Diagnostic Performance of Carotid Ring Sign on CT-Angiography in Internal Carotid True Occlusion.

BACKGROUND: To differentiate between pseudo occlusion (PO) and true occlusion (TO) of internal carotid artery (ICA) is important in thrombectomy treatment planning for patients with acute ischemic stroke. Although delayed contrast filling has been differentiated carotid PO from TO, its application has been limited by the implementations of multiphasic computed tomography angiography. In this study, we hypothesized that carotid ring sign, which is readily acquired from single-phasic CTA, can sufficiently differentiate carotid TO from PO. METHODS: One thousand four hundred and twenty patients with anterior circulation stroke receiving endovascular therapy were consecutively recruited through a hospital- and web-based registry. Two hundred patients with nonvisualization of the proximal ICA were included in the analysis after a retrospective screening. Diagnosis of PO or TO of the cervical segment of ICA was made based on digital subtraction angiography. Diagnostic performances of carotid ring sign on arterial-phasic CTA and delayed contrast filling on multiphasic computed tomography angiography were evaluated and compared. RESULTS: One-hundred twelve patients had ICA PO and 88 had TO. Carotid ring sign was more common in patients with TO (70.5% versus 6.3%; P<0.001), whereas delayed contrast filling was more common in PO (94.9% versus 7.7%; P<0.001). The sensitivity and specificity of carotid ring sign in diagnosing carotid TO were 0.70 and 0.94, respectively, whereas sensitivity and specificity of delayed contrast filling was 0.95 and 0.92 in judging carotid PO. CONCLUSIONS: Carotid ring sign is a potent imaging marker in diagnosing ICA TO. Carotid ring sign could be complementary to delayed contrast filling sign in differentiating TO from PO, in particular in centers with only single-phasic CTA.

The Protection of Astragalus Polysaccharide in BALB/C Mice during Brucella melitensis M5 Infection.

INTRODUCTION: Brucellosis is an important zoonosis worldwide, affecting humans and animals. There are no specific medicines available to treat brucellosis. Astragalus polysaccharide (APS) is derived from Astragalus membranaceus and exhibits impressive bioactivity, including anti-aging, anti-tumor, and immunomodulatory functions. METHODS: Mice were intraperitoneally inoculated with Brucella melitensis M5 and then treated with APS intraperitoneally injection daily for 7 d. RESULTS: Compared to the M5-infected group, the lower bacteria loads in the APS-treated groups were proved, especially at the acute stage of infection. APS treatment relieved splenomegaly, excess expressions of several pro-inflammatory cytokines (including CXCL1, IFN-γ, IL-1ß, IL-2, IL-12p70, and TNF-α). The raised level of IL-4 was observed in APS-treated mice. APS contributed to raising the ratio of M1 macrophage and reducing the ratio of M2 macrophage in the blood. DISCUSSION: The present study provides some evidence on the potential application of APS in controlling and treating brucellosis and should be further explored.

Associations of different types of statins with the risk of open-angle glaucoma: a systematic review and network meta-analysis.

PURPOSE: Previous studies implied that different types of statins may pose divergent impacts on the risk of glaucoma onset. This study aimed to comprehensively evaluate the effects of various statins on the risk of glaucoma occurrence. METHODS: PubMed, Cochrane CENTRAL, Embase, and Web of Science were searched from February 1994 to February 2024. We included studies that investigated the effects of various types of statins, fibrates, ezetimibe, cholestyramine, niacin, PCSK9 inhibitors, omega-3 fatty acids, and any cholesterol-lowering medications on glaucoma onset or progression. The revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) and the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-1) tool were used to assess the quality of randomized controlled trials (RCTs) and non-RCTs, respectively. The frequentist network meta-analysis framework was utilized to evaluate the comparative effectiveness, with the random effects model applied. RESULTS: This network meta-analysis comprised 12 studies, encompassing 262,217 individuals and including cholesterol-lowering medications such as statins, fibrates, ezetimibe, cholestyramine, niacin, and omega-3 fatty acids. Our findings demonstrate that comparing to the placebo, rosuvastatin (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.03 to 1.46), simvastatin (RR, 1.21; 95% CI, 1.02 to 1.43), and pravastatin (RR, 1.20; 95% CI, 1.01 to 1.43) increased the risk of glaucoma onset with statistical significance. CONCLUSION: Rosuvastatin, simvastatin, and pravastatin were each associated with a significantly increased risk of glaucoma onset. We advise medical practitioners to exercise caution when prescribing these specific statins for patients who are at risk of developing glaucoma. KEY MESSAGES: What is known Previous studies have suggested a link between statins and the risk of developing glaucoma. However, there is still ongoing debate regarding the specific effects of each type of statin on the onset of glaucoma. What is new This network meta-analysis comprehensively evaluated the effects of various statins on the risk of glaucoma onset. Rosuvastatin, simvastatin, and pravastatin were associated with a significantly increased risk of glaucoma onset.

High-Efficiency Ce3+ Activated Orthorhombic Lanthanide Silicate Blue Phosphors for Plant Growth Lighting.

Plant growth can be controlled and freed from natural environmental interference through indoor plant cultivation. Artificial light sources with better quality are required to promote indoor plant growth. In this study, we used a simple high-temperature solid-state reaction to synthesize high-efficiency Ce3+-activated NaGdSiO4 (NGSO) phosphors. X-ray diffraction and Rietveld refinement were performed to determine the detailed crystal structure of the NGSO:Ce3+ phosphors. The morphology of NGSO:Ce3+ and the elemental state of Ce3+ were measured and analyzed. Under near-ultraviolet (n-UV) light excitation, the Ce3+-activated NGSO phosphors exhibit a broad emission band from 375 to 500 nm, and their emission peaks are at approximately 401 nm. This asymmetrical blue emission band is caused by the spin-allowed 5d → 4f transition of Ce3+ and overlaps well with the blue absorption region of carotenoids and chlorophyll. The temperature-dependent luminescence spectra were utilized to assess the thermal stability of NGSO:Ce3+. The external quantum efficiency (EQE) was measured to be 60.91%, and the internal quantum efficiency (IQE) was measured to be 73.39%. A blue LED device assembled from the NGSO:Ce3+ phosphor has demonstrated the application potential in accelerating plant growth.

Eu3+ -activated red phosphor Ca3 YAl3 B4 O15 with low thermal quenching behaviour.

This paper reports a sequence of a Ca3 YAl3 B4 O15 :xEu3+ red phosphor prepared using a high-temperature solid-state reaction. At the excitation of 396 nm, the samples emitted intense red emission centred at ~623 nm, which could be attributed to the 5 D0 →7 F2 transition of the Eu3+ ion. The results showed that the optimum Eu3+ doping concentration of Ca3 YAl3 B4 O15 :Eu3+ phosphor was x = 80 mol%, and the concentration quenching mechanism of Ca3 YAl3 B4 O15 :Eu3+ red phosphor belonged to the exchange coupling between Eu3+ ions. The Commission Internationale de l'éclairage (CIE) coordinates and colour purity of Ca3 Y0.2 Al3 B4 O15 :0.8Eu3+ were calculated as (0.6375, 0.3476) and 95.5%, respectively. Moreover, the red emission of the obtained phosphor Ca3 YAl3 B4 O15 :0.8Eu3+ exhibited a low thermal quenching behaviour with an intensity retention rate of 92.85% at 150°C. The above results manifest that the Eu3+ -activated Ca3 YAl3 B4 O15 phosphor is predicted to be a promising red luminescent component for white light-emitting diodes.

The parental experience of participating in surgical decision-making regarding one's child with a congenital heart disease in Taiwan.

PURPOSE: This study explores how parents experienced the surgical decision-making process for their child with a congenital heart disease (CHD). DESIGN AND METHODS: Purposive sampling was used in this qualitative descriptive study at a medical center in Northern Taiwan. Twelve parents whose children had cardiac corrective surgery participated in one-to-one in-depth interviews. The interview content subsequently was transcribed verbatim and analyzed by content analysis. RESULTS: Five themes, with 2 to 3 subthemes, were identified: 1) accumulating medical knowledge in a short time, 2) trusting the medical teams but parents needing clear communication, 3) feeling pervasive uncertainty, 4) using self-talk to calm down, and 5) looking for positive energy from various sources. CONCLUSIONS: For the parents of these children with CHD, participating in surgical decision-making can be a difficult and stressful experience. When explaining the disease and treatment procedures, it is important for medical professionals to make sure of the individual parent's information needs, to use plain language and encourage parents to ask questions. PRACTICE IMPLICATIONS: Although the surgery is imperative and inevitable, understanding the parents' worries and providing adequate support can help them reduce feelings of uncertainty during the decision-making and surgical processes.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 µg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 µg/ml by BMD and 0.25 µg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 µg/ml and 0.5 µg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

Antihypertensive treatment and risk factors for syncope in asymptomatic aortic stenosis patients with hypertension.

BACKGROUND: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis(AS) is scarce. OBJECTIVES: Given the paucity of data on the relationship between syncope and antihypertensive treatment in aortic stenosis. This study sought to investigate this association in patients admitted to our hospital. METHODS: A total of 158 patients with asymptomatic moderate or severe aortic stenosis were analyzed. Follow-up was conducted by clinic visit, telephone contact, or review of electronic medical records. Outcomes were syncope. RESULTS: Hypertension were documented in 90 of the 158 patients with moderate or severe AS, and 77 of them received antihypertensive medications. During an average 28 months follow-up period, the occurrence of syncope was observed in 13 patients. Among them, 8 were in antihypertensive group (n = 77) and 5 in normotensive group (n = 68). There was no significant difference in incidence of syncope between the two groups. Patients with treated hypertension and syncope had a lower stroke volume index (SVi), a higher valve arterial impedance (ZVA), a smaller SAC than those without. Kaplan-Meier analysis showed that there was no significant difference in syncope cumulative incidence between antihypertensive group and normotensive group (log rank P = .478). Multivariate cox regression analysis showed that both ZVA (hazard ratio:19.006, 95% confidence interval: 4.664 to77.448;P = .002) and LVMI (hazard ratio:1.484, 95% confidence interval: 1.427 to 5.157;P = .016) were associated with development of syncope, whereas hypertension were not related independently to syncope (hazard ratio:0.935, 95% confidence interval: 0.786 to3.173; P = .869). CONCLUSIONS: In patients with moderate or severe AS, concomitant hypertension, and antihypertensive treatment didn't increase the occurrence of syncope, whereas higher ZVA was independently associated with greater risk of syncope.

A study of correlations between metabolic syndrome factors and osteosarcopenic adiposity.

BACKGROUND: Aging reduces the quality and strength of bones and muscles and increases body fat, which can lead to the simultaneous occurrence of sarcopenia, osteopenia, and adiposity, a condition referred to as OsteoSarcopenic Adiposity (OSA). While previous studies have demonstrated that metabolic syndrome is associated with sarcopenia, osteopenia, and adiposity, the relationship between metabolic syndrome and OSA remains largely unknown. METHODS: We analyzed data for a sample of middle-aged individuals from a Health Management Center database, which was collected in 2016-2018. There are 2991 cases of people over 50 years from a physical examination center in a hospital in Taiwan during 2016-2018. In addition to descriptive statistics, chi-squared test, analysis of variance, and multinomial logistic regression analysis were conducted to examine OSA risk and associated factors. RESULTS: Based on multinomial logistic regression analysis, in different OSA severity level (1-3 more serious), those who are with metabolic syndrome has increased the 2.49-2.57 times risk of OSA (p < 0.001) in OSA = 2 and 3 groups while there is no significant difference in OSA =1 group. CONCLUSION: The prevalence of OSA may impair the health and quality of life in the elderly group, especially those diagnosed with metabolic syndrome, increasing the risk of OSA. These results can help promote early diagnosis and treatment of OSA in clinical settings, particularly among aging individuals with abnormal physical function, the group with the highest OSA incidence.

FPCA-based method to select optimal sampling schedules that capture between-subject variability in longitudinal studies.

A critical component of longitudinal study design involves determining the sampling schedule. Criteria for optimal design often focus on accurate estimation of the mean profile, although capturing the between-subject variance of the longitudinal process is also important since variance patterns may be associated with covariates of interest or predict future outcomes. Existing design approaches have limited applicability when one wishes to optimize sampling schedules to capture between-individual variability. We propose an approach to derive optimal sampling schedules based on functional principal component analysis (FPCA), which separately characterizes the mean and the variability of longitudinal profiles and leads to a parsimonious representation of the temporal pattern of the variability. Simulation studies show that the new design approach performs equally well compared to an existing approach based on parametric mixed model (PMM) when a PMM is adequate for the data, and outperforms the PMM-based approach otherwise. We use the methods to design studies aiming to characterize daily salivary cortisol profiles and identify the optimal days within the menstrual cycle when urinary progesterone should be measured.

Comparative Study of Liraglutide and Insulin Glargine on Glycemic Control and Pancreatic ß-Cell Function in db/db Mice.

BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic ß-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 µg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 µg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 µg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age. Body weight, pancreatic weight, levels of blood glucose, triacylglycerol, C-peptide, and the intraperitoneal glucose tolerance test (IPGTT) were used. Expression levels of the INS1 gene were measured using reverse transcription polymerase chain reaction (RT-PCR), and pancreatic and duodenal homeobox 1 (Pdx1), paired box 4 (Pax4), and paired box 6 (Pax6) mRNA expression were measured. RESULTS Both insulin glargine and liraglutide improved glycemic control of db/db mice when compared with vehicle. The following were significantly increased in the HLG compared with the GG: the receiver operating characteristic (ROC) area under the curve (AUC) for the IPGTT; C-peptide levels; the pancreas to body weight coefficient; expression levels of the INS1 gene and pancreatic transcription factors Pdx1, Pax4 and Pax6. Liraglutide treatment was without hypoglycemic effects. CONCLUSIONS Liraglutide acted in a dose-dependent manner on glycemic control of db/db mice, and was more effective than insulin glargine, when administered at a high dose.

Study design in high-dimensional classification analysis.

Advances in high throughput technology have accelerated the use of hundreds to millions of biomarkers to construct classifiers that partition patients into different clinical conditions. Prior to classifier development in actual studies, a critical need is to determine the sample size required to reach a specified classification precision. We develop a systematic approach for sample size determination in high-dimensional (large [Formula: see text] small [Formula: see text]) classification analysis. Our method utilizes the probability of correct classification (PCC) as the optimization objective function and incorporates the higher criticism thresholding procedure for classifier development. Further, we derive the theoretical bound of maximal PCC gain from feature augmentation (e.g. when molecular and clinical predictors are combined in classifier development). Our methods are motivated and illustrated by a study using proteomics markers to classify post-kidney transplantation patients into stable and rejecting classes.

Susceptibilities of MDR Mycobacterium tuberculosis isolates to unconventional drugs compared with their reported pharmacokinetic/pharmacodynamic parameters.

Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation.

An open-label phase 2 trial of entospletinib (GS-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia.

Small-molecule inhibitors of kinases involved in B-cell receptor signaling are an important advance in managing lymphoid malignancies. Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. This multicenter, phase 2 study enrolled subjects with relapsed or refractory chronic lymphocytic leukemia (CLL; n = 41) or non-Hodgkin lymphoma (n = 145). Participants received 800 mg entospletinib twice daily. We report efficacy outcomes in the CLL cohort (n = 41) and safety outcomes in all cohorts (N = 186). The primary end point was a progression-free survival (PFS) rate at 24 weeks in subjects with CLL. The PFS rate at 24 weeks was 70.1% (95% confidence interval [CI], 51.3%-82.7%); median PFS was 13.8 months (95% CI, 7.7 months to not reached). The objective response rate was 61.0% (95% CI, 44.5%-75.8%), including 3 subjects (7.3%) who achieved nodal response with persistent lymphocytosis. Fifty-four subjects (29.0%) had serious adverse events (SAEs). The most common treatment-emergent SAEs included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia. Common grade 3/4 laboratory abnormalities included neutropenia (14.5%) and reversible alanine aminotransferase/aspartate aminotransferase elevations (13.4%). Entospletinib demonstrates clinical activity in subjects with relapsed or refractory CLL with acceptable toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01799889.

Application of the CellDetect® staining technique in diagnosis of human cervical cancer.

BACKGROUND: CellDetect® staining technique is a newly invented technique for cancer diagnosis. It easily distinguishes between normal and neoplastic cells including pre-cancer and squamous cell carcinoma (SCC) cells, based on staining color and morphology. In this study, application of CellDetect® staining technique was assessed in diagnosis of human cervical cancer as compared with hematoxylin and eosin (H&E) staining in conventional slides and Thinprep cytologic test (TCT) smears. METHODS: The conventional slides and TCT smears of 600 patients were stained and observed while comparing with H&E staining to assess sensitivity and specificity of CellDetect® staining technique in diagnosis of cervical cancer. Conventional smear slides (440 cases) were fixed in 95% ethanol or with CYTOFIX® Spray. TCT smears (160 cases) were processed based on manual. The paraffin sections from cervical intraepithelium neoplasia (CIN) 2-3 and SCC cases were prepared by biopsy. RESULTS: CellDetect® staining exhibited well cell morphology, simultaneously, showed dual color discrimination, the stain targeted cytoplasm in normal cells in green and dysplastic cells or neoplastic cells in purple/red. Both cervical cell smears or both fixation methods in conventional slides did not affect CellDetect® staining diagnosis, especially in tissue biopsies CellDetect® staining exhibited well epithelium layers to benefit the diagnosis of CIN grade. The sensitivity and specificity of CellDetect® staining technology in diagnosing CIN and SCC were 94.34% and 88.73%, respectively. CONCLUSIONS: CellDetect® staining technique provided a dual color discrimination and morphological analysis. It has the potential to become one of the most effective methods for cervical screening and early diagnosis.

Inhibitory effect of gut bacteria from the Japanese honey bee, Apis cerana japonica, against Melissococcus plutonius, the causal agent of European foulbrood disease.

European foulbrood is a contagious bacterial disease of honey bee larvae. Studies have shown that the intestinal bacteria of insects, including honey bees, act as probiotic organisms. Microbial flora from the gut of the Japanese honey bee, Apis cerana japonica F. (Hymenoptera: Apidae), were characterized and evaluated for their potential to inhibit the growth of Melissococcus plutonius corrig. (ex White) Bailey and Collins (Lactobacillales: Enterococcaceae), the causative agent of European foulbrood. Analysis of 16S rRNA gene sequences from 17 bacterial strains isolated by using a culture-dependent method revealed that most isolates belonged to Bacillus, Staphylococcus, and Pantoea. The isolates were screened against the pathogenic bacterium M. plutonius by using an in vitro growth inhibition assay, and one isolate (Acja3) belonging to the genus Bacillus exhibited inhibitory activity against M. plutonius. In addition, in vivo feeding assays revealed that isolate Acja3 decreased the mortality of honey bee larvae infected with M plutonius, suggesting that this bacterial strain could potentially be used as a probiotic agent against European foulbrood.

Inhibition of Paenibacillus larvae by lactic acid bacteria isolated from fermented materials.

We evaluated the potential application of lactic acid bacteria (LAB) isolated from fermented feeds and foods for use as probiotics against Paenibacillus larvae, the causal agent of American foulbrood (AFB) in vitro. We also assessed the ability of LAB to induce the expression of antimicrobial peptide genes in vivo. Screening of the 208 LAB isolated from fermented feeds and foods revealed that nine strains inhibited the in vitro growth of P. larvae. The LAB strains were identified by 16S rRNA gene sequencing as Enterococcus sp., Weissella sp. and Lactobacillus sp. These strains were screened for their abilities of immune activation in honeybees by real-time RT-PCR using antimicrobial peptide genes as markers. After oral administration of several of the screened LAB to larvae and adults, the transcription levels of antimicrobial peptide genes, such as abaecin, defensin and hymenoptaecin, were found to increase significantly. These findings suggested that selected LAB stimulate the innate immune response in honeybees, which may be useful for preventing bacterial diseases in honeybees. This is the first report to characterize the probiotic effects of LAB isolated from fermented feeds and foods in honeybees.

Characterization of bifidobacteria in the digestive tract of the Japanese honeybee, Apis cerana japonica.

Bifidobacteria were isolated from the intestinal tract of the Japanese honeybee, Apis cerana japonica, and investigated for potential application as a probiotic agent against Melissococcus plutonius, the causal agent of European foulbrood (EFB), based on the findings of in vitro inhibition assays. A total of 11 bifidobacteria strains (designated as AcjBF1-AcjBF11) were isolated using a culture-dependent method and their 16S rRNA gene sequences were analyzed. The AcjBF isolates belonged to three distinct bifidobacterial phylotypes that were similar to those found in the European honeybee, Apis mellifera. Although the Japanese and European honeybees are distinct species with different traits and habits, the observation that they share highly similar bifidobacterial phylotypes suggests that bifidobacteria are conserved among honeybee species. Despite having extremely high 16S rRNA gene sequence similarities, the AcjBF isolates had markedly different carbohydrate fermentation profiles. In addition, in vitro growth inhibition assays revealed that the cell-free supernatants of all AcjBF isolates exhibited antagonistic effects on M. plutonius growth. These results indicate that the bifidobacteria isolated from the gut of Japanese honeybee could potentially be employed as a new biological agent to control EFB.

Surveillance of multidrug-resistant tuberculosis in Taiwan, 2008-2019.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a major contributor to global cases of antimicrobial resistance and remains a public health challenge. To understand the extent and trend of DR-TB under an enhanced multidrug-resistant TB (MDR-TB) management program, we conducted a population-based retrospective study of 1511 Taiwanese MDR-TB cases reported from 2008 to 2019. METHODS: We obtained patient demographics and clinical and bacteriological information from the National TB Registry and the Infectious Disease Notification System. RESULTS: Of the 1511 MDR-TB patients, 941 were new cases, 485 were previously treated, and 85 had an unknown history of treatment. The male to female ratio was 2.75, and the median age of the patients was 57 years (IQR: 45-72). We observed a significant decline in MDR-TB cases, with annual percentage change (APC) of -4.17%. However, new and previously treated MDR-TB cases had APCs of -1.41% and -9.18%, respectively. The rates of MDR-TB resistance to ethambutol, streptomycin and pyrazinamide were 47.2%, 42.4% and 28.9%, respectively, whereas the rates of resistance to fluoroquinolones and second-line injectable drugs (SLIDs) were 4.1-7.1%, 9.0-14.1%; and the rate of extensively drug-resistant TB was 1.9%, respectively. Furthermore, we observed a decreasing trend of resistance to SLIDs (APCs -7.0% to -8.2%) in new cases and a significant decreasing trend of resistance to moxifloxacin (-24.6%) and levofloxacin (-23.3%) in previously treated cases. CONCLUSION: The decreasing trend of MDR-TB and resistance to second-line drugs suggested that our programmatic management of TB was effective and that the impact on TB control was profound.

Modeling the salivary cortisol profile in population research: the multi-ethnic study of atherosclerosis.

In many studies, it has been hypothesized that stress and its biologic consequences may contribute to disparities in rates of cardiovascular disease. However, understanding of the most appropriate statistical methods to analyze biologic markers of stress, such as salivary cortisol, remains limited. The authors explore the utility of various statistical methods in modeling daily cortisol profiles in population-based studies. They demonstrate that the proposed methods allow additional insight into the cortisol profile compared with commonly used summaries of the profiles based on raw data. For instance, one can gain insights regarding the shape of the population average curve, characterize the types of individual-level departures from the average curve, and better understand the relation between covariates and attained cortisol levels or slopes at various points of the day, in addition to drawing inferences regarding common features of the cortisol profile, such as the cortisol awakening response and the area under the curve. The authors compare the inference and interpretations drawn from these methods and use data collected as part of the Multi-Ethnic Study of Atherosclerosis to illustrate them.