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Antibacterial activities of the methanol extract, fractions and compounds from Elaeophorbia drupifera (Thonn.) Stapf. (Euphorbiaceae)
No full textAbstract
Background
Elaeophorbia drupifera (Thonn.) Stapf. (Euphorbiaceae) is used in Cameroonian folk medicine to treat several ailments including bacterial-related diseases such as skin infections. In this study, the methanol extract from the leaves (EDL), fractions (EDLa-d), sub-fractions EDLc1-7 and EDLc31-35 as well as isolated compounds were tested for their antimicrobial activities against a panel of Gram-negative and Gram-positive bacteria including multidrug resistant (MDR) phenotypes.
Methods
The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; column chromatography was used for the fractionation and purification of the leaves extract whilst the chemical structures of compounds were determined using spectroscopic techniques.
Results
Phytochemical investigation lead to the isolation of a mixture (1:3) of stigmasterol and \u3b2 -sitosterol ( 1 \u2009+\u2009 2 ), euphol ( 3 ), sitosterol -O-\u3b2- D - xylopyranoside ( 4 ), 3,3\u2032,4\u2032-tri- O- methylellagic acid ( 5 ), a mixture (1:1) of afzelin and quercetin-3- O-\u3b2 -
D
-xylopyranoside ( 6 \u2009+\u2009 7 ), 3,3\u2032,4\u2032-tri- O -methylellagic acid 4- O-\u3b2 -
D
-glucopyranoside ( 8 ), ellagic acid-4- O-\u3b2 -xylopyranoside-3,3\u2032,4\u2032-trimethyl ether ( 9 ) from EDLc. Crude extract and fractions displayed selective activities with MIC values ranged from 32 to 1024 \u3bcg/mL for EDL against 84.9% of the 33 tested bacteria, 93.9% for EDLc, 69.7% for EDLb, 33.4% for EDLa and 0.03% for EDLd. MIC values ranged from 16 to 1024 \u3bcg/mL were obtained with EDLc3 and EDLc4 on all tested bacteria meanwhile other sub-fractions displayed selective activities. MIC value of 32 \u3bcg/mL was obtained with fractions EDLa against Escherichia coli AG100, EDLc against Enterobacer aerogenes ATCC13048 and EA298. For sub-fractions obtained from EDLc, the lowest MIC value of 16 \u3bcg/mL was recorded with EDLc3 against Staphylococcus aureus MRSA11. A corresponding value of 8 \u3bcg/mL against Providencia stuartii NAE16 was recorded with EDLc33 obtained from further fractionation of EDLc3. EDLc3 had MIC values below 100 \u3bcg/mL against all tested bacteria. Compound 5 as well as the mixture (1:1) of 6 and 7 inhibited the growth of all the tested bacteria with MICs ranged from 64 to 256 \u3bcg/mL.
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Kudiezi injection mitigates myocardial injury induced by acute cerebral ischemia in rats
No full textAbstract
Background
Kudiezi (KDZ) injection is commonly used in traditional Chinese medicine as treatment for cerebral infarction and angina pectoris. The present study investigated the therapeutic effects of KDZ injection on myocardial injury induced by acute cerebral ischemia and the possibly protective mechanisms.
Methods
Rats were divided into three groups: sham, 6h-ischemia, and KDZ treatment (KDZ). The neurological deficits were determined by the Garcia score. The cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content was also evaluated. Serum creatinine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) activity, myocardial tissue malondialdehyde (MDA) levels, L-Glutathione (GSH) levels, and superoxide dismutase (SOD) activity as well as mitochondrial cytochrome c oxidase (COX) activity were determined. Mitochondrial COX I and COX III mRNA expressions of myocardial tissues were measured by RT-PCR.
Results
Impaired neurological function and brain edema were observed in the 6h-ischemia group. TTC staining showed that the 6h-ischemia group had larger infarct zones than the sham group. Myocardial ischemic changes (widened myocardial cell gap, cracks, and obvious edema) were detected in the 6h-ischemia group compared with the sham group, with elevated serum CK-MB activity and CK and LDH levels. Electrocardiography showed lower medium frequency (MF) and high frequency (HF) in the 6h-ischemia group compared with the sham group. In myocardial tissue, COX activity was elevated in the 6h-ischemia compared with the sham group, while SOD, GSH, and MDA levels, and COX I and COX III mRNA expressions remained unchanged. KDZ injection decreased neurological impairment, brain edema, gaps between cells, and infarct size. Compared with the 6h-ischemia group, it reduced serum CK-MB activity and CK and LDH levels, and MDA levels in myocardial tissue. KDZ significantly increased GSH levels, SOD activity, and mitochondria COX activity and the expression of COX I and COX III mRNA in myocardial tissue compared with the sham group.
Conclusion
KDZ injection had a protective effect against cerebral ischemia in rats. KDZ injection could also alleviate myocardial injury after acute cerebral ischemia in rats. The possible mechanisms involve the regulation of the oxidative stress/antioxidant capacity after cerebral ischemia
WhatsApp messenger as a tool to supplement medical education for medical students on clinical attachment
No full textAbstract
Background
Instant messaging applications have the potential to improve and facilitate communication between hospital doctors and students, hence generating and improving learning opportunities. This study aims to demonstrate the feasibility and acceptability of instant messaging communication to supplement medical education for medical students whilst on clinical attachment.
Methods
A total of 6 WhatsApp Messenger (WhatsApp Inc.) groups were created for medical students on clinical attachment. These were used to provide communication within Problem Based Learning (PBL) groups for a duration of 8\ua0weeks. The frequency and type of communication were recorded. Students\u2019 opinions were evaluated through a structured interview process at the end of the study period. A thematic analysis was performed on the content of the instant messaging groups and on the results of the structured interviews.
Results
All of the participants were active in their respective messaging groups (19 students and 6 tutors). A total of 582 messages, 22 images and 19 webpage links were sent. Thematic analysis on content of the instant messaging groups identified the following themes: organisational, educational and social. Thematic analysis on the content of interviews identified themes such as the ease of use of instant messaging, benefit of instant messaging to foster understanding and learning, and the ability to access recorded discussions.
Conclusion
The findings of this study illustrate a method by which communication within PBL groups can be facilitated by the use of instant messaging. The results indicate the feasibility and acceptability of WhatsApp Messenger in supplementing PBL teaching for medical students, and provides a framework for studies to investigate use amongst larger cohorts of students
Evaluation of the Tsima community mobilization intervention to improve engagement in HIV testing and care in South Africa: study protocol for a cluster randomized trial
No full textAbstract
Background
HIV transmission can be decreased substantially by reducing the burden of undiagnosed HIV infection and expanding early and consistent use of antiretroviral therapy (ART). Treatment as prevention (TasP) has been proposed as key to ending the HIV epidemic. To activate TasP in high prevalence countries, like South Africa, communities must be motivated to know their status, engage in care, and remain in care. Community mobilization (CM) has the potential to significantly increase uptake testing, linkage to and retention in care by addressing the primary social barriers to engagement with HIV care\u2014including poor understanding of HIV care; fear and stigma associated with infection, clinic attendance and disclosure; lack of social support; and gender norms that deter men from accessing care.
Methods/design
Using a cluster randomized trial design, we are implementing a 3-year-theory-based CM intervention and comparing gains in HIV testing, linkage, and retention in care among individuals residing in 8 intervention communities to that of individuals residing in 7 control communities. Eligible communities include 15 villages within a health and demographic surveillance site (HDSS) in rural Mpumalanga, South Africa, that were not exposed to previous CM efforts. CM activities conducted in the 8 intervention villages map onto six mobilization domains that comprise the key components for community mobilization around HIV prevention. To evaluate the intervention, we will link a clinic-based electronic clinical tracking system in all area clinics to the HDSS longitudinal census data, thus creating an open, population-based cohort with over 30,000 18\u201349-year-old residents. We will estimate the marginal effect of the intervention on individual outcomes using generalized estimating equations. In addition, we will evaluate CM processes by conducting baseline and endline surveys among a random sample of 1200 community residents at each time point to monitor intervention exposure and community level change using validated measures of CM.
Discussion
Given the known importance of community social factors with regard to ..
Current practice of antibiotic prophylaxis for surgical fixation of closed long bone fractures: a survey of 297 members of the Orthopaedic Trauma Association
No full textAbstract
Background
The risk of postoperative surgical site infection after long bone fracture fixation can be decreased with appropriate antibiotic use. However, there is no agreement on the superiority of a single- or multiple-dose perioperative regimen of antibiotic prophylaxis. The purpose of this study is to determine the following: 1) What are the current practice patterns of orthopaedic trauma surgeons in using perioperative antibiotics for closed long bone fractures? 2) What is the current knowledge of published antibiotic prophylaxis guidelines among orthopaedic trauma surgeons? 3) Are orthopaedic surgeons willing to change their current practices?
Methods
A questionnaire was distributed via email between September and December 2015 to 955 Orthopaedic Trauma Association members, of whom 297 (31%) responded.
Results
Most surgeons (96%) use cefazolin as first-line infection prophylaxis. Fifty-nine percent used a multiple-dose antibiotic regimen, 39% used a single-dose regimen, and 2% varied this decision according to patient factors. Thirty-six percent said they were unfamiliar with Centers for Disease Control and Prevention (CDC) antibiotic prophylaxis guidelines; only 30% were able to select the correct CDC recommendation from a multiple-choice list. However, 44% of surgeons said they followed CDC recommendations. Fifty-six percent answered that a single-dose antibiotic prophylaxis regimen was not inferior to a multiple-dose regimen. If a level-I study comparing a single preoperative dose versus multiple perioperative antibiotic dosing regimen for treatment of closed long bone fractures were published, most respondents (64%) said they would fully follow these guidelines, and 22% said they would partially change their practice to follow these guidelines.
Conclusion
There is heterogeneity in the use of single- versus multiple-dose antibiotic prophylaxis for surgical repair of closed long bone fractures. Many surgeons were unsure of current evidence-based recommendations regarding perioperative antibiotic use. Most respondents indicated they would be receptive to high-level evidence regarding the single- versus multiple-dose perioperative prophylactic antibiotics for the treatment of closed long bone fractures
EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth
No full textAbstract
Background
Activated protein C/endothelial protein C receptor (APC/EPCR) axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated.
Methods
Transcriptomic status of EPCR was examined in a cohort of 286 breast cancer patients. Cell growth kinetics was evaluated in control and EPCR and SPARC/osteonectin, Cwcv, and kazal-like domains proteoglycan (SPOCK1/testican 1) silenced breast cancer cells in 2D, 3D, and in co-culture conditions. Orthotopic tumor growth and lung and osseous metastases were evaluated in several human and murine xenograft breast cancer models. Tumor-stroma interactions were further studied in vivo by immunohistochemistry and flow cytometry. An EPCR-induced gene signature was identified by microarray analysis.
Results
Analysis of a cohort of breast cancer patients revealed an association of high EPCR levels with adverse clinical outcome. Interestingly, EPCR knockdown did not affect cell growth kinetics in 2D but significantly reduced cell growth in 3D cultures. Using several human and murine xenograft breast cancer models, we showed that EPCR silencing reduced primary tumor growth and secondary outgrowths at metastatic sites, including the skeleton and the lungs. Interestingly, these effects were independent of APC ligand stimulation in vitro and in vivo. Transcriptomic analysis of EPCR-silenced tumors unveiled an effect mediated by matricellular secreted proteoglycan SPOCK1/testican 1. Interestingly, SPOCK1 silencing suppressed in vitro 3D growth. Moreover, SPOCK1 ablation severely decreased orthotopic tumor growth and reduced bone metastatic osteolytic tumors. High SPOCK1 levels were also associated with poor clinical outcome in a subset breast cancer patients. Our results suggest that EPCR through SPOCK1 confers a cell growth advantage in 3D promoting breast tumorigenesis and metastasis.
Conclusions
EPCR represents a clinically relevant factor associated with poor outcome and a novel vulnerability to develop combination therapies for breast cancer patients
External validation of a clinical decision rule: we need events in a population in order to rule them out!
No full textAbstract
We respond to the Lorton et al. article on external validation of the PECARN study. With an event rate of only 0.6%, we believe that their study failed to confirm the safety of this rule. Such a low number of events should call for caution when interpreting the results of diagnostic tests
Can calculation of energy expenditure based on CO 2 measurements replace indirect calorimetry?
No full textAbstract
Background
Methods to calculate energy expenditure (EE) based on CO
2
measurements (EEVCO
2
) have been proposed as a surrogate to indirect calorimetry. This study aimed at evaluating whether EEVCO
2
could be considered as an alternative to EE measured by indirect calorimetry.
Methods
Indirect calorimetry measurements conducted for clinical purposes on 278 mechanically ventilated ICU patients were retrospectively analyzed. EEVCO
2
was calculated by a converted Weir\u2019s equation using CO
2
consumption (VCO
2
) measured by indirect calorimetry and assumed respiratory quotients (RQ): 0.85 (EEVCO
2
_0.85) and food quotient (FQ; EEVCO
2
_FQ). Mean calculated EEVCO
2
and measured EE were compared by paired t test. Accuracy of EEVCO
2
was evaluated according to the clinically relevant standard of 5% accuracy rate to the measured EE, and the more general standard of 10% accuracy rate. The effects of the timing of measurement (before or after the 7th ICU day) and energy provision rates (<90 or \u226590% of EE) on 5% accuracy rates were also analyzed (chi-square tests).
Results
Mean biases for EEVCO
2
_0.85 and EEVCO
2
_FQ were -21 and -48\ua0kcal/d ( p \u2009=\u20090.04 and 0.00, respectively), and 10% accuracy rates were 77.7 and 77.3%, respectively. However, 5% accuracy rates were 46.0 and 46.4%, respectively. Accuracy rates were not affected by the timing of the measurement, or the energy provision rates at the time of measurements.
Conclusions
Calculated EE based on CO
2
measurement was not sufficiently accurate to consider the results as an alternative to measured EE by indirect calorimetry. Therefore, EE measured by indirect calorimetry remains as the gold standard to guide nutrition therapy
Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models
No full textAbstract
Background
Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.
Results
I describe a new approach that uses a null model based on experimental measurements of a gene\u2019s site-specific amino-acid preferences generated by deep mutational scanning in the lab. This null model makes it possible to identify both diversifying selection for repeated amino-acid change and differential selection for mutations to amino acids that are unexpected given the measurements made in the lab. I show that this approach identifies sites of adaptive substitutions in four genes (lactamase, Gal4, influenza nucleoprotein, and influenza hemagglutinin) far better than a comparable method that simply compares the rates of nonsynonymous and synonymous substitutions.
Conclusions
As rapid increases in biological data enable increasingly nuanced descriptions of the constraints on individual protein sites, approaches like the one here can improve our ability to identify many interesting forms of selection in natural sequences.
Reviewers
This article was reviewed by Sebastian Maurer-Stroh, Olivier Tenaillon, and Tal Pupko. All three reviewers are members of the Biology Direct editorial board
Efficacy of gabapentin for prevention of postherpetic neuralgia: study protocol for a randomized controlled clinical trial
No full textAbstract
Background
Postherpetic neuralgia (PHN) is a chronic neuropathic pain that results from alterations of the peripheral nervous system in areas affected by the herpes zoster virus. The symptoms include pain, paresthesia, dysesthesia, hyperalgesia, and allodynia. Despite the availability of pharmacological treatments to control these symptoms, no treatments are available to control the underlying pathophysiology responsible for this disabling condition.
Methods/design
Patients with herpes zoster who are at least 50\ua0years old and have a pain score of 4 or higher on a visual analogue scale (VAS) will be recruited. The aim is to recruit 134 patients from the practices of general physicians. Participants will be randomized to receive gabapentin to a maximum of 1800\ua0mg/day for 5\ua0weeks or placebo. Both arms will receive 1000-mg caplets of valacyclovir three times daily for 7\ua0days (initiated within 72\ua0h of the onset of symptoms) and analgesics as needed. The primary outcome measure is the percentage of patients with a VAS pain score of 0 at 12\ua0weeks from rash onset. The secondary outcomes measures are changes in quality of life (measured by the SF-12 questionnaire), sleep disturbance (measured by the Medical Outcomes Study Sleep Scale), and percentage of patients with neuropathic pain (measured by the Douleur Neuropathique in 4 Questions).
Discussion
Gabapentin is an anticonvulsant type of analgesic that could prevent the onset of PHN by its antihypersensitivity action in dorsal horn neurons.
Trial registration
ISRCTN Registry identifier: ISRCTN79871784 . Registered on 2 May 2013