The combination of 18 to 69 hours of complete diaphragmatic inactivity and mechanical ventilation results in marked atrophy of human diaphragm myofibers. These findings are consistent with increased diaphragmatic proteolysis during inactivity.

To assess the effect of severe chronic obstructive pulmonary disease (COPD) on the ability of human diaphragmatic myofibers to aerobically generate ATP relative to ATP utilization, we obtained biopsy specimens of the costal diaphragm from seven patients with severe COPD (mean +/- SE; age 56 +/- 1 yr; forced expiratory volume in 1 s 23 +/- 2% predicted; residual volume 267 +/- 30% predicted) and seven age-matched control subjects. We categorized all fibers in these biopsies by using standard techniques, and we carried out the following quantitative histochemical measurements by microdensitometry: 1) succinate dehydrogenase (SDH) activity as an indicator of mitochondrial oxidative capacity and 2) calcium-activated myosin ATPase (mATPase) activity, the ATPase that represents a major portion of ATP consumption by contracting muscle. We noted the following: 1) COPD diaphragms had a larger proportion of type I fibers, a lesser proportion of type IIax fibers, and the same proportion of type IIa fibers as controls. 2) SDH activities of each of the fiber types were higher in COPD than control diaphragms (P < 0.0001); the mean increases (expressed as percent of control values) in types I, IIa, and IIax were 84, 114, and 130%, respectively. 3) COPD elicited no change in mATPase activity of type I and IIa fibers, but mATPase decreased in type IIax fibers (P = 0.02). 4) Mitochondrial oxidative capacity relative to ATP demand (i.e., SDH/mATPase) was higher (P = 0.03) in each of the fiber types in COPD diaphragms than in controls. These results demonstrate that severe COPD elicits an increase in aerobic ATP generating capacity relative to ATP utilization in all diaphragmatic fiber types as well as the previously described fast-to-slow fiber type transformation (Levine S, Kaiser L, Leferovich J, and Tikunov B, N Engl J Med 337: 1799-1806, 1997).

Diaphragm remodeling associated with chronic obstructive pulmonary disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsies on 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPD on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type II fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.

Our findings suggest that increased activity of the ubiquitin-proteasome pathway, marked decreases in MyHCs, and atrophic AKT-FOXO signaling play important roles in eliciting the myofiber atrophy and decreases in diaphragm force generation associated with prolonged human diaphragm disuse.

In this study, we use the case study methodology to examine the faculty recruiting and hiring practices within a school of education at a highly selective private research university. The research question was, what are the practices and policies at the school of education that either promote or detract from recruiting and hiring of faculty of color? In order to answer this question, we conducted a review of the extant literature pertaining to the recruitment of faculty of color to research universities, looking for specific strategies that are considered to have a substantial impact on this practice. Then we collected and analyzed institutional data on faculty recruitment practices in one school of education for the past 5 years, looking at applicant pools, advertising strategies, and hiring practices. Lastly, we conducted qualitative interviews with past search committee chairs, school administrators, and recently hired faculty of color to understand the decision-making processes as they pertain to general faculty recruitment as well as hurdles to, and incentives for, recruiting faculty of color.

Objectives The purpose of this study was to identify common components of diversity pipeline programs across a national sample of nursing institutions and determine what effect these programs have on increasing underrepresented minority enrollment and graduation. Design Linked data from an electronic survey conducted November 2012 to March 2013 and American Association of Colleges of Nursing baccalaureate graduation and enrollment data (2008 and 2012). Participants Academic and administrative staff of 164 nursing schools in 26 states, including Puerto Rico in the United States. Methods Chi-square statistics were used to (1) describe organizational features of nursing diversity pipeline programs and (2) determine significant trends in underrepresented minorities’ graduation and enrollment between nursing schools with and without diversity pipeline programs Results Twenty percent (n = 33) of surveyed nursing schools reported a structured diversity pipeline program. The most frequent program measures associated with pipeline programs included mentorship, academic, and psychosocial support. Asian, Hispanic, and Native Hawaiian/Pacific Islander nursing student enrollment increased between 2008 and 2012. Hispanic/Latino graduation rates increased (7.9%–10.4%, p = .001), but they decreased among Black (6.8%–5.0%, p = .004) and Native American/Pacific Islander students (2.1 %–0.3%, p ≥ .001). Conclusions Nursing diversity pipeline programs are associated with increases in nursing school enrollment and graduation for some, although not all, minority students. Future initiatives should build on current trends while creating targeted strategies to reverse downward graduation trends among Black, Native American, and Pacific Island nursing students.

In preliminary experiments we noted developmental (i.e., embryonic and neonatal) myosin heavy chains (MHCs) in the diaphragms of patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that this finding represented new fiber formation secondary to injury associated with the mechanical stress of COPD or previously undescribed MHCs in the human diaphragm. To distinguish between these possibilities, we analyzed diaphragmatic biopsies obtained from 9 patients with severe COPD (forced expiratory volume in 1 s = 21 +/- 2% predicted, residual volume = 283 +/- 22% predicted) and 10 age-matched controls. First, using immunocytochemistry with specific monoclonal antibodies, we noted that control diaphragms had greater proportions of fibers expressing embryonic (50 +/- 2 vs. 28 +/- 3%, P < 0.0001) and neonatal (52 +/- 2 vs. 32 +/- 3%, P < 0.001) MHCs than COPD diaphragms. Second, SDS-PAGE demonstrated that these developmental MHCs represented only a very small fraction of the diaphragmatic MHC content. Third, the RT-PCR demonstrated mRNA coding for embryonic and neonatal MHCs in COPD and control diaphragms. Last, COPD and control diaphragms exhibited normal histology on light microscopy. We conclude that the presence of developmental MHC isoforms does not indicate new fiber formation in diaphragms of patients with severe COPD. Although these results represent the first systematic description of embryonic and neonatal MHCs in normal adult human diaphragms, their function remains to be elucidated.

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