Notes

XRCC1 inhibits harmful PARP1 trapping during Genetic make-up bottom excision repair.
This protocol was successfully applied to generate human, baboon (Papio anubis), rhesus (Macaca mulatta), and cynomolgus macaque (Macaca fascicularis) iPSCs from skin fibroblasts. The resulting NHP-iPSCs provide a valuable resource for the preclinical testing of regenerative therapies in NHP.The prevalence of iron overload cardiomyopathy (IOC) is increasing. Patients with transfusion-dependent anemias or conditions associated with increased iron absorption over time are at a significant risk for the development of iron-overloaded states such as IOC. Current guidelines regarding the diagnostic evaluation and follow-up of patients at risk for IOC exist, and are composed of multiple components, including such as echocardiography, genetic testing, magnetic resonance imaging of liver, and cardiac magnetic resonance imaging (CMR). While these are considered reliable for the evaluation of patients at risk for an iron-overloaded state, there is an access challenge associated with initial and serial CMR scanning in this patient population. Furthermore, there are other limiting factors, such as patient characteristics that may preclude the use of CMR as a viable diagnostic imaging modality for these patients. On the other hand, recent evidence in the literature suggests that transthoracic echocardiography, which has had significant technological advances, can equal or even outperform CMR to identify cardiac functional abnormalities such as subclinical left ventricular strain and left atrial functional abnormalities in iron overload conditions. Therefore, there is a potential role of more frequent use of echocardiography for surveillance of the development of IOC. Our purpose with this narrative review is to describe recent advances in echocardiography and propose a potential increased use of echocardiography in the surveillance of the development of IOC.
Non-alcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease. Vitamin E (VE), an anti-oxidant, has shown improvement in NAFLD activity score (NAS) but not fibrosis. Pentoxiphylline (PTX), ananti-TNF-alpha agent, has been reported to reduce hepatic inflammation and fibrosis. We evaluated combination of these drugs in NASH patients.

In a prospective study, consecutive histologically proven patients with NASH were randomized to receive either PTX, 400mg thrice daily and VE 400IU twice daily (group PTVE, n = 36) or VE alone (group VE, n = 33). Clinical, dietary and biochemical follow-up was done till 12months. Primary end-point was change in alanine aminotransferase (ALT) levels. RESULTS Both groups were comparable at baseline. On a strict diet and lifestyle modification regimen, both groups had similar reduction in body mass index and waist circumference. There was asimilar reduction in ALT levels in the two groups. Oxaliplatin in vivo Metabolically, patients in PTVE group had greater reduction in fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) than VE group (p = 0.05). Tumor necrosis factor alpha (TNFα) levels were also significantly lower in PTVE group from 6months onwards. Twelve (10%) patients had repeat liver biopsy (7 in group PTVE, 5 in group VE) with no difference in reduction of NAS score (p = 0.45). However, there was a significant fibrosis regression in PTVE compared to VE group (p = 0.003).

These data show greater efficacy of a combination of PTX and VE in achieving fibrosis regression compared to VE alone with better metabolic homeostasis and amelioration of the pro-inflammatory status.

Clinical Trials Registry no. NCT01384578.
Clinical Trials Registry no. NCT01384578.An LC-MS/MS method has been developed for the sensitive and selective determination of 35 mycotoxins (biomarkers of exposure) in pig urine samples. Sample preparation includes creatinine adjustment (with the developed LC-UV method) with enzymatic hydrolysis of pig urine samples followed by liquid-liquid (LLE) extraction. The LLE protocol, as well as enzymatic hydrolysis for indirect mycotoxin glucuronides determination, was optimized in this study. Additionally, two other sample preparation protocols were compared with the developed LLE method immunoaffinity columns and solid-phase extraction cartridges (Oasis HLB). The detection and quantification of the biomarkers were performed using triple quadrupole mass spectrometry.The method was validated with regard to the guidelines specified by the EMEA (European Medicines Agency). The extraction recoveries were higher than 60% for 77% of the analytes studied, with the intra- and inter-day relative standard deviation being lower than 20% for most of the compounds at four different concentration levels. The limits of quantification ranged from 0.1 ng/mL for zearalenone and sterigmatocystin to 8 ng/mL for nivalenol. To the best knowledge of the authors, the matrix effect was evaluated for the first time in this study for six different urine samples, and the coefficient of variation was found to be lower than 15% for most analytes studied. Finally, the developed method was applied to analyse 56 pig urine samples. Deoxynivalenol (1-20 ng/mL), zearalenone (0.1-1.5 ng/mL) and ochratoxin A (1.5-15 ng/mL) were the main analytes detected in these samples. Moreover, the co-occurrence of alternariol monomethyl ether and alternariol in pig urine is reported herein for the first time.
Fragility hip fractures are common and costly. Secondary fracture prevention is a treatment goal following hip fracture; however, the number of those that proceed to fracture their contralateral hip in Ireland is unknown. There are plans to introduce a Fracture Liaison Service Database in Ireland which will aim to prevent secondary fractures. To establish a baseline figure for secondary hip fractures, the injury radiographs of 1284 patients from 6 teaching hospitals over a 1-year period were reviewed.

Irish Hip Fracture Datasheets and corresponding injury radiographs were reviewed locally for all hip fractures within each respective teaching hospital for a 1-year period (2019).

A total of 8.7% of all fragilityhip fractures across the 6 hospitals were secondary hip fractures (range 4.9-11.5%). 46% occurred within years 1 to 3 following index hip fracture. Forty-eight per cent of patients were started on bone protection medications following their second hip fracture.

Approximately 1 in 11 hip fractures treated across the 6 teaching hospitals assessed in 2019 was a patient's second hip fracture.
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