High-throughput and sensitive determination of urinary zearalenone and metabolites by UPLC-MS/MS and its application to a human exposure study.

Biomarker-based strategies to assess human exposure to mycotoxins have gained increased acceptance in recent years. In this study, an improved method based on UPLC-MS/MS following 96-well µElution solid-phase extraction was developed and validated for the sensitive and high-throughput determination of zearalenone (ZEN) and its five metabolites α-zearalenol (α-ZEL), ß-zearalenol (ß-ZEL), α-zearalanol (α-ZAL), ß-zearalanol (ß-ZAL), and zearalanone (ZAN) in human urine samples, using 13C-ZEN as an internal standard for accurate quantification. Two plates of samples (n = 192) could be processed within 2 h, and baseline separation of all the analytes was achieved in a total runtime of 6 min. The proposed method allowed ZEN and its metabolites to be sensitively determined in a high-throughput way for the first time, and with significantly improved efficiency and accuracy with respect to existing methods. The limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.02 to 0.06 ng mL-1 and from 0.05 to 0.2 ng mL-1, respectively. The recoveries for the spiked samples were from 87.9 to 100%, with relative standard deviations (RSDs) of less than 7%. 301 urine samples collected from healthy volunteers aged 0-84 years in China were analyzed with and without enzyme hydrolysis to determine total and free ZEN biomarkers, respectively. ZEN, ZAN, α-ZEL, and ß-ZEL were detected in 71.4% of the samples at levels of 0.02-3.7 ng mL-1 after enzyme hydrolysis. The estimated mean probable daily intake (PDI) was much lower than the tolerable daily intake (TDI). Adolescents had higher exposure than children, adults, and the elderly. Graphical abstract ᅟ.

[Occurrences of mycotoxins in human breast milk in 15 provinces in China in 2011].

OBJECTIVE: To investigate contamination levels of 10 mycotoxins in human breast milk from 15 provinces in China. METHODS: The human milk breast samples were collected from 15 provinces in China by aid of the second National Breast Milk Survey. After the pooled samples were made, concentrations of 10 main mycotoxins in breast milk pooled samples were measured by a UPLC-MS/MS with isotope dilution. RESULTS: aflatoxins B_1, aflatoxins M_1, deoxynivalenol, deepoxydeoxynivalenol, fumonisin B1 and fumonisin B2 were detected in breast milk samples of some provinces, while zearalenone, α-zearalenol, ß-zearalenol and ochratoxin A were not detected in all the samples. CONCLUSION: The average load levels in human body of mycotoxins in human milk form Chinese general populations are relatively low. However, the effects of aflatoxins, deoxynivalenol and fumonisins on health risks for the baby should be paid attention.

A systematic review and bayesian meta-analysis of medical devices used in chronic pain management.

Whilst. pharmacological therapies remain the cornerstone of pain management in chronic pain, factors including the current opioid epidemic have led to non-pharmacological techniques becoming a more attractive proposition. We explored the prevalence of medical device use and their treatment efficacy in non-cancer pain management. A systematic methodology was developed, peer reviewed and published in PROSPERO (CRD42021235384). Key words of medical device, pain management devices, chronic pain, lower back pain, back pain, leg pain and chronic pelvic pain using Science direct, PubMed, Web of Science, PROSPERO, MEDLINE, EMBASE, PorQuest and ClinicalTrials.gov. All clinical trials, epidemiology and mixed methods studies that reported the use of medical devices for non-cancer chronic pain management published between the 1st of January 1990 and the 30th of April 2022 were included. 13 studies were included in systematic review, of these 6 were used in the meta-analysis. Our meta-analysis for pain reduction showed that transcutaneous electrical nerve stimulation combined with instrument-assisted soft tissue mobilization treatment and pulsed electromagnetic therapy produced significant treatment on chronic lower back pain patients. Pooled evidence revealed the use of medical device related interventions resulted in 0.7 degree of pain reduction under a 0-10 scale. Significant improvement in disability scores, with a 7.44 degree reduction in disability level compared to a placebo using a 50 score range was also seen. Our analysis has shown that the optimal use of medical devices in a sustainable manner requires further research, needing larger cohort studies, greater gender parity, in a more diverse range of geographical locations.

A systematic review and network meta-analysis of pharmaceutical interventions used to manage chronic pain.

It is estimated 1.5 billion of the global population suffer from chronic pain with prevalence increasing with demographics including age. It is suggested long-term exposure to chronic could cause further health challenges reducing people's quality of life. Therefore, it is imperative to use effective treatment options. We explored the current pharmaceutical treatments available for chronic pain management to better understand drug efficacy and pain reduction. A systematic methodology was developed and published in PROSPERO (CRD42021235384). Keywords of opioids, acute pain, pain management, chronic pain, opiods, NSAIDs, and analgesics were used across PubMed, Science direct, ProQuest, Web of science, Ovid Psych INFO, PROSPERO, EBSCOhost, MEDLINE, ClinicalTrials.gov and EMBASE. All randomised controlled clinical trials (RCTs), epidemiology and mixed-methods studies published in English between the 1st of January 1990 and 30th of April 2022 were included. A total of 119 studies were included. The data was synthesised using a tri-partied statistical methodology of a meta-analysis (24), pairwise meta-analysis (24) and network meta-analysis (34). Mean, median, standard deviation and confidence intervals for various pain assessments were used as the main outcomes for pre-treatment pain scores at baseline, post-treatment pain scores and pain score changes of each group. Our meta-analysis revealed the significant reduction in chronic pain scores of patients taking NSAID versus non-steroidal opioid drugs was comparative to patients given placebo under a random effects model. Pooled evidence also indicated significant drug efficiency with Botulinum Toxin Type-A (BTX-A) and Ketamine. Chronic pain is a public health problem that requires far more effective pharmaceutical interventions with minimal better side-effect profiles which will aid to develop better clinical guidelines. The importance of understanding ubiquity of pain by clinicians, policy makers, researchers and academic scholars is vital to prevent social determinant which aggravates issue.

Risk assessment of deoxynivalenol in high-risk area of China by human biomonitoring using an improved high throughput UPLC-MS/MS method.

A risk assessment of deoxynivalenol (DON) was recently conducted for the residents in Henan province, China, where wheat as the staple food are highly consumed. A high-throughput sensitive UPLC-MS/MS method following 96-well µElution solid-phase extraction (SPE) were developed and validated for the determination of DON biomarkers in human urine. Isotope labelled internal standard, 13C-DON, was used for accurate quantification. Urinary samples collected from 151 healthy Chinese aged 2-78 years were processed with and without enzyme hydrolysis to determine total and free biomarkers, respectively. DON, and de-epoxy-deoxynivalenol (DOM-1) to a lesser extent, can be frequently detected in these samples both with and without enzyme hydrolysis. Free DOM-1 was detected at low level in human urine for the first time. Total DON was detected in all samples with a mean concentration at 47.6 ng mL-1. The mean and median probable daily intakes (PDI) for the whole participants, estimated to be 1.61 µg/kg bw and 1.10 µg/kg bw, both exceeded the PMTDI (1 µg/kg bw/day), indicating a potential risk for the residents in this area, especially for children and adolescents.

Indium-111 Capromab Pendetide (ProstaScint(®)) Demonstrates Renal Cell Carcinoma and Aortocaval Nodal Metastases from Prostate Adenocarcinoma.

A 62-year-old male with a history of radical prostatectomy for a Gleason 9 (4 + 5) pT3N0Mx prostate cancer presented with rising prostate-specific antigen of 9.0 ng/dl. A contrast-enhanced computerized tomography (CT) revealed an enhancing left upper pole renal mass and aortocaval lymph nodes. Indium (In)-111 Capromab Pendetide (ProstaScint(®)) single-photon emission computerized tomography-CT showed abnormal increased uptake in left renal mass and aortocaval lymph nodes with no uptake in the prostate bed or pelvic lymph nodes. He underwent left radical nephrectomy and dissection of aortocaval lymph nodes. Pathology showed renal clear cell carcinoma and metastatic prostate adenocarcinoma involving aortocaval lymph nodes. Our case demonstrates a rare combination of two different malignancies, prostate cancer and clear cell renal cell cancer, showing In-111 ProstaScint(®) uptake. Though ProstaScint(®) uptake in renal cell carcinoma and in metastatic aortocaval lymph nodes from prostate cancer may be seen in clinical practice, this combination has not been reported previously.

Active herpes zoster infection with cutaneous manifestation and adenopathy on FDG PET/CT.

We report a patient with history of Hodgkin lymphoma. Six months after treatment, 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography and/or computed tomography ([18F] FDG PET/CT) scan showed abnormal uptake in right axillary lymph nodes concerning for recurrence. In addition, PET/CT showed a new hypermetabolic skin lesion overlying the right scapula. Clinical evaluation was consistent with shingles, and the patient was treated with valacyclovir. Subsequent PET/CT scan was normal with no evidence of lymphoma. Although there have been reported cases of abnormal FDG in nodes or in skin due to herpes zoster, our case is unique in the literature in that the PET/CT demonstrates abnormalities involving both the skin and associated lymph nodes. The possibility of false positive uptake, not because of recurrent malignancy, must always be considered when abnormal FDG uptake is noted in the follow-up of oncology patients. Careful review of the scan and correlation with clinical findings can avoid false positive interpretation and facilitate patient management.

In vitro, ex vivo, and in vivo evaluation of the effect of saturated fat acid chain length on the transdermal behavior of ibuprofen-loaded microemulsions.

In this study, the effect of the saturated fatty acid (FA) chain length in the oil phase on the behavior of Ibuprofen (IBU)-loaded transdermal microemulsion (ME) was evaluated in vitro, ex vivo, and in vivo. Three oils classified as long (LFA), medium (MFA), and short (SFA) chain length oils, Cremophor RH40 (surfactant) and Transcutol P (cosurfactant) were selected after experimental optimization. The physicochemical properties of ME were characterized, including IBU solubility in excipients, pseudo-ternary phase diagram construction, particle size, zeta potential, viscosity, and stability. Permeation flux and residual amount of IBU ex vivo using Franz cell system occurred in the following order: MFA-based ME > LFA-based ME > SFA-based ME, which correlated well with the results of confocal scanning laser microscopy study and the in vivo retention study. The results of in vitro cytotoxicity study and skin irritation tests measured by differential scanning calorimetry were ranked in the following order: LFA-based ME > MFA-based ME > SFA-based ME. Moreover, MFA-based ME has the highest analgesic activity among all the treatment groups. MFA was found to be an optimal oil phase with appropriate FA chain length for IBU-loaded transdermal ME, which exhibited excellent physicochemical properties, low toxicity, and good permeability profile.

Non-azygos accessory fissure in right upper lobe associated with superior and inferior accessory fissures in right lower lobe.

Accessory fissures in the lungs are common congenital variations, usually detected as incidental findings in radiographs or CT scan. Accessory fissures can act as an anatomic barrier to the spread of inflammatory or neoplastic disease, as well as due to the variant anatomy, mimic lesions. It is important to recognize the presence of accessory fissures, as they affect surgical planning of pulmonary lobectomy and segmentectomy. Accessory fissure in the right upper lobe other than due to the anomalous course of azygos vein is very rare. We report a case of non-azygos accessory fissure, between the apical and the anterior segments of right upper lobe, along with superior and inferior accessory fissures in the right lower lobe.