A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites

Toxicogenetic

Subcutaneous Stimulation as Add-on Therapy to Spinal Cord Stimulation in Patients With Persistent Spinal Pain Syndrome Significantly Increases the Total Electrical Charge per Second: Aspects on Stimulation Parameters and Energy Requirements of the Implanted Neurostimulators.

OBJECTIVE: In our previous multicenter randomized controlled trial, we demonstrated the clinical effectiveness of peripheral nerve field stimulation (PNFS) as add-on therapy to spinal cord stimulation (SCS) for the treatment of chronic back pain in patients with persistent spinal pain syndrome (PSPS) or failed back surgery syndrome (FBSS). To our knowledge, no previous study has investigated the effect of PNFS as an add-on to SCS on the energy consumption of the implanted neurostimulators. Therefore, in this study, we compared the specific stimulation parameters and energy requirements of a previously unreported group of patients with only SCS with those of a group of patients with SCS and add-on PNFS. We also investigated differences that might explain the need for PNFS in the treatment of chronic low back pain. MATERIALS AND METHODS: We analyzed 75 patients with complete sets of stimulation parameters, with 21 patients in the SCS-only group and 54 patients in the SCS + PNFS group. Outcome measures were average visual analog scale score, SCS parameters (voltage, frequency, and pulse width), SCS charge per second, and total charge per second. We analyzed baseline characteristics and differences between and within groups over time. RESULTS: Both groups had comparable patient characteristics at baseline and showed a significant decrease in back and leg pain. SCS charge per second did not significantly differ between the groups at baseline or at 12 months. The total charge per second was significantly higher in the active SCS + PNFS group than in the SCS-only group at baseline; in the SCS + PNFS group, this persisted for up to 12 months, and the SCS charge per second and total charge per second increased significantly over time. CONCLUSIONS: Our results show that add-on PNFS increases the total charge per second compared with SCS alone, as expected. However, further research is needed because our results do not directly explain why some patients require add-on PNFS to treat low back pain

Spinal Cord Stimulation With Additional Peripheral Nerve/Field Stimulation Versus Spinal Cord Stimulation Alone on Back Pain and Quality of Life in Patients With Persistent Spinal Pain Syndrome.

INTRODUCTION: Persistent spinal pain syndrome (PSPS) or failed back surgery syndrome (FBSS) refers to new or persistent pain following spinal surgery for back or leg pain in a subset of patients. Spinal cord stimulation (SCS) is a neuromodulation technique that can be considered in patients with predominant leg pain refractory to conservative treatment. Patients with predominant low back pain benefit less from SCS. Another neuromodulation technique for treatment of chronic low back pain is subcutaneous stimulation or peripheral nerve field stimulation (PNFS). We investigated the effect of SCS with additional PNFS on pain and quality of life of patients with PSPS compared with that of SCS alone after 12 months. MATERIALS AND METHODS: This is a comparative study of patients with PSPS who responded to treatment with either SCS + PNFS or SCS only following a multicenter randomized clinical trial protocol. In total, 75 patients completed the 12-month follow-up: 21 in the SCS-only group and 54 in the SCS + PNFS group. Outcome measures were pain (visual analog scale), quality of life (36-Item Short Form Survey [SF-36]), anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), overall health (EuroQol Five-Dimension [EQ-5D]), disability (Oswestry Disability Index [ODI]), and pain assessed by the McGill questionnaire. RESULTS: There were no significant differences in baseline characteristics between the two groups. Both groups showed a significant reduction in back and leg pain at 12 months compared with baseline measurements. No significant differences were found between the groups in effect on both primary (pain) and secondary parameters (SF-36, HADS, EQ-5D, ODI, and McGill pain). CONCLUSION: In a subgroup of patients with chronic back and leg pain, SCS alone provided similar long-term pain relief and quality-of-life improvement as PNFS in addition to SCS. In patients with refractory low back pain not responding to SCS alone, adding PNFS should be recommended. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT01776749

Nonpeptidergic allosteric antagonists differentially bind to the CXCR2 chemokine receptor

The chemokine receptor CXCR2 is involved in different inflammatory diseases, like chronic obstructive pulmonary disease, psoriasis, rheumatoid arthritis, and ulcerative colitis; therefore, it is considered an attractive drug target. Different classes of small CXCR2 antagonists have been developed. In this study, we selected seven CXCR2 antagonists from the diarylurea, imida-zolylpyrimide, and thiazolopyrimidine class and studied their mechanisms of action at human CXCR2. All compounds are able to displac

Thyroid function in neonates conceived after hysterosalpingography with iodinated contrast

STUDY QUESTION: Does exposure to preconceptional hysterosalpingography (HSG) with iodinated oil-based contrast affect neonatal thyroid function as compared to iodinated water-based contrast? SUMMARY ANSWER: Preconceptional HSG with iodinated contrast did not influence the neonatal thyroid function. WHAT IS KNOWN ALREADY: HSG is a commonly applied tubal patency test during fertility work-up in which either oil- or water-based contrast is used. Oil-based contrast contains more iodine compared to water-based contrast. A previous study in an East Asian population found an increased risk of congenital hypothyroidism (CH) in neonates whose mothers were exposed to high amounts of oil-based contrast during HSG. STUDY DESIGN, SIZE, DURATION: This is a retrospective data analysis of the H2Oil study, a randomized controlled trial (RCT) comparing HSG with the use of oil- versus water-based contrast during fertility work-up. After an HSG with oil-based contrast, 214 women had an ongoing pregnancy within 6 months leading to a live birth compared to 155 women after HSG with water-based contrast. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 369 women who had a live born infant, 208 consented to be approached for future research and 138 provided informed consent to collect data on the thyroid function tests of their offspring (n = 140). Thyroid function tests of these children were retrieved from the Dutch neonatal screening program, which includes the assessment of total thyroxine (T4) in all newborns, followed by thyroid-stimulating hormone only in those with a T4 level of = -0.8 SD score. Furthermore, amount of contrast medium used and time between HSG and conception were compared between the two study groups. MAIN RESULTS AND THE ROLE OF CHANCE: Data were collected from 140 neonates conceived after HSG with oil-based (n = 76) or water-based (n = 64) contrast. The median T4 concentration was 87.0 nmol/l [76.0-96.0] in the oil group and 90.0 nmol/l [78.0-106.0] in the water group (P = 0.13). None of the neonates had a positive screening result for CH. The median amount of contrast medium used was 9.0 ml [interquartile range (IQR), 6.0-11.8] in the oil-group and 10.0 ml [IQR, 7.5-14.0] in the water group (P = 0.43). No influence of the amount of contrast on the effect of contrast group on T4 concentrations was found (P-value for interaction, 0.37). LIMITATIONS, REASONS FOR CAUTION: A relatively small sample size and possible attrition at follow-up are limitations of this study. Although our results suggest that the use of iodinated contrast media for HSG is safe for the offspring, the impact of a decrease in maternal thyroid function on offspring neurodevelopment could not be excluded, as data on maternal thyroid function after HSG and during conception were lacking. WIDER IMPLICATIONS OF THE FINDINGS: As HSG with oil-based contrast does not affect thyroid function of the offspring, there is no reason to withhold this contrast to infertile women undergoing HSG. Future studies should investigate whether HSG with iodinated contrast influences the periconceptional maternal thyroid function and, consequently, offspring neurodevelopment