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Showing papers by "Saint Louis University published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
TL;DR: Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote optimal health in children and adolescents using a modified RAND Appropriateness Method.
Abstract: Sleep is essential for optimal health in children and adolescents. Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote op...

843 citations


Journal ArticleDOI
TL;DR: The new ICD‐10‐CM (M62.84) code for sarc Openia represents a major step forward in recognizing sarcopenia as a disease and should lead to an increase in availability of diagnostic tools and the enthusiasm for pharmacological companies to develop drugs for sarc openia.
Abstract: The new ICD-10-CM (M62.84) code for sarcopenia represents a major step forward in recognizing sarcopenia as a disease. This should lead to an increase in availability of diagnostic tools and the enthusiasm for pharmacological companies to develop drugs for sarcopenia.

678 citations


Journal ArticleDOI
TL;DR: A brief, inexpensive screening test for sarcopenia would be helpful for clinicians and their patients by developing a simple five‐item questionnaire (SARC‐F) based on cardinal features or consequences of sarc Openia.
Abstract: Background A brief, inexpensive screening test for sarcopenia would be helpful for clinicians and their patients. To screen for persons with sarcopenia, we developed a simple five-item questionnaire (SARC-F) based on cardinal features or consequences of sarcopenia. Methods We investigated the utility of SARC-F in the African American Health (AAH) study, Baltimore Longitudinal Study of Aging (BLSA), and National Health and Nutrition Examination Survey (NHANES). Internal consistency reliability for SARC-F was determined using Cronbach's alpha. We evaluated SARC-F factorial validity using principal components analysis and criterion validity by examining its association with exam-based indicators of sarcopenia. Construct validity was examined using cross-sectional and longitudinal differences among those with high (≥4) vs. low (<4) SARC-F scores for mortality and health outcomes. Results SARC-F exhibited good internal consistency reliability and factorial, criterion, and construct validity. AAH participants with SARC-F scores ≥ 4 had more Instrumental Activity of Daily Living (IADL) deficits, slower chair stand times, lower grip strength, lower short physical performance battery scores, and a higher likelihood of recent hospitalization and of having a gait speed of <0.8 m/s. SARC-F scores ≥ 4 in AAH also were associated with 6 year IADL deficits, slower chair stand times, lower short physical performance battery scores, having a gait speed of <0.8 m/s, being hospitalized recently, and mortality. SARC-F scores ≥ 4 in the BLSA cohort were associated with having more IADL deficits and lower grip strength (both hands) in cross-sectional comparisons and with IADL deficits, lower grip strength (both hands), and mortality at follow-up. NHANES participants with SARC-F scores ≥ 4 had slower 20 ft walk times, had lower peak force knee extensor strength, and were more likely to have been hospitalized recently in cross-sectional analyses. Conclusions The SARC-F proved internally consistent and valid for detecting persons at risk for adverse outcomes from sarcopenia in AAH, BLSA, and NHANES.

578 citations


Journal ArticleDOI
TL;DR: The identification of frailty as a target for implementing preventive interventions against age-related conditions is pivotal and every effort should be made by health care authorities to maximize efforts in this field.

465 citations


Journal ArticleDOI
TL;DR: Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote optimal health in children and adolescents using a modified RAND Appropriateness Method after review of 864 published articles.
Abstract: Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote optimal health in children and adolescents using a modified RAND Appr...

387 citations


Journal ArticleDOI
TL;DR: In this article, the authors used logistic regression to calculate odds ratios (ORs) for variables associated with fracture nonunion and found that increased nonunion risk was associated with severe fracture (e.g., open fracture, multiple fractures), high body mass index, smoking, and alcoholism.
Abstract: Importance Failure of bone fracture healing occurs in 5% to 10% of all patients. Nonunion risk is associated with the severity of injury and with the surgical treatment technique, yet progression to nonunion is not fully explained by these risk factors. Objective To test a hypothesis that fracture characteristics and patient-related risk factors assessable by the clinician at patient presentation can indicate the probability of fracture nonunion. Design, Setting, and Participants An inception cohort study in a large payer database of patients with fracture in the United States was conducted using patient-level health claims for medical and drug expenses compiled for approximately 90.1 million patients in calendar year 2011. The final database collated demographic descriptors, treatment procedures as per Current Procedural Terminology codes; comorbidities as per International Classification of Diseases, Ninth Revision codes; and drug prescriptions as per National Drug Code Directory codes. Logistic regression was used to calculate odds ratios (ORs) for variables associated with nonunion. Data analysis was performed from January 1, 2011, to December 31, 2012, Exposures Continuous enrollment in the database was required for 12 months after fracture to allow sufficient time to capture a nonunion diagnosis. Results The final analysis of 309 330 fractures in 18 bones included 178 952 women (57.9%); mean (SD) age was 44.48 (13.68) years. The nonunion rate was 4.9%. Elevated nonunion risk was associated with severe fracture (eg, open fracture, multiple fractures), high body mass index, smoking, and alcoholism. Women experienced more fractures, but men were more prone to nonunion. The nonunion rate also varied with fracture location: scaphoid, tibia plus fibula, and femur were most likely to be nonunion. The ORs for nonunion fractures were significantly increased for risk factors, including number of fractures (OR, 2.65; 95% CI, 2.34-2.99), use of nonsteroidal anti-inflammatory drugs plus opioids (OR, 1.84; 95% CI, 1.73-1.95), operative treatment (OR, 1.78; 95% CI, 1.69-1.86), open fracture (OR, 1.66; 95% CI, 1.55-1.77), anticoagulant use (OR, 1.58; 95% CI, 1.51-1.66), osteoarthritis with rheumatoid arthritis (OR, 1.58; 95% CI, 1.38-1.82), anticonvulsant use with benzodiazepines (OR, 1.49; 95% CI, 1.36-1.62), opioid use (OR, 1.43; 95% CI, 1.34-1.52), diabetes (OR, 1.40; 95% CI, 1.21-1.61), high-energy injury (OR, 1.38; 95% CI, 1.27-1.49), anticonvulsant use (OR, 1.37; 95% CI, 1.31-1.43), osteoporosis (OR, 1.24; 95% CI, 1.14-1.34), male gender (OR, 1.21; 95% CI, 1.16-1.25), insulin use (OR, 1.21; 95% CI, 1.10-1.31), smoking (OR, 1.20; 95% CI, 1.14-1.26), benzodiazepine use (OR, 1.20; 95% CI, 1.10-1.31), obesity (OR, 1.19; 95% CI, 1.12-1.25), antibiotic use (OR, 1.17; 95% CI, 1.13-1.21), osteoporosis medication use (OR, 1.17; 95% CI, 1.08-1.26), vitamin D deficiency (OR, 1.14; 95% CI, 1.05-1.22), diuretic use (OR, 1.13; 95% CI, 1.07-1.18), and renal insufficiency (OR, 1.11; 95% CI, 1.04-1.17) (multivariate P Conclusions and Relevance The probability of fracture nonunion can be based on patient-specific risk factors at presentation. Risk of nonunion is a function of fracture severity, fracture location, disease comorbidity, and medication use.

384 citations


Journal ArticleDOI
TL;DR: A tool that simultaneously incorporates multiple health characteristics to estimate a person's probable long-term risk of ESRD if that person does not donate a kidney was developed and may be used to inform acceptance criteria for kidney donors.
Abstract: BackgroundEvaluation of candidates to serve as living kidney donors relies on screening for individual risk factors for end-stage renal disease (ESRD). To support an empirical approach to donor selection, we developed a tool that simultaneously incorporates multiple health characteristics to estimate a person’s probable long-term risk of ESRD if that person does not donate a kidney. MethodsWe used risk associations from a meta-analysis of seven general population cohorts, calibrated to the population-level incidence of ESRD and mortality in the United States, to project the estimated long-term incidence of ESRD among persons who do not donate a kidney, according to 10 demographic and health characteristics. We then compared 15-year projections with the observed risk among 52,998 living kidney donors in the United States. ResultsA total of 4,933,314 participants from seven cohorts were followed for a median of 4 to 16 years. For a 40-year-old person with health characteristics that were similar to those of...

320 citations


Journal ArticleDOI
TL;DR: This paper developed a theory of metajournalistic discourse that connects three components-actors, sites/audiences, and topics-to processes of definition making, boundary work, and legitimation.
Abstract: Situating journalism as a cultural practice charged with delivering valid accounts of the world necessitates a theory of metajournalistic discourse to explain how meanings around journalism develop. Through metajournalistic discourse, various actors inside and outside of journalism compete to construct, reiterate, and even challenge the boundaries of acceptable journalistic practices and the limits of what can or cannot be done. Based on the premises that journalism is variable, reliant on context, and produced through social relationships, this article develops a theory of metajournalistic discourse that connects three components-actors, sites/audiences, and topics-to processes of definition making, boundary work, and legitimation. [ABSTRACT FROM AUTHOR]

320 citations


Journal ArticleDOI
TL;DR: A scoping review of the literature and national statistics on Hispanic health in the USA using a modified social-ecological framework that includes social determinants of health, health disparities, risk factors, and health services, as they shape the leading causes of morbidity and mortality.
Abstract: Hispanics are the largest minority group in the USA. They contribute to the economy, cultural diversity, and health of the nation. Assessing their health status and health needs is key to inform health policy formulation and program implementation. To this end, we conducted a scoping review of the literature and national statistics on Hispanic health in the USA using a modified social-ecological framework that includes social determinants of health, health disparities, risk factors, and health services, as they shape the leading causes of morbidity and mortality. These social, environmental, and biological forces have modified the epidemiologic profile of Hispanics in the USA, with cancer being the leading cause of mortality, followed by cardiovascular diseases and unintentional injuries. Implementation of the Affordable Care Act has resulted in improved access to health services for Hispanics, but challenges remain due to limited cultural sensitivity, health literacy, and a shortage of Hispanic health care providers. Acculturation barriers and underinsured or uninsured status remain as major obstacles to health care access. Advantageous health outcomes from the “Hispanic Mortality Paradox” and the “Latina Birth Outcomes Paradox” persist, but health gains may be offset in the future by increasing rates of obesity and diabetes. Recommendations focus on the adoption of the Health in All Policies framework, expanding access to health care, developing cultural sensitivity in the health care workforce, and generating and disseminating research findings on Hispanic health.

287 citations


Journal ArticleDOI
TL;DR: In this paper, the authors show that short interest is arguably the strongest known predictor of aggregate stock returns and that short sellers are informed traders who are able to anticipate future aggregate cash flows and associated market returns.
Abstract: We show that short interest is arguably the strongest known predictor of aggregate stock returns. It outperforms a host of popular return predictors both in and out of sample, with annual r-squared statistics of 12.89% and 13.24%, respectively. In addition, short interest can generate utility gains of over 300 basis points per annum for a mean-variance investor. A vector autoregression decomposition shows that the economic source of short interest’s predictive power stems predominantly from a cash flow channel. Overall, our evidence indicates that short sellers are informed traders who are able to anticipate future aggregate cash flows and associated market returns.The appendices for this paper are available at the following URL: http://ssrn.com/abstract=2675298

Journal ArticleDOI
TL;DR: With growing interest in perennial crops as valuable components of sustainable agriculture, rootstocks provide one mechanism by which to improve and expand woody perennial cultivation in a range of environmental conditions.

Journal ArticleDOI
TL;DR: In this paper, the authors show that short interest is arguably the strongest known predictor of aggregate stock returns and that short sellers are informed traders who are able to anticipate future aggregate cash flows and associated market returns.

Journal ArticleDOI
TL;DR: A number of consensus groups have provided similar definitions where sarcopenia is now defined as loss of function coupled with loss of muscle mass, and all of the definitions have been demonstrated to predict functional decline, hospitalization, and mortality in both community-dwelling older persons and residents in nursing homes.

Journal ArticleDOI
TL;DR: This work assessed the safety and efficacy of SOF‐containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR) and concluded that these regimens should be considered as safe and effectiveixtures.
Abstract: Background & Aims Renal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR). Methods HCV-TARGET database is a multicentre, longitudinal ‘real-world’ treatment cohort. Results A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4–6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m2. Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400–1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82–83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31–45 had similar frequencies of efficacy and safety outcomes. Conclusions Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m2) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.

Journal ArticleDOI
TL;DR: Secukinumab had a favorable safety profile, had no meaningful difference between the 300- and 150-mg doses and, in terms of safety, was comparable to etanercept over 52 weeks in patients with moderate to severe plaque psoriasis.
Abstract: Background Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe plaque psoriasis. Objective We reviewed safety data from the secukinumab psoriasis phase II/III program. Methods Data were pooled from 10 phase II/III secukinumab psoriasis studies. Results Analysis included 3993 subjects; 3430 received secukinumab, representing 2725 subject-years (SYs) of exposure. Over 52 weeks, for secukinumab 300 mg, 150 mg, and etanercept, respectively, exposure-adjusted incidence rates (IRs) per 100 SYs were comparable across treatments for total adverse events (AEs; 236.1, 239.9, and 243.4, respectively); infections (91.1, 85.3, and 93.7, respectively); serious AEs (7.4, 6.8, and 7.0, respectively); serious infections (1.4, 1.1, and 1.4, respectively); malignant or unspecified tumors (0.77, 0.97, and 0.68, respectively); and adjudicated major adverse cardiovascular events (0.42, 0.35, and 0.34, respectively). AEs were not dose-related except for nonserious, mild/moderate, skin/mucosal candidiasis (IRs 3.55, 1.85, and 1.37 for secukinumab 300 mg, 150 mg, and etanercept, respectively). Limitations There was a limited number of patients in comparator groups and the exposure to placebo was short. Conclusion Secukinumab had a favorable safety profile, had no meaningful difference between the 300- and 150-mg doses and, in terms of safety, was comparable to etanercept over 52 weeks in patients with moderate to severe plaque psoriasis.

Journal ArticleDOI
TL;DR: PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD, and a graded association between duration of PPI exposure and risk of renal outcomes among those exposed for ≤30 days is detected.
Abstract: The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI ( n =173,321) and new users of histamine H 2 -receptor antagonists (H 2 blockers; n =20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H 2 blockers group, had an increased risk of incident eGFR 2 and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31–90, 91–180, 181–360, and 361–720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H 2 blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.

Journal ArticleDOI
TL;DR: The implication of a non-uniform use of the term chronic disease is that a detailed read of each study is necessary to avoid erroneous conclusions regarding interventions necessary to reduce chronic disease burden for the individual and society.
Abstract: One important element of effective communication is having a shared language or at least a shared understanding of the meaning of the central words used in a conversation. One term that is often used in discussions between patients and medical providers, in the academic literature, and in policy discussions, is “chronic disease.” There is not only tremendous variation in the diseases that are included under the umbrella term “chronic disease” but also variation in the time a disease must be present for something to be referred to as chronic. Furthermore, there is a move to include chronic conditions that are not indicators of disease, but long-standing functional disabilities, including developmental disorders and visual impairment (1–4). Within professional communities (i.e., medical, public health, academic, and policy), there is a large degree of variation in the use of the term chronic disease. For example, the Centers for Disease Control (CDC) classify the following as chronic diseases: heart disease, stroke, cancer, type 2 diabetes, obesity, and arthritis (5). The Centers for Medicare and Medicaid Services have a more extensive list of 19 chronic conditions that includes Alzheimer’s disease, depression, and HIV, to name a few. This difference, within the Department of Health and Human Services alone, although not surprising to those in the field, has the potential to create confusion and misunderstanding when speaking in generalities about the impact of chronic disease, the cost of chronic disease, and overall measures to reduce chronic disease. The academic literature is not immune to the same kind of terminology variation. Differences in how “chronic disease” is used are largely dependent on the data used for the research and the discipline of the lead authors (i.e., public health and sociology). For example, one study, authored by individuals from Harvard Medical School, explored the prevalence of chronic disease using NHANES data (1999–2004). The study classifies the following as chronic diseases: cardiovascular disease, hypertension, diabetes mellitus, hypercholesterolemia, asthma, COPD, and previous cancer (6). Another academic study on chronic disease, authored by a geriatrician, classifies chronic illness as “conditions that last a year or more and require ongoing medical attention and/or limit activities of daily living” (7). The implication of a non-uniform use of the term is that a detailed read of each study is necessary to avoid erroneous conclusions regarding interventions necessary to reduce chronic disease burden for the individual and society. Popular Internet sources used by the general public to gather medical information use the terms “chronic disease” or “chronic condition” to mean slightly different things. For example, MedicineNet describes a chronic disease as,

Journal ArticleDOI
TL;DR: Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma, and no difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR.
Abstract: Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB–IV melanoma. Lesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions [uninjected]), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (n = 295) who experienced a durable response (continuous partial or complete response for ≥6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or >25 % increase in total baseline tumor area. T-VEC resulted in a decrease in size by ≥50 % in 64 % of injected lesions (N = 2116), 34 % of uninjected non-visceral lesions (N = 981), and 15 % of visceral lesions (N = 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR. Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC.

Journal ArticleDOI
28 Jul 2016
TL;DR: Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to the use of augmentation therapy (that is, infusions of human plasma-derived, purified α1-antitrypsin).
Abstract: α1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD) or cryptogenic liver disease. The most frequent disease-associated mutations include the S allele and the Z allele of SERPINA1, which lead to the accumulation of misfolded α1-antitrypsin in hepatocytes, endoplasmic reticulum stress, low circulating levels of α1-antitrypsin and liver disease. Currently, there is no cure for severe liver disease and the only management option is liver transplantation when liver failure is life-threatening. A1ATD-associated lung disease predominately occurs in adults and is caused principally by inadequate protease inhibition. Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to the use of augmentation therapy (that is, infusions of human plasma-derived, purified α1-antitrypsin). New therapies that target the misfolded α1-antitrypsin or attempt to correct the underlying genetic mutation are currently under development.

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TL;DR: In this article, a literature search resulted in 57 studies on the effectiveness of mindfulness meditation in reducing stress and anxiety in college students, including self-reported stress, selfreported stress in 34, physiological stress in 11, and mindfulness in 24.

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TL;DR: In this paper, the authors evaluated clinical outcomes and safety of EUS-guided drainage of pancreatic pseudocysts and walled-off necrosis (WON) by using a novel lumen-apposing, fully covered, self-expandable metal stent.

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TL;DR: The (Brazilian) Portuguese-translated version of the SARC-F questionnaire was validated and its performance in the separate sarcopenia screening and muscle function evaluation contexts verified and a substantial improvement in sensitivity was achieved without compromising the remaining parameters.

Journal ArticleDOI
TL;DR: The emerging mechanisms of the replication-stress response in mammalian cells are reviewed and how they may influence the dynamics of the core DNA replication complex is considered.
Abstract: The replication-stress response enables the DNA replication machinery to overcome DNA lesions or intrinsic replication-fork obstacles, and it is essential to ensure faithful transmission of genetic information to daughter cells. Multiple replication stress–response pathways have been identified in recent years, thus raising questions about the specific and possibly redundant functions of these pathways. Here, we review the emerging mechanisms of the replication-stress response in mammalian cells and consider how they may influence the dynamics of the core DNA replication complex.


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TL;DR: In this review, the most recent trends in 3D-printed microfluidic devices are discussed, and a focus is given to the fabrication aspects of these devices.
Abstract: A mini-review with 79 references. In this review, the most recent trends in 3D-printed microfluidic devices are discussed. In addition, a focus is given to the fabrication aspects of these devices, with the ESI containing detailed instructions for designing a variety of structures including: a microfluidic channel, threads to accommodate commercial fluidic fittings, a flow splitter; a well plate, a mold for PDMS channel casting; and how to combine multiple designs into a single device. The advantages and limitations of 3D-printed microfluidic devices are thoroughly discussed, as are some future directions for the field.


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TL;DR: It is suggested that PM1 and constituents from combustion and secondary aerosols might be important characteristics of PM pollution associated with cardiovascular mortality in Guangzhou and they remained consistent in various sensitivity analyses by changing model parameters.

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TL;DR: Despite the evolution of medical technology and use of contemporary therapeutic measures, in-hospital mortality in CS-AMI patients who are managed invasively continues to rise and additional research and targeted efforts are indicated to improve outcomes.
Abstract: Objectives The purpose of this study was to examine the temporal trends in demographics, clinical characteristics, management strategies, and in-hospital outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (CS-AMI) who underwent percutaneous coronary intervention (PCI) from the Cath-PCI Registry (2005 to 2013). Background The authors examined contemporary use and outcomes of PCI in patients with CS-AMI. Methods The authors used the Cath-PCI Registry to evaluate 56,497 patients (January 2005 to December 2013) undergoing PCI for CS-AMI. Temporal trends in clinical variables and outcomes were assessed. Results Compared with cases performed from 2005 to 2006, CS-AMI patients receiving PCI from 2011 to 2013 were more likely to have diabetes, hypertension, dyslipidemia, previous PCI, dialysis, but less likely to have chronic lung disease, peripheral vascular disease, or heart failure within 2 weeks (p Conclusions Our study shows that despite the evolution of medical technology and use of contemporary therapeutic measures, in-hospital mortality in CS-AMI patients who are managed invasively continues to rise. Additional research and targeted efforts are indicated to improve outcomes in this high-risk cohort.

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TL;DR: Positive outcomes from mixtures are identified including increased biodiversity, water quality, esthetic and recreational values, as well as reduced stand vulnerability to pest and pathogen damage.
Abstract: Whereas there is evidence that mixed-species approaches to production forestry in general can provide positive outcomes relative to monocultures, it is less clear to what extent multiple benefits can be derived from specific mixed-species alternatives. To provide such insights requires evaluations of an encompassing suite of ecosystem services, biodiversity, and forest management considerations provided by specific mixtures and monocultures within a region. Here, we conduct such an assessment in Sweden by contrasting even-aged Norway spruce (Picea abies)-dominated stands, with mixed-species stands of spruce and birch (Betula pendula or B. pubescens), or spruce and Scots pine (Pinus sylvestris). By synthesizing the available evidence, we identify positive outcomes from mixtures including increased biodiversity, water quality, esthetic and recreational values, as well as reduced stand vulnerability to pest and pathogen damage. However, some uncertainties and risks were projected to increase, highlighting the importance of conducting comprehensive interdisciplinary evaluations when assessing the pros and cons of mixtures.