Drug interactions between hormonal contraceptives and antiretrovirals

To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals

Isolation, purification, and full NMR assignments of cyclopamine from Veratrum californicum

The Hedgehog signaling pathway is essential for embryogenesis and for tissue homeostasis in the adult. However, it may induce malignancies in a number of tissues when constitutively activated, and it may also have a role in other forms of normal and maladaptive growth. Cyclopamine, a naturally occurring steroidal alkaloid, specifically inhibits the Hedgehog pathway by binding directly to Smoothened, an important Hedgehog response element. To use cyclopamine as a tool to explore and/or inhibit the Hedgehog pathway in vivo, a substantial quantity is required, and as a practical matter cyclopamine has been effectively unavailable for usage in animals larger than mice

Determining the Phosphorus Release Curve for Smizyme TS G5 2,500 Phytase from 500 to 2,500 FTU/kg in Nursery Pig Diets

A total of 320 pigs (DNA 241 × 600; initially 26.2 ± 0.48 lb BW) were used in a 21-d growth study to determine the available P (aP) release curve for Smizyme TS G5 2,500 (Barentz, Woodbury, MN). At approximately 19 d of age, pigs were weaned, randomly allotted to pens, and fed common starter diets. Pigs were blocked by average pen body weight (BW) and randomly allotted to 1 of 8 dietary treatments on d 18 post-weaning, considered d 0 of the study. Dietary treatments were derived from a single basal diet and ingredients including phytase, monocalcium P, limestone, and sand were added to create the treatment diets. Treatments included 3 diets containing increasing (0.11, 0.19, and 0.27%) inorganic P from monocalcium P, or 5 diets with increasing phytase (500, 1,000, 1,500, 2,000, or 2,500 FTU/kg) added to the diet containing 0.11% aP. All diets were corn-soybean meal-canola meal-based and were formulated to contain 1.24% SID Lys and an analyzed Ca:P ratio of 1.10:1. Prior to the beginning of the study, all pigs were fed a diet containing 0.11% aP for a 2-d period (d 16 to 18 post-weaning). At the conclusion of the study, 1 pig, closest to the mean weight of each pen, was euthanized and the right fibula, rib, and metacarpal were collected to determine bone ash, density, and total bone P. For the overall experimental period, pigs fed increasing inorganic P had improved (quadratic, P ≤ 0.053) ADG, ADFI, F/G, and final BW. Pigs fed increasing phytase had improved (quadratic, P ≤ 0.004) ADG, F/G, and final BW and increased (linear, P = 0.019) ADFI. For fibula, rib, and metacarpal characteristics, pigs fed increasing levels of aP from inorganic P had increased (linear, P \u3c 0.001) bone ash weight, bone ash percentage, bone density, and bone P. Additionally, pigs fed increasing phytase had increased (P \u3c 0.05) bone ash weight, bone ash percentage, bone density, and bone P in either a linear or quadratic manner depending upon bone. The available P release curve generated for Smizyme TS G5 2,500 for percentage bone ash is: aP = (0.219 × FTU) ÷ (993.238 + FTU)

A Landscape Analysis of Offering HIV Testing Services Within Family Planning Service Delivery

Introduction: Offering HIV testing services (HTS) within sexual and reproductive health (SRH) services is a priority, especially for women who have a substantial risk. To reach women with HIV who do not know their status and prevent mother-to-child HIV transmission, the World Health Organization (WHO) recommends routinely offering HTS as part of family planning (FP) service delivery in high HIV burden settings. We conducted a landscape analysis to assess HTS uptake and HIV positivity in the context of FP/SRH services. Assessment of Research and Programs: We searched records from PubMed, four gray literature databases, and 13 organization websites, and emailed 24 organizations for data on HTS in FP/SRH services. We also obtained data from International Planned Parenthood Federation (IPPF) affiliates in Eswatini, Kenya, Lesotho, Malawi, Namibia, Uganda, Zambia, and Zimbabwe. Unique programs/studies from records were included if they provided data on, or barriers/facilitators to, offering HTS in FP/SRH. Overall, 2,197 records were screened and 12 unique programs/studies were eligible, including 10 from sub-Saharan Africa. Four reported on co-delivery of SRH services (including FP), with reported HTS uptake between 17 and 94%. Six reported data on HTS in FP services: four among general FP clients; one among couples; and one among female sex workers, adolescent girls, and young women. Two of the six reported HTS uptake >50% (51%, 419/814 Kenya; 63%, 5,930/9,439 Uganda), with positivity rates of 2% and 4.1%, respectively. Uptake was low (8%, 74/969 Kenya) in the one FP program offering pre-exposure prophylaxis. In the IPPF program, seven countries reported HTS uptake in FP services and ranged from 4% in Eswatini to 90% in Lesotho; between 0.6% (Uganda) and 8% (Eswatini) of those tested were HIV positive. Implications: Data on providing HTS in FP/SRH service delivery were sparse and HTS uptake varied widely across programs. Actionable Recommendations: As countries expand HTS in FP/SRH appropriate to epidemiology, they should ensure data are reported and monitored for progress and impact

PREDICTING THE SUMMER TEMPERATURE OF SMALL STREAMS IN SOUTHWESTERN WISCONSIN 1

One of the biggest challenges in managing cold water streams in the Midwest is understanding how stream temperature is controlled by the complex interactions among meteorologic processes, channel geometry, and ground water inflow. Inflow of cold ground water, shade provided by riparian vegetation, and channel width are the most important factors controlling summer stream temperatures. A simple screening model was used to quantitatively evaluate the importance of these factors and guide management decisions. The model uses an analytical solution to the heat transport equation to predict steady-state temperature throughout a stream reach. The model matches field data from four streams in southwestern Wisconsin quite well (typically within 1°C) and helps explain the observed warming and cooling trends along each stream reach. The distribution of ground water inflow throughout a stream reach has an important influence on stream temperature, and springs are especially effective at providing thermal refuge for fish. Although simple, this model provides insight into the importance of ground water and the impact different management strategies, such as planting trees to increase shade, may have on summer stream temperature.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74032/1/j.1752-1688.2005.tb03714.x.pd

SUMOylation of Syntaxin1A regulates presynaptic endocytosis

Neurotransmitter release from the presynaptic terminal is under very precise spatial and temporal control. Following neurotransmitter release, synaptic vesicles are recycled by endocytosis and refilled with neurotransmitter. During the exocytosis event leading to release, SNARE proteins provide most of the mechanical force for membrane fusion. Here, we show one of these proteins, Syntaxin1A, is SUMOylated near its C-terminal transmembrane domain in an activity-dependent manner. Preventing SUMOylation of Syntaxin1A reduces its interaction with other SNARE proteins and disrupts the balance of synaptic vesicle endo/exocytosis, resulting in an increase in endocytosis. These results indicate that SUMOylation regulates the emerging role of Syntaxin1A in vesicle endocytosis, which in turn, modulates neurotransmitter release and synaptic function

A preferentially segregated recycling vesicle pool of limited size supports neurotransmission in native central synapses

At small central synapses, efficient turnover of vesicles is crucial for stimulus-driven transmission, but how the structure of this recycling pool relates to its functional role remains unclear. Here we characterize the organizational principles of functional vesicles at native hippocampal synapses with nanoscale resolution using fluorescent dye labeling and electron microscopy. We show that the recycling pool broadly scales with the magnitude of the total vesicle pool, but its average size is small (∼45 vesicles), highly variable, and regulated by CDK5/calcineurin activity. Spatial analysis demonstrates that recycling vesicles are preferentially arranged near the active zone and this segregation is abolished by actin stabilization, slowing the rate of activity-driven exocytosis. Our approach reveals a similarly biased recycling pool distribution at synapses in visual cortex activated by sensory stimulation in vivo. We suggest that in small native central synapses, efficient release of a limited pool of vesicles relies on their favored spatial positioning within the termina

Synapsin- and Actin-Dependent Frequency Enhancement in Mouse Hippocampal Mossy Fiber Synapses

The synapsin proteins have different roles in excitatory and inhibitory synaptic terminals. We demonstrate a differential role between types of excitatory terminals. Structural and functional aspects of the hippocampal mossy fiber (MF) synapses were studied in wild-type (WT) mice and in synapsin double-knockout mice (DKO). A severe reduction in the number of synaptic vesicles situated more than 100 nm away from the presynaptic membrane active zone was found in the synapsin DKO animals. The ultrastructural level gave concomitant reduction in F-actin immunoreactivity observed at the periactive endocytic zone of the MF terminals. Frequency facilitation was normal in synapsin DKO mice at low firing rates (∼0.1 Hz) but was impaired at firing rates within the physiological range (∼2 Hz). Synapses made by associational/commissural fibers showed comparatively small frequency facilitation at the same frequencies. Synapsin-dependent facilitation in MF synapses of WT mice was attenuated by blocking F-actin polymerization with cytochalasin B in hippocampal slices. Synapsin III, selectively seen in MF synapses, is enriched specifically in the area adjacent to the synaptic cleft. This may underlie the ability of synapsin III to promote synaptic depression, contributing to the reduced frequency facilitation observed in the absence of synapsins I and II

Oral Health in Women During Preconception and Pregnancy: Implications for Birth Outcomes and Infant Oral Health

The mouth is an obvious portal of entry to the body, and oral health reflects and influences general health and well being. Maternal oral health has significant implications for birth outcomes and infant oral health. Maternal periodontal disease, that is, a chronic infection of the gingiva and supporting tooth structures, has been associated with preterm birth, development of preeclampsia, and delivery of a small-for-gestational age infant. Maternal oral flora is transmitted to the newborn infant, and increased cariogenic flora in the mother predisposes the infant to the development of caries. It is intriguing to consider preconception, pregnancy, or intrapartum treatment of oral health conditions as a mechanism to improve women's oral and general health, pregnancy outcomes, and their children's dental health. However, given the relationship between oral health and general health, oral health care should be a goal in its own right for all individuals. Regardless of the potential for improved oral health to improve pregnancy outcomes, public policies that support comprehensive dental services for vulnerable women of childbearing age should be expanded so that their own oral and general health is safeguarded and their children's risk of caries is reduced. Oral health promotion should include education of women and their health care providers ways to prevent oral disease from occurring, and referral for dental services when disease is present