Drug interactions between rifamycin antibiotics and hormonal contraception: a systematic review.

BACKGROUND: Rifamycin antibiotics are commonly used for treatment of tuberculosis, but may reduce the effectiveness of hormonal contraception (HC). OBJECTIVES: To determine whether interactions between rifamycins and HC result in decreased effectiveness or increased toxicity of either therapy. SEARCH STRATEGY: We searched MEDLINE, Embase, Cochrane and clinicaltrials.gov through May 2017. SELECTION CRITERIA: We included trials, cohort, and case-control studies addressing pregnancy rates, pharmacodynamics or pharmacokinetic (PK) outcomes when HC and rifamycins were administered together versus apart. Of 7291 original records identified, 11 met inclusion criteria after independent review by two authors. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted study details and assessed study quality using the United States Preventive Services Task Force grading system. Findings are reported descriptively. MAIN RESULTS: Studies only addressed combined oral contraceptives (COCs) and none reported pregnancy rates. Quality ranged from good to poor. Rifampin increased the frequency of ovulation in two of four studies, and reduced estrogen and/or progestin exposure in five studies. Rifabutin led to smaller PK changes than rifampin in two studies. In one study each, rifaximin and rifalazil did not alter hormone PK. CONCLUSIONS: No studies evaluated pregnancy risk or non-oral HCs. PK and ovulation outcomes support a clinically concerning drug interaction between COCs and rifampin, and to a lesser extent rifabutin. Data are limited for other rifamycins. TWEETABLE ABSTRACT: Rifampin and rifabutin reduce systemic exposure of oral contraceptives, but no studies have evaluated pregnancy risk.

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

BACKGROUND: We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. METHODS: Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. RESULTS: Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). CONCLUSIONS: nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients.

Induction of STEAP4 correlates with 1,25-dihydroxyvitamin D3 stimulation of adipogenesis in mesenchymal progenitor cells derived from human adipose tissue.

The vitamin D receptor (VDR) is expressed in human adipocytes and is transiently induced during early adipogenesis in mesenchymal progenitor cell models. VDR null mice exhibit enhanced energy expenditure and reduced adiposity even when fed high fat diets. Adipocyte-specific transgenic-expression of human VDR in mice enhances adipose tissue mass, indicating that VDR activation in adipocytes enhances lipid storage in vivo. In these studies, we conducted genomic profiling and differentiation assays in primary cultures of human adipose-derived mesenchymal progenitor cells to define the role of the VDR and its ligand 1,25-dihydroxyvitamin D3 (1,25D) in adipogenesis. In the presence of adipogenic media, 1,25D promoted lipid accumulation and enhanced the expression of FABP4, FASN, and PPARγ. Mesenchymal cells derived from 6-month old VDR null mice exhibited impaired adipogenesis ex vivo but differentiation was restored by stable expression of human VDR. STEAP4, a gene that encodes a metalloreductase linked to obesity, insulin sensitivity, metabolic homeostasis and inflammation, was highly induced in human adipose cells differentiated in the presence of 1,25D but was minimally affected by 1,25D in undifferentiated precursors. These studies provide a molecular basis for recent epidemiological associations between vitamin D status, body weight and insulin resistance which may have relevance for prevention or treatment of metabolic syndrome and obesity.

Thorium-230 ages of corals and duration of the last interglacial sea-level high stand on oahu, hawaii.

Thorium-230 ages of emergent marine deposits on Oahu, Hawaii, have a uniform distribution of ages from approximately 114,000 to approximately 131,000 years, indicating a duration for the last interglacial sea-level high stand of approximately 17,000 years, in contrast to a duration of approximately 8000 years inferred from the orbitally tuned marine oxygen isotope record. Sea level on Oahu rose to >/=1 to 2 meters higher than present by 131,000 years ago or approximately 6000 years earlier than inferred from the marine record. Although the latter record suggests a shift back to glacial conditions beginning at approximately 119,000 years ago, the Oahu coral ages indicate a near present sea level until approximately 114,000 years ago.

Photometric observations of jupiter at 2400 angstroms.

The photopolarimeter instrument on Voyager 2 was used to obtain a map of Jupiter at an effective wavelength of 2400 angstroms. Analysis of a typical north-south swath used to make this map shows strong absorption at high latitudes by a molecular or particulate constituent in the Jovian atmosphere. At 65 degrees north latitude, the absorbing constituent extends to altitudes above the 50-millibar pressure level.

Mass-Spectrometric 230Th-234U-238U Dating of the Devils Hole Calcite Vein.

The Devils Hole calcite vein contains a long-term climatic record, but requires accurate chronologic control for its interpretation. Mass-spectrometric U-series ages for samples from core DH-11 yielded (230)Th ages with precisions ranging from less than 1,000 years (2sigma) for samples younger than approximately 140 ka (thousands of years ago) to less than 50,000 years for the oldest samples ( approximately 566 ka). The (234)U/(238)U ages could be determined to a precision of approximately 20,000 years for all ages. Calcite accumulated continuously from 566 ka until approximately 60 ka at an average rate of 0.7 millimeter per 10(3) years. The precise agreement between replicte analyses and the concordance of the (230)Th/(238)U (234)U/(238)U ages for the oldest samples indicate that the DH-11 samples were closed systems and validate the dating technique in general.

Photopolarimetry from voyager 2; preliminary results on saturn, titan, and the rings.

The Voyager 2 photopolarimeter was reprogrammed prior to the August 1981 Saturn encounter to perform orthogonal-polarization, two-color measurements on Saturn, Titan, and the rings. Saturn's atmosphere has ultraviolet limb brightening in the mid-latitudes and pronounced polar darkening north of 65 degrees N. Titan's opaque atmosphere shows strong positive polarization at all phase angles (2.7 degrees to 154 degrees ), and no single-size spherical particle model appears to fit the data. A single radial stellar occultation of the darkened, shadowed rings indicated a ring thickness of less than 200 meters at several locations and clear evidence for density waves caused by satellite resonances. Multiple, very narrow strands of material were found in the Encke division and within the brightest single strand of the F ring.

Photometry from voyager 2: initial results from the uranian atmosphere, satellites, and rings.

The Voyager 2 photopolarimeter successfully completed the Uranus encounter, acquiring new data on the planet's atmosphere, its principal satellites, and its ring system. Spatially resolved photometry of the atmosphere at 0.27 micrometer shows no enhancement in absorption toward the pole, unlike the case for Jupiter and Saturn. Stellar occultation measurements indicate the temperature at the 1-millibar level over the north pole is near 90 kelvins. The geometric albedos of the five large satellites of Uranus were measured at 0.27 and 0.75 micrometer and indicate the presence of low albedo, spetrally flat absorbing material. Titania seems to have a fluffy surface, as indicated by its phase curve. The nine ground-based rings were detected, and their internal structure, optical depths, and positions were determined. The sharp edges of the in ring made it possible to measure its edge thickness (less than 150 meters) and particle sizes (less than 30 meters); little or no dust was detcted. New narrow rings and partial rings (arcs) were measured, and the narrow component of the eta ring was found to be discontinuous.

Galileo ultraviolet spectrometer experiment: initial venus and interplanetary cruise results.

The Galileo Extreme Ultraviolet Spectrometer obtained a spectrum of Venus atmospheric emissions in the 55.0- to 125.0-nanometer (nm) wavelength region. Emissions of helium (58.4 nm), ionized atomic oxygen (83.4 nm), and atomic hydrogen (121.6 nm), as well as a blended spectral feature of atomic hydrogen (Lyman-beta) and atomic oxygen (102.5 nm), were observed at 3.5-nm resolution. During the Galileo spacecraft cruise from Venus to Earth, Lyman-alpha emission from solar system atomic hydrogen (121.6 nm) was measured. The dominant source of the Lyman-alpha emission is atomic hydrogen from the interstellar medium. A model of Galileo observations at solar maximum indicates a decrease in the solar Lyman-alpha flux near the solar poles. A strong day-to-day variation also occurs with the 27-day periodicity of the rotation of the sun.

Photometry from voyager 2: initial results from the neptunian atmosphere, satellites, and rings.

The Voyager photopolarimeter successfully accomplished its objectives for the Neptune encounter, performing measurements on the planet, several of its satellites, and its ring system. A photometric map of Neptune at 0.26 micrometer (microm) shows the planet to be bland, with no obvious contrast features. No polar haze was observed. At 0.75 microm, contrast features are observed, with the Great Dark Spot appearing as a low-albedo region and the bright companion as being substantially brighter than its surroundings, implying it to be at a higher altitude than the Great Dark Spot. Triton's linear phase coefficients of 0.011 magnitudes per degree at 0.26 microm and 0.013 magnitudes per degree at 0.75 microm are consistent with a solid-surface object possessing high reflectivity. Preliminary geometric albedos for Triton, Nereid, and 1989N2 were obtained at 0.26 and 0.75 microm. Triton's rotational phase curve shows evidence of two major compositional units on its surface. A single stellar occultation of the Neptune ring system elucidated an internal structure in 1989N1R, in the approximately 50-kilometer region of modest optical depth. 1989N2R may have been detected. The deficiency of material in the Neptune ring system, when compared to Uranus', may imply the lack of a "recent" moon-shattering event.

Understanding the Clinical Implications of Resident Involvement in Uncommon Operations.

OBJECTIVE: The objective of this study was to examine uncommon operations in greater detail given that the outcomes of uncommon operations are largely understudied. This study examines the incidence of postoperative events and the role of the resident following uncommon operations. DESIGN: We identified uncommon general surgical operations using the ACS National Surgical Quality Improvement Program Participant Use file (2008-2011). Death or serious morbidity (DSM) within 30 days of the operation was the primary outcome of interest. Failure to rescue (FTR) and prolonged operative time (PRopt) were evaluated as secondary outcome measures. PRopt was defined as ≥90 percentile of operative time for each procedure type. Independent multivariate logistic regression models were generated to examine the impact of these descriptors on the outcomes of interest. SETTING/PARTICIPANTS: The dataset utilized was the United States National Surgical Quality Improvement Program Participant Use File which leverages data points from over 700 hospitals that range from primary to quaternary care centers. Resident participation was defined as resident involved (RI) or no resident involved (NRI), and stratified by postgraduate year (PGY): 1-3, 4-5, and 6+. RESULTS: Resident participant data was available for 21,453 (84.5%) uncommon operations with NRI in 25.4% (5447). With regard to resident participation, PGY1-3 were found in 12.6% (2699), PGY4-5 in 50.4% (10,817), and PGY6+ in 11.6% (2490). The overall observed DSM rate was 28.6% and the observed FTR rate was 5.8%. Overall, there was no difference in DSM by RI status (NRI: 1528; 28.1% vs RI: 4602; 28.8%; p = 0.324); however, PGY level was associated with DSM (PGY1-3: 774, 28.7%, PGY4-5: 3210, 29.7%, PGY6+: 618, 24.8%; p < 0.001). Any RI was associated with a lower rate of FTR (5.1%) when compared to NRI (8.3%, p < 0.001) with decreasing FTR events by increasing PGY (PGY1-3: 6.4%, PGY4-5: 5.2%, PGY6+: 3.3%; p < 0.001). After adjustment for patient risk factors, any RI remained associated with a lower likelihood of FTR than NRI (odds ratio: 0.65, 95% confidence interval: 0.49-0.87) while only the PGY4-5 and PGY6+ groups were associated with lower likelihood of FTR in comparison to NRI. RI was associated with PRopt in univariate and multivariable analyses. CONCLUSIONS: Uncommon operations were associated with substantial DSM. The involvement of PGY4-5 residents was associated with the greatest likelihood of DSM. With increasing PGY of the involved resident, cases with PGY > 5 demonstrated a lower likelihood of risk-adjusted FTR. The explanation for these findings is not clear; however, the involvement of more senior residents in the technical aspects of uncommon operations may lead to improved results.

Ability of transstadially infected Ixodes pacificus (Acari: Ixodidae) to transmit West Nile virus to song sparrows or western fence lizards.

The hypothesis that Ixodes pacificus Cooley & Kohls (Acari: Ixodidae) may serve as a reservoir and vector of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) in California was tested by determining the ability of this tick species to become infected with the NY99 strain of WNV while feeding on viremic song sparrows, to maintain the infection transstadially, and then to transmit WNV to recipient naive song sparrows and western fence lizards during the nymphal stage. The percentage of ticks testing positive by reverse transcription-polymerase chain reaction (RT-PCR) decreased from 77% of 35 larvae at day 6 after ticks were transferred to donor song sparrows (day of detachment) to 23% of 35 nymphs at 59 d postinfestation (approximately 19 d after molting to the nymphal stage). However, the percentage of ticks positive by RT-PCR from which infectious virus was recovered by Vero cell assay decreased from 59% on day 6 to 12% on day 59, even though there was no statistically significant decrease in the quantity of RNA within positive ticks. Attempts to improve the sensitivity of plaque assays by blind passage through C6/36 cell cultures were unsuccessful. These data indicated that ticks maintained viral RNA but not necessarily infectious virus over time. Nymphs from larvae that fed on song sparrows with peak viremias ranging from 7.2 to 8.5 log10 plaque-forming units (PFU) per ml were used in transmission attempts. From one to seven RNA-positive nymphal ticks engorged and detached from each of four recipient song sparrows or western fence lizards. Blood samples from sparrows and lizards remained negative, indicating that transmission did not occur. An additional four lizards inoculated with 1,500 PFU of WNV developed moderate viremias, ranging from 4.2 to 5.6 log10 PFU/ml. Our data and data from previous studies collectively indicated that ixodid ticks were not able to experimentally transmit WNV and therefore most likely would not be important vectors in WNV transmission cycles.

Strategic Shift to a Diagnostic Model of Care in a Multi-Site Group Dental Practice.

BACKGROUND: Documenting standardized dental diagnostic terms represents an emerging change for how dentistry is practiced. We focused on a mid-sized dental group practice as it shifted to a policy of documenting patients' diagnoses using standardized terms in the electronic health record. METHODS: Kotter's change framework was translated into interview questions posed to the senior leadership in a mid-size dental group practice. In addition, quantitative content analyses were conducted on the written policies and forms before and after the implementation of standardized diagnosis documentation to assess the extent to which the forms and policies reflected the shift. Three reviewers analyzed the data individually and reached consensuses where needed. RESULTS: Kotter's guiding change framework explained the steps taken to 97 percent utilization rate of the Electronic Health Record and Dental Diagnostic Code. Of the 96 documents included in the forms and policy analysis, 31 documents were officially updated but only two added a diagnostic element. CONCLUSION: Change strategies established in the business literature hold utility for dental practices seeking diagnosis-centered care. PRACTICAL IMPLICATIONS: A practice that shifts to a diagnosis-driven care philosophy would be best served by ensuring that the change process follows a leadership framework that is calibrated to the organization's culture.

Growth hormone and craniofacial changes: preliminary data from studies in Turner's syndrome.

Normal craniofacial and dental growth and development is dependent on growth hormone (GH) and insulin-like growth factor I (IGF-I). Deficiencies of either during childhood cause diminished growth of the maxilla and (to a greater degree) the mandible. Dental development/eruption also is compromised. Conversely, excessive GH/insulin-like growth factor I causes overgrowth, with the mandible again more affected than the maxilla. Replacement therapy in deficiency conditions generally normalizes craniofacial growth. Systemic GH also has been used in other disorders for which overt deficiency of GH has not been demonstrated. One such condition, Turner's syndrome, is now widely treated with GH. Although systemic GH in Turner's syndrome has been shown to positively affect stature, the effects on craniofacial growth and dental development/eruption are largely unknown. To explore these issues, standardized lateral radiographs of seven untreated patients with Turner's syndrome were analyzed and revealed hypoplasias of the cranial base, maxilla, and mandible. Dental development/eruption of patients with Turner's syndrome was found to be significantly advanced (by 0.63 years), relative to control subjects, in a separate study. Annual radiocephalometric measurements of 19 patients with Turner's syndrome treated with GH were compared with nonaffected control subjects over 1 year of treatment. Compared with age-matched historic control subjects, all maxillary-and most mandibular-growth measures were within 2 standard deviations of control. However, in our patients with Turner's syndrome, we found two measures of mandibular growth that deviated by more than 3 standard deviations from control. These data, although preliminary and only encompassing a short period, indicate that mandibular growth may be more affected than is maxillary growth by GH treatment and should be monitored over long-term-therapy.

Acute repeated nicotine injections increase enkephalin and decrease AP-1 DNA binding activity in rat adrenal medulla.

Previously we reported that a single injection of nicotine decreased AP-1 DNA binding activity in adrenal medullae, although chronic bidaily nicotine (and saline) injections increased this binding activity [15]. Repeated acute nicotine injections (3 mg/kg i.p., 7 injections equi-spaced over a 3 h period) effectively increased adrenal tyrosine hydroxylase [3] and [Met5]enkephalin levels and also profoundly decreased adrenal medulla AP-1 DNA binding activity for over 8 h.

An intraventricular infusion model for inducing morphine dependence in rats: quantitative assessment of precipitated withdrawal.

An experimental model of morphine dependence, in which rats were made dependent upon morphine by intraventricular infusion, is described. Morphine dependence was assessed and quantified by a series of withdrawal signs that were induced by the intraperitoneal administration of the morphine antagonist naloxone. The infusion of different concentrations of morphine resulted in the production of physical dependence, the severity of which was directly correlated with the concentration of morphine infused. A weak to moderate degree of dependence characterized by such withdrawal signs as teeth chattering, whole-body shakes, and vocalization was produced by infusions of morphine less than 5 micrograms/hr. A strong degree of physical dependence characterized by additional dominant withdrawal signs such as jumping and launching was produced by the infusion of 50 micrograms/hr morphine. The morphine pellet model that most closely approximated this degree of dependence was a three-pellet model in which a single 75-mg morphine pellet was implanted at 48-hr intervals. Abstinence precipitated by removal of the morphine-containing osmotic minipumps was characterized primarily by teeth chattering and whole-body shakes which persisted for at least 48 hr.

Effect of clindamycin and lincomycin therapy on faecal flora.

Bacterial counts were carried out on the faeces of 160 patients receiving clindamycin or lincomycin treatment for bacterial infections. In all the patients the total bacteroides count was significantly reduced while strains of Enterobacteriaciae, yeasts, and streptococci were correspondingly increased. Severe diarrhoea developed in 25 (16%) patients, but this could not be related to a change in faecal flora. Diarrhoea was most common when clindamycin was given prophylactically, women were more affected than men, and the incidence was highest in those aged over 60 years. No cases of pseudomembranous colitis were seen. Although clindamycin is a valuable antibiotic for treating established severe anaerobic bacterial infections it should be used cautiously in elderly patients.

Bacterial flora of the appendix fossa in appendicitis and postoperative wound infection.

Bacteria were isolated from 153 (47.5%) swabs of the appendix fossa in 322 patients undergoing appendicectomy. The commonest organism was Bacteroides species found in 78% of specimens. Other Gram-negative bacilli such as Klebsiella, or Enterobacter, and Esch. coli were present in 29 and 27% respectively. Gram-positive cocci were less frequently isolated.A positive culture was obtained more commonly in perforated appendicitis (79%) than where chronic fibrosis, lymphoid hyperplasia, or acute appendicitis was present or when the appendix was normal. Bacteroides was isolated twice as often in perforated appendicitis. The incidence of wound infection was 19% and varied according to the state of the appendix, being 63% in perforated appendicitis and 9.5% where lymphoid hyperplasia was present. Bacteroides was isolated from over 90% of the wound infections. In the patients with perforated appendicitis where effective chemotherapy was given the incidence of wound infection was 15% whereas in untreated or inappropriately treated patients it was over 50%. The isolation of bacteroides requires special precautions to be taken both in the collection of the specimen and laboratory culture. It is important that the chemotherapy of postappendicectomy infections include an antibiotic active against bacteroides.