Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins.

BACKGROUND: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

Spontaneous Membranization in a Silk-Based Coacervate Protocell Model.

Molecularly crowded coacervate micro-droplets are useful protocell constructs but the absence of a physical membrane limits their application as cytomimetic models. Auxiliary surface-active agents have been harnessed to stabilize the coacervate droplets by irreversible shell formation but endogenous processes of reversible membranization have received minimal attention. Herein, we describe a dynamic alginate/silk coacervate-based protocell model in which membrane-less droplets are reversibly reconfigured and inflated into semipermeable coacervate vesicles by spontaneous self-organization of amphiphilic silk polymers at the droplet surface under non-neutral charge conditions in the absence of auxiliary agents. We show that membranization can be reversibly controlled endogenously by programming the pH within the protocells using an antagonistic enzyme system such that structural reconfigurations in the protocell microstructure are coupled to the trafficking of water-soluble solutes. Our results open new perspectives in the design of hybrid protocell models with dynamical structural properties.

The Hassan Neonatal Morbidity Composite Scale and Neonatal Length of Stay-A Validation Study.

OBJECTIVE: Obstetric studies often report neonatal morbidity as a composite score. Composite scores can simplify data analysis when multiple outcomes of interest are present and allows researchers to conduct smaller, more manageable trials. The Hassan scale is a neonatal morbidity composite scale that assigns high scores to infants with multiple morbidities and low scores to infants without or with single morbidities. The objective of this study was to validate the association between scores on the Hassan scale and neonatal intensive care unit (NICU) length of stay STUDY DESIGN: We conducted a cohort study of all infants born between 22 and 366/7 weeks' gestation and cared for within 419 neonatal units in the Pediatrix Medical Group between 1997 and 2018. Each infant was assigned a Hassan's score based on the number of neonatal morbidity events that occurred during the delivery hospitalization. The association between Hassan's scores and neonatal length of stay was evaluated using linear regression. Multivariable models were constructed to determine if the Hassan score was independently associated with neonatal length of stay. RESULTS: There were 760,037 infants included. The median (interquartile range [IQR]) gestational age of delivery was 34 (31, 35) weeks and the median (IQR) birth weight at delivery was 2,000 (1,503, 2,430) g. The median length of stay for infants discharged home was 17 (10-33) days. A Hassan's score was able to be assigned to 699,206 (92%) patients. Neonatal morbidities included in the Hassan scale were more common among infants born earlier in gestation. On adjusted analysis, the Hassan scale was found to be independently associated with neonatal length of stay (p < 0.001, coefficient = 10.4 days [95% confidence interval (CI): 10.3, 10.4 days]) with higher scores associated with longer lengths of stay. CONCLUSION: The Hassan scale, more than a binary composite score, is able to differentiate preterm infants with prolonged hospitalizations from those with short hospitalizations. KEY POINTS: · The Hassan scale is an independent predictor of neonatal length of stay.. · Classification of infants based on number of morbidities correlates with neonatal length of stay.. · The Hassan scale provided better discrimination than binary composite morbidity scores.. · The Hassan scale may be an economic predictor of health-related costs..

Hydrogel-Immobilized Coacervate Droplets as Modular Microreactor Assemblies.

Immobilization of compartmentalized microscale objects in 3D hydrogels provides a step towards the modular assembly of soft functional materials with tunable architectures and distributed functionalities. Herein, we report the use of a combination of micro-compartmentalization, immobilization, and modularization to fabricate and assemble hydrogel-based microreactor assemblies comprising millions of functionalized polysaccharide-polynucleotide coacervate droplets. The heterogeneous hydrogels can be structurally fused by interfacial crosslinking and coupled as input and output modules to implement a UV-induced photocatalytic/peroxidation nanoparticle/DNAzyme reaction cascade that generates a spatiotemporal fluorescence read-out depending on the droplet number density, intensity of photoenergization, and chemical flux. Our approach offers a route to heterogeneous hydrogels with endogenous reactivity and reconfigurable architecture, and provides a step towards the development of soft modular materials with programmable functionality.

Programmed assembly of synthetic protocells into thermoresponsive prototissues.

Although several new types of synthetic cell-like entities are now available, their structural integration into spatially interlinked prototissues that communicate and display coordinated functions remains a considerable challenge. Here we describe the programmed assembly of synthetic prototissue constructs based on the bio-orthogonal adhesion of a spatially confined binary community of protein-polymer protocells, termed proteinosomes. The thermoresponsive properties of the interlinked proteinosomes are used collectively to generate prototissue spheroids capable of reversible contractions that can be enzymatically modulated and exploited for mechanochemical transduction. Overall, our methodology opens up a route to the fabrication of artificial tissue-like materials capable of collective behaviours, and addresses important emerging challenges in bottom-up synthetic biology and bioinspired engineering.

The Effect of Blood Loss on Cefazolin Levels in Women Undergoing Cesarean Delivery.

OBJECTIVE: To quantify the effects of operative blood loss during cesarean on tissue and plasma cefazolin concentrations. STUDY DESIGN: This was a prospective observational study of singleton pregnancies undergoing scheduled cesarean between 34 and 40 weeks. Cefazolin administered prior to skin incision. Maternal plasma samples were obtained (Time 1[T1]: immediately, T2: 20 minutes, T3: 40 minutes, and T4: 60 minutes after cefazolin infusion). Subcutaneous adipose tissue sampled before and after fascia. Primary outcome was subcutaneous adipose cefazolin level after fascial closure. Formal quantitative blood loss (QBL) performed. Women with higher QBL, those at/above 75% of QBL in this population, were compared with those with lower QBL (QBL below 75%). Data analyzed using bivariable statistics. RESULTS: Ninety-two women were screened, 32 were eligible, and 20 enrolled. Median QBL was 630 mL (interquartile range [IQR]: 473-818) and 1,160 mL (IQR: 1,000-1,560) in the low and high QBL groups, respectively. Demographics and operative characteristics were similar. Median adipose cefazolin level after fascial closure did not differ between the groups (3.5 vs. 3.9 µg/g, p = 0.75). No differences in maternal plasma cefazolin concentrations between the groups at any time point or in pharmacokinetic parameters were seen. CONCLUSION: Intraoperative maternal plasma concentrations and adipose levels of cefazolin are similar between women with high and low blood loss at the time of cesarean delivery.

Impact of toothpaste on oral health-related quality of life in people with dentine hypersensitivity.

BACKGROUND: Dentine hypersensitivity can impact functional status and everyday activities such as eating and talking. This study aimed to assess changes in oral health-related quality of life measures in individuals with dentine hypersensitivity following long-term use (24 weeks) of a commercially available toothpaste marketed for dentine hypersensitivity relief. METHODS: This study was conducted across two sites and enrolled 75 adults with ≥2 non-adjacent sensitive teeth. Participants were assigned to twice-daily brushing with toothpaste containing 0.454% w/w stannous fluoride (1100 ppm fluoride). Every 4 weeks, participant-reported outcomes were assessed using the Dentine Hypersensitivity Experience Questionnaire (DHEQ), a condition specific oral health-related quality of life scale that has five domains and includes questions on social and emotional impact, restrictions, adaptations and effect on life overall. Responses to a clinically applied evaporative (air) stimulus were assessed using the examiner-observed Schiff sensitivity scale and Labelled Magnitude Scales (LMS), which included dentine hypersensitivity-specific descriptors of intensity, duration, tolerability and descriptive qualities of the participant's response. RESULTS: Participant-reported outcomes demonstrated reduction of the impact of dentine hypersensitivity over time on health-related quality of life, as measured by the DHEQ. This reached statistical significance from Week 8 onwards (p < 0.0001 versus baseline) for the Total DHEQ score, with scores continually decreasing at each timepoint. Most domain scores followed a similar pattern. Statistically significant reductions were also detected for the examiner-observed Schiff Sensitivity Scale scores at all timepoints (including at 4 weeks) (p < 0.05), which were mirrored by LMS responses. The toothpaste was generally well-tolerated. CONCLUSIONS: These results show that long-term use of a sensitivity toothpaste containing 0.454% w/w stannous fluoride has a beneficial, ongoing, impact on the oral health-related quality of life of people with dentine hypersensitivity. TRIAL REGISTRATION: This study was registered at Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT02752958 ) on April 27, 2016.

Randomized Controlled Clinical Study to Determine the Oral and Dermal Tolerability of an Experimental Denture Wipe.

PURPOSE: To evaluate oral and dermal tolerance following use and user acceptability of an experimental denture-cleansing wipe. An exploratory objective was to develop a method to assess denture wipe effectiveness in removing debris from denture surfaces. MATERIALS AND METHODS: This was a single-center, randomized, controlled, parallel-group, examiner-blind study in participants with ≥1 full/partial denture. Participants were randomized to clean their dentures with the denture wipe (n = 76) or water (n = 76) up to 4 times per day for 14 days. Tolerability was assessed by treatment-emergent adverse events (TEAEs), oral soft tissue examination, and lead hand dermatological assessment. Acceptability was assessed by questionnaire. The feasibility of a methodology to assess the efficacy of the wipe at removing food particles was also evaluated through determination of the mass of chewed peanut particles that the wipe removed after a single use (n = 31). RESULTS: The proportion of participants experiencing oral TEAEs by day 14 was 0.039% with the denture wipe (lip injury [n = 1], mouth injury [n = 2]) and 0.013% with the water rinse (coated tongue [n = 1]). There were no dermal TEAEs and no TEAE-related study withdrawals. Skin irritation scores with the denture wipe remained unchanged from baseline. Comparing before vs. after cleaning with the denture wipe, a higher proportion of participants rated their dentures as feeling extremely/very fresh (28.9% pre-/85.5% post-cleaning), feeling extremely/very clean (34.2%/86.8%) and looking extremely/very clean (43.5%/85.5%). More denture-wipe group participants than water-rinse group participants were extremely/very satisfied with the amount of debris removed from their dentures (88.1% vs 72.4%). The methodology used to assess the weight of peanut particles captured from the wipes/dentures appeared to be a feasible investigation technique. CONCLUSIONS: The denture wipe was generally well-tolerated and had good user acceptability. The methodology for assessing the mass of peanut particles removed by denture wipes was successful.

Modulation of Higher-order Behaviour in Model Protocell Communities by Artificial Phagocytosis.

Collective behaviour in mixed populations of synthetic protocells is an unexplored area of bottom-up synthetic biology. The dynamics of a model protocell community is exploited to modulate the function and higher-order behaviour of mixed populations of bioinorganic protocells in response to a process of artificial phagocytosis. Enzyme-loaded silica colloidosomes are spontaneously engulfed by magnetic Pickering emulsion (MPE) droplets containing complementary enzyme substrates to initiate a range of processes within the host/guest protocells. Specifically, catalase, lipase, or alkaline phosphatase-filled colloidosomes are used to trigger phagocytosis-induced buoyancy, membrane reconstruction, or hydrogelation, respectively, within the MPE droplets. The results highlight the potential for exploiting surface-contact interactions between different membrane-bounded droplets to transfer and co-locate discrete chemical packages (artificial organelles) in communities of synthetic protocells.

Ionization of Submicrometer-Sized Particles by Laser-Induced Radiofrequency Plasma for Mass Spectrometric Analysis.

A laser-induced rf plasma (LIRFP) ion source was developed to ionize submicrometer-sized particles for the first time. The LIRFP ion source can increase the charge of those particles to several thousand charges via charge exchange reactions so that those particles can be trapped and analyzed with a charge detection quadrupole ion trap-mass spectrometer (CD QIT-MS). Different reagent gases for charge exchange reaction were investigated, viz. argon, nitrogen, oxygen, methane, helium, krypton, xenon, argon/methane (with ratios of 10:1 and 2:1), argon/nitrogen (with a ratio of 1:1), nitrogen/oxygen (10:1), krypton/methane (10:1), and air. The average charge of 0.75 µm polystyrene particles could reach 1631 using an argon/methane mixture with a ratio of ∼10:1. The average charges for freeze-dried Escherichia coli EC11303, Escherichia coli strain W, and Staphylococcus aureus were 842, 1112, and 971, respectively, with a mass-to-charge ratio ( m/ z) range from 107 to 108; and the average masses were 3.5 × 1010 Da, 6.0 × 1010 Da, and 5.6 × 1010 Da, respectively. The average mass and charge of the vaccinia virus were ∼9.1 × 109 Da and ∼708 with a m/ z of ∼107. This LIRFP CD QIT-MS method was rapid with only 20 min for each sample measurement.

Fabrication of Micropatterned Dipeptide Hydrogels by Acoustic Trapping of Stimulus-Responsive Coacervate Droplets.

Acoustic standing waves offer an excellent opportunity to trap and spatially manipulate colloidal objects. This noncontact technique is used for the in situ formation and patterning in aqueous solution of 1D or 2D arrays of pH-responsive coacervate microdroplets comprising poly(diallyldimethylammonium) chloride and the dipeptide N-fluorenyl-9-methoxy-carbonyl-D-alanine-D-alanine. Decreasing the pH of the preformed droplet arrays results in dipeptide nanofilament self-assembly and subsequent formation of a micropatterned supramolecular hydrogel that can be removed as a self-supporting monolith. Guest molecules such as molecular dyes, proteins, and oligonucleotides are sequestered specifically within the coacervate droplets during acoustic processing to produce micropatterned hydrogels containing spatially organized functional components. Using this strategy, the site-specific isolation of multiple enzymes to drive a catalytic cascade within the micropatterned hydrogel films is exploited.

Construction of supramolecular hydrogels using photo-generated nitric oxide radicals.

Photo-generated nitric oxide radicals (NO˙) derived from sodium nitroprusside dihydrate (SNP) are employed for the construction of supramolecular hydrogels based on an amino acid derivative precursor, N-fluorenylmethyloxycarbonyl tyrosine phosphate (FYP), which through dephosphorylation produces the gelator, N-fluorenylmethyloxycarbonyl tyrosine (FY). Self-assembly of the amphiphilic gelator yields high-aspect ratio nanofilaments that entangle to form self-supporting, viscoelastic hydrogels. The presence of photolyzed SNP yields periodically twisted nanofilaments with opposite chirality to filaments formed through conventional hydrogelation routes.

Differences in Type I interferon response in human lung epithelial cells infected by highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses.

Influenza A virus infection induces type I interferons (IFNs α/ß) which activate host antiviral responses through a cascade of IFN signaling events. Herein, we compared highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses isolated from India, for their replication kinetics and ability to induce IFN-ß and interferon-stimulating genes (ISGs). The H5N1 virus showed a higher replication rate and induced less IFN-ß and ISGs compared to the H11N1 virus when grown in the human lung epithelial A549 cells, reflecting the generation of differential innate immune responses during infection by these viruses. The non-structural 1 (NS1) protein, a major IFN-antagonist, known to help the virus in evading host innate immune response was compared from both the strains using bioinformatics tools. Analyses revealed differences in the composition of the NS1 proteins from the two strains that may have an impact on the modulation of the innate immune response. Intriguingly, H5N1 virus attenuated IFN-ß response in a non-NS1 manner, suggesting the possible involvement of other viral proteins (PB2, PA, PB1/PB1-F2) of H5N1 in synergy with NS1. Preliminary analyses of the above proteins of the two strains by sequence comparison show differences in charged residues. The insight gained will be useful in designing experimental studies to elucidate a probable role of the polymerase protein(s) in association with NS1 in inhibiting the IFN signaling and understanding the molecular mechanism governing the difference.

Bioinformatics characterization of envelope glycoprotein from Kyasanur Forest disease virus.

BACKGROUND & OBJECTIVES: Kyasanur Forest disease (KFD) is a febrile illness characterized by haemorrhages and caused by KFD virus (KFDV), which belongs to the Flaviviridae family. It is reported to be an endemic disease in Shimoga district of Karnataka State, India, especially in forested and adjoining areas. Several outbreaks have been reported in newer areas, which raised queries regarding the changing nature of structural proteins if any. The objective of the study was to investigate amino acid composition and antigenic variability if any, among the envelope glycoprotein (E-proteins) from old and new strains of KFDV. METHODS: Bioinformatic tools and techniques were used to predict B-cell epitopes and three-dimensional structures and to compare envelope glycoprotein (E-proteins) between the old strains of KFDV and those from emerging outbreaks till 2015. RESULTS: The strain from recent outbreak in Thirthahalli, Karnataka State (2014), was similar to the older strain of KFDV (99.2%). Although mutations existed in strains from 2015 in Kerala KFD sequences, these did not alter the epitopes. INTERPRETATION & CONCLUSIONS: The study revealed that though mutations existed, there were no drastic changes in the structure or antigenicity of the E-proteins from recent outbreaks. Hence, no correlation could be established between the mutations and detection in new geographical areas. It seems that KFDV must be present earlier also in many States and due to availability of testing system and alertness coming into notice now.

Uterocervical Angle Measurement Improves Prediction of Preterm Birth in Twin Gestation.

OBJECTIVE: Twin pregnancies are associated with an increased risk of spontaneous preterm birth. Our objective was to compare the performance of uterocervical angle to cervical length as predictors of spontaneous preterm birth in this population. METHODS: We conducted a retrospective cohort study of twin gestations at a single center from May 2008 to 2016 who received a transvaginal ultrasound for the evaluation of the cervix between 16 0/7 and 23 0/7 weeks. The primary outcome was prediction of preterm birth <28 and <32 weeks by uterocervical angle and cervical length. RESULTS: Among 259 women with twin gestation, the mean gestational age at birth was 34.83 ± 3.48 weeks. Receiver operator characteristic curves demonstrated optimal prediction of spontaneous preterm birth prior to 32 weeks at a uterocervical angle >110° (80% sensitivity, 82% specificity) [odds ratio (OR), 15.7 (95% confidence interval (CI), 7.2-34.4)] versus cervical length <20 mm (53% sensitivity, 85% specificity; p < 0.001, OR, 6.4 [95% CI, 2.3-17.8]) and similarly, prior to 28 weeks at a uterocervical angle >114° (OR, 24.3 [95% CI, 6.7-88.5]) compared with cervical length <20 mm (OR, 11.4 [95% CI, 3.5-36.7]). CONCLUSION: Uterocervical angles >110° performed better than cervical length for the prediction of spontaneous preterm birth in twin gestations.

An exploratory study to investigate stain build-up with long term use of a stannous fluoride dentifrice.

PURPOSE: To monitor extrinsic stain formation over 24 weeks with twice-daily use of an anhydrous 0.454% SnF2 dentifrice containing 5% sodium tripolyphosphate (STP) ('Test'), compared to a standard fluoride dentifrice (0.76% fluoride as sodium monofluorophosphate [SMFP\) ('Comparator') following a professional prophylaxis. METHODS: Primary efficacy variables were between-treatment differences in extrinsic dental stain of anterior teeth after 4, 8, 12, and 24 weeks' use using mean area and intensity scores of the MacPherson modification of the Lobene stain index (MLSI), and to monitor oral tolerability. RESULTS: Overall, 214 subjects were randomized to treatment. The Test dentifrice group demonstrated statistically significantly less stain compared with the Comparator at each timepoint for all outcome variables (MLSI - Area × Intensity, Area only, and Intensity only) with the exception of MLSI (Area × Intensity) at Week 12. Products were generally well tolerated with 26 treatment-related adverse events (TRAEs) reported (10 with Test, 16 with Comparator). Five subjects withdrew from the 24-week study due to TRAEs, three in the Test group, two in the Comparator group. Statistically significantly less anterior tooth staining was observed with up to 24 weeks twice-daily brushing with a 0.454% SnF2/5% STP anhydrous dentifrice compared to a marketed fluoride dentifrice with 0.76% SMFP. CLINICAL SIGNIFICANCE: Long term use of a SnF2/STP dentifrice demonstrated minimal stain build-up after 24 weeks, twice-daily use; products were generally well-tolerated.

Transplacental Passage of Acetaminophen in Term Pregnancy.

Objective The objective of this study was to determine the maternal and fetal pharmacokinetic (PK) profiles of acetaminophen after administration of a therapeutic oral dose. Study Design After obtaining Institutional Review Board approval and their written informed consent, pregnant women were given a single oral dose (1,000 mg) of acetaminophen upon admission for scheduled cesarean delivery. Maternal venous blood and fetal cord blood were obtained at the time of delivery and acetaminophen levels were measured using gas chromatography-mass spectroscopy. PK parameters were calculated by noncompartmental analysis. Nonparametric correlation of maternal/fetal acetaminophen levels and PK curves were calculated. Results In this study, 34 subjects were enrolled (median, 32 years; range, 25-39 years). The median maternal weight was 82 kg (range, 62-100 kg). All but two subjects were delivered beyond 39 weeks' gestation. The median newborn birth weight was 3,590 g (interquartile range, 3,403-3,848 g). Noncompartmental analysis described similar PK parameters in the maternal (T1/2, 84 minutes; apparent clearance [Cl/F], 28.8 L/h; apparent volume of distribution [Vd/F], 57.5 L) and fetal compartments (T1/2, 82 minutes; Cl/F, 31.2 L/h; Vd/F, 61.2 L). Paired maternal/fetal acetaminophen levels were highly correlated (p < 0.0001). Conclusion Fetal acetaminophen PKs in the fetus parallels that in the mother suggesting that placental transfer is flow limited. Maternal acetaminophen levels can be used as a surrogate for fetal exposure.

Laparoscopic donor nephrectomy in unusual venous anatomy - donor and recepient implications.

OBJECTIVES: Laparoscopic donor nephrectomy is now a commonly performed procedure in most of renal transplantation centers. However, the suitability of laparoscopy for donors with abnormal venous anatomy is still a subject of debate. MATERIALS AND METHODS: Between August 2007 and August 2014, 243 laparoscopic donor nephrectomies were performed in our institution. All donors were evaluated with preoperative three-dimensional spiral computed tomography (CT) angiography Thirteen (5.35%) donors had a left renal vein anomaly. A retrospective analysis was performed to collect donor and recipient demographics and perioperative data. RESULTS: Four donors had a type I retroaortic vein, seven had type II retroaortic vein and a circumaortic vein was seen in three donors. The mean operative time was 114±11 minutes and mean warm ischemia time was 202±12 seconds. The mean blood loss was 52.7±18.4mL and no donor required blood transfusion. Mean recipient creatinine at the time of discharge was 1.15±0.18mg/dL, and creatinine at six months and one year follow-up was 1.12±0.13mg/dL and 1.2±0.14mg/dL, respectively. There were no significant differences in operative time, blood loss, warm ischemia time, donor hospital stay or recipient creatinine at 6 months follow-up, following laparoscopic donor nephrectomy in patients with or without left renal vein anomalies. CONCLUSION: Preoperative delineation of venous anatomy using CT angiography is as important as arterial anatomy. Laparoscopic donor nephrectomy is safe and feasible in patients with retroaortic or circumaortic renal vein with good recipient outcome.