A knife-edge method is used here to measure the beam width of the highly repetitive high-power thin disk Yb:KYW femtosecond laser (MABEL-Mannheim Biomedical Engineering Lab, University of Heidelberg, Germany). Presented in this paper is the detailed measuring process together with the results verified by theoretical calculating and scanning electron microscope measurements respectively. Therefore, it is concluded that the knife-dege method is an effective beam width measurement tool of high-power femtosecond lasers.
Bioengineering ; instrumentation ; Lasers ; Microscopy, Electron, Scanning ; instrumentation

OBJECTIVETo compare the preemptive analgesia efficacy between two cycloxygenase-2 inhibitors, rofecoxib and etoricoxib in the ambulatory uterine evacuation patients.

METHODSIn this randomized, double-blinded, placebo-controlled trial 60 patients were randomly divided into three groups and received a single dose of placebo, rofecoxib 50 mg, or etoricoxib 120 mg, respectively, before operation. Patient's visual analogue score (VAS) was rated postoperatively at 15 min, 30 min, 60 min, time-to-discharge, 6 h and 24 h. Fentanyl (in post-anesthesia care unit) and paracetamol (at home) were supplementary analgesics and the dosage was also recorded. Patient's satisfaction score was rated at 24 h postoperatively.

RESULTSEtoricoxib 120 mg and rofecoxib 50 mg were significantly superior to placebo at 6 h postoperatively (P < 0.05) while there was no significant differences of VAS at other time points. The amounts of Fentanyl used in post-anesthesia care unit were similar in three groups, but paracetamol taken at home was much less in rofecoxib group and etoricoxib group than in placebo group (P < 0.01). Compared to rofecoxib, etoricoxib provided better pain relief after discharge (P < 0.05). The overall pain management satisfaction score was significantly higher in etoricoxib group (96 +/- 7) than in other groups (P < 0.01).

CONCLUSIONPreemptive rofecoxib 50 mg and etoricoxib 120 mg may significantly decrease VAS at 6 h postoperatively, and reduce the usage of analgesics in ambulatory uterine evacuation patients. Etoricoxib 120 mg offeres better pain relief at home compared with rofecoxib 50 mg.

Abortion, Induced ; adverse effects ; Acetaminophen ; therapeutic use ; Adolescent ; Adult ; Ambulatory Surgical Procedures ; Analgesics, Non-Narcotic ; therapeutic use ; Analgesics, Opioid ; therapeutic use ; Cyclooxygenase Inhibitors ; therapeutic use ; Double-Blind Method ; Female ; Fentanyl ; therapeutic use ; Humans ; Lactones ; therapeutic use ; Pain Measurement ; Pain, Postoperative ; prevention & control ; Preoperative Care ; Pyridines ; therapeutic use ; Sulfones ; therapeutic use

OBJECTIVETo investigate the association of retinal vascular calibers with hyperuricemia in a middle-aged and elderly population.

METHODSA cross-sectional design was applied in this study and 869 participants aged =40 years from a high-risk group for diabetes were recruited. All participants received the anthropometrical measurements and laboratory tests. Retinal arteriolar and venular caliber of the participants were measured with a semi-automated system. Hyperuricemia was defined as a serum uric acid level >420 μmol/L in men and >360 μmol/L in women. Linear regression models were used to assess the association of hyperuricemia with retinal vascular calibers. These models were additionally adjusted for age, central obesity, hypertension, dyslipidemia, weekly activity, smoking status, and education.

RESULTSAmong the 869 participants, 133 (15.3%) suffered from hyperuricemia. The crude mean serum uric acid level was 312.3 μmol/L (Standard Deviation 79.5); mean concentration was 355.0 μmol/L (SD 75.5) in male participants, and 288.0 μmol/L (SD 71.1) in female participants (age-adjusted difference 58.1 μmol/L, 95% Confidence Internal 48.5, 67.6). After adjusting for additional covariates, male participants with hyperuricemia had 3.77 μm (95% CI -0.46, 8.00) smaller arteriolar caliber and 6.20 μm (95% CI 0.36, 12.04) larger venule than those without hyperuricemia; the corresponding numbers among female participants were 1.57 μm (95% CI -1.07, 4.21) for retinal arteriolar caliber and 2.28 μm (95% CI -1.72, 6.27) for retinal venular caliber.

CONCLUSIONHyperuricemia was associated with smaller retinal arteriolar caliber and larger venular caliber mainly in male participants in this study.

Adult ; Aged ; China ; epidemiology ; Diabetes Mellitus ; epidemiology ; Female ; Humans ; Hyperuricemia ; complications ; Male ; Middle Aged ; Retinal Vessels ; pathology ; Risk Factors ; Sex Characteristics

We present a case of intracranial aneurysm located in the P1 segment of left posterior cerebral artery in the context of tetralogy of Fallot. Complex variations included right aortic arch with abnormal branching. Also, the bilateral vertebral arteries were absent, with a type I persistent proatlantal intersegmental artery of the left side. The aneurysm was treated with endovascular intervention with a Tubridge flow diverter and was noted to be completely cured on 6-month follow-up. We discuss the many considerations in this patient including developmental and modern-era treatment.

Cellular therapies are becoming increasingly important in treating cancer, hematologic malignancies, autoimmune disorders, and damaged tissue. These therapies are becoming more effective and are being used more frequently, but they are also becoming more complex. As a result, quality testing is becoming an increasingly important part of cellular therapy. Cellular therapies should be tested at several points during their production. The starting material, intermediate products and the final product are usually analyzed. Products are evaluated at critical steps in the manufacturing process and at the end of production prior to the release of the product for clinical use. In addition, the donor of the starting biologic material is usually evaluated. The testing of cellular therapies for stability, consistency, comparability and potency is especially challenging. We and others have found that global gene and microRNA expression analysis is useful for comparability testing and will likely be useful for potency, stability and consistency testing. Several examples of the use of gene expression analysis for assessing cellular therapies are presented.
Gene Expression ; Gene Expression Profiling ; Hematologic Neoplasms ; Humans ; MicroRNAs ; Tissue Donors

Reasonable sampling scheme is the important basis for establishing reliable population pharmacokinetic model. It is an effective method for estimation of population pharmacokinetic parameters with sparse data to perform population pharmacokinetic analysis using the nonlinear mixed-effects models. We designed the sampling scheme for amlodipine based on D-optimal sampling strategy and Bayesian estimation method. First, optimized sample scenarios were designed using WinPOPT software according to the aim, dosage regimen and visit schedule of the clinical study protocol, and the amlodipine population model reported by Rohatagi et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample scenario via Monte Carlo simulation. Third, the estimation of amlodipine pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on the simulation results. All modeling and simulation exercises were conducted with NONMEM version 7.2. Finally, the accuracy and precision of the estimated parameters were evaluated using the mean prediction error (MPE) and the mean absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3, respectively. MAPE is 0.7% for both schemes. There is no significant difference in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final sample scenario because it has good accuracy and precision and less sample points. This research aims to provide scientific and effective sampling scheme for population pharmacokinetic (PK) study of amlodipine in patients with renal impairment and hypertension, provide a scientific method for an optimum design in clinical population PK/PD (pharmacodynamics) research.
Adult ; Age Factors ; Alanine Transaminase ; blood ; Amlodipine ; pharmacokinetics ; pharmacology ; Antihypertensive Agents ; pharmacokinetics ; pharmacology ; Bayes Theorem ; Body Weight ; Calcium Channel Blockers ; pharmacokinetics ; pharmacology ; Humans ; Hypertension ; metabolism ; Metabolic Clearance Rate ; Middle Aged ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Renal Insufficiency ; metabolism ; Software

Humans ; Carcinoma, Mucoepidermoid/pathology* ; Thyroid Neoplasms/pathology* ; Eosinophilia/pathology*

Background. The growing resistance of microorganisms to antimicrobial agents is a pressing public health issue. Bioprospecting efforts have mainly focused on well-known environments such as soil and animal gut in search for microorganisms with antibiotic production or antimicrobial activity, or terrestrial ecosystems for endemic plants with bioactive compounds. However, microbial communities thriving in stressed environments such as hot springs, are potential sources of metabolites that can be screened for antimicrobial activity. There is a need for research on bioprospecting of fungi as potential sources of antimicrobials.

Objectives. The study aimed to test the antimicrobial activity of endophytic and rhizospheric fungi associated with soft fern (Christella spp.) and Cinderella weed (Synederella nodiflora) inhabiting a hot spring in Los Baños, Laguna, Philippines.

Methods. A total of 23 endophytic and rhizospheric fungi isolated from soft fern and Cinderella weed were purified and phenotypically identified. These isolates were subjected to agar well diffusion and agar plug diffusion methods as preliminary assays for antimicrobial activity against Bacillus subtilis var. spizizenii (ATCC® 6633™), Staphylococcus  aureus (ATCC® 25923™), four multi-antibiotic resistant Escherichia coli (OT11, OT16, OT18, OT22), and Cladosporium  cladosporioides. Based on the results of the preliminary screening, ethyl-acetate extracts of selected fungal isolates were subjected to broth microdilution assay to determine the minimum inhibitory concentrations (MICs) for antibacterial activity, as well as poisoned food technique to determine the percent mycelial inhibition for antifungal activity. The nearest phylogenetic affiliations of fungal isolates with higher antimicrobial activities were determined.

Results. Ten rhizospheric fungal isolates from Cinderella weed and seven rhizospheric and six endophytic fungal isolates from soft fern were phenotypically identified as Aspergillus, Coniothyrium, Fusarium, Penicillium, Talaromyces,  and Trichoderma species. Ethyl acetate extracts from endophytic fungal isolates UL1 (Trichoderma sp.) and UL2 (Trichoderma sp.) and rhizospheric fungal isolates UR1 (Trichoderma sp.) and UR3 (Trichoderma sp.) showed activity against the test bacteria at 128-256 ?g/mL concentrations. Isolates UL1, UL2, and UR3, which exhibited higher antibacterial activities, were sequenced and confirmed to be most phylogenetically related to Trichoderma  virens. Eleven fungal isolates belonging to Aspergillus spp., Coniothyrium spp., Fusarium spp., Penicillium spp., and Talaromyces spp. demonstrated antagonism against C. cladosporioides. The rhizospheric fungal isolate FCRU4 (Talaromyces sp.), from where ethyl acetate extracts were recovered for testing mycelial inhibition, was confirmed to be most phylogenetically related to Talaromyces islandicus.

Conclusion. Endophytic and rhizospheric fungi asso ciated with Cinderella weed (Synedrella nodiflora) and soft fern (Christella sp.) from a hot spring in Los Baños, Laguna, Philippines have antimicrobial activity.

Hot Springs ; Tracheophyta

Cancer immunotherapy uses the host′s immune system to mobilize immune cells to rec-ognize and eventually eliminate cancer cells .At present, studies in terms of cancer immunotherapy mainly focus on programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4 ) antibody, chimeric antigen receptor T-cell immunotherapy (CAR-T), T cell receptor Immunotherapy (TCR-T), etc.Despite the fact that cancer immunotherapies elicit unprecedented durable responses in clinical therapy , they appear to be ineffective to some patients .In addition, some responders relapse and show resistance to immunotherapies even if their symptoms are re -lieved for a time .Resistance to cancer immunotherapy can be categorized into primary , adaptive and ac-quired, which can occur in every stage during the process of anti-tumor response.In this review, we discuss the known mechanisms of resistance and provide a rationale for the use of combination therapy to overcome resistance.

During spermatogenesis, developing germ cells that lack the cellular ultrastructures of filopodia and lamellipodia generally found in migrating cells, such as macrophages and fibroblasts, rely on Sertoli cells to support their transport across the seminiferous epithelium. These include the transport of preleptotene spermatocytes across the blood-testis barrier (BTB), but also the transport of germ cells, in particular developing haploid spermatids, across the seminiferous epithelium, that is to and away from the tubule lumen, depending on the stages of the epithelial cycle. On the other hand, cell junctions at the Sertoli cell-cell and Sertoli-germ cell interface also undergo rapid remodeling, involving disassembly and reassembly of cell junctions, which, in turn, are supported by actin- and microtubule-based cytoskeletal remodeling. Interestingly, the underlying mechanism(s) and the involving biomolecule(s) that regulate or support cytoskeletal remodeling remain largely unknown. Herein, we used an in vitro model of primary Sertoli cell cultures that mimicked the Sertoli BTB in vivo overexpressed with the ribosomal protein S6 (rpS6, the downstream signaling protein of mammalian target of rapamycin complex 1 [mTORC1]) cloned into the mammalian expression vector pCI-neo, namely, quadruple phosphomimetic and constitutively active mutant of rpS6 (pCI-neo/p-rpS6-MT) versus pCI-neo/rpS6-WT (wild-type) and empty vector (pCI-neo/Ctrl) for studies. These findings provide compelling evidence that the mTORC1/rpS6 signal pathway exerted its effects to promote Sertoli cell BTB remodeling. This was mediated through changes in the organization of actin- and microtubule-based cytoskeletons, involving changes in the distribution and/or spatial expression of actin- and microtubule-regulatory proteins.
Actins/metabolism* ; Animals ; Blood-Testis Barrier/metabolism* ; Cells, Cultured ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Permeability ; Rats ; Ribosomal Protein S6/metabolism* ; Seminiferous Epithelium/metabolism* ; Sertoli Cells/metabolism* ; Signal Transduction/physiology*