Quantification of Plasma and Urine Thymidine and 2'-Deoxyuridine by LC-MS/MS for the Pharmacodynamic Evaluation of Erythrocyte Encapsulated Thymidine Phosphorylase in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disorder caused by mutations in TYMP, leading to a deficiency in thymidine phosphorylase and a subsequent systemic accumulation of thymidine and 2'-deoxyuridine. Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is under clinical development as an enzyme replacement therapy for MNGIE. Bioanalytical methods were developed according to regulatory guidelines for the quantification of thymidine and 2'-deoxyuridine in plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for supporting the pharmacodynamic evaluation of EE-TP. Samples were deproteinized with 5% perchloric acid (v/v) and the supernatants analyzed using a Hypercarb column (30 × 2.1 mm, 3 µm), with mobile phases of 0.1% formic acid in methanol and 0.1% formic acid in deionized water. Detection was conducted using an ion-spray interface running in positive mode. Isotopically labelled thymidine and 2'-deoxyuridine were used as internal standards. Calibration curves for both metabolites showed linearity (r > 0.99) in the concentration ranges of 10-10,000 ng/mL for plasma, and 1-50 µg/mL for urine, with method analytical performances within the acceptable criteria for quality control samples. The plasma method was successfully applied to the diagnosis of two patients with MNGIE and the quantification of plasma metabolites in three patients treated with EE-TP

Perceived vocal morbidity in a problem asthma clinic

<p>Aims: Asthma treatment has the potential to affect patients' voices. We undertook detailed characterisation of voice morbidity in patients attending a problem asthma clinic, and we determined how patients' perceptions related to objective assessment by an experienced observer.</p> <p>Methods: Forty-three patients took part in the study. Subjects completed the self-administered voice symptom score (VoiSS) questionnaire and underwent digital voice recording. These voice recordings were scored using the grade–roughness–breathiness–asthenicity–strain system (GRBAS). Laryngoscopy was also performed.</p> <p>Results: The median VoiSS was 26 (range three to 83). VoiSS were significantly lower in the 17 patients with normal laryngeal structure and function (range four to 46; median 22), compared with the 26 patients with functional or structural laryngeal abnormality (range three to 83; median 33) (95 per cent confidence intervals for difference 0.0–21.0; p = 0.044). The overall grade score for the GRBAS scale did not differ between these two groups, and only 13 patients had a GRBAS score of one or more, recognised as indicating a voice problem. There were positive correlations between related GRBAS score and voice symptom score subscales. Although voice symptom scores were significantly more abnormal in patients with structural and functional abnormalities, this score performed only moderately well as a predictive tool (sensitivity 54 per cent; specificity 71 per cent). Nevertheless, the voice symptom score performed as well as the more labour-intensive GRBAS score (sensitivity 57 per cent; specificity 60 per cent). Patients' inhaled corticosteroid dose (median dose 1000 µg beclomethasone dipropionate or equivalent) had a statistically significant relationship with their overall grade score for the GRBAS scale (r = 0.56; p < 0.001), but not with their VoiSS. Only one patient had evidence of laryngeal candidiasis, and only two had any evidence of abnormality suggesting steroid-induced myopathy.</p> <p>Conclusions: Vocal morbidity is common in patients with asthma, and should not be immediately attributed to steroid-related candidiasis. The VoiSS merits further, prospective validation as a screening tool for ENT and/or speech and language therapy referral in patients with asthma.</p&gt

The effects of obesity with pregnancy termination: a literature review

Obesity has become a major health problem in the United States as well as globally which may affect the safety of pregnancy termination. Thus, a literature review was conducted to determine the available evidence regarding the effects of obesity with pregnancy termination to assist with patient care and counseling. The available evidence is limited by small numbers and descriptive study design. While pregnancy termination upon obese women may impart additional technical challenges, experienced providers complete procedures upon obese women without statistically significant differences in procedure or patient outcomes compared to normal weight women for first trimester gestations. Pharmacological abortion may be a more practical option in some very obese women

Look before you LEEP: patient reported pain with IV sedation vs local analgesia

Objective: Examine the effectiveness of IV sedation in addition local analgesia compared to local analgesia alone for LEEP pain management. Methods: This quality improvement project surveyed 89 patients who underwent a LEEP procedure: 26 in the local only group and 63 in the IV + local group. Patients completed a visual analog scale and pain survey immediately following their LEEP. Results: The local analgesia + IV sedation group reported a lower average pain score compared to the local analgesia only group (2.4 ± 2.2 v 3.6 ± 2.7). However, this was not statistically significant, p 0.47. Patients found it was helpful to know what to expect prior to the LEEP and utilized various means of pain relief in addition to the primary treatments assessed. Conclusions: There is a need for high quality trials to determine best practices of pain management

Full thickness epidermal burn from a heating pad on a cesarean incision with silver dressing: a case report

We present a case of a full thickness epidermal burn resulting from an all-natural clay-based heating pad over a cesarean incision silver dressing to bring awareness to the risks associated with nonpharmacologic management of post cesarean pain. There is limited guidance on nonpharmacological management of post cesarean pain. It is important that providers are able to advise their patients about their options, including to be wary of using heating pads on post-cesarean dressings, especially with pain in the early post-partum period

Validity and Reliability of Electronic Devices to Measure Muscular Power during Linear Weight Lifting Movements

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Anatomic brain asymmetry in vervet monkeys.

Asymmetry is a prominent feature of human brains with important functional consequences. Many asymmetric traits show population bias, but little is known about the genetic and environmental sources contributing to inter-individual variance. Anatomic asymmetry has been observed in Old World monkeys, but the evidence for the direction and extent of asymmetry is equivocal and only one study has estimated the genetic contributions to inter-individual variance. In this study we characterize a range of qualitative and quantitative asymmetry measures in structural brain MRIs acquired from an extended pedigree of Old World vervet monkeys (n = 357), and implement variance component methods to estimate the proportion of trait variance attributable to genetic and environmental sources. Four of six asymmetry measures show pedigree-level bias and one of the traits has a significant heritability estimate of about 30%. We also found that environmental variables more significantly influence the width of the right compared to the left prefrontal lobe

Planned use of long acting reversible postpartum contraception in low-risk women in CenteringPregnancy® group versus individual physician prenatal care

Introduction: Education on effective contraceptive methods is necessary during the prenatal period to help women achieve optimal birth spacing. This study identified rates of long-acting reversible contraception (LARC) uptake in women who attended CenteringPregnancy® (CP) group prenatal care versus individual physician care (IP). Methods: Charts for low-risk women who participated in group CP or IP prenatal care between March 2012 and May 2016 were reviewed. Charts of IP subjects were randomly selected in each year to achieve a CP:IP ratio of at least 1:3. The primary outcome was rate of LARC use at discharge and within 8 weeks postpartum. Pearson chi-squared test and Wilcoxon rank-sum tests were performed, and a p-value <0.05 was considered significant. Results: 129 women participated in CP care and 412 in IP care. CP women were more likely nulliparous (91, or 70.5% vs 212, or 51.5%, p=0.0001) and more likely to attend at least 15 prenatal visits (54, or 41.9% vs 62, or 15.1%, p<0.0001). LARC use rates at discharge and at the postpartum visit were similar (36, or 27.9% vs 89, or 21.6%, p=0.142; 39, or 32.2% vs 110, or 29.4%, p=0.557). Rates of women using effective contraception (LARC and other hormonal options, including oral contraceptives and Depo Provera) at discharge and at the postpartum visit were similar (59, or 45.7% vs 206, or 50.0%, p=0.177; 72, or 59.5% vs 229, or 61.2%, p=0.157). IUD use was greater than subdermal implant use in both groups (31, or 24.0% vs 5, or 3.9%; 72, or 17.5% vs 17, or 4.1%; p=0.081). Rates of routine postpartum visit attendance at 6-8 weeks postpartum were similar and high in both groups (121, or 93.8% vs 374, or 90.8%; adjusted p-value=0.164). Conclusion: Although CP subjects had more prenatal visits and spent more time with providers, there was no difference on uptake of LARC or effective contraception at discharge or at the postpartum visit when compared to IP subjects

Management of vaginal wall perforation during a second trimester dilation and evacuation

Background: We report an unusual case involving vaginal perforation associated with second trimester dilation and evacuation. Review of the literature fails to identify additional reports. Case: A 22 year G3P1011 female at 16 weeks gestation referred for evaluation following incomplete dilation and evacuation was found to have vaginal perforation, and communication with the peritoneal cavity on pelvic examination. Examination under anesthesia and laparoscopy confirmed multiple vaginal perforations with intraperitoneal defects and hematomas but no viscus involvement. Cervical dilation was accomplished with osmotic dilators placed under ultrasound guidance during exam under anesthesia, with evacuation completed approximately 16 hours later without further complication. Conclusion: This is the first case of vaginal perforation at time of dilation and evacuation reported in the literature. Laparoscopy should be performed to evaluate for intraabdominal injury to bowel, bladder and/or blood vessels. Use of osmotic dilators during the second trimester could potentially decrease the risk of vaginal perforation during the dilation portion of the procedure

Postpartum LARC use in low-risk women in CenteringPregnancy® versus traditional certified nurse midwife prenatal care

Contraception satisfaction and utilization is linked to pre-use clinical counseling. Group prenatal care may offer increased opportunity for education on postpartum contraception options. This study evaluated postpartum long acting reversible contraception (LARC) rates in women who attend CenteringPregnancy® group prenatal (CP) care versus individual prenatal care with Certified Nurse Midwives (CNM)