Mast cell tumours in dogs less than 12 months of age: a multi-institutional retrospective study.

OBJECTIVES: To describe the clinicopathological and genetic characteristics of mast cell tumours in dogs less than 12 months old. MATERIALS AND METHODS: Retrospective review of dogs aged less than 12 months when diagnosed with mast cell tumours at three referral hospitals in the UK. RESULTS: Sixteen pure-bred dogs were included, of which 11 were female. The median age at first presentation and diagnosis were 7.6 and 9 months, respectively. In 13 dogs the mast cell tumours were cutaneous and in three they were subcutaneous. Four cutaneous mast cell tumours were described as high-grade (Patnaik or Kiupel) and nine were Patnaik grade II; three had mitotic index of >5 in 10 high-power fields. Of the three subcutaneous tumours, two had an infiltrative growth pattern and one had mitotic index of 10 per 10 high-power fields. Of 10 tested dogs, seven had c-kit mutations in exon 11 and Ki-67 score was above the cut-off value in nine. Four of 12 cases showed evidence of metastasis in the regional lymph nodes. After varying treatment protocols, all patients were alive and disease free at a median of 1115 days after diagnosis. CLINICAL SIGNIFICANCE: The prognosis of mast cell tumours in dogs less than a year old appears better than the adult counterparts, even without extensive treatment.

Genome-wide analysis of canine oral malignant melanoma metastasis-associated gene expression.

Oral malignant melanoma (OMM) is the most common canine melanocytic neoplasm. Overlap between the somatic mutation profiles of canine OMM and human mucosal melanomas suggest a shared UV-independent molecular aetiology. In common with human mucosal melanomas, most canine OMM metastasise. There is no reliable means of predicting canine OMM metastasis, and systemic therapies for metastatic disease are largely palliative. Herein, we employed exon microarrays for comparative expression profiling of FFPE biopsies of 18 primary canine OMM that metastasised and 10 primary OMM that did not metastasise. Genes displaying metastasis-associated expression may be targets for anti-metastasis treatments, and biomarkers of OMM metastasis. Reduced expression of CXCL12 in the metastasising OMMs implies that the CXCR4/CXCL12 axis may be involved in OMM metastasis. Increased expression of APOBEC3A in the metastasising OMMs may indicate APOBEC3A-induced double-strand DNA breaks and pro-metastatic hypermutation. DNA double strand breakage triggers the DNA damage response network and two Fanconi anaemia DNA repair pathway members showed elevated expression in the metastasising OMMs. Cross-validation was employed to test a Linear Discriminant Analysis classifier based upon the RT-qPCR-measured expression levels of CXCL12, APOBEC3A and RPL29. Classification accuracies of 94% (metastasising OMMs) and 86% (non-metastasising OMMs) were estimated.

MicroRNAs in equine veterinary science.

MicroRNAs are small noncoding RNAs that play a pivotal role in diverse cellular processes through post-transcriptional regulation of gene expression. The dysregulation of specific microRNAs is associated with disease development and progression. In this review, we summarise how microRNAs modulate gene expression, and explain microRNA nomenclature. We discuss the potential applications of microRNAs in equine disease diagnosis and treatment, in the context of the sum of current knowledge about microRNA expression in normal and diseased equine tissues.

Obese asthmatics are characterized by altered adipose tissue macrophage activation.

BACKGROUND: Adipose tissue-derived inflammation is linked to obesity-related comorbidities. This study aimed to quantify and immuno-phenotype adipose tissue macrophages (ATMs) from obese asthmatics and obese non-asthmatics and to examine associations between adipose tissue, systemic and airway inflammation. METHODS: Visceral (VAT) adipose tissue and subcutaneous (SAT) adipose tissue were collected from obese adults undergoing bariatric surgery and processed to obtain the stromovascular fraction. Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages were quantified by flow cytometry. Cytospins of induced sputum were stained for differential cell counts. Plasma C-reactive protein (CRP) and CD163 were measured by ELISA. RESULTS: VAT contained a higher number of ATMs compared to SAT. A higher percentage of M1 ATMs was observed in VAT of obese asthmatics compared to obese non-asthmatics. The M1:M2 ratio in VAT was negatively associated with FEV1 %. Sputum macrophage count was correlated positively with M1 ATMs and negatively with M2 ATMs in VAT. In obese asthmatics, CRP was positively associated with M1:M2 ratio in VAT. There were no associations with CD163. An elevated ratio of M1:M2 ATMs was observed in VAT of obese asthmatics with increased disease severity. CONCLUSIONS AND CLINICAL RELEVANCE: Visceral inflammation with increased pro-inflammatory macrophages (M1) occurs in obese asthma and may be a determinant of systemic inflammation and asthma severity.

A preliminary investigation of the effect of sample collection technique on the cell and RNA content of fine-needle aspirates of five canine tumours.

OBJECTIVES: To evaluate the effect of syringe size, needle size, number of needle passes and operator experience on cell yield from tumour fine-needle aspirates, and the quantity and quality of extractable RNA. MATERIALS AND METHODS: Fine-needle aspirates were collected from canine lymphoma, cutaneous mast cell tumour, anal gland adenocarcinoma, fibrosarcoma and oral malignant melanoma using nine different techniques. RESULTS: There was a significant difference in cell yield between fine-needle aspirate techniques for melanoma, lymphoma and anal gland adenocarcinoma. The application of suction yielded the largest number of cells. Cell numbers in lymphoma and fibrosarcoma aspirates collected by different veterinary surgeons were not significantly different. Use of a smaller gauge needle and suction increased the quantity of RNA isolated from fibrosarcoma and anal gland adenocarcinoma aspirates, but did not influence RNA integrity. CLINICAL SIGNIFICANCE: Suction during fine-needle aspiration increases cell numbers obtained from five common canine tumours. Suction increases the quantity of RNA isolated from anal gland adenocarcinoma and fibrosarcoma aspirates without affecting RNA quality. Junior veterinary surgeons gain comparable cell numbers to senior staff.

Metastasis-associated microRNA expression in canine uveal melanoma.

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumour in dogs. There is no effective means of predicting whether a tumour will metastasize. microRNA (miRNA) metastasis signatures have been identified for several human cancers, including UM. AIMS: In this study we investigated whether metastasizing and non-metastasizing canine UMs can be distinguished by miRNA expression levels. MATERIALS AND METHODS: miRNA microarray profiling was used to compare miRNA expression in 8 metastasizing and 12 non-metastasizing formalin-fixed, paraffin-embedded (FFPE) primary UM biopsies. RESULTS: Fourteen miRNAs exhibited statistically significant differences in expression between the metastasizing and non-metastasizing tumours. Class prediction analysis pinpointed 9 miRNAs which categorized tumours as metastasizing or non-metastasizing with an accuracy of 89%. Of the discriminating miRNAs, 8 were up-regulated in metastasizing UM, and included 3 miRNAs implicated as potential "metastasis activators" in human cutaneous melanoma. The expression of 4 of the miRNAs was subsequently measured using the quantitative reverse transcription polymerase chain reaction (RT-qPCR), and their up-regulation in metastasizing tumours validated. CONCLUSION: miRNA expression profiles may potentially be used to identify UMs that will metastasize, and miRNAs that are up-regulated in metastasizing tumours may be targets for therapeutic intervention.

Targeting PP2A and proteasome activity ameliorates features of allergic airway disease in mice.

BACKGROUND: Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed whether enhancing PP2A activity with fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S) ), or inhibiting proteasome activity with bortezomib (BORT), could suppress experimental AAD. METHODS: Acute AAD was induced in C57BL/6 mice by intraperitoneal sensitization with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL(S) , BORT or AAL(S) +BORT and hallmark features of AAD assessed. RESULTS: AAL(S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus-secreting cell (MSC) numbers, type 2-associated cytokines (interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13 and AHR. Combined treatment with AAL(S) +BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type 2 cytokines and AHR. AAL(S) , BORT and AAL(S) +BORT also reduced airway remodelling in chronic AAD. CONCLUSION: These findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.

Diagnosis of acute gout: a Clinical Practice Guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the diagnosis of gout. METHODS: This guideline is based on a systematic review of published studies on gout diagnosis, identified using several databases, from database inception to February 2016. Evaluated outcomes included the accuracy of the test results; intermediate outcomes (results of laboratory and radiographic tests, such as serum urate and synovial fluid crystal analysis and radiographic or ultrasonography changes); clinical decision making (additional testing and pharmacologic or dietary management); short-term clinical (patient-centered) outcomes, such as pain and joint swelling and tenderness; and adverse effects of the tests. This guideline grades the evidence and recommendations by using the ACP grading system, which is based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians, and the target patient population includes adults with joint inflammation suspected to be gout. RECOMMENDATION: ACP recommends that clinicians use synovial fluid analysis when clinical judgment indicates that diagnostic testing is necessary in patients with possible acute gout. (Grade: weak recommendation, low-quality evidence).

A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.

Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization.

Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contributes to allergic sensitization, although the mechanisms governing this process remain unclear. Lung mucosal uric acid has also been linked to allergic sensitization. The links among PM exposure, uric acid, and allergic sensitization remain unexplored. We therefore investigated the mechanisms behind PM-induced allergic sensitization in the context of lung mucosal uric acid. PM10 and house dust mite exposure selectively induced lung mucosal uric acid production and secretion in vivo, which did not occur with other challenges (lipopolysaccharide, virus, bacteria, or inflammatory/fibrotic stimuli). PM10-induced uric acid mediates allergic sensitization and augments antigen-specific T-cell proliferation, which is inhibited by uricase. We then demonstrate that human airway epithelial cells secrete uric acid basally and after stimulation through a previously unidentified mucosal secretion system. Our work discovers a previously unknown mechanism of air pollution-induced, uric acid-mediated, allergic sensitization that may be important in the pathogenesis of asthma.

Risk assessment and prevention of pressure ulcers: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations based on the comparative effectiveness of risk assessment scales and preventive interventions for pressure ulcers. METHODS: This guideline is based on published literature on this topic that was identified by using MEDLINE (1946 through February 2014), CINAHL (1998 through February 2014), the Cochrane Library, clinical trials registries, and reference lists. Searches were limited to English-language publications. The outcomes evaluated for this guideline include pressure ulcer incidence and severity, resource use, diagnostic accuracy, measures of risk, and harms. This guideline grades the quality of evidence and strength of recommendations by using ACP's clinical practice guidelines grading system. The target audience for this guideline includes all clinicians, and the target patient population is patients at risk for pressure ulcers. RECOMMENDATION 1: ACP recommends that clinicians should perform a risk assessment to identify patients who are at risk of developing pressure ulcers. (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians should choose advanced static mattresses or advanced static overlays in patients who are at an increased risk of developing pressure ulcers. (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 3: ACP recommends against using alternating-air mattresses or alternating-air overlays in patients who are at an increased risk of developing pressure ulcers. (Grade: weak recommendation, moderate-quality evidence).(AU)

Treatment of pressure ulcers: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations based on the comparative effectiveness of treatments of pressure ulcers. METHODS: This guideline is based on published literature on this topic that was identified by using MEDLINE, EMBASE, CINAHL, EBM Reviews, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and the Health Technology Assessment database through February 2014. Searches were limited to English-language publications. The outcomes evaluated for this guideline include complete wound healing, wound size (surface area, volume, and depth) reduction, pain, prevention of sepsis, prevention of osteomyelitis, recurrence rate, and harms of treatment (including but not limited to pain, dermatologic complications, bleeding, and infection). This guideline grades the quality of evidence and strength of recommendations by using ACP's clinical practice guidelines grading system. The target audience for this guideline includes all clinicians, and the target patient population is patients with pressure ulcers. RECOMMENDATION 1: ACP recommends that clinicians use protein or amino acid supplementation in patients with pressure ulcers to reduce wound size. (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians use hydrocolloid or foam dressings in patients with pressure ulcers to reduce wound size. (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians use electrical stimulation as adjunctive therapy in patients with pressure ulcers to accelerate wound healing. (Grade: weak recommendation, moderate-quality evidence).

Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of preventive dietary and pharmacologic management of recurrent nephrolithiasis in adults. METHODS: This guideline is based on published literature on this topic that was identified using MEDLINE, the Cochrane Database of Systematic Reviews (through March 2014), Google Scholar, ClinicalTrials.gov, and Web of Science. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline include symptomatic stone recurrence, pain, urinary tract obstruction with acute renal impairment, infection, procedure-related illness, emergency department visits, hospitalizations, quality of life, and end-stage renal disease. This guideline grades the quality of evidence and strength of recommendations using ACP's clinical practice guidelines grading system. The target audience for this guideline is all clinicians, and the target patient population is all adults with recurrent nephrolithiasis (≥1 prior kidney stone episode). RECOMMENDATION 1: ACP recommends management with increased fluid intake spread throughout the day to achieve at least 2 L of urine per day to prevent recurrent nephrolithiasis. (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 2: ACP recommends pharmacologic monotherapy with a thiazide diuretic, citrate, or allopurinol to prevent recurrent nephrolithiasis in patients with active disease in which increased fluid intake fails to reduce the formation of stones. (Grade: weak recommendation, moderate-quality evidence).(AU)

Nonsurgical management of urinary incontinence in women: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the nonsurgical management of urinary incontinence (UI) in women. METHODS: This guideline is based on published English-language literature on nonsurgical management of UI in women from 1990 through December 2013 that was identified using MEDLINE, the Cochrane Library, Scirus, and Google Scholar. The outcomes evaluated for this guideline include continence, improvement in UI, quality of life, adverse effects, and discontinuation due to adverse effects. It grades the evidence and recommendations by using ACP's guideline grading system. The target audience is all clinicians, and the target patient population is all women with UI. RECOMMENDATION 1: ACP recommends first-line treatment with pelvic floor muscle training in women with stress UI. (Grade: strong recommendation, high-quality evidence). RECOMMENDATION 2: ACP recommends bladder training in women with urgency UI. (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 3: ACP recommends pelvic floor muscle training with bladder training in women with mixed UI. (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 4: ACP recommends against treatment with systemic pharmacologic therapy for stress UI. (Grade: strong recommendation, low-quality evidence). RECOMMENDATION 5: ACP recommends pharmacologic treatment in women with urgency UI if bladder training was unsuccessful. Clinicians should base the choice of pharmacologic agents on tolerability, adverse effect profile, ease of use, and cost of medication. (Grade: strong recommendation, high-quality evidence). RECOMMENDATION 6: ACP recommends weight loss and exercise for obese women with UI. (Grade: strong recommendation, moderate-quality evidence).(AU)

Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the diagnosis of obstructive sleep apnea in adults. METHODS: This guideline is based on published literature on this topic that was identified by using MEDLINE (1966 through May 2013), the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular mortality, nonfatal cardiovascular disease, stroke, hypertension, type 2 diabetes, postsurgical outcomes, and quality of life. Sensitivities, specificities, and likelihood ratios were also assessed as outcomes of diagnostic tests. This guideline grades the evidence and recommendations by using ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends a sleep study for patients with unexplained daytime sleepiness. (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 2: ACP recommends polysomnography for diagnostic testing in patients suspected of obstructive sleep apnea. ACP recommends portable sleep monitors in patients without serious comorbidities as an alternative to polysomnography when polysomnography is not available for diagnostic testing. (Grade: weak recommendation, moderate-quality evidence).(AU)

Prospective study to investigate the use of fine needle aspiration techniques in UK veterinary practice.

OBJECTIVES: To document the fine needle aspiration methods used by UK veterinary practitioners for the assessment of cutaneous masses and relate this to the achievement of a representative sample. METHODS: An internet-based questionnaire was designed and publicised in the UK national veterinary press, at a national surgical meeting, and in letters to veterinary surgeons. RESULTS: One hundred and seventy respondents replied to the questionnaire: 58 · 2% sampled cutaneous masses on the basis of appearance or behaviour; 41 · 3% sampled every cutaneous mass. Practitioners with a greater oncological caseload or who graduated more recently were more likely to recommend fine needle aspiration for every cutaneous mass (P = 0 · 019 and P = 0 · 0002 respectively); 66 · 5% of respondents applied suction during fine needle aspiration; 89% of all respondents used a 2 or 5 mL syringe in combination with a 21 or 23 G needle. There was no statistically significant association between achievement of a representative sample and syringe (P = 0 · 64) or needle size (P = 0 · 63). CLINICAL SIGNIFICANCE: Fine needle aspiration is widely used in UK practice, but may be underutilised in practices with lower oncological caseloads. Survey participants reported a high rate of representative samples obtained using all the commonly used techniques. Further work is required to confirm these observations.

Tumor necrosis factor-related apoptosis-inducing ligand translates neonatal respiratory infection into chronic lung disease.

Respiratory infections in early life can lead to chronic respiratory disease. Chlamydia infections are common causes of respiratory disease, particularly pneumonia in neonates, and are linked to permanent reductions in pulmonary function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. Here we identify novel roles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in promoting Chlamydia respiratory infection-induced pathology in early life, and subsequent chronic lung disease. By infecting TRAIL-deficient neonatal mice and using neutralizing antibodies against this factor and its receptors in wild-type mice, we demonstrate that TRAIL is critical in promoting infection-induced histopathology, inflammation, and mucus hypersecretion, as well as subsequent alveolar enlargement and impaired lung function. This suggests that therapeutic agents that target TRAIL or its receptors may be effective treatments for early-life respiratory infections and associated chronic lung disease.

Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the screening, monitoring, and treatment of adults with stage 1 to 3 chronic kidney disease. METHODS: This guideline is based on a systematic evidence review evaluating the published literature on this topic from 1985 through November 2011 that was identified by using MEDLINE and the Cochrane Database of Systematic Reviews. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, chronic heart failure, composite vascular outcomes, composite renal outcomes, end-stage renal disease, quality of life, physical function, and activities of daily living. This guideline grades the evidence and recommendations by using ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends against screening for chronic kidney disease in asymptomatic adults without risk factors for chronic kidney disease. (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 2: ACP recommends against testing for proteinuria in adults with or without diabetes who are currently taking an angiotensin-converting enzyme inhibitor or an angiotensin II-receptor blocker. (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians select pharmacologic therapy that includes either an angiotensin-converting enzyme inhibitor (moderate-quality evidence) or an angiotensin II-receptor blocker (high-quality evidence) in patients with hypertension and stage 1 to 3 chronic kidney disease. (Grade: strong recommendation). RECOMMENDATION 4: ACP recommends that clinicians choose statin therapy to manage elevated low-density lipoprotein in patients with stage 1 to 3 chronic kidney disease. (Grade: strong recommendation, moderate-quality evidence).(AU)

Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians

"DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the treatment of anemia and iron deficiency in adult patients with heart disease. METHODS: This guideline is based on published literature in the English language on anemia and iron deficiency from 1947 to July 2012 that was identified using MEDLINE and the Cochrane Library. Literature was reassessed in April 2013, and additional studies were included. Outcomes evaluated for this guideline included mortality; hospitalization; exercise tolerance; quality of life; and cardiovascular events (defined as myocardial infarction, congestive heart failure exacerbation, arrhythmia, or cardiac death) and harms, including hypertension, venous thromboembolic events, and ischemic cerebrovascular events. The target audience for this guideline includes all clinicians, and the target patient population is anemic or iron-deficient adult patients with heart disease. This guideline grades the evidence and recommendations using the ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends using a restrictive red blood cell transfusion strategy (trigger hemoglobin threshold of 7 to 8 g/dL compared with higher hemoglobin levels) in hospitalized patients with coronary heart disease. (Grade: weak recommendation; low-quality evidence) RECOMMENDATION 2: ACP recommends against the use of erythropoiesis-stimulating agents in patients with mild to moderate anemia and congestive heart failure or coronary heart disease. (Grade: strong recommendation; moderate-quality evidence)."

Social and ecological change over a decade in a village hunting system, central Gabon.

Despite widespread recognition of the major threat to tropical forest biological diversity and local food security posed by unsustainable bushmeat hunting, virtually no long-term studies tracking the socioecological dynamics of hunting systems have been conducted. We interviewed local hunters and collected detailed hunting data to investigate changes in offtake and hunter characteristics over 10 years (2001-2010) in Dibouka and Kouagna villages, central Gabon, in the context of hunter recollections of longer term trends since the 1950s. To control for changes in hunter behavior, such as trap location and characteristics, we report hunting offtake data per trap. Our results suggest the hunting area was already highly depleted by 2001; local hunters reported that 16 large-bodied prey species had become rare or locally extirpated over the last 60 years. Overall, we observed no significant declines in hunting offtake or changes in species composition from 2001 to 2010, and offtakes per trap increased slightly between 2004 and 2010. However, trapping distance from the villages increased, and there was a switch in hunting techniques; a larger proportion of the catch was hunted with guns in 2010. The number of hunters declined by 20% from 2004 to 2010, and male livelihood activities shifted away from hunting. Hunters with the lowest hunting incomes in 2004 were more likely than successful hunters to have moved away from the village by 2010 (often in response to alternative employment opportunities). Therefore, changes in trap success (potentially related to biological factors) were interacting with system-level changes in hunter number and composition (related to external socioeconomic factors) to produce a relatively static overall offtake. Our results highlight the importance of understanding the small-scale context of hunting to correctly interpret changes or apparent stasis in hunting effort and offtake over time.