The association between the introduction of quantitative assessment of postpartum blood loss and institutional changes in clinical practice: an observational study.

BACKGROUND: Imprecise visual estimates of blood loss contribute to morbidity from postpartum hemorrhage. We examined the impact of quantitative assessment of postpartum blood loss on clinical practice and outcomes. METHODS: An observational study comparing blood loss, management and outcomes between two historical cohorts (August 2016 to January 2017 and August 2017 to January 2018) at an academic tertiary care center. Patients in the intervention group (second period) had blood loss quantified compared with visual estimation for controls. RESULTS: We included 7618 deliveries (intervention group n=3807; control group n=3811). There was an increase in the incidence of hemorrhage (blood loss >1 L) in the intervention group for both vaginal (2.2% vs 0.5%, P <0.001) and cesarean delivery (12.6% vs 6.4%, P <0.001). There was also a difference in median blood loss for vaginal (258 mL [151-384] vs 300 mL [300-350], P <0.001); and for cesarean delivery (702 mL [501-857] vs 800 mL [800-900], P <0.001). The median red blood cell units transfused was different in the intervention group having cesarean delivery (2 units [1-2] vs 2 units [2-2], P=0.043). Secondary uterotonic usage was greater in the intervention group for vaginal (22% vs 17.3%, P <0.001) but not cesarean delivery (7.0% vs 6.0%, P=0.177). Laboratory costs were different, but not the re-admission rate or length of stay. CONCLUSIONS: Quantifying blood loss may result in increased vigilance for vaginal and cesarean delivery. We identified an association between quantifying blood loss and improved identification of postpartum hemorrhage, patient management steps and cost savings.

Physical exercise and non-insulin glucose-lowering therapies in the management of Type 2 diabetes mellitus: a clinical review.

In the UK the National Institute of Health and Care Excellence (NICE) advocates intensive lifestyle programmes that attain the levels of daily physical activity set out by the Chief Medical Officer as a first-line strategy for improving the health of people at risk of developing diabetes or reducing the risk of development of Type 2 diabetes. For people with Type 2 diabetes, lifestyle measures complement pharmacological treatments that include both oral and injectable therapies. In line with this, NICE guidelines also support intensification of efforts to improve patient lifestyle along with these glucose-lowering therapies. There is a paucity of evidence, however, in the available published literature examining the association between glucose-lowering therapies and exercise metabolism. In the present review we explore the current knowledge with regard to the potential interactions of oral and non-insulin injectable therapies with physical activity in people at risk of, or who have, Type 2 diabetes, and present evidence that may inform healthcare professionals of the need to monitor patients more closely in their adaptation to both pharmacological therapy and physical activity.

Wide anterior neck dissection for management of recurrent thyroglossal duct cysts in adults.

OBJECTIVE: Thyroglossal duct cyst recurrence following resection is attributed to anatomical variability and residual thyroglossal ducts. In adults, thyroglossal duct cyst recurrence is extremely rare and a surgical solution is yet to be well explored. This paper describes our approach to the management of recurrent thyroglossal duct cysts and sinuses in adults using a wide anterior neck dissection. METHOD: A retrospective review was performed to identify adults who underwent a wide anterior neck dissection for recurrent thyroglossal duct cyst management between 1 January 2009 and 1 January 2015. RESULTS: Six males and one female were included in the series (mean age, 26.4 ± 10.9 years). Recurrence occurred at a mean of 18 ± 9.8 months following primary surgical management (3 patients underwent cystectomy and 4 had a Sistrunk procedure). All patients subsequently underwent wide anterior neck dissection; there was no further recurrence over the 12-month average follow-up period. CONCLUSION: This paper describes a wide anterior neck dissection technique for the management of recurrent thyroglossal duct cysts or sinuses in adults; this approach addresses the variable anatomy of the thyroglossal duct and is associated with minimal morbidity.

Phosphonic Acids for Interfacial Engineering of Transparent Conductive Oxides.

Transparent conducting oxides (TCOs), such as indium tin oxide and zinc oxide, play an important role as electrode materials in organic-semiconductor devices. The properties of the inorganic-organic interface-the offset between the TCO Fermi level and the relevant transport level, the extent to which the organic semiconductor can wet the oxide surface, and the influence of the surface on semiconductor morphology-significantly affect device performance. This review surveys the literature on TCO modification with phosphonic acids (PAs), which has increasingly been used to engineer these interfacial properties. The first part outlines the relevance of TCO surface modification to organic electronics, surveys methods for the synthesis of PAs, discusses the modes by which they can bind to TCO surfaces, and compares PAs to alternative organic surface modifiers. The next section discusses methods of PA monolayer deposition, the kinetics of monolayer formation, and structural evidence regarding molecular orientation on TCOs. The next sections discuss TCO work-function modification using PAs, tuning of TCO surface energy using PAs, and initiation of polymerizations from TCO-tethered PAs. Finally, studies that examine the use of PA-modified TCOs in organic light-emitting diodes and organic photovoltaics are compared.

Enhanced permittivity and energy density in neat poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) terpolymer films through control of morphology.

Polymer materials with large dielectric constants are desirable for the development of high energy density capacitors. We show that the dielectric properties of poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) [P(VDF-TrFE-CTFE)] can be improved by the use of processing conditions that favor formation of a highly crystalline morphology of the nonpolar α-phase. Through the use of spin coating, thermal treatment above the melting temperature, and quenching, we were able to attain a highly crystalline, α-phase rich morphology that has a quite large dielectric constant of 77 ± 10 at 1 kHz. The final morphology and phase composition of the terpolymer films depend strongly on the postprocessing thermal treatment and the quality of the solvent. Evaluation of the polarization behavior of the terpolymer films as a function of electric field reveal that the polymer exhibits a relaxor-ferroelectric behavior and has a substantial energy density of 9.7 J/cm(3) at fields of up to approximately 470 V/µm. Under millisecond pulsed charge-discharge measurements a 3-fold increase in energy density (27 J/cm(3)) is obtained at high fields (∼600 V/µm). Our study demonstrates that the processing conditions and morphology of fluorinated terpolymer films are controlling factors for achievement of high dielectric permittivity and energy density that are critical for high performance capacitors.

High-energy-density sol-gel thin film based on neat 2-cyanoethyltrimethoxysilane.

Hybrid organic-inorganic sol-gel dielectric thin films from a neat 2-cyanoethyltrimethoxysilane (CNETMS) precursor have been fabricated and their permittivity, dielectric strength, and energy density characterized. CNETMS sol-gel films possess compact, polar cyanoethyl groups and exhibit a relative permittivity of 20 at 1 kHz and breakdown strengths ranging from 650 V/µm to 250 V/µm for film thicknesses of 1.3 to 3.5 µm. Capacitors based on CNETMS films exhibit extractable energy densities of 7 J/cm(3) at 300 V/µm, as determined by charge-discharge and polarization-electric field measurements, as well as an energy extraction efficiency of ~91%. The large extractable energy resulting from the linear dielectric polarization behavior suggests that CNETMS films are promising sol-gel materials for pulsed power applications.

The effects of a community-based partnership, Project Access Dallas (PAD), on emergency department utilization and costs among the uninsured.

BACKGROUND: Approximately 19% of non-elderly adults are without health insurance. The uninsured frequently lack a source of primary care and are more likely to use the emergency department (ED) for routine care. Improving access to primary care for the uninsured is one strategy to reduce ED overutilization and related costs. METHODS: A comparison group quasi-experimental design was used to evaluate a broad-based community partnership that provided access to care for the uninsured-Project Access Dallas (PAD)-on ED utilization and related costs. Eligible uninsured patients seen in the ED were enrolled in PAD (n = 265) with similar patients not enrolled in PAD (n = 309) serving as controls. Study patients were aged 18-65 years, <200% of the federal poverty level and uninsured. Outcome measures include the number of ED visits, hospital days and direct and indirect costs. RESULTS: PAD program enrollees had significantly fewer ED visits (0.93 vs. 1.44; P < 0.01) and fewer inpatient hospital days (0.37 vs. 1.07; P < 0.05) than controls. Direct hospital costs were ∼60% less ($1188 vs. $446; P < 0.01) and indirect costs were 50% less ($313 vs. $692; P < 0.01). CONCLUSIONS: A broad-based community partnership program can significantly reduce ED utilization and related costs among the uninsured.

Membrane permeability of human oocytes in the presence of the cryoprotectant propane-1,2-diol.

OBJECTIVE: To determine the permeability of unfertilized human oocytes to water and the cryoprotectant propane-1,2-diol over a range of temperatures and to use these data to predict osmotic responses under given conditions. DESIGN: Laboratory-based study. SETTING: Teaching hospital. PATIENT(S): Infertility patients donating unfertilized oocytes in excess of those required for treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Water and cryoprotectant permeability were determined from measurements of oocyte volume excursions on exposure to 1.5 M propane-1,2-diol at 30 degrees C, 24 degrees C, and 10 degrees C. RESULT(S): Permeability of human oocytes to water and cryoprotectant increased as temperature increased. The predicted response of oocytes, based on these data, closely matched the measured response of an oocyte on exposure to a widely used method for addition of cryoprotectant before freezing. CONCLUSION(S): Commonly used cryopreservation protocols involving slow cooling in the presence of propane-1,2-diol cause potentially damaging excursions in cell volume on exposure to cryoprotectant. Modifications that can be expected to reduce cell volume excursions, based on oocyte permeability data, are suggested.

Fine-mapping, genomic organization, and transcript analysis of the human ubiquitin-conjugating enzyme gene UBE2L3.

The human UBE2L3 gene encodes the ubiquitin-conjugating enzyme UbcH7, demonstrated to participate in the ubiquitination of p53, c-Fos, and NF-kappaB in vitro. We report the fine-mapping of this four-exon gene to chromosome 22q11.2. We have constructed a comprehensive genomic clone contig across this gene, demonstrating that the gene lies adjacent to the microsatellite marker D22S446 and spans approximately 57 kb. Four mRNA species are transcribed from this gene, differing in the length of their 3' UTR. Sequence comparison of the UBE2L3 cDNA with its murine homologue reveals a remarkably high degree of sequence conservation within the 3'UTR.

Vitrification of mature mouse oocytes in a 6 M Me2SO solution supplemented with antifreeze glycoproteins: the effect of temperature.

Oocytes have been successfully cryopreserved using rapid and slow freezing procedures. However, variability in the success of replicates has limited its practical application. In the present study, mature mouse oocytes were vitrified in 6 M dimethyl sulfoxide supplemented with 1 mg/ml antifreeze glycoproteins (AFGP) (solution known as VSD + AFGP) from the blood of Antarctic notothenioid fish. Such AFGPs have been used to protect mammalian cells during hypothermia and cryopreservation. However, the degree of protection afforded is a contentious issue. Stepwise addition of cryoprotectant was performed either at room temperature (19-21 degreesC) or on ice (2-4 degreesC), at the final stage of which oocytes were pipetted into 0.25 ml plastic insemination straws and held in liquid nitrogen vapor at -140 degreesC for 3 min before being plunged into liquid nitrogen. Thawing involved holding the straw in the air for 10 s and then in water at 20 degreesC for 10 s before dilution of the VSD solution with 1 M sucrose. Viability was assessed by in vitro fertilization; results have been quoted as median (range). Statistical analyses were performed using Kruskall-Wallis and Mann-Whitney U tests (P < 0.05). Of the oocytes cryopreserved following exposure to VSD + AFGP at room temperature (n = 518, 15 experimental runs), 78% (0-94%) retained normal morphology and, of these, 53% (0-100%) cleaved to two cells. Of these two-cell embryos, 56% (0-100%) went on to develop to blastocyst. The overall percentage development to blastocyst, i.e., number of blastocysts/total number of oocytes treated x 100, was 20% (0-76%). Exposure of oocytes to the VSD + AFGP on ice prior to cryopreservation yielded significantly improved rates of fertilization (94%, 82-100%) and overall development to blastocyst (66%, 24-89%) when compared with oocytes cryopreserved following exposure to the VSD + AFGP at room temperature. Rates of normality (86%, 35-95%) and development to blastocyst (89%, 64-100%) were also improved. Cryopreservation in 6 M dimethyl sulfoxide supplemented with 1 mg/ml AFGP resulted in poor rates of survival which were highly variable when exposure to cryoprotective agent (CPA) was performed at room temperature. Lowering the temperature of exposure to CPA prior to cryopreservation resulted in improved viability.

Regression of feline immunodeficiency virus infection.

Regression of feline immunodeficiency virus (FIV) infection was observed in seven of nine vertically infected kittens born to two chronically infected mother cats. Both provirus and nonmaternal FIV antibody were detected in all kittens by 4 weeks of age but only three of the seven kittens were positive by blood mononuclear cell coculture. Between 10 and 14 months of age blood mononuclear cells from each of the seven cats were negative at least once by polymerase chain reaction (PCR), but evidence of virus infection was detected by coculture and/or PCR in biopsied lymph node or bone marrow from five of the seven cats. Despite this evidence of persistent tissue provirus, antibody production did not persist in any of the cats beyond 1 year of age. All seven cats remained asymptomatic although CD4 and CD8 T cell counts were in the low normal range throughout the study. By contrast, two additional perinatally infected littermates that were persistently virus isolation positive developed rapid CD4 depletion and progressed to terminal immunodeficiency by 9 weeks of age. Thus FIV infection can be downregulated and/or sequestered to extremely low levels barely detectable with the assays available, although absolute clearance of virus may not occur. These observations are relevant to human immunodeficiency virus (HIV) infection in paralleling both the apparent "regression" of HIV infection reported in some perinatally infected infants and the low-level, apparently stable, infection established by attenuated simian immunodeficiency viruses.

Vitrification of mature mouse oocytes: improved results following addition of polyethylene glycol to a dimethyl sulfoxide solution.

Oocytes have been successfully cryopreserved using rapid and slow freezing procedures; however, variability in the success of replicates has limited its practical application. We have evaluated the potentially beneficial effects of adding 1 mg/ml of the polymer polyethylene glycol (PEG) (M(r) 8000) to a 6 M dimethyl sulfoxide (Me2SO) vitrification solution. Stepwise addition of cryoprotectant, either with or without PEG, was performed at room temperature (19-21 degrees C). Oocytes were then loaded in plastic insemination straws and held in liquid nitrogen vapour at -140 degrees C for 3 min prior to storage in liquid nitrogen. Oocytes were warmed rapidly to room temperature and removal of cryoprotective agent was effected in the presence of 1 M sucrose solution. Viability was assessed by vitro fertilization. Oocytes cryopreserved after exposure to 6 M Me2SO in the absence of PEG showed 60% normality, 80% fertilization, and 55% development to blastocyst, median of 11 replicate experiments (191 oocytes). Individual replicates yield highly variable survival which ranged from 0 to 100%. The addition of PEG significantly improved oocyte normality to 95% (range 76-100%; median of 9 replicate experiments, 301 oocytes). Rates of fertilization (91%; 60-100%) and development of blastocyst (73%; 67-92) were also improved. The addition of 1 mg/ml PEG to a 6 M Me2SO solution resulted in greatly improved viability of oocytes following cryopreservation and vastly reduced the variability seen with Me2SO solution alone.

Mucosal transmission of cell-associated and cell-free feline immunodeficiency virus.

Mucosal infection by feline immunodeficiency virus (FIV) was assessed via a single exposure of the vaginal or rectal mucosa to either infectious peripheral blood mononuclear cells (PBMCs), infectious plasma, or cell-free cultured virus. All cats inoculated with cell-free cultured virus (100 or 400 TCID) and 9 of 10 cats inoculated with infected PBMCs (2 x 10(7) or 2 x 10(5)) became persistently viremic within 3 weeks. Neither cat inoculated with 2 x 10(3) PBMCs became viremic. Rectal and vaginal exposure were equally effective routes to induce viremia. CD4+ T cells and mitogen-stimulated PBMC proliferation declined in all infected cats. However, a transient PBMC proliferative response to FIV p24gag occurred in most virus-exposed cats, especially those that did not develop detectable infection. FIV was not transmitted by mucosal exposure to infectious virus in plasma (100 TCID), a dose > 10-fold that needed for infection by parental injection. In vitro studies suggested that a plasma heat-stable virus-neutralizing factor may be associated with failure of plasma virus to establish infection via the mucosal route. Mucosal FIV infection provides a new model with which to study early stages of infection and intervention in transmucosal lentivirus infections.

Frequent perinatal transmission of feline immunodeficiency virus by chronically infected cats.

Vertical transmission of feline immunodeficiency virus (FIV) was studied in cats infected with either of two FIV clinical isolates (FIV-B-2542 or FIV-AB-2771) prior to breeding and conception. Queens infected 4 to 30 months (mean = 14 months) prior to conception transmitted FIV to 59 of 83 (71%) kittens; 50.6% were virus positive on the day of birth. To examine potential routes of FIV transmission from mother to offspring, kittens were delivered via either vaginal or cesarean birth and nursed by either their virus-infected natural mothers or uninfected surrogate mothers. Comparison of FIV infection rates at birth with those at 6 months of age in kittens delivered by cesarean and surrogate raised demonstrated that late in utero transmission occurred in approximately 20% of kittens. Comparison of kittens nursed by FIV mothers with those by uninfected surrogate mothers demonstrated a 13.5% increase in infection rate of kittens exposed to milk-borne virus. Isolation of virus from 40% of maternal vaginal wash samples and the slightly greater infection rate in vaginally versus cesarean-delivered surrogate-nursed kittens suggested that intrapartum transmission may occur. In addition, we found that low maternal CD4 count (<200 cells per microl), longer duration of maternal infection (>15 months), and maternal symptoms of clinical immunodeficiency correlated with increased rates of mother-to-kitten FIV transmission, paralleling observations in human immunodeficiency virus-infected women. We conclude that FIV infection provides a model in which to explore aspects of human immunodeficiency virus vertical transmission and intervention difficult to address in human patients.

Plasma viral RNA load predicts disease progression in accelerated feline immunodeficiency virus infection.

Viral RNA load has been shown to indicate disease stage and predict the rapidity of disease progression in human immunodeficiency virus type 1 (HIV-1)-infected individuals. We had previously demonstrated that feline immunodeficiency virus (FIV) RNA levels in plasma correlate with disease stage in infected cats. Here we expand upon those observations by demonstrating that plasma virus load is 1 to 2 logs higher in cats with rapidly progressive FIV disease than in long-term survivors. Differences in plasma FIV RNA levels are evident by 1 to 2 weeks after infection and are consistent throughout infection. We also evaluated humoral immune responses in FIV-infected cats for correlation with survival times. Total anti-FIV antibody titers did not differ between cats with rapidly progressive FIV disease and long-term survivors. These findings indicate that virus replication plays an important role in FIV disease progression, as it does in HIV-1 disease progression. The parallels in virus loads and disease progressions between HIV-1 and FIV support the idea that the accelerated disease model is well suited for the study of therapeutic agents directed at reducing lentiviral replication.

Vertical transmission of feline immunodeficiency virus.

We studied vertical transmission of feline immunodeficiency virus (FIV) to determine whether it might provide a model with which to study intervention strategies for mother-to-offspring transmission of human immunodeficiency virus (HIV). We found that pregnant cats acutely infected with FIV (FIV-CSU-2771) transmitted the virus to their offspring via both prenatal and postnatal routes. In utero transmission led to several pathogenic consequences including arrested fetal development, abortion, stillbirth, subnormal birth weights, and birth of viable, virus-infected, and asymptomatic but T cell-deficient kittens. Postnatal milk-borne FIV transmission was demonstrated by the presence of cell-free and cell-associated virus in colostrum and milk and through a foster-nursing experiment. The potential for intrapartum FIV transmission was documented by frequent virus isolation from vaginal wash cells in both the pre- and postpartum periods. FIV transmission was efficient during acute maternal infection, leading to an overall infection rate of 70%. We conclude that FIV vertical transmission may be a useful model with which to evaluate intervention strategies for HIV transmission from mother to child.

Induction of accelerated feline immunodeficiency virus disease by acute-phase virus passage.

Development of feline immunodeficiency virus (FIV) infection in cats as a small animal model for lentiviral immunodeficiency disease has been hampered by the prolonged and variable disease course following experimental infection. To address this issue, we generated high-titer, unselected FIV stocks by pooling plasma from cats acutely infected with a subgroup C FIV isolate designated CABCpadyOOC (FIV-C-PGammer). Subsequent infection with this virus pool resulted in rapidly progressive, fatal disease in greater than 50% of infected cats. Accelerated FIV disease was characterized by rapid and progressive CD4+ T-cell loss, lymphadenopathy, weight loss, lymphoid depletion, and severe thymic atrophy. Mortality and rate of disease progression were affected by the age of each cat at infection and whether the virus source animal was in the acute or chronic stage of infection. The rapid FIV disease syndrome was consistently associated with systemic lymphoid depletion, clinical disease, and susceptibility to opportunistic infections, analogous to accelerated and/or terminal HIV-1 infection. The results of this study demonstrate that FIV infection is a valid small animal model for lentiviral immunodeficiency disease.