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Agonistic encounters necessary for territory establishment and maintenance can be stressful for those involved. Stress responsiveness associated with territorial behavior can occur on both acute and chronic temporal scales contingent upon social status. Social interactions that recur for territory maintenance pose periodic stressors that incur variable physiological costs across social ranks. Adult males of the Green Anole, Anolis carolinensis, experience stressful social encounters during territorial disputes as individuals contest status within a dominance hierarchy. Dominant males in stable territories are known to exhibit greener body coloration and lower levels of stress hormone, corticosterone, relative to their subordinate counterparts. Periodic interactions with novel competitors, however, may induce comparable levels of cumulative glucocorticoid secretion regardless of social status. Glucocorticoid metabolites excreted in feces can be quantified to assess the chronic hypothalamic–pituitary–adrenal (HPA) axis response to periodic social stressors. Fecal glucocorticoid metabolite (FGM) levels in male A. carolinensis were hypothesized to increase in response to novel social encounters that simulated territory establishment and maintenance. Adrenocortical response to recurring episodes of territoriality was predicted to generate similar longitudinal FGM levels across social ranks. FGM analysis was combined with behavioral assessment of body coloration to further contextualize measured stress levels of dominant and subordinate anoles. Prolonged social interaction led to similarly increased levels of fecal glucocorticoid metabolites in both dominant and subordinate anoles relative to those that were solitary. This study provides an alternative perspective on the activity of the HPA axis in dominant–subordinate relationships of A. carolinensis over prolonged periods of territoriality.

As our populations grow older and more of us survive to very mature ages, the financial services industry is beginning to respond to the risks of financial exploitation. For example, money transfer companies like Western Union started working several years ago with law-enforcement and consumerprotection agencies around the world to educate people about the most common types of fraud, including “grandparent scams” (see, http://www.wu.com/fraudawareness). In January 2014, the financial world experienced a milestone event in its approach to aging. Cynthia Hutchins, a 30-year veteran of the financial services industry and a recent graduate of USC Davis School of Gerontology, was appointed as the first-ever Director of Financial Gerontology at Bank of America Merrill Lynch—the first person to work for a financial services company in that role (Franklin, 2014). It was also the year in which Wells Fargo revolutionized its operating procedures to take account of the potential risks to its older clients (Long, 2016) Many older people, with finances to manage, may face the prospect of declining mental capacity. As a result of this troubling confluence, recent years have seen a growing problem of elder financial abuse. Scammers and schemers— known to the elder victim or not—follow the Willie Sutton bank robber analogy: steal from affluent elders because that is where the money is. And that is where a lot of money is: Peter Laibson of Harvard reports that, in 2011, people over the age of 65—12% of the population—were in possession of one-third of the nation’s assets: $18 trillion out of a total of $53 trillion. Or, as put here by Daniel Marson (2016), the population that has amassed the greatest wealth is at the greatest risk. There are multiple risks and sources of such risks. In Europe and the United Kingdom, it is little different. As chronicled by Gilhooly et al. (2016), to have lost accumulated wealth can result in economic destitution, depression, embarrassment, isolation, and suicide with the perpetrators including malicious inheritance schemes, opportunistic intrusions, and duplicitous friendships. The vulnerabilities that invite these perpetrators range from neglect, misplaced moral justification, loss of financial skills, misjudgment, to significant cognitive decline. As seen here, much attention is now being paid to detection, prevention, and intervention around elder financial abuse. Elders, their families, and advocates have an obvious stake in eliminating these practices. Financial institutions that hold both elders’ assets and their trust (in multiple meanings) have both a communityand self-interest in protecting their clients. Government, charged with promoting the general welfare, cannot look aside, and the newfound prominence of adult protective services and other elder justice programs reflect a growing concern. Yet, the problem comes with a number of complexities. Most center on preventing, uncovering, and addressing fraudulent behaviors, and these can be addressed through research and experimentation as seen in several efforts below. But, as well, there are ethical issues that compound detection and intervention efforts. Values of privacy, autonomy, and choice come up against those of paternalism, supervision, and control. Who can and should “take away the financial keys” has clear moral, legal, and affective dimensions, which clearly complicate whatever empirical understandings of a given situation may suggest. In short, the problem is complex, but it is also a problem that unquestionably exists and is assuming remarkably large personal, monetary, and social dimensions. That being the case makes the articles below of great value. They deepen our understanding of the elder financial abuse problem, but present clear, tested, and promising strategies to detect and root out these malicious practices. The opening article by Mary Gilhooly and colleagues (2016) introduces the topic of financial elder abuse and reports on the development and promise of a bystander intervention model (BIM) to address the problem. The Manuscript received XXXX XX, XXXX; accepted XXXX XX, XXXX.

Cannabinoids, the active components of Cannabis sativa Linnaeus, have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, an- ti-inflammatory effects and tumor regression, but their use in chemotherapy is limited by their psychotropic activity. To date, cannabinoids have been successfully used in the treatment of nau- sea and vomiting, two common side effects that accompany chemotherapy in cancer patients. Most non-THC plant cannabinoids e.g. cannabidiol and cannabigerol, seem to be devoid of psychotropic properties. However, the precise pathways through which these molecules produce an antitumor effect have not yet been fully characterized. We therefore investigated the antitumor and anti-in- flammatory activities of cannabidiol (CBD) in human prostate cancer cell lines LNCaP, DU145, PC3, and assessed whether there is any advantage in using cannabis extracts enriched in cannabidiol and low in THC. Results obtained in a panel of prostate cancer cell lines clearly indicate that can- nabidiol is a potent inhibitor of cancer cell growth, with significantly lower potency in non-cancer cells. The mRNA expression level of cannabinoid receptors CB1 and CB2, vascular endothelial growth factor (VEGF), PSA (prostate specific antigen) are significantly higher in human prostate cell lines. Treatment with Cannabis extract containing high CBD down regulates CB1, CB2, VEGF, PSA, pro-inflammatory cytokines/chemokine IL-6/IL-8. Our overall findings support the concept that cannabidiol, which lacks psychotropic activity, may possess anti-inflammatory property and down regulates both cannabinoid receptors, PSA, VEGF, IL-6 and IL-8. High CBD cannabis extracts are cytotoxic to androgen responsive LNCaP cells and may effectively inhibit spheroid formation in cancer stem cells. This activity may contribute to its anticancer and chemosensitizing effect against prostate cancer. Cannabidiol and other non-habit forming cannabinoids could be used as novel therapeutic agents for the treatment of prostate cancer.

Medicinally, sandalwood oil (SO) has been attributed with antiinflammatory properties; however, mechanism(s) for this activity have not been elucidated. To examine how SOs affect inflammation, cytokine antibody arrays and enzyme-linked immunosorbent assays were used to assess changes in production of cytokines and chemokines by co-cultured human dermal fibroblasts and neo-epidermal keratinocytes exposed to lipopolysaccharides and SOs from Western Australian and East Indian sandalwood trees or to the primary SO components, α-santalol and β-santalol. Lipopolysaccharides stimulated the release of 26 cytokines and chemokines, 20 of which were substantially suppressed by simultaneous exposure to either of the two sandalwood essential oils and to ibuprofen. The increased activity of East Indian SO correlated with increased santalol concentrations. Purified α-santalol and β-santalol equivalently suppressed production of five indicator cytokines/chemokines at concentrations proportional to the santalol concentrations of the oils. Purified α-santalol and β-santalol also suppressed lipopolysaccharide-induced production of the arachidonic acid metabolites, prostaglandin E2, and thromboxane B2, by the skin cell co-cultures. The ability of SOs to mimic ibuprofen non-steroidal antiinflammatory drugs that act by inhibiting cyclooxygenases suggests a possible mechanism for the observed antiinflammatory properties of topically applied SOs and provides a rationale for use in products requiring antiinflammatory effects.

Background: Mechanical ventilation is a life-saving intervention for patients with respiratory failure. Unfortunately, a major complication associated with prolonged mechanical ventilation is ventilator-induced diaphragmatic atrophy and contractile dysfunction, termed ventilator-induced diaphragmatic dysfunction (VIDD). Emerging evidence suggests that positive pressure ventilation (PPV) promotes lung damage (ventilator-induced lung injury [VILI]), resulting in the release of signaling molecules that foster atrophic signaling in the diaphragm and the resultant VIDD. Although a recent report suggests that negative pressure ventilation (NPV) results in less VILI than PPV, it is unknown whether NPV can protect against VIDD. Therefore, the authors tested the hypothesis that compared with PPV, NPV will result in a lower level of VIDD. Methods: Adult rats were randomly assigned to one of three experimental groups (n = 8 each): (1) acutely anesthetized control (CON), (2) 12 h of PPV, and (3) 12 h of NPV. Dependent measures included indices of VILI, diaphragmatic muscle fiber cross-sectional area, diaphragm contractile properties, and the activity of key proteases in the diaphragm. Results: Our results reveal that no differences existed in the degree of VILI between PPV and NPV animals as evidenced by VILI histological scores (CON = 0.082 ± 0.001; PPV = 0.22 ± 0.04; NPV = 0.25 ± 0.02; mean ± SEM). Both PPV and NPV resulted in VIDD. Importantly, no differences existed between PPV and NPV animals in diaphragmatic fiber cross-sectional area, contractile properties, and the activation of proteases. Conclusion: These results demonstrate that NPV and PPV result in similar levels of VILI and that NPV and PPV promote comparable levels of VIDD in rats.

MicroRNAs are a primordial mechanism of gene expression control that appear to be crucial to cellular development and may play an important role in tumor development. Much is known about the genetics of medullary thyroid carcinomas, as approximately 25% are hereditary and harbor germ line activating mutations in the RET gene. Somatic RET mutations are also seen in roughly 50% of sporadic medullary thyroid carcinomas. Few studies, however, have evaluated the role of microRNA expression in these tumors. DNA and RNA were extracted from formalin-fixed paraffin-embedded tissue blocks of 15 medullary thyroid carcinomas [10 with RET mutations (3 hereditary) and 5 without RET mutations] and 5 non-tumor thyroid glands. miRNA expression of 754 targets was quantitated by real time PCR using the ABI OpenArray miRNA assay. Three miRNAs showed significant differential expression and were validated in a larger cohort of 59 cases by real-time PCR. Expression of potential downstream targets and upstream regulators were also investigated by real-time PCR. miR-375 and miR-10a were significantly overexpressed, while miR-455 was underexpressed in medullary thyroid carcinomas. Expression of all 3 miRNAs were validated in the larger cohort of cases (miR-375, p = 3.3×10−26; miR-10a, p = 5.6×10−14; miR-455, p = 2.4×10−4). No significant differences in miRNA expression were found between RET mutation positive and negative tumors nor between sporadic and hereditary tumors. Expression of the potential downstream targets of miR-375, YAP1 (a growth inhibitor) and SLC16a2 (a transporter of thyroid hormone), was downregulated in the tumors suggesting that miR-375 is a negative regulator of the expression of these genes. Thus, differential expression of miR-375, miR-10a and miR-455 may be important for tumor development and/or the reflect c-cell lineage of medullary thyroid carcinoma. Furthermore, the growth inhibitor YAP1 is identified as a potential important downstream target of miR-375.

Background Despite increased risk for cardiovascular disease (CVD) and related conditions, evaluations of health interventions indicate that Black/African American women are less likely to benefit than their white counterparts and are not as likely to engage in behaviors that reduce CVD risk. The purpose of this study was to test the feasibility and effectiveness of civic engagement as an intervention strategy to address heart health in Black/African American women. Methods Using a quasi-experimental pre-post study design, civic engagement was tested by convening a convenience sample of self-identified Black/African American women, ages 30–70 years, English-speaking, and BMI ≥25.0 (n = 28) into “Change Clubs” in four churches. Feasibility was examined through adherence, satisfaction, retention, and ability of Change Clubs to meet at least 50% of self-identified action steps for community change. Effectiveness data included: dietary intake, measures of physical activity, cardiorespiratory fitness, blood pressure, and anthropometrics. Psychosocial factors hypothesized to serve as the mechanisms by which civic engagement enacts behavior change were also assessed. Results At baseline, the study sample (n = 28) had a mean age of 50.5 y; 53.6% had an associate degree or higher; 60.7% had an income of $35,000 or higher; and 57.4% were employed full time. At the conclusion of the study, all participants were satisfied with the progress of their Change Club and with the overall experience and Change Clubs met their self-identified action steps for community change. The intervention had a significant effect on finish time on the cardiorespiratory fitness test (p

In their later years, baby boomers will encounter a political world far different from that experienced by either their parents or grandparents. On the one hand, they will face greatly altered economic, ideological, and budgetary circumstances; on the other, their generation’s size and influence will cast them in a more glaring light than was true for those elders who came before them. These factors—both internal and external to the boomers—will have profound effects on the policy experiences of this 76 million member cohort. A promising way of appreciating and anticipating these changes is to explore how older adults, understood as a target population of political and policy activity, have changed over time. Using a typology of such populations, we can see that political perceptions of older people have shifted at least twice over the course of the past several decades. Anne Schneider and Helen Ingram (1993) proposed a simple twodimension, four-fold model to characterize how different target populations of policy-related activity can be understood politically. As seen in Table 1, the first dimension speaks to legitimacy (high or low) and the second addresses political power (high or low). The four derivative target categories are: advantaged (high legitimacy; high power); dependent (high legitimacy; low power); deviant (low legitimacy; low power); and contender (low legitimacy; high power). Writing in the 1990s, Schneider and Ingram found the elderly to be Exhibit #1 in the advantaged grouping, a categorization that few would have disputed. What the authors did not address is how these characterizations can change over time. In the case of older adults, that possibility is a two-time

In the United States' changing health care climate, an updated picture of evidence-based practice (EBP) in the hospital setting is needed. Researchers explored EBP activities that interdisciplinary therapy team members used most frequently to acquire and appraise clinical evidence, therapists' perceptions of EBP, and barriers and enablers to EBP implementation within two similar acute-care hospitals in the Midwest.An electronic survey was distributed to 190 therapy practitioners working in two acute-care hospital settings. Eighty-four practitioners completed the 54-item electronic survey (n=84; 44% response rate). The sample consisted of 21 speech-language pathologists, 19 occupational therapists, 30 physical therapists, and 14 physical or occupational therapy assistants.Practitioners reported utilizing past experience and colleague interaction most frequently to acquire and appraise evidence; participants used self-reflective activities, such as journal clubs and carrying out research, infrequently. All disciplines placed high personal and professional value on EBP but indicated only moderate amounts of workplace support and personal preparedness to acquire, critique, and implement evidence. All disciplines indicated time was the largest EBP barrier. For enablers of EBP, disciplines responded differently, reporting support in the form of resources, training, and departmental goals.Pooled results indicated EBP activities used most frequently were of the lowest levels of clinical evidence; more effective EBP activities, such as self-reflection and participation in research, were rarely used. Hospital-based interdisciplinary therapy practitioners valued EBP but reported workplace constraints limiting implementation. Barriers to EBP were similar across disciplines, while enablers differed between disciplines.

The Nuclear Criticality Safety Program operated under the direction of Dr. Jerry McKamy completed the first NNSA Nuclear Accident Dosimetry exercise on May 27, 2016. Participants in the exercise were from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Sandia National Laboratory (SNL), Savanah River Site (SRS), Pacific Northwest National Laboratory (PNNL), US Navy, the Atomic Weapons Establishment (United Kingdom) under the auspices of JOWOG 30, and the Institute for Radiological Protection and Nuclear Safety (France) by special invitation and NCSP memorandum of understanding. This exercise was the culmination of a series of Integral Experiment Requests (IER) that included the establishment of the Nuclear Criticality Experimental Research Center, (NCERC) the startup of the Godiva Reactor (IER-194), the establishment of a the Nuclear Accident Dosimetry Laboratory (NAD LAB) in Mercury, NV, and the determination of reference dosimetry values for the mixed neutron and photon radiation field of Godiva within NCERC.

BACKGROUND AND OBJECTIVES: Patients with decompensated cirrhosis rarely receive palliative and supportive care interventions, which are routine in other life-limiting diseases. We aimed to design and evaluate a prognostic screening tool to routinely identify inpatients with decompensated cirrhosis at high risk of dying over the coming year, alongside the development of a supportive care intervention.DESIGN: Clinical notes from consecutive patients admitted as an emergency to University Hospitals Bristol with a diagnosis of cirrhosis over two distinct 90-day periods were scrutinised retrospectively for the presence or absence of five evidence-based factors associated with poor prognosis. These were analysed against their ability to predict mortality at 1 year. 'Plan-Do-Study-Act' (PDSA) methodology was used to incorporate poor-prognosis screening into the routine assessment of patients admitted with cirrhosis, and develop a supportive care intervention.RESULTS: 73 admissions were scrutinised (79.5% male, 63% alcohol-related liver disease, median age 54). The presence of three or more poor-prognosis criteria at admission predicted 1-year mortality with sensitivity, specificity and positive predictive value of 72.2%, 83.8% and 81.3%, respectively, and was used as a trigger for implementing the supportive care intervention. Following modification from six PDSA cycles, prognostic screening was integrated into the assessment of all patients admitted with decompensated cirrhosis, with the supportive care intervention (developed simultaneously) instigated for appropriate patients.CONCLUSIONS: We describe a model of care which identifies inpatients with cirrhosis at significant risk of dying over the coming year, and describe development of a supportive care intervention, which can be offered to suitable patients in parallel to ongoing active management.

Friction dampers are utilized in turbomachinery to reduce blade vibrations resulting from aeroelastic interactions. In this paper, the microslip friction model is applied to a blade with blade to ground damper and subjected to negative damping. Analysis using the describing function method, also known as the method of harmonic balance, is used to identify the behavior of the system and the maximum negative damping that can be stabilized by such a damper. These results are compared to those for the macroslip friction model.

In brief: Although preparticipation examinations are required for all Special Olympics athletes, information in the medical literature is limited concerning the difficulty in screening this group and in clearing them for competition. The results of 176 preparticipation exams are included in this report. The most striking finding was deficient visual acuity in half the athletes tested. Ruling out atlantoaxial subluxation in the athletes with Down's syndrome presented a special problem. The author suggests that the most effective method for screening Special Olympics athletes is a single-station/single-examiner format performed during school hours. She suggests improvements in the design of the consent forms to make physicians and parents aware of the special needs of these athletes.

The objective was to determine if acute alcohol consumption is associated with differences in injury pattern among young adult patients with traumatic injuries presenting to emergency medical services (EMS). A cross-sectional, retrospective review of prehospital patient care reports (PCRs) was conducted evaluating injured patients who presented to a collegiate EMS agency from January 1, 2011 to December 31, 2012. Included patients were age 18-24 y and sustained an injury within the previous 24 h. PCRs were reviewed independently by two abstractors to determine if the patient was documented to have acutely consumed alcohol proximate to his/her injury. Primary and secondary sites of regional body injury were recorded. Injury severity was recorded using the Revised Trauma Score (RTS). The association between primary injury site and acute alcohol use was assessed using a chi-square test. Multiple logistic regression was used to control for sex in predicting injury type. Of 440 injured patients, 135 (30.6%) had documented alcohol use prior to injury. Acute alcohol consumption altered the overall pattern of regional injury (p < 0.001). Alcohol users were more likely to present with injury secondary to assault, fall/trip, and unknown mechanism of injury (p < 0.001, all comparisons). RTS scores were statistically lower in the alcohol group (p < 0.001), although the clinical significance of this is unclear. Controlling for sex, acute alcohol consumption predicted increased risk of head/neck injury 5.59-fold (p < 0.001). Acute alcohol use in collegiate EMS patients appears to alter injury patterns in young adults and increases risk of head/neck injury. EMS providers in similar agencies should consider these trends when assessing and treating injured college-aged patients.

Foamy gland carcinoma is a variant of prostatic acinar adenocarcinoma characterized by abundant foamy cytoplasm and often pyknotic nuclei. Limited data exist regarding outcome and the clinicopathologic attributes of this variant. We screened 477 radical prostatectomies for foamy gland carcinoma to determine the incidence, amount, and Gleason grade/score of foamy gland carcinoma within the prostate. Time until prostate-specific antigen biochemical recurrence after radical prostatectomy was compared for both foamy and control/nonfoamy cases. For validation of incidence, Gleason grade, and pathologic stage, a second series of 100 consecutive radical prostatectomies was screened for foamy gland carcinoma. Foamy gland carcinoma was found in 69 (14.5%) of 477 cases. The median Gleason score of the foamy component was 7, which was not significantly different from the Gleason score of the nonfoamy component within those cases or the 408 nonfoamy cases. The most common Gleason score was 7 (44/69). There was no difference between foamy gland and nonfoamy gland cases in recurrence rate (23% versus 22%) or the average time to prostate-specific antigen recurrence (130 versus 151 months). In the second series, foamy gland carcinoma was found in 23% of cases and had a median Gleason score of 7; and the most common Gleason score was 7 (11/23). Foamy gland carcinoma exists in a significant subset of prostatic carcinomas. This variant does not appear to harbor a different prognosis compared with usual acinar adenocarcinoma, but diagnostic recognition of foamy gland carcinoma is important because there is a Gleason grade 4 element in the majority of cases.

Objective: Diaphragmatic weakness, due to both atrophy and contractile dysfunction, is a well-documented response following prolonged mechanical ventilation. Evidence indicates that activation of the proteases calpain and caspase-3 is essential for mechanical ventilation-induced diaphragmatic weakness to occur. We tested the hypothesis that a regulatory cross-talk exists between calpain and caspase-3 in the diaphragm during prolonged mechanical ventilation. To test this prediction, we determined whether selective pharmacological inhibition of calpain would prevent activation of caspase-3 and conversely whether selective inhibition of caspase-3 would abate calpain activation. Design: Animal study. Setting: University Research Laboratory. Subjects: Female Sprague-Dawley rats. Interventions: Animals were randomly divided into control or one of three 12-hr mechanical ventilation groups that were treated with/without a selective pharmacological protease inhibitor: 1) control, 2) mechanical ventilation, 3) mechanical ventilation with a selective caspase-3 inhibitor, and 4) mechanical ventilation with a selective calpain inhibitor. Measurements and Main Results: Compared to control, mechanical ventilation resulted in calpain and caspase-3 activation in the diaphragm accompanied by atrophy of type I, type IIa, and type IIx/IIb fibers. Independent inhibition of either calpain or caspase-3 prevented this mechanical ventilation-induced atrophy. Pharmacological inhibition of calpain prevented mechanical ventilation-induced activation of diaphragmatic caspase-3 and inhibition of caspase-3 prevented activation of diaphragmatic calpain. Furthermore, calpain inhibition also prevented the activation of caspase-9 and caspase-12, along with the cleavage of Bid to tBid, all upstream signals for caspase-3 activation. Lastly, caspase-3 inhibition prevented the mechanical ventilation-induced degradation of the endogenous calpain inhibitor, calpastatin. Conclusions: Collectively, these results indicate that mechanical ventilation-induced diaphragmatic atrophy is dependent on the activation of both calpain and caspase-3. Importantly, these findings provide the first experimental evidence in diaphragm muscle that calpain inhibition prevents the activation of caspase-3 and vice versa and caspase-3 inhibition prevents the activation of calpain. These findings support our hypothesis that a regulatory calpain/caspase-3 cross-talk exists whereby calpain can promote caspase-3 activation and active caspase-3 can enhance calpain activity in diaphragm muscle during prolonged mechanical ventilation.

Variability exists regarding the surgical technique in breast conservation therapy. The purpose of this project was to determine differences between single (SH) or flanking (FH) hooked needle localization wires used for nonpalpable breast lesions. We retrospectively reviewed 201 female patients at a single institution from 2004 to 2008. All patients had biopsy-proven ductal carcinoma in situ or invasive disease. Comparisons were made in regard to margin status, reoperation, completion mastectomy, size of lesion, and breast specimen volume. SH was placed in 122 patients (61%) and FH in 79 patients (39%). In SH, 23 patients (18%) had positive margins and 31 patients (25%) had reoperations as compared with 31 patients (25%) with positive margin and 36 patients (44%) in the FH cohort ( P = 0.039 and 0.0037). Average lesion size and volume resected was 1.5 cm and 137 cm3 in SH and 2.85 cm and 188 cm3 in FH, respectively ( P = 0.0001 and 0.006). Positive margins were associated with lesion size and not volume of tissue excised. The FH technique was associated with more positive margins, reoperation, and completion mastectomy.

Previous workers have demonstrated that controlled mechanical ventilation results in diaphragm inactivity and elicits a rapid development of diaphragm weakness as a result of both contractile dysfunction and fiber atrophy. Limited data exist regarding the impact of pressure support ventilation, a commonly used mode of mechanical ventilation-that permits partial mechanical activity of the diaphragm-on diaphragm structure and function. We carried out the present study to test the hypothesis that high-level pressure support ventilation decreases the diaphragm pathology associated with CMV.Sprague-Dawley rats were randomly assigned to one of the following five groups:1) control (no mechanical ventilation); 2) 12 hrs of controlled mechanical ventilation (12CMV); 3) 18 hrs of controlled mechanical ventilation (18CMV); 4) 12 hrs of pressure support ventilation (12PSV); or 5) 18 hrs of pressure support ventilation (18PSV).We carried out the following measurements on diaphragm specimens: 4-hydroxynonenal-a marker of oxidative stress, active caspase-3 (casp-3), active calpain-1 (calp-1), fiber type cross-sectional area, and specific force (sp F). Compared with the control, both 12PSV and 18PSV promoted a significant decrement in diaphragmatic specific force production, but to a lesser degree than 12CMV and 18CMV. Furthermore, 12CMV, 18PSV, and 18CMV resulted in significant atrophy in all diaphragm fiber types as well as significant increases in a biomarker of oxidative stress (4-hydroxynonenal) and increased proteolytic activity (20S proteasome, calpain-1, and caspase-3). Furthermore, although no inspiratory effort occurs during controlled mechanical ventilation, it was observed that pressure support ventilation resulted in large decrement, approximately 96%, in inspiratory effort compared with spontaneously breathing animals.High levels of prolonged pressure support ventilation promote diaphragmatic atrophy and contractile dysfunction. Furthermore, similar to controlled mechanical ventilation, pressure support ventilation-induced diaphragmatic atrophy and weakness are associated with both diaphragmatic oxidative stress and protease activation.

Employing the political construct of "target" populations, we suggest that the Boomers in old age will constitute a conceptually distinct population from that represented by either their parents or grandparents. A fourfold typology organized along the dimensions posited by Schneider and Ingram (1993) yields categorizations of target populations as Dependent, Deviant, Advantaged, or Contender. Although these authors labeled the aged as Advantaged, categorizations of target populations can and do change over time. Using historical analysis, we explore, first, the transformation of the aged from Dependent to Advantaged and the more recent transformation to Contender status. This latest shift is reinforced by the perceived characteristics of the Boomer cohort itself now entering old age and by economic and political circumstances severely constraining policy agendas and options. We argue that the combination of weakened legitimacy in the face of pressing needs among many of the Boomer population may result in a fracturing of elders' longstanding singular political imagery. More affluent Boomers will continue to fight for their benefits as Contenders, whereas vulnerable Boomers may be relegated back to the Dependent categorization.

TBR1 encodes a transcription factor with critical roles in corticogenesis, including cortical neuron migration and axon pathfinding, establishment of regional and laminar identity of cortical neurons, and control of glutamatergic neuronal cell fate. Based upon TBR1’s role in cortical development, we sought to investigate TBR1 hemizygosity in individuals referred for genetic evaluation of intellectual disability and developmental delay. We describe 4 patients with microdeletions identified by molecular cytogenetic techniques, encompassing TBR1 and spanning 2q24.1q31.1, ranging in size from 2.17 to 12.34 Mb. Only the patient with the largest deletion had a possible cortical malformation. Mild ventriculomegaly is the only common brain anomaly, present in all patients; a Chiari I malformation is seen in 2 patients, and mega cisterna magna is seen in a third. Our findings are consistent with Tbr1 mouse models showing that hemizygosity of the gene requires additional genetic factors for the manifestation of severe structural brain malformations. Other syndromic features are present in these patients, including autism spectrum disorders, ocular colobomas, and craniosynostosis, features that are likely affected by the deletion of genes other than TBR1.

White House Conferences on Aging, dating to 1961, have long captured policy-relevant understandings about the status of older adults in American life. The initial Conference rallied support for the major legislative achievements of 1965—Medicare, Medicaid, and the Older Americans Act. The 1971 Conference came together with enormous energy, both celebrating and contributing to the major legislative accomplishments of the 1965–1974 decade. The Conference in 1981 was marked by heated exchanges between insurgent Reagan administration officials and those pressing for further aging policy initiatives. In 1995, the Conference stood as a modest firewall against cuts to Medicare and Medicaid being proposed by House Speaker Newt Gingrich and the Republican “Class of ‘94.” The Conference in 2005 was notable, in part, because for the first time the President did not participate—George W. Bush’s visiting an upscale retirement community on the day he was most likely to make an appearance—but also because of widespread concern among delegates regarding the President’s attempt to partially privatize Social Security. This year’s Conference is centered on highlighting both the needs and the contributions of the nation’s seniors. Organizers have identified four overarching themes critical to elders’ well-being: healthy aging, retirement security, long-term supports and services, and elder justice. While not being unmindful of the larger political realities surrounding the Conference, the rights, roles, and needs of seniors will hold center stage. It is important that such deliberations take place because the demographics and economics of aging continue to shift in important ways. Long gone—thanks largely to public policy—are days when elders were singularly poor and frail. Yet, a new series of pressures associated with extended lives, income differentials, and living environments will mark aging in the years ahead. Complex as these changes may be, they very often fall along a “cumulative advantage/disadvantage” faultline (Crystal & Shea, 1990). As such, it is essential that Conference participants recognize and address the structured diversity that marks contemporary aging by race, gender, age, and region. The articles in the following pages address each of the

Extracts of Echinacea species were used traditionally in North America for the treatment of infections and wounds, and preparations derived from Echinacea purpurea ‐ cytotoxic concentrations. The immune modulation is manifest in two ways: as a stimulation of phagocytosis and other functions in various types of immune cells, and as an antiinflammatory agent in epithelial and other cells infected with proinflammatory viruses and microbes. Studies of gene expression in infected and uninfected cells have revealed that Echinacea extracts can bring about numerous changes in expression of cytokine, chemokine, and many other immune ‐ related genes. Thus Echinacea causes many alterations in signaling pathways involved in control of various immunological functions, resulting in control of the invading pathogen and amelioration of associated symptoms.

Cedar leaf oil (CLO), derived from the Western red cedar, Thuja plicata, was evaluated as a safe and acceptable broad spectrum antimicrobial agent, with a view to its potential applications in buildings, including the alleviation of sick building syndrome. Various Gram-positive and Gram-negative human bacteria, and two fungal organisms, all known to be common environmental sources of potential infection, were selected and tested quantitatively, and all of them were found to be susceptible to CLO liquid and vapor. Bacterial spores and Aspergillus niger were sensitive, although less so than the vegetative bacteria. Similar tests with cultured human lung cells showed that continuous exposure to CLO vapor for at least 60 minutes was not toxic to the cells. Based on these results, CLO shows promise as a prospective safe, green, broad-spectrum anti-microbial agent for decontamination of buildings.

Extramedullary hematopoiesis (EMH) is the production of mature blood elements outside of the bone marrow and can occur as a compensatory result of a marrow replacing process or from marrow space occupying lesions such as tumor or marrow fibrosis. EMH can also be induced by factors elicited by neoplasms, such as vascular endothelial growth factor (VEGF). Usually, EMH is a diffuse process most commonly observed in lymph nodes, liver, and spleen. Rarely, EMH can form a mass lesion. Although the spleen is a common site for diffuse EMH, it is a rare location for a mass forming EMH. Hemangiomas are the most common benign tumors of the spleen. A case of a discrete, 8 cm lesion was noted incidentally on CT scan in a 59-year-old man with no significant past medical history. Endoscopic ultrasound guided fine-needle aspiration (EUS FNA) biopsy was performed and cytologic examination revealed trilinear hematopoiesis, with the most distinctive elements being megakaryocytes and erythroid precursors. A diagnosis of EMH was made. On resection, the mass was a hemangioma with EMH. EUS guided FNA is a useful tool for diagnosing splenic masses. Awareness of EMH, both as a mass forming lesion and a feature associated with benign and malignant vascular lesions is important, especially in patients with hematologic malignancies or marrow replacing processes.

Background: Dried blood spot (DBS) sampling, the collection of whole blood samples on paper, is being evaluated for its use in quantitative analysis. The aim of this investigation was to evaluate the impact of sample hematocrit (HCT) and punch location on assay bias in the measurement of compounds with varying physicochemical properties, when a portion of a DBS sample is analyzed. In addition, the statistical significance of factors such as compound, card type, HCT level, spot position on a card and the location of the punch on the spot were evaluated. Results: The results of this work indicate that for quantitative analysis using a portion of the DBS, notable bias (>15%) exists due to the effect of HCT and nonhomogeneous distribution of compound across the spot. The statistical analysis of results from a split-split-plot designed study showed that the factors of compound, card type and HCT were statistically significant (p < 0.05) both individually and in complex interactions, which affect the accuracy of quantitative concentrations obtained from DBS samples for each compound on each card type. Conclusion: To achieve the acceptance criteria (±15%) for accuracy when removing a portion of the DBS spot for quantitative analysis, HCT and punch location for each selected card type will need to be assessed during validation and sample analysis.

The observation that muscular exercise is associated with oxidative stress in humans was first reported over 30 years ago. Since this initial report, numerous studies have confirmed that prolonged or high-intensity exercise results in oxidative damage to macromolecules in both blood and skeletal muscle. Although the primary tissue(s) responsible for reactive oxygen species (ROS) production during exercise remains a topic of debate, compelling evidence indicates that muscular activity promotes oxidant production in contracting skeletal muscle fibers. Mitochondria, NADPH oxidase, PLA₂-dependent processes, and xanthine oxidase have all been postulated to contribute to contraction-induced ROS production in muscle but the primary site of contraction-induced ROS production in muscle fibers remains unclear. Nonetheless, contraction-induced ROS generation has been shown to play an important physiological function in the regulation of both muscle force production and contraction-induced adaptive responses of muscle fibers to exercise training. Although knowledge in the field of exercise and oxidative stress has grown markedly during the past 30 years, this area continues to expand and there is much more to be learned about the role of ROS as signaling molecules in skeletal muscle.

Patients with altered renal function are frequently encountered in the emergency department (ED) and emergency physicians often play an important role in the evaluation and management of renal disease. Early recognition, diagnosis, prevention of further iatrogenic injury, and management of renal disease have important implications for long-term morbidity and mortality. This article reviews basic renal physiology, discusses the differential diagnosis and approach to therapy, as well as strategies to prevent further renal injury, for adult patients who present to the ED with renal injury or failure.

We report on recent DIII-D experiments that integrate edge localized mode (ELM) suppression using resonant magnetic perturbations (RMPs) with divertor heat flux reduction under radiating divertor conditions. Our results illustrate the limitations in maintaining ELM suppression at gas puffing levels that were representative of good puff and pump operation in previous experiments without RMP. The electron pressure gradient in the pedestal (∇Pe) increased steadily during gas puffing and ELMs returned once ∇Pe reached values consistent with the peeling–ballooning stability limit, as determined by edge stability analysis. Even with this return of ELMs, a radiating divertor with RMP generated higher levels of total radiated power (∼40%) than comparable standard ELMing discharges without RMP at the same density. Differences in the accumulation of the seed argon in the core plasma between RMP and non-RMP during puff and pump were less than 20%.

Mechanical ventilation is a life-saving intervention used to provide adequate pulmonary ventilation in patients suffering from respiratory failure. However, prolonged mechanical ventilation is associated with significant diaphragmatic weakness resulting from both myofiber atrophy and contractile dysfunction. Although several signaling pathways contribute to diaphragm weakness during mechanical ventilation, it is established that oxidative stress is required for diaphragmatic weakness to occur. Therefore, identifying the site(s) of mechanical ventilation- induced reactive oxygen species production in the diaphragm is important.These experiments tested the hypothesis that elevated mitochondrial reactive oxygen species emission is required for mechanical ventilation-induced oxidative stress, atrophy, and contractile dysfunction in the diaphragm.Cause and effect was determined by preventing mechanical ventilation-induced mitochondrial reactive oxygen species emission in the diaphragm of rats using a novel mitochondria-targeted antioxidant (SS-31).None.Compared to mechanically ventilated animals treated with saline, animals treated with SS-31 were protected against mechanical ventilation-induced mitochondrial dysfunction, oxidative stress, and protease activation in the diaphragm. Importantly, treatment of animals with the mitochondrial antioxidant also protected the diaphragm against mechanical ventilation-induced myofiber atrophy and contractile dysfunction.These results reveal that prevention of mechanical ventilation-induced increases in diaphragmatic mitochondrial reactive oxygen species emission protects the diaphragm from mechanical ventilation-induced diaphragmatic weakness. This important new finding indicates that mitochondria are a primary source of reactive oxygen species production in the diaphragm during prolonged mechanical ventilation. These results could lead to the development of a therapeutic intervention to impede mechanical ventilation-induced diaphragmatic weakness.

Extracts of Echinacea species have been used traditionally in North America for the control of symptoms of colds, influenza, and other diseases, and some of them have become very popular as “herbal medicines”. Recent studies have revealed that preparations derived from certain species and plant parts, but not all of them, possess potent antiviral activities, at non-cytotoxic concentrations, particularly against membrane-containing viruses. Thus all strains of human and avian influenza viruses tested (including a Tamiflu-resistant strain), as well as herpes simplex virus, respiratory syncytial virus, and rhinoviruses, were very sensitive to a standardized Echinacea purpurea preparation. In mechanistic studies the influenza virus-specific hemagglutinin and neuraminidase were inhibited. In addition some extracts displayed anti-inflammatory activity in virus-infected cells, and numerous other effects on the expression of cellular genes. Multiple components, either discrete compounds or mixtures, appeared to be responsible for the various antiviral activities.

Background Prolonged mechanical ventilation (MV) results in a rapid onset of diaphragmatic atrophy that is primarily due to increased proteolysis. Although MV-induced protease activation can involve several factors, it is clear that oxidative stress is a required signal for protease activation in the diaphragm during prolonged MV. However, the oxidant-producing pathways in the diaphragm that contribute to MV-induced oxidative stress remain unknown. We have demonstrated that prolonged MV results in increased diaphragmatic expression of a key stress-sensitive enzyme, heme oxygenase (HO)-1. Paradoxically, HO-1 can function as either a pro-oxidant or an antioxidant, and the role that HO-1 plays in MV-induced diaphragmatic oxidative stress is unknown. We tested the hypothesis that HO-1 acts as a pro-oxidant in the diaphragm during prolonged MV. Methods To determine whether HO-1 functions as a pro-oxidant or an antioxidant in the diaphragm during MV, we assigned rats into three experimental groups: (1) a control group, (2) a group that received 18 h of MV and saline solution, and (3) a group that received 18 h of MV and was treated with a selective HO-1 inhibitor. Indices of oxidative stress, protease activation, and fiber atrophy were measured in the diaphragm. Results Inhibition of HO-1 activity did not prevent or exacerbate MV-induced diaphragmatic oxidative stress (as indicated by biomarkers of oxidative damage). Further, inhibition of HO-1 activity did not influence MV-induced protease activation or myofiber atrophy in the diaphragm. Conclusions Our results indicate that HO-1 is neither a pro-oxidant nor an antioxidant in the diaphragm during MV. Furthermore, our findings reveal that HO-1 does not play an important role in MV-induced protease activation and diaphragmatic atrophy.