Effects of Sex Differences and Combined Use of Clozapine on Initial Dosage Optimization of Valproic Acid in Patients with Bipolar Disorder.

BACKGROUND: Due to the narrow therapeutic window and large pharmacokinetic variation of valproic acid (VPA), it is difficult to make an optimal dosage regimen. The present study aims to optimize the initial dosage of VPA in patients with bipolar disorder. METHODS: A total of 126 patients with bipolar disorder treated by VPA were included to construct the VPA population pharmacokinetic model retrospectively. Sex differences and combined use of clozapine were found to significantly affect VPA clearance in patients with bipolar disorder. The initial dosage of VPA was further optimized in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. RESULTS: The CL/F and V/F of VPA in patients with bipolar disorder were 11.3 L/h and 36.4 L, respectively. It was found that sex differences and combined use of clozapine significantly affected VPA clearance in patients with bipolar disorder. At the same weight, the VPA clearance rates were 1.134, 1, 1.276884, and 1.126 in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. This study further optimized the initial dosage of VPA in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. CONCLUSION: This study is the first to investigate the initial dosage optimization of VPA in patients with bipolar disorder based on sex differences and the combined use of clozapine. Male patients had higher clearance, and the recommended initial dose decreased with increasing weight, providing a reference for the precision drug use of VPA in clinical patients with bipolar disorder.

Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study.

The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.

Developing antibiotics-based strategies to efficiently enrich ammonia-oxidizing archaea from wastewater treatment plants.

The effects of five antibiotics (i.e., ampicillin, streptomycin, carbenicillin, kanamycin and tetracycline) on ammonia-oxidizing archaea (AOA) enrichment from anoxic activated sludge were investigated. The combined use of five antibiotics during 90-day cultivation could selectively inhibit nitrite-oxidizing bacteria (NOB) and ammonia-oxidizing bacteria (AOB) with AOA unaffected, as evidenced by the nitrite accumulation ratio of 100 % and the proportion of AOA in ammonia-oxidizing microbes over 91 %. The alternative use of five antibiotics was the optimal approach to screening for AOA during 348-day cultivation, which inhibited AOB growth at a level equivalent to the combined use of five antibiotics (the AOB-amoA gene decreased by over 99.90 %), further promoted AOA abundance (the much higher AOA-amoA to AOB-amoA gene copy number ratio (1453.30) than that in the groups with the combined use of five antibiotics (192.94)), eliminated bacterial adaptation to antibiotics and reduced antibiotic-resistant bacteria to form Nitrocosmicus-dominant community (42.35 % in abundance).

Combined Use of Serum N-terminal Pro-B-Type Natriuretic Peptide and Glypican-6 in the Diagnosis of Heart Failure.

OBJECTIVE: The aim of this study was to investigate the efficacy of serum glypican-6 (GPC-6) levels and the combination of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and GPC-6 in the diagnosis of heart failure (HF). METHODS: In this prospective study, patients older than 18 years of age, admitted to the emergency department of our hospital between December 2021 and April 2022, diagnosed with heart failure (patient group), and healthy volunteers with similar sociodemographic characteristics (control group) were included. The disease severity classification of the patient group was made according to the 2021 ESC guidelines, using echocardiographic findings. Serum GPC-6 and NT-ProBNP levels were measured by the enzyme-linked immunosorbent assay (ELISA) method, which determines the antigen-antibody relationship. Optimal GPC-6 and NT-ProBNP levels for the diagnosis of HF were determined by receiver operating characteristic (ROC) analysis. The patients were divided into three groups according to these levels. Group 1 consisted of patients with both markers below the cutoff values, Group 2 consisted of patients with either of these markers above the cutoff values, and Group 3 consisted of patients with both markers above the cutoff values. RESULTS: The study included 65 heart failure patients and 20 healthy volunteers. When the patient and control groups were compared in terms of serum GPC-6 and serum NT-ProBNP levels, both parameters were evaluated as significantly higher in the patient group (p=0.038 and p<0.001; respectively). In the ROC analysis, it was determined that GPC-6 indicated HF with 58.46% sensitivity and 75% specificity for an optimal cutoff value of 390 pg/ml. In the ROC analysis, it was determined that serum NT-ProBNP indicated HF with 89.23% sensitivity and 70% specificity for an optimal cutoff value of 122 pg/ml. When the groups were compared according to the rate of HF, it was found to be higher in Group 3 compared to Group 2 (97.1% vs. 70.3%, p<0.002) and Group 1 (97.1% vs. 38.5%, p<0.001). This rate was seen to be significantly higher in Group 2 compared to Group 1 (70.3% vs. 38.5%, p=0.042). CONCLUSION: The combination of GPC-6 and NT-ProBNP may help diagnose HF patients admitted to the emergency department.

Combined Use of Anti-VEGF Drugs Before and During Pars Plana Vitrectomy for Severe Proliferative Diabetic Retinopathy.

INTRODUCTION: This study aimed to evaluate the combined administration of anti-vascular endothelial growth factor (anti-VEGF) drugs before and during pars plana vitrectomy (PPV) and to explore its efficacy and safety in the treatment of patients with severe proliferative diabetic retinopathy (PDR). METHODS: This retrospective case series included consecutive patients who underwent PPV. Patients were categorized into two groups: the preoperative group was injected with anti-VEGF drugs before PPV, and the combination group was injected with anti-VEGF drugs before and during PPV. Preoperative, intraoperative, and postoperative clinical data were collected for analysis. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) and occurrence of postoperative vitreous cavity haemorrhage (POVCH). RESULTS: In total, 63 eyes of 60 patients with severe PDR were analysed. The operative duration and occurrence of intraoperative haemorrhage, iatrogenic retinal breaks, and silicone oil tamponade were similar between the two groups. The benefits on BCVA, and CRT after 1 week postoperatively, were more obvious in the combination group (P < 0.01). Combination therapy had the potential to reduce the incidence of POVCH. No ocular or systemic adverse events occurred in either group. CONCLUSIONS: The combined use of anti-VEGF drugs before and during PPV in patients with severe PDR not only includes the advantages of preoperative injection, but also has more significant prognostic benefits and favourable safety profiles.

Combined Use of Antimicrobial Peptides with Antiseptics against Multidrug-Resistant Bacteria: Pros and Cons.

Antimicrobial peptides (AMPs) are acknowledged as a promising template for designing new antimicrobials. At the same time, existing toxicity issues and limitations in their pharmacokinetics make topical application one of the less complicated routes to put AMPs-based therapeutics into actual medical practice. Antiseptics are one of the common components for topical treatment potent against antibiotic-resistant pathogens but often with toxicity limitations of their own. Thus, the interaction of AMPs and antiseptics is an interesting topic that is also less explored than combined action of AMPs and antibiotics. Herein, we analyzed antibacterial, antibiofilm, and cytotoxic activity of combinations of both membranolytic and non-membranolytic AMPs with a number of antiseptic agents. Fractional concentration indices were used as a measure of possible effective concentration reduction achievable due to combined application. Cases of both synergistic and antagonistic interaction with certain antiseptics and surfactants were identified, and trends in the occurrence of these types of interaction were discussed. The data may be of use for AMP-based drug development and suggest that the topic requires further attention for successfully integrating AMPs-based products in the context of complex treatment. AMP/antiseptic combinations show promise for creating topical formulations with improved activity, lowered toxicity, and, presumably, decreased chances of inducing bacterial resistance. However, careful assessment is required to avoid AMP neutralization by certain antiseptic classes in either complex drug design or AMP application alongside other therapeutics/care products.

Efficacy of Fractional Carbon Dioxide Laser versus Fractional Carbon Dioxide Laser with Platelet-Rich Plasma in Treatment of Striae Distensae in a Tertiary Care Center: A Comparative Study.

Background: Striae distensae are atrophic scars that are often cosmetically distressing. The efficacy of fractional carbon dioxide (CO2) laser and platelet-rich plasma (PRP) in treating striae individually has been evaluated previously. However, not many studies described the combined efficacy of both. Aims and Objectives: The aim of this study was to compare the efficacy and safety of fractional CO2 laser alone and in combination with PRP. Materials and Methods: Twenty-four patients with striae presenting bilaterally in the abdomen, upper limbs, and lower limbs were included. PRP was prepared by double-spin method and cell count was done to ensure at least fourfold concentration of platelets. The patients were treated CO2 laser on both sides and PRP on the left side along with laser, every month for three sessions. Digital photography and dermoscopy were done at baseline, every treatment session, and 6 months after treatment. Clinical improvement was assessed by comparing photographs and patient satisfaction before and after treatment. Results: All patients showed improvement on both sides. In CO2-laser-treated patients, responses in 6 patients (25%) were moderate, 14 (56%) were good, and 4 (16.6%) were excellent. In CO2-laser and PRP-treated patients, responses in 5 patients (20.8%) were moderate, 11 (45.8%) were good, and 8 (33.3%) were excellent. Hyperpigmentation was the most common side-effect seen (19 patients) on both sides, which resolved spontaneously by 6 months. Conclusion: These results support the use of ablative CO2 fractional laser as effective and safe treatment modalities for striae. However, slightly better efficacy was noted with the addition of PRP.

Clinical value of the combined use of P-wave dispersion and troponin values to predict atrial fibrillation recurrence in patients with paroxysmal atrial fibrillation.

INTRODUCTION: P-wave dispersion (PWD) and cardiac troponin levels are independently associated with the recurrence of atrial fibrillation (AF) in patients with paroxysmal AF (PAF). We investigated the clinical usefulness of combining PWD and cardiac troponin I to predict AF recurrence in patients presenting to the emergency department with PAF. METHODS: This study included 65 patients with PAF who were divided into three groups according to baseline troponin I and PWD values (group 1, troponin I<0.11 ng/dl and PWD<44.5 ms; group II, troponin I<0.11 ng/dl and PWD≥44.5 ms, or troponin I≥0.11 ng/dl and PWD<44.5 ms; group III, troponin I≥0.11 ng/dl and PWD≥44.5 ms). RESULTS: The AF recurrence rate was significantly higher in group III than in groups I and II. Multivariate analysis revealed that the troponin I and PWD values in group III (odds ratio: 7.236, 95% confidence interval: 1.879-27.861, p=0.004) were independent predictors of AF recurrence. CONCLUSIONS: The combined use of PWD and basal troponin I levels is a better predictor of AF recurrence than either value alone.

Split-face Comparative Study of Efficacy of Platelet-rich Plasma Combined with Microneedling versus Microneedling alone in Treatment of Post-acne Scars.

CONTEXT: Skin conditions contribute substantial burden toward global morbidity and mortality. Acne vulgaris, with its rising prevalence, has become a cause of concern among researchers as well as dermatologists due to scarring. AIMS: The aim of this study was to compare the efficacy of microneedling alone versus microneedling combined with platelet-rich plasma (PRP) in post-acne scars using a split-face method. MATERIALS AND METHODS: Thirty patients with atrophic post-acne facial scars were offered four sittings of treatment monthly once. As a standard protocol, the right side of the face was subjected to microneedling with PRP (Group A) and the left side of the face with microneedling alone (Group B). Objective evaluation of improvement was performed by the physician recording the acne scar assessment score at baseline and thereafter at every visit using Goodman and Baron scale. Alongside patients also graded the improvement in acne scars at the end of the study. STATISTICAL ANALYSIS USED: The collected information was entered in MS Excel (Bellevue, WA, USA) and analyzed using appropriate statistical methods with Statistical Package for the Social Sciences software (IBM Corp., Armonk, NY). The significance of the outcomes of the study was assessed by calculating the P value and the value of P < 0.05 was considered statistically significant. RESULTS: The mean age of patients was 25 years. Thirteen (43%) patients in Group A had an excellent response as compared to 6 (20%) patients in Group B according to physician assessment. Patient's satisfaction was more in Group A as compared to Group B as 11 (36%) patients had more than 75% improvement in Group A as compared to 1 (3%) patient in Group B. CONCLUSION: The study showed a decrease in scar severity grade in all the patients enrolled for treatment. However, the combined use of microneedling and PRP was found to be more effective than a single method used for treatment of acne scars.

[Combined Use of Zirconium-Modified Bentonite Capping and Calcium Nitrate Addition to Control the Release of Phosphorus from Sediments].

In this study, sediment incubation experiments were carried out to investigate the efficiency and mechanism of the control of phosphorus (P) release from sediments. The results showed that under anoxic conditions, P could be released from the sediment into the pore water first and then the dissolved P in the pore water could be transported into the overlying water, leading to high concentrations of soluble reactive P (SRP) and diffusive gradient in thin-films (DGT)-labile P in the overlying water. However, the combined use of calcium nitrate (CN) addition and zirconium-modified bentonite (ZB) capping could effectively control the release of P from sediment, resulting in the low concentrations of SRP and DGT-labile P in the overlying water. Furthermore, the combined use of CN addition and ZB capping could significantly decrease the concentrations of SRP and DGT-labile P in the sediment. In addition, the combined utilization of CN addition and ZB capping also could result in a reduction of redox sensitive P (BD-P) in the uppermost sediment layer. The reduction of pore water SRP, DGT-labile P, and BD-P in sediment solids is of great importance to the control of sediment-P liberation by the combined use of CN addition and ZB capping. The reduction efficiency of overlying water SRP by combined CN addition/ZB capping technology was higher than that of single CN addition technology. Compared to that of single CN addition technology, the reduction efficiencies of pore water SRP, SRP diffusion flux across the sediment/overlying water interface (SWI), and BD-P in the sediment by the combined use of CN addition and ZB capping were also higher. The combined technology based on CN addition and ZB capping had a higher reduction efficiency of overlying water SRP during the late stage of sediment remediation than the single technology based on ZB capping, and the former had higher reduction efficiencies of pore water SRP, DGT-labile P, and SRP diffusion flux across the SWI and apparent P diffusion flux through the SWI than the latter. The results of this work indicate that the combined use of CN addition and ZB capping is a very promising method for the control of P release from sediments.

Motivations to combine alcohol and nicotine in college students: A validation of the Alcohol and Nicotine Motives Scale.

INTRODUCTION: Research on combining alcohol and nicotine (ALCNIC) has shown this risky behavior results in significantly more consequences than using either alcohol or nicotine alone. No measures currently exist to assess ALCNIC motives limiting intervention and prevention efforts. The present study developed a psychometrically sound and multidimensional measure of ALCNIC motives (the ANMS). METHODS: An initial item pool of ALCNIC items was developed from literature on college student drinking, focus groups, and individual interviews. Study 1 involved students from a northeastern university who completed an online survey on the ALCNIC items (N = 55; 57.1% female; Mage = 20.3). Analysis focused on reliability (exploratory factor analysis). Study 2 involved a cross-validation national sample of college students (N = 336; 49.7% female; Mage = 21.2) completing the same survey items. Confirmatory factor analysis, criterion-related validity (ALCNIC/weekend drinking), and discriminant validity (social desirability) were assessed using structural equation modeling. RESULTS: Results across two studies revealed three factors to engage in ALCNIC: antagonistic (party longer), synergistic (enhanced effects), and social (peer pressure); and one factor to avoid ALCNIC: negative effects (feeling anxious) (all alphas > 0.7). In study 2, criterion-related validity revealed that synergistic motives were significantly positively associated with ALCNIC use; and negative effects motives were significantly negatively associated with ALCNIC use. Discriminant validity showed ALCNIC subscales were not significantly associated with social desirability (except social). CONCLUSIONS: The study developed a reliable and valid measure of motives for ALCNIC use. Results were robust to cross-validation across two samples of college students. These measures provide targets for intervention and prevention efforts.

Association of combination opioid, benzodiazepine, and muscle relaxant usage with emergency department visits in a nationwide cohort in the United States.

Background Concurrent opioid and benzodiazepine use ("double-threat") and opioid, benzodiazepine, and muscle relaxant use ("triple-threat") are linked to increased adverse events compared to opioid use alone. Objectives To assess prevalence of double-threat and triple-threat in the US and to measure association between double- and triple-threat and emergency department visits. Setting Nationally representative, 2-year health database of the United States. Method A retrospective cohort study was conducted using the national medical expenditure panel survey. Two-year prevalence of combination use was measured. Association between 2013-2014 double- and triple-threat exposure and emergency department visit compared to non-users, opioid-users, and all other exposure combinations assessed using logistic regression. Main outcome measures Survey-weighted prevalence of triple-threat and double-threat in 2013 and 2014 was measured. The outcome variable of at least one emergency department visit in a study year was utilized for the logistic regression. Results Opioids, benzodiazepines, and muscle relaxants were used in 11.9% (38.4 million lives), 4.2% (13.5 million), and 3.4% (10.9 million) individuals respectively in 2013, and 12.2% (39.3 million), 4.6% (14.8 million), and 3.6% (11.6 million), respectively in 2014. Prevalence of individuals on double-threat rose from 1.6 to 1.9% from 2013 to 2014. Triple-threat prevalence was unchanged at 0.53% in that interval. Triple-threat patients had increased emergency department visit probability with ORs of 9.19 (95% CI 9.17-9.22) in 2013, 9.82 (95% CI 9.79-9.85) in 2014, and 5.90 (95% CI 5.89-5.92) for longitudinal 2013-2014 analysis compared to non-users. Double-threat patients had increased emergency department visit probability with ORs of 4.57 (95% CI 4.56-4.58) in 2013, 6.66 (95% CI 6.65-6.68) in 2014, and 4.49 (95% CI 4.48-4.50) for 2013-2014 analysis compared to non-users. Conclusions Concurrent opioid and benzodiazepine use and opioid, benzodiazepine, and muscle relaxant use increased probability of emergency department visit. Amplified efforts in surveillance, prescribing, and default follow-up for concurrent opioid, benzodiazepine, muscle relaxant use are needed to reduce this public health concern.

Anti-tumor Mechanism of Xihuangwan and Research Progress on Its Combined Use in Anti-tumor Treatment / 中国实验方剂学杂志

Xihuangwan is composed of four Chinese medicines： Bovis Calculus， Olibanum， Myrrha， and Moschus. Modern pharmacology studies have shown that Xihuangwan has anti-inflammatory， antibacterial， anti-tumor， anti-mammary gland hyperplasia effect， and can enhance the body's immune function. Cancer seriously endangers public health and safety-of-life， and is a major cause of mortality of Chinese citizens. It is a disease with intricate etiopathogenesis caused by the joint action of circumstances and hereditary factors. At present， anti-tumor chemotherapy drugs in clinical application not only have toxic and side effect， but also affect clinical efficacy and prognosis of patients. Long-term use will also lead to drug resistance of tumors. As a traditional classic anti-cancer prescription， Xihuangwan has been used more and more in tumor research with the rise of Chinese medicine culture. It is provided with remarkable inhibitory effect on liver cancer， gastric cancer， carcinoma of the lungs， mammary gland， colorectal carcinoma and other malignant tumors. In clinical practice， Xihuangwan ， mostly used as adjuvant drugs in combined use with chemotherapy drugs for anti-tumor effect， can reduce the side effect of chemotherapy drugs and the untoward reaction of sufferers， improve the survivability of patients to chemotherapy， reduce or delay postoperative tumor recurrence， enhance the body's immune function， and reverse the tolerance of tumor cells. Based on the anti-tumor research of Xihuangwan， we summarized its mechanisms in inducing cell apoptosis， regulating amino acid metabolism， reversing drug resistance， interfering with cell cycle， resisting tumor metastasis and invasion， regulating immune function， improving tumor microenvironment， and regulating signal pathways， as well as its clinical combination with chemotherapeutic anti-tumor drugs， analyzed the current anti-tumor research status of Xihuangwan's research， and put forward the shortcomings and unresolved problems in order to provide theoretical basis for further research and clinical application of Xihuangwan.

A Case of Methemoglobinemia Thought to Have Been Caused by the Combined Use of Propitocaine and Nitroglycerin During General Anesthesia.

This is a case report of methemoglobinemia presumably caused by the combined use of prilocaine (propitocaine) and nitroglycerin under general anesthesia. Methemoglobinemia is reportedly caused by the administration of prilocaine at a dose of ≥8 mg/kg. Moreover, ≥3 µg/kg/min of nitroglycerin can also trigger methemoglobinemia. In this patient, methemoglobinemia occurred despite neither drug having been administered at the aforementioned doses. Even if individual doses of drugs predisposed to causing methemoglobinemia are low, combined use may increase the risk of methemoglobinemia.

Development and application progress of physiologically based pharmacokinetic modeling and its combined use with other modeling methods / 中国临床药理学与治疗学

Physiologically based pharmacokinetics (PBPK) is one of the main research fields of pharmacometrics, and it plays an important role at all the stages of drug development and clinical practice. In early drug discovery and development, human pharmacokinetics (PK) could be predicted by PBPK modeling using in silico, in vitro and preclinical in vivo data. During clinical studies, PBPK model could be used to investigate the effects of various physiological and pathological factors on PK, such as age, gender, liver/kidney impairment, and to guide dose adjustment of special population (pregnant women, children, etc.). Furthermore, PBPK modeling is now becoming more appealing with the ability to predict drug-drug interaction (DDI) in the case of co-administration of multiple drugs. In recent years, the application of PBPK modeling in industry has increased widely. Also, regulatory agencies have recognized the potential of PBPK and its impact on labeling recommendations. As the popularity of model-informed drug development, the combination of PBPK modeling with other commonly used modeling methods, such as population pharmacokinetics (PopPK), pharmacokinetic/pharmacodynamic (PK/PD) modeling and model-based meta-analysis (MBMA), has shown attractive advantages. In this paper, the origin and development, as well as the application status of PBPK are introduced briefly, and the application of PBPK modeling merged with PopPK, PK/PD and MBMA is reviewed.

Can the Combined Use of Two Screening Instruments Improve the Predictive Power of Dependency in (Instrumental) Activities of Daily Living, Mortality and Hospitalization in Old Age?

BACKGROUND: Due to differences in the definition of frailty, many different screening instruments have been developed. However, the predictive validity of these instruments among community-dwelling older people remains uncertain. OBJECTIVE: To investigate whether combined (i.e. sequential or parallel) use of available frailty instruments improves the predictive power of dependency in (instrumental) activities of daily living ((I)ADL), mortality and hospitalization. DESIGN, SETTING AND PARTICIPANTS: A prospective cohort study with two-year follow-up was conducted among pre-frail and frail community-dwelling older people in the Netherlands. MEASUREMENTS: Four combinations of two highly specific frailty instruments (Frailty Phenotype, Frailty Index) and two highly sensitive instruments (Tilburg Frailty Indicator, Groningen Frailty Indicator) were investigated. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for all single instruments as well as for the four combinations, sequential and parallel. RESULTS: 2,420 individuals participated (mean age 76.3 ± 6.6 years, 60.5% female) in our study. Sequential use increased the levels of specificity, as expected, whereas the PPV hardly increased. Parallel use increased the levels of sensitivity, although the NPV hardly increased. CONCLUSIONS: Applying two frailty instruments sequential or parallel might not be a solution for achieving better predictions of frailty in community-dwelling older people. Our results show that the combination of different screening instruments does not improve predictive validity. However, as this is one of the first studies to investigate the combined use of screening instruments, we recommend further exploration of other combinations of instruments among other study populations.

Effects of Probiotic Use on Bacterial Translocation in Created Rat Models with Biliary Obstructions.

OBJECTIVE: The aim of this study was to investigate the protective effects of the combined use of probiotic strains on the development of bacterial translocation in addition to liver and intestinal tissue damage due to biliary obstruction in rats. MATERIALS AND METHODS: Here, 3 groups each consisting of 10 rats were created:group 1 (sham group), group 2 (obstructive jaundice), and group 3 (obstructive jaundice+probiotic). Groups 1 and 2 were given 1 cc physiological saline solution by oral gavage twice a day; group 3 was given a probiotic solution that included Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Enterococcus faecium, and Bifidobacterium longum microorganisms by oral gavage twice a day. RESULTS: Markers for liver damage were also found to be significantly improved (p<0.05) in the treatment group (group 3). When compared with groups 2 and 3 in terms of liver histology, damage was found to be significantly more severe in group 2 (p<0.01). With regard to ileal villous depth and ileal inflammation, the pathology was found to be significantly more severe in group 2 than that in group 3 (p<0.05). In blood, spleen, and mesenteric lymph node cultures, group 2 showed a microbiological growth rate of 33.8-58.8%, whereas group 3 showed a microbiological growth rate of 14.3-28.6%. This reduction was evaluated to be statistically significant (p<0.05). CONCLUSION: Our study showed that the combined use of a probiotic in bile duct obstructions reduced bacterial translocation and alleviated pathological changes arising in the liver and terminal ileum histology.

Remote monitoring: Doomed to let down or an attractive promise?

Device interrogation and management are time consuming, representing a relevant burden for pacing centers. In several situations, patients' management requires additional follow up visits. Remote Monitoring (RM) allows an optimal recall management and a rapid diagnosis of device or lead failure, without the need of additional in office visits. Further it allows a significant delay reduction between the adverse event and the reaction to the alarm, shortening the time needed to make a clinical decision. A role in risk-predicting patient-related outcomes has also been shown. RM permits detection of the arrhythmia from 1 to 5 months in advance compared to in-office visits. Importantly, by using specific algorithms with multiparametric analysis, RM has been studied as a potential instrument to identify early patients on risk of worsening HF using specific algorithms. Although the use of RM in HF setting remains controversial, it has been proposed to improve HF clinical outcomes and survival in clinical trials. In this sense, RM success could require a standardization of process within a management model, that may involve different health care professionals. In this review, we examine recent advances of RM providing an update of this tool through different clinical scenarios.

Combined Treatment with Triptolide and Tyrosine Kinase Inhibitors Synergistically Enhances Apoptosis in Non-small Cell Lung Cancer H1975 Cells but Not H1299 Cells through EGFR/Akt Pathway.

Lung cancer is one of the most common malignant cancers in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a second- or third-line therapy for mutated non-small cell lung cancer (NSCLC). It usually becomes drug resistance after a period of treatment. Triptolide (TPL) is an epoxy diterpenoid lactone compound extracted from Tripterygium wilfordii HOOK. F. and many studies demonstrated that TPL has a synergistic effect when combined with chemotherapy drugs. In this research, we plan to evaluate the combined effect of TPL and EGFR-TKIs (Gefitinib, Erlotinib, and Icotinib) and investigate the possible mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to detect the cell viabilities, combined effect was evaluated by Combination Index. Molecular docking study was used to predict the binding ability of TPL. The expression of proteins was detected by Western blot. MTT results showed TPL had synergistic effect with three EGFR-TKIs at different concentrations on H1975 cells but not on H1299 cells. Molecular docking study demonstrated that TPL with T790M/L858R EGFR can form a more stable compound than that with wild type EGFR. Western blot results showed TPL inhibited the EGFR/Akt pathway and increased the expression of Bax and the ratio of Bax and Bcl-2 in H1975 cells. In conclusion, TPL had synergistic effect with three EGFR-TKIs on H1975 cells but not on H1299 cells, which may be due to the binding ability of TPL and different-type EGFR. The synergistic effect of TPL on H1975 cells may be partly related to the inhibition of the EGFR/Akt pathway.

Principles of digital PCR and its applications in current obstetrical and gynecological diseases.

Digital PCR (dPCR) is a revolutionary technique to precisely quantify nucleic acids. For its high sensitivity and specificity, this technique has been widely replicated worldwide. To verify its applicability, we reviewed all the related articles in PubMed database published before May 10, 2019. Original articles and reviews on the topics were selected. Entered key words included "digital PCR/dPCR", "advantage", "combined use", "microfluidic chip", "gynecological cancer/tumor". We found that dPCR has shown great potential in clinical operations, like tumor liquid biopsy, non-invasive prenatal diagnosis, microorganism detection, and next-generation sequencing library quality-control.