Correction of fetal umbilical vein flow imbalance following laser surgery for twin-twin transfusion syndrome.

OBJECTIVES: Twin-twin transfusion syndrome (TTTS) is characterized by unequal hemodynamics between the twins. We aimed to assess preoperatively the difference in umbilical vein flow (UVF) between the recipient and donor monochorionic diamniotic twins and evaluate the change in UVF following laser surgery in both twins. METHODS: This was a retrospective cohort study of differences in UVF that occurred following laser surgical treatment of TTTS. Sonographic assessment of the umbilical vein before and 24 h after fetoscopic laser surgery for TTTS was performed. Umbilical vein diameter and time-averaged maximum velocity were measured, and UVF per kg (UVF/kg) was converted into a Z-score by a calculator created using gestational age as an independent variable. Z-score values were converted into centiles, which were evaluated statistically. Median differences in UVF/kg centile values were adjusted for TTTS stage and presence of arterioarterial anastomoses. RESULTS: The study population consisted of 363 TTTS patients. The adjusted preoperative median difference in UVF/kg centile between the recipient vs donor twin was 17.9% (-17.1% to 57.6%), P < 0.0001. The adjusted median difference in UVF/kg centile between the postoperative vs preoperative period among recipients was 2.2% (-10.8% to 13.8%), P < 0.0001, while the adjusted median difference among donors was 27.3% (8.2%-34.6%), P < 0.0001. CONCLUSION: The preoperative difference in UVF between the recipient and donor twins confirms the pathophysiology of TTTS. Postoperatively, the substantial increase in UVF of the donor twin and the relatively small increase in UVF of the recipient twin confirm that ablation of the vascular communications resulted in rapid improvement in perfusion of the donor twin. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The pharmacokinetics, metabolism and urinary detection time of tramadol in camels.

The pharmacokinetics of tramadol in camels (Camelus dromedarius) were studied following a single intravenous (IV) and a single intramuscular (IM) dose of 2.33 mg kg(-1) bodyweight. The drug's metabolism and urinary detection time were also investigated. Following both IV and IM administration, tramadol was extracted from plasma using an automated solid phase extraction method and the concentration measured by gas chromatography-mass spectrometry (GC/MS). The plasma drug concentrations after IV administration were best fitted by an open two-compartment model. However a three-compartment open model best fitted the IM data. The results (means+/-SEM) were as follows: after IV drug administration, the distribution half-life (t(1/2)(alpha)) was 0.22+/-0.05 h, the elimination half-life (t(1/2)(beta)) 1.33+/-0.18 h, the total body clearance (Cl(T)) 1.94+/-0.18 L h kg(-1), the volume of distribution at steady state (Vd(ss)) 2.58+/-0.44 L kg(-1), and the area under the concentration vs. time curve (AUC(0-infinity)) 1.25+/-0.13 mg h L(-1). Following IM administration, the maximal plasma tramadol concentration (C(max)) reached was 0.44+/-0.07 microg mL(-1) at time (T(max)) 0.57+/-0.11h; the absorption half-life (t(1/2 ka)) was 0.17+/-0.03 h, the (t(1/2)(beta)) was 3.24+/-0.55 h, the (AUC(0-infinity)) was 1.27+/-0.12 mg h L(-1), the (Vd(area)) was 8.94+/-1.41 L kg(-1), and the mean systemic bioavailability (F) was 101.62%. Three main tramadol metabolites were detected in urine. These were O-desmethyltramadol, N,O-desmethyltramadol and/or N-bis-desmethyltramadol, and hydroxy-tramadol. O-Desmethyltramadol was found to be the main metabolite. The urinary detection times for tramadol and O-desmethyltramadol were 24 and 48 h, respectively. The pharmacokinetics of tramadol in camels was characterised by a fast clearance, large volume of distribution and brief half-life, which resulted in a short detection time. O-Desmethyltramadol detection in positive cases would increase the reliability of reporting tramadol abuse.

Tristetraprolin regulates Cyclin D1 and c-Myc mRNA stability in response to rapamycin in an Akt-dependent manner via p38 MAPK signaling.

The differential expression of the critical cell cycle control proteins cyclin D1 and c-myc has been shown to result in Akt-dependent hypersensitivity of tumor cells to mTOR inhibitors. We have previously demonstrated that the differential utilization of internal ribosome entry sites within the mRNAs of these transcripts allows maintenance of protein synthesis in the face of rapamycin (rapa) exposure in an Akt-dependent manner. Here, we demonstrate that in addition to this mechanism, cyclin D1 and c-myc mRNA stability is also coordinately regulated following rapa treatment depending on Akt activity status. We identify A/U-rich response elements within the 3' untranslated regions (UTRs) of these transcripts, which confer the observed differential stabilities and show that the RNA-binding protein, tristetraprolin (TTP), interacts with these elements. We also present evidence that TTP accumulates in response to rapa exposure, binds to the cis-acting elements within the cyclin D1 and c-myc 3' UTRs and is differentially serine phosphorylated in an Akt-dependent manner. Furthermore, the differential phosphorylation status of TTP results in its sequestration by 14-3-3 proteins in quiescent Akt-containing cells. Finally, siRNA-mediated knockdown of TTP expression or inhibiting a known regulator of TTP phosphorylation, p38 MAP kinase, abolishes the effects on cyclin D1 and c-myc mRNA stability. We assume that the differential control of cyclin D1 and c-myc mRNA stability and translational efficiency constitutes a coordinate response to rapa contributing to the maintenance of expression of these determinants in rapa-resistant quiescent Akt-containing cells following exposure.

Is vitamin A deficiency a problem among pregnant Emirati women in Al-Ain City?

Vitamin A deficiency (VAD) can have a negative impact on pregnancy but there have been no studies in Al-Ain on the vitamin A status of pregnant women. We studied 198 pregnant Emirati women aged 15-49 years attending antenatal clinics in Al-Ain Medical District (1999-2000) to assess the prevalence of VAD. Sociodemographic and health information about the women was collected by questionnaire and they all underwent blood and serum analysis. Of the 198 women, only 6 (3%) had vitamin A deficiency (plasma vitamin A < 20 microg/dL), indicating only a mild problem according to WHO criteria. There was no significant association between the occurrence of VAD and any of the characteristics studied. While the mean values of all the haematological indices were slightly lower in the vitamin A deficient group, this was not significant.

Is vitamin A deficiency a problem among pregnant Emirati women in Al-Ain City?

Vitamin A deficiency [VAD] can have a negative impact on pregnancy but there have been no studies in Al-Ain on the vitamin A status of pregnant women. We studied 198 pregnant Emirati women aged 15-49 years attending antenatal clinics in Al-Ain Medical District [1999-2000] to assess the prevalence of VAD. Sociodemographic and health information about the women was collected by questionnaire and they all underwent blood and serum analysis. Of the 198 women, only 6 [3%] had vitamin A deficiency [plasma vitamin A < 20 micro g/dL], indicating only a mild problem according to WHO criteria. There was no significant association between the occurrence of VAD and any of the characteristics studied. While the mean values of all the haematological indices were slightly lower in the vitamin A deficient group, this was not significant