Improving the hepatitis C virus care cascade with the in-hospital Reflex tEsting ALarm-C (REAL-C) model.

BACKGROUND: The World Health Organization (WHO) has set targets to eliminate viral hepatitis, including hepatitis C virus (HCV) infection, by 2030. We present the results of the in-hospital Reflex tEsting ALarm-C (REAL-C) model, which incorporates reflex HCV RNA testing and sending alerts to physicians. METHODS: We conducted a retrospective study analysing the data of 1730 patients who newly tested positive for anti-HCV between March 2020 and June 2023. Three distinct periods were defined: pre-REAL-C (n = 696), incomplete REAL-C (n = 515) and complete REAL-C model periods (n = 519). The primary outcome measure was the HCV RNA testing rate throughout the study period. Additionally, we assessed the referral rate to the gastroenterology department, linkage time for diagnosis and treatment and the treatment rate. RESULTS: The rate of HCV RNA testing increased significantly from 51.0% (pre-REAL-C) to 95.6% (complete REAL-C). This improvement was consistent across clinical departments, regardless of patients' comorbidities. Among patients with confirmed HCV infection, the gastroenterology referral rate increased from 57.1% to 81.1% after the REAL-C model. The treatment rate among treatment-eligible patients was 92.4% during the study period. The mean interval from anti-HCV positivity to HCV RNA testing decreased from 45.1 to 1.9 days. The mean interval from the detection of anti-HCV positivity to direct-acting antiviral treatment also decreased from 89.5 to 49.5 days with the REAL-C model. CONCLUSION: The REAL-C model, featuring reflex testing and physician alerts, effectively increased HCV RNA testing rates and streamlined care cascades. Our model facilitated progress towards achieving WHO's elimination goals for HCV infection.

Oral phosphate binders and incident osteoporotic fracture in patients on dialysis.

BACKGROUND AND HYPOTHESIS: End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients. METHODS: We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both calcium and non-calcium-based binders (Mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality. RESULTS: Out of 69 368 incident dialysis patients, 22 326, 5020, 2853, and 39 169 were included in the CBPB, NCBPB, mixed, and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared to non-users. Specifically, only the CBPB group showed a reduced risk of vertebral (adjusted hazard ratio (aHR) 0.83 [0.76-0.92]), hip (aHR 0.81 [0.74-0.89]), and distal radius (aHR 0.88 [0.78-0.99]) fractures compared to non-users. This relationship was represented by a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months (aHR 0.9 [0.83-0.99]) and ≥ 6 months (aHR 0.83 [0.78-0.89]), compared to those using CBPB for less than 3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest, and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared to non-users. CONCLUSIONS: Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared to non-users.

Increasing the Beam Width and Intensity with Refraction Power Effect Using a Combination of Beam Mirrors and Concave Mirrors for Surgical-Fluorescence-Emission-Guided Cancer Monitoring Method.

The primary goal during cancer removal surgery is to completely excise the malignant tumor. Because the color of the tumor and surrounding tissues is very similar, it is difficult to observe with the naked eye, posing a risk of damaging surrounding blood vessels during the tumor removal process. Therefore, fluorescence emission is induced using a fluorescent contrast agent, and color classification is monitored through camera imaging. LEDs must be irradiated to generate the fluorescent emission electromotive force. However, the power and beam width of the LED are insufficient to generate this force effectively, so the beam width and intensity must be increased to irradiate the entire lesion. Additionally, there should be no shaded areas in the beam irradiation range. This paper proposes a method to enhance the beam width and intensity while eliminating shadow areas. A total reflection beam mirror was used to increase beam width and intensity. However, when the beam width increased, a shadow area appeared at the edge, limiting irradiation of the entire lesion. To compensate for this shadow area, a concave lens was combined with the beam mirror, resulting in an increase in beam width and intensity by more than 1.42 times and 18.6 times, respectively. Consequently, the beam width reached 111.8°, and the beam power was 13.6 mW. The proposed method is expected to be useful for observing tumors through the induction of fluorescence emission during cancer removal surgery or for pathological examination in the pathology department.

De novo major cardiovascular events in kidney transplant recipients: a comparative matched cohort study.

BACKGROUND: Although cardiovascular disease is known to be one of the leading causes of death after kidney transplantation (KT), evidence on the risk difference of de novo major adverse cardiovascular events (MACEs) in kidney transplant recipients (KTRs) compared with that in dialysis patients or the general population (GP) remains rare. METHODS: We identified KTRs using the nationwide health insurance database in South Korea and then 1:1 matched them with the dialysis and GP controls without a pre-existing MACE. The primary endpoint was defined as de novo MACEs consisting of myocardial infarction, coronary revascularization and ischemic stroke. The secondary endpoints were all-cause mortality and death-censored graft failure (DCGF) in KTRs. RESULTS: We included 4156 individuals in each of the three groups and followed them up for 4.7 years. De novo MACEs occurred in 3.7, 21.7 and 2.5 individuals per 1000 person-years in the KTRs, dialysis controls and GP controls, respectively. KTRs showed a lower MACE risk {adjusted hazard ratio (aHR) 0.16 [95% confidence interval (CI) 0.12-0.20], P < .001} than dialysis controls, whereas a similar MACE risk to GP controls [aHR 0.81 (95% CI 0.52-1.27), P = .365]. In addition, KTRs showed a similar MACE risk compared with the GP group, regardless of age, sex and the presence of comorbidities, including hypertension, diabetes and dyslipidemia. Among KTRs, de novo MACEs were associated with an increased risk of all-cause mortality, but not with DCGF. CONCLUSIONS: De novo MACEs in KTRs were much lower than that in dialysis patients and had a similar risk to the GP, but once it occurred it caused elevated mortality risk in KTRs.

Intra-individual comparison of lumbar spine CT, abdomen-pelvis contrast enhanced CT, and low-dose chest CT for bone density measurement.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) is the reference standard for the measurement of bone mineral density (BMD) and subsequent diagnosis of osteoporosis. Since various computed tomography (CT) protocols are scanned for various indications, we can incidentally measure BMD using CT. Previous studies have revealed a correlation between BMD and Hounsfield unit (HU) values obtained with different CT protocols. PURPOSE: To compare the diagnostic value of CT protocols (lumbar spine CT [LSCT], abdomen-pelvis contrast-enhanced CT [APCT], and low-dose chest CT [LDCT]) for osteoporosis. MATERIAL AND METHODS: We retrospectively included 17 patients (6 men, 11 women; mean age=68 years) who had undergone all four imaging studies within six months, during 2011-2021. HU values were manually measured at the center of the L1 vertebra by a radiology resident. Pearson correlation test was performed between HU values and BMD of L1 vertebra. The diagnostic performance of each CT protocol was assessed with receiver operating characteristic (ROC) analysis. Intra-individual concordance of the four tests to diagnose osteoporosis was analyzed by tabulating. RESULTS: The mean HU values were 104.4 ± 47.2 HU with LSCT, 149.0 ± 56.9 HU with APCT, and 114.3 ± 60.0 HU with LDCT. HU values from each protocol were positively correlated (r = 0.676-0.735; P < 0.005) with BMD. LDCT had the highest diagnostic performance (area under the ROC curve [AUC] = 0.701) and APCT the lowest (AUC = 0.569). APCT was discordant with the other protocols for diagnosing osteoporosis. CONCLUSION: LDCT had the highest diagnostic performance for osteoporosis with predetermined cutoff value. APCT requires the increase of cutoff value for osteoporosis diagnosis.

CORO7 functions as a scaffold protein for the core kinase complex assembly of the Hippo pathway.

The Hippo pathway controls organ size and tissue homeostasis through the regulation of cell proliferation and apoptosis. However, the exact molecular mechanisms underpinning Hippo pathway regulation are not fully understood. Here, we identify a new component of the Hippo pathway: coronin 7 (CORO7), a coronin protein family member that is involved in organization of the actin cytoskeleton. pod1, the Drosophila ortholog of CORO7, genetically interacts with key Hippo pathway genes in Drosophila. In mammalian cells, CORO7 is required for the activation of the Hippo pathway in response to cell-cell contact, serum deprivation, and cytoskeleton damage. CORO7 forms a complex with the core components of the pathway and functions as a scaffold for the Hippo core kinase complex. Collectively, these results demonstrate that CORO7 is a key scaffold controlling the Hippo pathway via modulating protein-protein interactions.

Economic Impact of Donating a Kidney on Living Donors: A Korean Cohort Study.

RATIONALE & OBJECTIVE: Although existing studies have reported adverse health outcomes after kidney donation, its socioeconomic impact on living donors requires further study. STUDY DESIGN: A retrospective observational cohort study including a matched comparison group. SETTING & PARTICIPANTS: 1,285 living kidney donors from 7 tertiary hospitals between 2003 and 2016, and a matched comparison group consisting of the same number of health screening examinees with similar baseline clinical characteristics and socioeconomic status. All participants were receiving Korean national health insurance. EXPOSURE: Kidney donation as reflected in the Korean National Health Insurance System (NHIS) database. OUTCOME: Changes in household economic status estimated by Korean national health insurance fees and changes in employment status reflected in the NHIS database. ANALYTICAL APPROACH: The outcomes of the donor group and matched control group were compared annually using multivariable logistic regression analyses adjusted for clinical and demographic characteristics. RESULTS: The median ages of the donors and matched controls were 45 and 46 years, respectively; 44.6% of both groups were male. Compared to the comparison group, living donors were at higher risk of being unemployed or losing employment during the first 2 years after donation (eg, first-year loss of employment: odds ratio (OR), 2.27 [95% CI, 1.55-3.33]); however, this association did not persist. Donors also had a significantly lower odds of improvement in economic status (OR, 0.57 [95% CI, 0.47-0.71]) and a higher odds of deterioration in financial status (OR, 1.54 [95% CI, 1.23-1.93]) in the first year after transplantation and subsequently. LIMITATIONS: Unmeasured differences between donors and matched controls creating residual selection bias and confounding. CONCLUSIONS: Living kidney donors may suffer loss of employment and poor economic status after their voluntary donation. The socioeconomic impact on these donors should be considered in conjunction with the potential long-term adverse health outcomes after donation.

Optimal application of soft-palate webbing flap pharyngoplasty combined with nasal surgery for surgical treatment of primary snoring and obstructive sleep apnea.

BACKGROUND: Excessive collapse of the soft palate and lateral pharyngeal wall narrowing are established causes of loud snoring and sleep apnea in subjects with obstructive sleep apnea (OSA). Therefore, delicate surgical techniques are needed to reshape the soft palate and create sufficient tension in the lateral pharyngeal wall. This study aimed to determine the therapeutic outcome and favorable indications of soft-palate webbing flap pharyngoplasty in subjects with OSA and primary snoring. METHODS: A total of 174 subjects who underwent soft-palate webbing flap pharyngoplasty combined with uvulopalatal flap and septoturbinoplasty from August 2015 to February 2020 were included in this study. Medical records, including pre- and postoperative sleep parameters, were retrospectively reviewed. The primary outcome measure was the degree of improvement in AHI after surgery. Other outcomes were differences in surgical response rates, subjective visual analog score (VAS) for snoring, sleep quality, and complications. RESULTS: Polysomnographic results showed that apnea-hypopnea index (AHI) scores were significantly reduced from 39.6 ± 6.1 to 22.9 ± 3.6 following soft-palate webbing flap pharyngoplasty in 59 subjects, and overall success and response rates of this technique were analyzed with 71%. We found that the successful outcomes were observed in 50% of mild (n = 12) and 56% of moderate (n = 16) subjects with OSA subjects due to lateral pharyngeal wall collapse. The success rate of soft-palate webbing flap pharyngoplasty was relatively higher in subjects with mild and moderate OSA than those with severe OSA. Additionally, the mean VAS snoring scale was 4.7 and subjects' primary snoring intensity significantly improved to 2.9 after soft-palate webbing flap pharyngoplasty. Subjective symptoms such as daytime sleepiness and sleep quality also showed improvement. Most complications were found to be minimal and improved by 1 month after the operation. CONCLUSION: Our data demonstrate that soft-palate webbing flap pharyngoplasty is an effective treatment for OSA and primary snoring and may be a promising technique to reduce lateral pharyngeal wall collapse.

Tumor necrosis factor inhibitor (TNFi) persistence and reasons for discontinuation in a predominantly male cohort with axial spondyloarthritis.

Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10 year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12 months; 63.5% and 47.1% at 24 and 36 months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3 years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed.

Inositol polyphosphate multikinase mediates extinction of fear memory.

Inositol polyphosphate multikinase (IPMK), the key enzyme for the biosynthesis of higher inositol polyphosphates and phosphatidylinositol 3,4,5-trisphosphate, also acts as a versatile signaling player in regulating tissue growth and metabolism. To elucidate neurobehavioral functions of IPMK, we generated mice in which IPMK was deleted from the excitatory neurons of the postnatal forebrain. These mice showed no deficits in either novel object recognition or spatial memory. IPMK conditional knockout mice formed cued fear memory normally but displayed enhanced fear extinction. Signaling analyses revealed dysregulated expression of neural genes accompanied by selective activation of the mechanistic target of rapamycin (mTOR) regulatory enzyme p85 S6 kinase 1 (S6K1) in the amygdala following fear extinction. The IPMK mutants also manifested facilitated hippocampal long-term potentiation. These findings establish a signaling action of IPMK that mediates fear extinction.

Core-Shell ZnO@Microporous Organic Polymer Nanospheres as Enhanced Piezo-Triboelectric Energy Harvesting Materials.

Core-shell nanospheres were prepared by the homogeneous coating of piezoelectric ZnO nanorod aggregates with triboelectric microporous organic polymer (MOP). The small energy harvesting performance of ZnO@MOP was significantly enhanced, compared with those of ZnO and MOP, due to the piezoelectrification-induced polarization of inner ZnO and the enhanced generation of tribopositive charges of MOP. Piezo-triboelectric nanogenerators (PTENGs) fabricated with ZnO@MOP showed peak-to-peak voltages of up to 534 V and a maximum power density of 1.19 mW cm-2 . In addition, the PTENGs showed excellent durability for 30 000 cycles, demonstrating as efficient power sources for charging electrolytic capacitors and for operating 200 green light emitting diode bulbs.

Haploinsufficiency of Cyfip2 Causes Lithium-Responsive Prefrontal Dysfunction.

OBJECTIVE: Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2+/- ) mice to understand their neurobehavioral phenotypes and the underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2+/- mice and specified a neuronal function mediating its efficacy. METHODS: We performed behavioral analyses of Cyfip2+/- mice. We combined molecular, ultrastructural, and in vitro and in vivo electrophysiological analyses of Cyfip2+/- prefrontal neurons. We also selectively reduced CYFIP2 in the prefrontal cortex (PFC) of mice with virus injections. RESULTS: Adult Cyfip2+/- mice exhibited lithium-responsive abnormal behaviors. We found increased filamentous actin, enlarged dendritic spines, and enhanced excitatory synaptic transmission and excitability in the adult Cyfip2+/- PFC that was restricted to layer 5 (L5) neurons. Consistently, adult Cyfip2+/- mice showed increased seizure susceptibility and auditory steady-state responses from the cortical electroencephalographic recordings. Among the identified prefrontal defects, lithium selectively normalized the hyperexcitability of Cyfip2+/- L5 neurons. RNA sequencing revealed reduced expression of potassium channel genes in the adult Cyfip2+/- PFC. Virus-mediated reduction of CYFIP2 in the PFC was sufficient to induce L5 hyperexcitability and lithium-responsive abnormal behavior. INTERPRETATION: These results suggest that L5-specific prefrontal dysfunction, especially hyperexcitability, underlies both the pathophysiology and the lithium-mediated amelioration of neurobehavioral phenotypes in adult Cyfip2+/- mice, which can be implicated in CYFIP2-associated brain disorders. ANN NEUROL 2020;88:526-543.

Functional Voice and Swallowing Outcome Analysis After Thyroid Lobectomy: Transoral Endoscopic Vestibular Versus Open Approach.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a scarless remote-access thyroidectomy technique. This study compared subjective and objective voice outcomes and swallowing outcomes of patients who underwent thyroid lobectomy using the TOETVA versus conventional open thyroidectomy (OT). METHODS: In addition to questionnaires, acoustic and aerodynamic analyses were performed to compare subjective and objective voice outcomes of the two groups. Swallowing outcome analyses were conducted using Swallowing Impairment Index-6 (SIS-6) scores. Assessments were performed preoperatively and 3 and 6 months after surgery. Propensity score matching was performed to compare the outcomes of the two groups. RESULTS: One hundred and two patients were included in this study (52 TOETVA and 50 OT). Excluding two patients who had vocal cord palsy and open conversion in the TOETVA group, 100 patients completed 3-month postoperative surveys. There were no significant differences between the groups in VAS, GRBAS, or VHI-10 scores at the preoperative and 3- and 6-month assessments. For both groups, there were no significant changes in acoustic or aerodynamic parameters during the 3-6-month postoperative period. The TOETVA group had lower SIS-6 scores at the postoperative 6-month assessment, but the SIS-6 scores after 12 months were similar between groups before and after propensity score matching. CONCLUSIONS: Following TOETVA lobectomy, there were no significant changes in voice outcomes 3 and 6 months after surgery, and the outcomes were comparable with those of OT. The TOETVA group also had swallowing outcomes that were comparable with the OT group.

The REMOTE-control system: a system for reversible and tunable control of endogenous gene expression in mice.

We report here a robust, tunable, and reversible transcription control system for endogenous genes. The REMOTE-control system (Reversible Manipulation of Transcription at Endogenous loci) employs enhanced lac repression and tet activation systems. With this approach, we show in mouse embryonic stem cells that endogenous Dnmt1 gene transcription could be up- or downregulated in a tunable, inducible, and reversible manner across nearly two orders of magnitude. Transcriptional repression of Dnmt1 by REMOTE-control was potent enough to cause embryonic lethality in mice, reminiscent of a genetic knockout of Dnmt1 and could substantially suppress intestinal polyp formation when applied to an ApcMin model. Binding by the enhanced lac repressor was sufficiently tight to allow strong attenuation of transcriptional elongation, even at operators located many kilobases downstream of the transcription start site and to produce invariably tight repression of all of the strong viral/mammalian promoters tested. Our approach of targeting tet transcriptional activators to the endogenous Dnmt1 promoter resulted in robust upregulation of this highly expressed housekeeping gene. Our system provides exquisite control of the level, timing, and cell-type specificity of endogenous gene expression, and the potency and versatility of the system will enable high resolution in vivo functional analyses.

Anterior capsular abnormality: another important MRI finding for the diagnosis of adhesive capsulitis of the shoulder.

OBJECTIVE: To evaluate the usefulness of anterior capsular abnormality, thickening, and abnormal signal intensity on MRI for the diagnosis of adhesive capsulitis of the shoulder. MATERIALS AND METHODS: This retrospective study included 29 patients with adhesive capsulitis and 20 controls. Clinical criteria with significant restricted passive motion was used for the diagnosis of adhesive capsulitis. The anterior capsular thickness and signal intensity were evaluated on the thickest portion of anterior glenohumeral joint capsule, located deep to the subscapularis muscle. In addition, the previously known MR findings of adhesive capsulitis, such as humeral and glenoid capsular thickness in axillary recess, maximal axillary capsular thickness, and coracohumeral ligament thickness, were measured. The presence of humeral and glenoid capsular abnormal hyperintensity in axillary recess, abnormal hyperintensity, and obliteration of the subcoracoid fat triangle were also evaluated. RESULTS: All MRI findings significantly differed between adhesive capsulitis and controls. Among MR findings, multivariable analysis showed that anterior capsular thickness, maximal axillary capsular thickness, and anterior capsular abnormal hyperintensity were variables that could differentiate adhesive capsulitis from the control group, with odds ratios of 7.97, 17.75, and 12.41, respectively (p < 0.05). In ROC analysis, the anterior capsular thickness showed high diagnostic performances with an AUC of 0.897. The cut-off value of anterior capsular thickness at 3.5 mm showed excellent diagnostic accuracy, with sensitivity of 68.97% and specificity of 100%. CONCLUSIONS: Anterior capsular abnormality, thickening, and abnormal hyperintensity can be used for the diagnosis of adhesive capsulitis of shoulder, in addition to previously known abnormal MRI findings.

Laser asymmetric ablation method to improve corneal shape.

This study aims to assess whether central-symmetric corneal thickness reduces off-centered corneal shift caused by intraocular pressure (IOP). In this retrospective study, 122 healthy eyes of 62 presbyopic patients, mostly myopic, were divided into two groups. Two distinct asymmetric corneal ablations were applied in peripheral presbyopia correction to produce central-symmetric corneal thickness, which reduces the off-centered corneal shift by utilizing intraocular pressure. The first method used a 90° angled combination in group 1 and the second method used a 45° angled combination in group 2. Target refraction was spherical equivalent of - 1D. Self-developed image processing algorithm analyzed the change in thickness and the posterior cone, and obtained two factors: central symmetry (f) and visual axis deviation (d), from each eye's pre and postoperative maps of Orbscan II. UDVA and UNVA were also analyzed. In both groups, mean SE was about - 1D and there was no significant difference in UDVA. UNVA was better in group 2 than group 1. Only in group 2, corneal thickness and posterior cone became central-symmetric and the posterior corneal apex point relocated towards the visual axis. The p values were 0.03, 0.04, and 0.03, respectively. This is the first study to control corneal shape by utilizing the interaction between intraocular pressure and corneal thickness. Only group 2 was applied with asymmetric corneal ablation created by the 45° angled combination of semi-cylindrical ablation patterns, and intraocular pressure contributed significantly to reduce the off-centered corneal shift and reshaped the posterior corneal cone to the center.

Determination of metoserpate, buquinolate, and diclofenac in pork, eggs, and milk using liquid chromatography-tandem mass spectrometry.

In this work, a method was developed for the simultaneous determination of residual metoserpate, buquinolate and diclofenac in pork, milk, and eggs. Samples were extracted with 0.1% formic acid in acetonitrile, defatted with n-hexane, and filtered prior to analysis using liquid chromatography-tandem mass spectrometry. The analytes were separated on a C18 column using 0.1% acetic acid and methanol as the mobile phase. The matrix-matched calibration curves showed good linearity over a concentration range of 5-50 ng/g with coefficients of determination (R2 ) ≥0.991. The intra- and inter-day accuracies (expressed as recovery percentage values) calculated using three spiking levels (5, 10, and 20 µg/kg) were 80-108.65 and 74.06-107.15%, respectively, and the precisions (expressed as relative standard deviation) were 2.86-13.67 and 0.05-11.74%, respectively, for the tested drugs determined in various matrices. The limits of quantification (1 and 2 µg/kg) were below the uniform residual level (0.01 mg/kg) set for compounds that have no specific maximum residue limit (MRL). The developed method was tested using market samples and none of the target analytes was detected in any of the samples. The validated method proved to be practicable for detection of the tested analytes in pork, milk, and eggs.

Development and validation of a simple solid-phase extraction method coupled with liquid chromatography-triple quadrupole tandem mass spectrometry for simultaneous determination of lincomycin, tylosin A and tylosin B in royal jelly.

We have developed an analytical method for the determination of lincomycin, tylosin A and tylosin B residues in royal jelly using liquid chromatography-triple quadrupole tandem mass spectrometry analysis. For extraction and purification, we employed 1% trifluoroacetic acid and 0.1 m Na2 EDTA solutions along with an Oasis HLB cartridge. The target antibiotics were well separated in a Kinetex EVO C18 reversed-phase analytical column using a combination of 0.1% formate acid in ultrapure water (A) and acetonitrile (B) as the mobile phase. Good linearity was achieved over the tested concentration range (5-50 µg/kg) in matrix-matched standard calibration. The coefficients of determination (R2 ) were 0.9933, 0.9933 and 0.996, for tylosin A, tylosin B and lincomycin, respectively. Fortified royal jelly spiked with three different concentrations of the tested antibiotics (5, 10 and 20 µg/kg) yielded recoveries in the range 80.94-109.26% with relative standard deviations ≤4%. The proposed method was applied to monitor 11 brand of royal jelly collected from domestic markets and an imported brand from New Zealand; all the samples tested negative for lincomycin, tylosin A and tylosin B residues. In conclusion, 1% trifluoroacetic acid and 0.1 m Na2 EDTA aqueous solvents combined with solid-phase extraction could effectively complete the sample preparation process for royal jelly before analysis. The developed approach can be applied for a routine analysis of lincomycin, tylosin A and tylosin B residues in royal jelly.

Epithelial cell shape change of Drosophila as a biomonitoring model for the dose assessment of environmental radiation.

Inevitable exposure to ionizing radiation from natural and human-made sources has been increasing over time. After nuclear disasters, such as the Fukushima accident, the public concerns on health risk of radiation exposure because of radioactive contamination of the environment have increased. However, it is very difficult to assess the biological effects of exposure caused by environmental radiation. A reliable and rapid bioassay to monitor the physiological effects of radiation exposure is therefore needed. Here, we quantitatively analyzed the changes in cell shape in Drosophila epidermis after irradiation as a model for biomonitoring of radiation. Interestingly, the number of irregularly shaped epithelial cells was increased by irradiation in a dose-dependent manner. A dose-response curve constructed with the obtained data suggests that the measurement of the number of irregular shaped cell in the epidermis is useful for the assessment of radiation dose. In addition, a comparison of the variation in the different samples and the data scored by different observers showed that our evaluation for cellular morphology was highly reliable and accurate and would, therefore, have immense practical application. Overall, our study suggests that detection of morphological changes in the epithelial cells is one of the efficient ways to quantify the levels of exposure to radioactive radiation from the environment.