-PK IVIVC model. To experimentally determine the biphasic dissolution profiles of the ER tablets, another in vitro dissolution test was conducted by switching dissolution medium pH based on an in vivo estimate of gastric emptying time. The model estimated, using linear regression, that in vivo initial maximum dissolution rate (Vmax(0)in vivo) was highly correlated (r2 > 0.998) with in vitro (Vmax(0)in vitro), indicating that in vivo dissolution profiles obtained from POP-PK modeling could be converted to in vitro dissolution profiles and vice versa. Monte Carlo simulations were performed for model validation, and prediction errors for Cmax and AUC were all within the acceptable range (90 to 110%) according to the FDA guidelines. The developed model was successfully applied for the prediction of in vivo pharmacokinetics of a loxoprofen double-layered tablet using the in vitro dissolution profile. In conclusion, a level A IVIVC approach was developed and validated using population modeling that accounted for pH-dependent dissolution and site-specific absorption. Excellent correlations were observed between in vitro and in vivo dissolution profiles. This new approach holds great promise for the establishment of IVIVCs for drug and formulation development where absorption kinetics strongly depend on complex physiologically absorption processes.

Comparison of Growth Performance of the BacT/ALERT VIRTUO and BACTEC FX Blood Culture Systems Under Simulated Bloodstream Infection Conditions.

BACKGROUND: We evaluated growth performance of the BacT/ALERT VIRTUO and the BACTEC FX blood culture (BC) systems based on recovery rate and time to detect microorganisms under simulated bloodstream infection conditions. METHODS: Three expected concentrations of 125, 30, and 5 CFU/mL of eighteen reference microorganisms were diluted with 5 mL blood for adult aerobic/anaerobic culture and with 3 mL for pediatric aerobic culture and inoculated, and each of three BC bottles were loaded into the two BC systems. RESULTS: A total of 405 comparative bottles were analyzed in this study. The percent agreement between the BacT/ ALERT VIRTUO and BACTEC FX systems after comparing the positive results was 96.8% (392/405). The BacT/ ALERT VIRTUO and BACTEC FX systems yielded 100% positive signals at 125 and 30 CFU/mL, whereas there were 5.2% (7/135) and 8.1% (11/135) false-negative results at 5 CFU/mL, respectively. No statistical difference in recovery rate based on the overall concentration of microorganisms was observed between the two BC systems (p = 0.329). No statistical difference in time to detection (TTD) was observed between the two BC systems based on the overall concentration of microorganisms (p = 0.067). Inter-instrument comparisons of TTD resulted in a good correlation (r = 0.947) for all inoculated bottles. CONCLUSIONS: The BacT/ALERT VIRTUO showed similar recovery rate and TTD of microorganisms, compared to BACTEC FX BC system. Due to its versatility to accommodate a higher workload through automated loading and unloading of BC bottles with faster detection of pathogens from bloodstream, the BacT/ALERT VIRTUO system may establish itself as a useful alternative.

Evaluation of the Three Customized MSI Panels to Improve the Detection of Microsatellite Instability in Gastric Cancer.

BACKGROUND: We designed and evaluated the suitability of three customized microsatellite instability (MSI) panels using a combination of mono- and dinucleotide markers to improve the detection of MSI status in 56 matched normal and gastric cancer specimens. METHODS: An MSI analysis was performed to optimize the panel of microsatellite markers to detect instability using two different microsatellite panels: (1) mononucleotide marker panel consisting of mononucleotide markers BAT25, BAT26, BAT40, BAT-RII, NR21, NR22, NR24, and NR27 and (2) dinucleotide marker panel containing D2S123, D5S346, D17S250, D17S261, D17S520, D18S34, and D18S58. The customized panels consisted of five, seven, or ten markers with two, three, or four mononucleotide markers, respectively, among fifteen MSI markers described above to fulfill the MSI-H and MSI-L definition based on the revised Bethesda Guidelines. The "Proposal5" panel consisted of BAT40, BAT26, D18S34, D2S123, and D17S520. "Proposal-7" consisted of "Proposal-5" with BAT25 and D18S58. "Proposal-10" consisted of "Proposal-7" with NR27, D17S250, and D17S261. RESULTS: Immunohistochemical staining for MMR protein expressions such as mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) revealed that among 56 matched specimens, 13 had defective DNA mismatch repair (MMR) proteins and 43 had proficient MMR proteins. Out of thirteen specimens with defective MMR expression, eight specimens (62%, 8/13) were classified as MSI-H with an instability at ≥ 6 markers and five (38%, 5/13) were MSIL with instability at ≤ 5 markers using all fifteen MSI markers. On the other hand, the analytical sensitivity and specificity of all three customized panels to detect MMR-deficient specimens were 92% (12/13) and 100% (43/43), respectively. In comparison, the sensitivity and specificity of the Bethesda and QMR panels were 62% (8/13) and 100% (43/43). All customized panels could represent the detection of MSI-L tumors rather than the Bethesda and the QMR panels. CONCLUSIONS: The increased sensitivity to detect MSI-unstable tumors with customized panels including BAT40 and D18S34 indicates that precise MSI screening to discriminate MSI-H from MSS and MSI-L may be feasible for gastric cancer.