Acute febrile illness is associated with Rickettsia spp infection in dogs

BACKGROUND: Rickettsia conorii is transmitted by Rhipicephalus sanguineus ticks and causes Mediterranean Spotted Fever (MSF) in humans. Although dogs are considered the natural host of the vector, the clinical and epidemiological significance of R. conorii infection in dogs remains unclear. The aim of this prospective study was to investigate whether Rickettsia infection causes febrile illness in dogs living in areas endemic for human MSF. METHODS: Dogs from southern Italy with acute fever (n = 99) were compared with case–control dogs with normal body temperatures (n = 72). Serology and real-time PCR were performed for Rickettsia spp., Ehrlichia canis, Anaplasma phagocytophilum/A. platys and Leishmania infantum. Conventional PCR was performed for Babesia spp. and Hepatozoon spp. Acute and convalescent antibodies to R. conorii, E. canis and A. phagocytophilum were determined. RESULTS: The seroprevalence rates at first visit for R. conorii, E. canis, A. phagocytophilum and L. infantum were 44.8%, 48.5%, 37.8% and 17.6%, respectively. The seroconversion rates for R. conorii, E. canis and A. phagocytophilum were 20.7%, 14.3% and 8.8%, respectively. The molecular positive rates at first visit for Rickettsia spp., E. canis, A. phagocytophilum, A. platys, L. infantum, Babesia spp. and Hepatozoon spp. were 1.8%, 4.1%, 0%, 2.3%, 11.1%, 2.3% and 0.6%, respectively. Positive PCR for E. canis (7%), Rickettsia spp. (3%), Babesia spp. (4.0%) and Hepatozoon spp. (1.0%) were found only in febrile dogs. The DNA sequences obtained from Rickettsia and Babesia PCRs positive samples were 100% identical to the R. conorii and Babesia vogeli sequences in GenBank®, respectively. Febrile illness was statistically associated with acute and convalescent positive R. conorii antibodies, seroconversion to R. conorii, E. canis positive PCR, and positivity to any tick pathogen PCRs. Fourteen febrile dogs (31.8%) were diagnosed with Rickettsia spp. infection based on seroconversion and/or PCR while only six afebrile dogs (12.5%) seroconverted (P = 0.0248). The most common clinical findings of dogs with Rickettsia infection diagnosed by seroconversion and/or PCR were fever, myalgia, lameness, elevation of C-reactive protein, thrombocytopenia and hypoalbuminemia. CONCLUSIONS: This study demonstrates acute febrile illness associated with Rickettsia infection in dogs living in endemic areas of human MSF based on seroconversion alone or in combination with PCR

Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI.</p> <p>Methods and Results</p> <p>In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone.</p> <p>Conclusion</p> <p>Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.</p

Maternal characteristics associated with the dietary intake of nitrates, nitrites, and nitrosamines in women of child-bearing age: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Multiple <it>N</it>-nitroso compounds have been observed in animal studies to be both mutagenic and teratogenic. Human exposure to <it>N</it>-nitroso compounds and their precursors, nitrates and nitrites, can occur through exogenous sources, such as diet, drinking water, occupation, or environmental exposures, and through endogenous exposures resulting from the formation of <it>N</it>-nitroso compounds in the body. Very little information is available on intake of nitrates, nitrites, and nitrosamines and factors related to increased consumption of these compounds.</p> <p>Methods</p> <p>Using survey and dietary intake information from control women (with deliveries of live births without major congenital malformations during 1997-2004) who participated in the National Birth Defects Prevention Study (NBDPS), we examined the relation between various maternal characteristics and intake of nitrates, nitrites, and nitrosamines from dietary sources. Estimated intake of these compounds was obtained from the Willet Food Frequency Questionnaire as adapted for the NBDPS. Multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the consumption of these compounds by self-reported race/ethnicity and other maternal characteristics.</p> <p>Results</p> <p>Median intake per day for nitrates, nitrites, total nitrites (nitrites + 5% nitrates), and nitrosamines was estimated at 40.48 mg, 1.53 mg, 3.69 mg, and 0.472 μg respectively. With the lowest quartile of intake as the referent category and controlling for daily caloric intake, factors predicting intake of these compounds included maternal race/ethnicity, education, body mass index, household income, area of residence, folate intake, and percent of daily calories from dietary fat. Non-Hispanic White participants were less likely to consume nitrates, nitrites, and total nitrites per day, but more likely to consume dietary nitrosamines than other participants that participated in the NBDPS. Primary food sources of these compounds also varied by maternal race/ethnicity.</p> <p>Conclusions</p> <p>Results of this study indicate that intake of nitrates, nitrites, and nitrosamines vary considerably by race/ethnicity, education, body mass index, and other characteristics. Further research is needed regarding how consumption of foods high in nitrosamines and <it>N</it>-nitroso precursors might relate to risk of adverse pregnancy outcomes and chronic diseases.</p

Osteoarthritis and functional disability: results of a cross sectional study among primary care patients in Germany

Contains fulltext : 52359.pdf ( ) (Open Access)BACKGROUND: The aim of the study was to determine factors associated with functional disability in patients with OA. METHODS: 1250 questionnaires were distributed to OA outpatients from 75 general practices; 1021 (81.6%) were returned. Questionnaires included sociodemographic data, the short form of the Arthritis Impact Measurement Scale (AIMS2-SF), and the Patient Health Questionnaire (PHQ-9) to assess concomitant depression. A hierarchical stepwise multiple regression analysis with the AIMS2-SF dimension "lower body" as dependent was performed. RESULTS: Main factors associated with functional disability were depression symptoms, as reflected in a high score of the PHQ-9 (beta = 0.446; p < 0.0009), pain as reflected in the AIMS2-SF symptom scale (beta = 0.412; p = 0.001), and few social contacts (beta = 0.201; p < 0.042). A high body mass index was associated with lower functional ability (beta = 0.332; p = 0.005) whereas a higher educational level (beta = -0.279; p = 0.029) predicted less impairment. Increased age was a weak predictor (beta = 0.178; p = 0.001) of disability. With a p of 0.062 the radiological severity according to the grading of Kellgren and Lawrence slightly surpassed the required significance level for remaining in the final regression model. CONCLUSION: The results emphasize that psychological as well as physical factors need to be addressed similarly to improve functional ability of patients suffering from OA. More research with multifaceted and tailored interventions is needed to determine how these factors can be targeted appropriately

Positioning pharmacists’ roles in primary health care: a discourse analysis of the compensation plan in Alberta, Canada

Abstract Background A comprehensive Compensation Plan for pharmacy services delivered by community pharmacists was implemented in Alberta, Canada in July 2012. Services covered by the Compensation Plan include care planning services, prescribing services such as adapting prescriptions, and administering a drug or publicly-funded vaccine by injection. Understanding how the Compensation Plan was framed and communicated provides insight into the roles of pharmacists and the potential influence of language on the implementation of services covered by the Compensation Plan by Albertan pharmacists. The objective of this study is to examine the positioning of pharmacists’ roles in documents used to communicate the Compensation Plan to Albertan pharmacists and other audiences. Methods Publicly available documents related to the Compensation Plan, such as news releases or reports, published between January 2012 and December 2015 were obtained from websites such as the Government of Alberta, Alberta Blue Cross, the Alberta College of Pharmacists, the Alberta Pharmacists’ Association, and the Blueprint for Pharmacy. Searches of the Canadian Newsstand database and Google identified additional documents. Discourse analysis was performed using social positioning theory to explore how pharmacists’ roles were constructed in communications about the Compensation Plan. Results In total, 65 publicly available documents were included in the analysis. The Compensation Plan was put forward as a framework for payment for professional services and formal legitimization of pharmacists’ changing professional roles. The discourse associated with the Compensation Plan positioned pharmacists’ roles as: (1) expanding to include services such as medication management for chronic diseases, (2) contributing to primary health care by providing access to services such as prescription renewals and immunizations, and (3) collaborating with other health care team members. Pharmacists’ changing roles were positioned in alignment with the aims of primary health care. Conclusions Social positioning theory provides a useful lens to examine the dynamic and evolving roles of pharmacists. This study provides insight into how communications regarding the Compensation Plan in Alberta, Canada positioned pharmacists’ changing roles in the broader context of changes to primary health care delivery. Our findings may be useful for other jurisdictions considering implementation of remunerated clinical services provided by pharmacists

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

High-frequency stimulation of the infralimbic cortex, following behavioral suppression of PTSD-like symptoms, prevents symptom relapse in mice.

BACKGROUND: We have previously demonstrated, in mice, that antidepressant treatment can prevent relapse of PTSD-like behaviors (avoidance, hyperarousal, and anxiety) through increased activation in the infralimbic cortex (IL) of the medial prefrontal cortex. OBJECTIVE: Here, we examined whether direct high-frequency stimulation (HFS) of the IL, provoking its heightened activation (i.e., long-term potentiation, LTP), would also prevent the return of PTSD-like symptoms. METHODS: A 1.5-mA foot-shock was used to generate PTSD-like symptoms in Swiss mice. In Experiment 1, local field potentials were recorded in the IL to test whether normal IL LTP can be induced after the suppression of PTSD-like symptoms. In Experiment 2, IL HFS was applied after symptom suppression, but prior to the provocation of relapse, to test HFS effect on symptom return. RESULTS: We observed that PTSD-like state was associated with impairment in IL HFS-induced IL LTP. However, IL LTP induction was near normal when PTSD-like symptoms were suppressed. We then found that IL HFS, applied after symptom suppression, prevented symptom return. CONCLUSIONS: Increased activation of the IL may be a key mechanism preventing PTSD relapse. Prefrontal cortex deep brain stimulation may, therefore, be relevant for preventing PTSD symptom return in remitted high-risk patients

Effects of paroxetine on PTSD-like symptoms in mice.

peer reviewedRATIONALE: After exposure to a severe traumatic event, avoidance, fear sensitization, and increased anxiety are among features that can persist over time in people developing posttraumatic stress disorder (PTSD). Basic research on treatment interfering with these symptoms can provide insights to improve PTSD treatment. OBJECTIVES: The purposes of the present study were to induce these behavioral changes in mice and examine whether paroxetine would interfere with their expression. METHODS: Mice were submitted to avoidance training with a low (0.4 mA) or high (1.5 mA) foot-shock intensity, as mild and severe stressors, respectively, and posttraining avoidance was evaluated 1 and 12 days later. Fear sensitization, measured as increased freezing to a neutral tone, and enhanced contextual fear, measured as increased freezing to a conditioned context (wherein all mice received a 0.4-mA foot-shock), were assessed during this time window. An elevated plus maze test was also used to assess mouse anxiety-like behavior. RESULTS: Persistent avoidance, persistent fear sensitization, and long-term enhancement of contextual fear and increased anxiety-like behavior were established only in mice that received the 1.5-mA foot-shock during avoidance training. Paroxetine (at 8 mg/kg/day), injected from day 5 to day 11 after avoidance training, suppressed all of these behavioral changes. CONCLUSIONS: These data provide additional evidence for the role of paroxetine against expression of PTSD-like behaviors in mice

Paroxetine treatment, following behavioral suppression of PTSD-like symptoms in mice, prevents relapse by activating the infralimbic cortex.

peer reviewedClinical studies have shown that post-traumatic stress disorder (PTSD) remission, induced by selective serotonin reuptake inhibitor (SSRI) treatment, is associated with increased prefrontal activation during post-treatment symptom provocation. Other studies have shown that continuation SSRI treatment after remitting from PTSD reduces the rate of relapse. The aim of the present preclinical study was to investigate the relationship between post-treatment prefrontal changes and PTSD relapse prevention. Avoidance conditioning (with a 1.5-mA foot-shock), avoidance extinction and a trauma priming exposure (with a 0.3-mA foot-shock) were used in mice to induce, suppress and reactivate PTSD-like symptoms (including avoidance, fear sensitization, enhanced contextual fear, and anxiety-like behavior), respectively. Paroxetine, injected at 8 mg/kg/day (7 days), was used as SSRI treatment. PTSD-like symptoms were present for at least 30 days and resistant to paroxetine treatment. However, after extinction training (suppressing all PTSD-like symptoms), paroxetine treatment prevented symptom reactivation. Paroxetine treatment also induced infralimbic neuronal activation. However, infralimbic functional tetrodotoxin inactivation abolished the preventive effect of paroxetine treatment on symptom reactivation. The data reveal a potential ability of treatments inducing infralimbic activation to provide prophylactic protection against PTSD relapse