BackgroundOsteolysis of the femur has been a serious problem associated with some designs of total hip-replacement implants; it frequently leads to failure of the femoral component. We evaluated the ...effect of a circumferential plasma-spray porous coating on the rate of osteolysis in a study that included two groups of hips, each of which received an implant with the same design except for the extent of the porous coating. Our goal was to determine the possible role of circumferential porous coating in protecting the bone-implant interface from osteolysis. MethodsA series of consecutive primary total hip replacements performed with insertion of the Mallory-Head implant without cement was divided into two study groups. The first 126 hips (Group 1) were treated with a femoral stem that had a noncircumferential plasma-spray porous titanium coating. The next ninety hips (Group 2) were treated with a circumferentially coated stem of the same design. The average duration of radiographic follow-up was 7.8 years in Group 1 and 7.5 years in Group 2. ResultsThe average rate of polyethylene wear was similar for the two groups (0.187 millimeter per year in Group 1 and 0.189 millimeter per year in Group 2). The prevalence of osteolysis in Group 1 (40 percent; fifty of 126 hips) was significantly higher than that in Group 2 (10 percent; nine of ninety hips) (p < 0.001). Osteolysis remote from the joint space (distal to zones 1 and 7) was found in 11 percent (fourteen) of the hips in Group 1 but in none of those in Group 2 (p = 0.0004). The average total area of osteolysis in Group 1 (5.0 square centimeters) was significantly larger than that in Group 2 (2.9 square centimeters) (p < 0.05). ConclusionsA circumferential plasma-spray titanium porous coating on the femoral component of a total hip-replacement prosthesis inserted without cement appears to provide an effective barrier preventing wear debris from gaining access to the endosteal surface of the femur and the greater trochanter. This finding supports the hypothesis of the so-called effective joint space, which predicts that wear debris from the joint bearing can migrate, driven by intracapsular pressures, to all areas to which joint fluid has access and thus can result in osteolysis. The reduction of the prevalence of osteolysis and the elimination of osteolysis from the zones remote from the joint space by the use of a circumferential plasma-spray porous coating indicates that the femur was effectively sealed off from the joint space. We believe that the durability and longevity of the femoral component should be enhanced by the use of such a coating.
An important goal is to identify the direct activation domain (AD)-interacting components of the transcriptional machinery
within the context of native complexes. Toward this end, we first ...demonstrate that the multisubunit TFIID, SAGA, mediator,
and Swi/Snf coactivator complexes from transcriptionally competent whole-cell yeast extracts were all capable of specifically
interacting with the prototypic acidic ADs of Gal4 and VP16. We then used hexahistidine tags as genetically introduced activation
domain-localized cross-linking receptors. In combination with immunological reagents against all subunits of TFIID and SAGA,
we systematically identified the direct AD-interacting subunits within the AD-TFIID and AD-SAGA coactivator complexes enriched
from whole-cell extracts and confirmed these results using purified TFIID and partially purified SAGA. Both ADs directly cross-linked
to TBP and to a subset of TFIID and SAGA subunits that carry histone-fold motifs.
The inherent pressures of high-acuity, critical illness in the emergency department create a unique environment whereby acute goals-of-care discussions must be had with patients or substitute ...decision makers to rapidly decide between divergent treatment paths. Among university-affiliated hospitals, resident physicians are often conducting these highly consequential discussions. This study aimed to use qualitative methods to explore how emergency medicine residents make recommendations regarding life-sustaining treatments during acute goals-of-care discussions in critical illness.
Using qualitative methods, semistructured interviews were conducted with a purposive sample of emergency medicine residents in Canada from August to December 2021. Inductive thematic analysis of the interview transcripts was conducted using line-by-line coding, and key themes were identified through comparative analysis. Data collection continued until thematic saturation was reached.
Seventeen emergency medicine residents from 9 Canadian universities were interviewed. Two factors guided residents’ treatment recommendations (a duty to provide a recommendation and the balance between disease prognosis and patient values). Three factors influenced residents’ comfort when making recommendations (time constraints, uncertainty, and moral distress).
While conducting acute goals-of-care discussions with critically ill patients or their substitute decision makers in the emergency department, residents felt a sense of duty to provide a recommendation informed by an intersection between the patient’s disease prognosis and the patient’s values. Their comfort in making these recommendations was limited by time constraints, uncertainty, and moral distress. These factors are important for informing future educational strategies.
Serum lipoproteins and cardiovascular risk are affected by endogenous and exogenous sex hormones. As part of a multicenter evaluation of a permeation-enhanced testosterone transdermal system (TTD), ...the interrelationships among serum lipoproteins, hormone levels, anthropometric parameters, and age were investigated in 29 hypogonadal men. Subjects (aged 21-65 yr) were first studied during prior treatment with im testosterone esters (IM-T), then during an 8-week period of androgen withdrawal resulting in a hypogonadal state (HG), and finally during a 1-yr treatment period with the TTD. Compared with treatment with IM-T, the HG period produced increases in high density lipoprotein HDL; 12.0 +/- 1.6% (+/-SEM); P<0.001 and total cholesterol (4.2 +/- 1.9%; P: = 0.02) and a decrease in the cholesterol/HDL ratio (-9.7 +/- 2.8%; P = 0.02). Compared with the HG period, TTD treatment produced decreases in HDL (-7.6 +/- 2.5%; P = 0.002) and increases in the cholesterol/HDL ratio (9.0 +/- 2.5%; P = 0.01) and triglycerides (20.7 +/- 6.4%; P: = 0.03). Small decreases in total cholesterol (-1.2 +/- 1.8%; P: = 0.1) and low density lipoprotein (-0.8 +/- 2.6%; P = 0.07) were also observed during TTD, but did not reach statistical significance. Likewise, there were no significant differences between the IM-T and TTD treatments. Serum HDL levels showed a strong negative correlation with body mass index and other obesity parameters in all three study periods (r < -0.45; P < 0.02). During treatment with TTD, serum testosterone levels also correlated negatively with body mass index (r = -0.621; P < 0.001). As a consequence of these relationships, a positive trend was observed between HDL and testosterone levels during TTD treatment (r = 0.336; P = 0.07). Interestingly, the changes in lipoprotein levels during TTD treatment indicated a more favorable profile (decrease in cholesterol and low density lipoprotein levels) with increasing age of the patients. In hypogonadal men the effects of transdermal testosterone replacement on serum lipoproteins appear consistent with the physiological effects of testosterone in eugonadal men.
This phenomenological qualitative study describes students' experiences and counter-stories of school climate and how school climate matters for their academic achievement in an urban school ...district. The study uses a critical race perspective to help understand contextual influences on school climate. Data were collected through eight focus group interviews comprised of students conducted in middle and high schools in a large Midwest urban school district. Themes emerged within each school climate domain: teacher support, teacher expectations, safety, and peer social and emotional competence. The study results describe how students experience and understand school climate--perception of safety in schools with a mix of safe and unsafe home-community climate--and demonstrate how students acknowledge the relationship between school climate and academic achievement. Urban secondary students are observant of the social-emotional learning of their peers and maintain awareness of group differences as expressed in their counter-stories. The findings advanced our understanding of school climate in urban contexts where social-contextual-struggles experienced by people of color affect their school experiences. The discussion includes practical implications for educators and administrators and directions for future research.
GLP-1 tablet in type 2 diabetes in fasting and postprandial conditions.
M K Gutniak ,
H Larsson ,
S W Sanders ,
O Juneskans ,
J J Holst and
B Ahrén
Vällingby Medical Center, Stockholm, Sweden. ...mark.gutniak@mailbox.swipnet.se
Abstract
OBJECTIVE: To examine the absorption of glucagon-like peptide (GLP)-1(7-36) amide from the buccal mucosa of type 2 diabetic
patients. Previously, the effects of the peptide have been studied following intravenous and subcutaneous injection. Now,
a mucoadhesive, biodegradable buccal GLP-1 tablet (9 mm) containing 119 nmol has been developed as a possible alternative
to injection. RESEARCH DESIGN AND METHODS: A total of 10 type 2 diabetic patients received a single tablet under fasting conditions
and before a standard meal in this randomized placebo-controlled study. RESULTS: The mean peak GLP-1 concentration was 125.1
pmol/l and occurred 30 min after application. The mean placebo-adjusted area under the curve was 5,334 min pmol/l, consistent
with a relative bioavailability of 6% vs. intravenous injection and 42% vs. subcutaneous injection. The half-life of total
peptide activity after buccal administration was 17 min. The placebo-adjusted glucose concentrations decreased by 1.4 mmol/l
in fasting experiments and by 4.2 mmol/l after a standard mixed meal. In the fasting state at 30 min, plasma insulin increased
by 185% and glucagon decreased by 20%, consistent with the increase in plasma GLP-1 concentrations. The peptide exerted a
significant insulinotropic effect during meals (calculated as an insulinogenic index, 0-120 min; 84.1 vs. 45.7 in placebo
experiments). CONCLUSIONS: Potentially therapeutic plasma levels of GLP-1 were achieved after administration of a single buccal
tablet in type 2 diabetic patients. The peptide had a marked glucose-lowering effect during the first 2 h. This new GLP-1
tablet may become a feasible alternative treatment for type 2 diabetic patients, although a more prolonged pharmacokinetic
profile is required.
We compared gastric pH values after therapeutic doses of lansoprazole and omeprazole in 17 healthy adult men. The pharmacokinetics of the two drugs were studied. A three-way crossover design compared ...the effects on gastric pH of 15 and 30 mg lansoprazole and 20 mg omeprazole-each given once daily for 5 days. Ambulatory 24-h intragastric pH levels were measured before dosing, after the first and fifth doses in each period, and 15 days after each dosing period. A positive relationship between the lansoprazole or omeprazole area under the curve (AUCs) and the 24-h mean pH values was found for each regimen. No differences in maximum concentration (Cmax) and AUC were noted from day 1 to day 5 for the two lansoprazole doses. With omeprazole, both Cmax and AUC levels were greater on day 5 than on day 1. All three regimens increased 24-h mean gastric pH, although 30 mg lansoprazole had the most significant effect. The percentage of time that gastric pH was >3, >4, and >5 was also significantly higher with 30 mg lansoprazole. All three regimens were associated with reversible elevations of serum gastrin, which more than doubled at some points. No clinically significant adverse events were documented.
Internalized racism, also referred to as appropriated racial oppression, refers to the phenomenon of people of color adopting negative racist messages about their worth and abilities. The ...internalization of racism by members of the targeted group results in an experience of self-degradation and self-alienation and the assumption of one's inferiority, which is directly related to issues of self-esteem, self-confidence, shame, depression, and anxiety. This study used structural regression with moderation and mediation to explore the possibility of internalized racism as a mediating variable and black identity and perceived social support as possible moderators. A sample of 639 participants (MAge = 35.29, SDAge = 10.09) who identified as Black and/or African American were included in the study. The findings indicated that internalized racism partially mediated the relationship between racial microaggressions and depression and anxiety, where approximately 50 percent of the relationships were explained by internalized racism. Additionally, the findings indicated that centrality and private regard aspects of Black identity weakened the relationship between racial microaggressions and depression and anxiety. Finally, the findings indicated that social support weakens the relationship between racial microaggressions and depression and anxiety.
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