Who tells the story of burns in low-and-middle income countries? - A bibliometric study.

INTRODUCTION: Low- and middle-income countries (LMICs) remain drastically underrepresented in health research, with African countries producing less than 1% of the global output. This work investigates authorship patterns of publications on burns in LMICs. Original research studies addressing burn injuries in LMICs and published between 1st January 2015 and 31st December 2020 were included in the review. Descriptive statistics were performed for country affiliations of authors, World Bank Country Income Groups, WHO group, study-focus and country studied. Of the 458 results, 426 studies met the inclusion criteria. Nearly a quarter of papers on burns in LMICs had both first and senior authors from high-income countries (HICs, n = 95, 24.4%), more than half of the papers had both first and senior authors from upper middle- income countries (upper MICs, n = 222, 57.2%), while less than 1% (n = 3) had first and senior authors exclusively from lower-income countries (LICs). Eleven percent (n = 41/388) of all papers were written without either first nor senior author being from the country studied, and 17 of them (41%) had both first and senior authors from the USA. Twenty-five (6%) of the papers had the first author and not the senior author from the country of focus, while six (2%) had the senior and not the first author from the country of interest. To overcome global health challenges such as burns, locally led research is imperative. The maximum benefit of HIC-LMIC collaborations is achieved when LMICs play an active role in leading the research. When LMICs direct the research being conducted in their country, the harm of inherently inequitable relationships is minimized.

Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Long-term outcomes of thigh circumference, stifle range-of-motion, and lameness after unilateral tibial plateau levelling osteotomy.

Our study evaluated thigh circumference (TC), stifle range of motion (ROM), and lameness in dogs one to five years after unilateral tibial plateau levelling osteotomy (TPLO). We hypothesised that TC, stifle ROM, and lameness would not be different to the unoperated limb (control), one to five years after surgery. Patients that were one to five years post-TPLO were reviewed and were included if they had a unilateral TPLO, and no additional clinical evidence of orthopaedic disease. Standing mid-thigh TC measurements and stifle extension and flexion angles were made in triplicate. Clinical lameness was graded blindly. Data were evaluated statistically using paired t-tests for TC and stifle flexion and extension. Significance was set at p <0.05. Twenty-nine dogs met the inclusion criteria. Mean results for the surgery limbs and control limbs were 39.5 +/- 5.5 cm and 40.1 +/- 5.6 cm for TC, 36.6 +/- 6.8 degrees and 28.6 +/- 4.3 degrees for stifle flexion, and 155.2 +/- 6.6 degrees and 159.8 +/- 4.9 degrees for stifle extension, respectively. The mean TC for the operated limb was 98.5% of the control limb. A significant difference was found between the operated and the control limbs for all measurements. Time after surgery had no apparent affect on outcome. Four of 29 dogs (14%) exhibited some lameness in the TLPO limb during evaluation (one dog was 1 to 2 years postoperative and three dogs were 2 to 3 years postoperative). These results indicate that TC and stifle ROM in the TLPO limb do not return to control-limb measurements one to five years after a TPLO surgery. The clinical significance is unknown as TC returned to 98.5% of control, and the source of lameness in the lame dogs was not identified.

Characterisation and physical stability of PEGylated glucagon.

Glucagon was mono-PEGylated with PEG 5000 at Lys-12 to examine the effect on conformation and physical stability during purification and freeze-drying. The model peptide glucagon is highly unstable and readily forms fibrils in solution. Secondary structure was determined by FTIR and far-UV CD and physical stability was assessed by the Thioflavin T assay. Glucagon samples were included, which underwent the same RP-HPLC purification and/or freeze-drying as glucagon-PEG 5000. After purification and freeze-drying glucagon samples showed formation of intermolecular beta-sheet by FTIR, this correlated with shorter lag-times for fibrillation in the Thioflavin T assay. Formation of intermolecular beta-sheet was less apparent for glucagon-PEG 5000 and no fibrillation was detected by Thioflavin T assay. Apparently PEGylation significantly improved the physical stability of glucagon after purification and freeze-drying, possibly by steric hindrance of peptide-peptide interactions. Alterations in the secondary structure were observed for freeze-dried and reconstituted peptide samples by liquid FTIR. The peak for alpha-helix shifted to 1664 cm(-1), which could possibly be explained by formation of 3(10)-helix. Neither 3(10)-helix nor intermolecular beta-sheet could be detected by far-UV CD, where all peptide samples showed similar spectra. In conclusion, glucagon-PEG 5000 showed a significantly improved physical stability during purification and freeze-drying compared to glucagon.

Comparison of various doses of carbon 13-labeled aminopyrine for a carbon 13-labeled aminopyrine demethylation blood test in healthy dogs.

OBJECTIVE: To determine an optimal dose of carbon 13 ((13)C)-labeled aminopyrine for use in a (13)C-aminopyrine demethylation blood test in healthy dogs. ANIMALS: 9 adult dogs. PROCEDURES: Food was withheld from each dog for 12 hours. A 2-mL baseline blood sample was obtained from each dog and placed into an evacuated tube containing sodium heparin. Carbon 13-labeled aminopyrine was administered IV at doses of 1, 2, 5, or 10 mg/kg. Additional blood samples (2 mL) were obtained and placed into evacuated tubes containing sodium heparin 30, 45, 60, and 75 minutes after (13)C-aminopyrine administration. Hydrochloric acid was used to extract CO(2) from blood samples. The extracted gas was analyzed by fractional mass spectrometry to determine the percentage dose of (13)C administered as (13)C-aminopyrine and recovered in extracted gas (PCD). RESULTS: Gross evidence of clinical adverse effects was not detected in any dog after administration of (13)C-aminopyrine. The mean coefficient of variation (CV) for PCD was significantly lower than the mean CV for the summation of PCD values up to a given sampling time (CUMPCD). Mean PCD values among the 4 doses for each sample time were not significantly different. Administration of (13)C-aminopyrine at a dose of 2 mg/kg resulted in the lowest interindividual variability. CONCLUSIONS AND CLINICAL RELEVANCE: The PCD is superior to CUMPCD for the quantification of aminopyrine demethylation. Administration of (13)C-(13)C-aminopyrine at a dose of 2 mg/kg is appropriate for use in the (13)C-aminopyrine demethylation blood test in healthy dogs.

Change in tibial plateau angle after tibial plateau leveling osteotomy in dogs.

OBJECTIVE: To determine the change in tibial plateau angle (TPA) during healing after tibial plateau leveling osteotomy (TPLO) performed for cranial cruciate ligament insufficiency in dogs and to examine factors that may be associated with the change. STUDY DESIGN: Retrospective study. STUDY POPULATION: One hundred and forty-nine canine stifles after TPLO procedure. METHODS: Records of dogs that had TPLO were reviewed. Patient age, weight, sex, breed, pre- and postoperative TPA, recheck TPA, time to recheck, type of implant used, and radiographic evidence of healing were analyzed. RESULTS: Mean time to recheck evaluation was 46 days (range, 28-65 days). Mean difference between immediate postoperative and recheck TPA measurements was 1.5 degrees (range, -3 to 9 degrees). Recheck TPA was a significantly greater (numerically higher) than immediate postoperative TPA (P<.0001). There was no significant effect of patient weight, type of plate used, or healing status of the osteotomy at the time of recheck. No correlation between pre- or postoperative TPA angles and change in TPA angle was detected. CONCLUSIONS: TPA changes during osteotomy healing after TPLO, but factors influencing this change were not identified. CLINICAL RELEVANCE: TPA may increase during healing after TPLO despite apparently adequate osteotomy fixation. The clinical relevance of this increase is unknown but is likely minimal.

Preparing and evaluating delivery systems for proteins.

From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping and long-term storage of the formulation. Therefore, the development and evaluation of successful and promising drug delivery systems is essential. In the present review, some of the particulate drug delivery systems for parenteral delivery of protein are presented and discussed. The challenge for incorporation of protein in particulate delivery systems is exemplified by water-in-oil emulsions.

Kinetic analysis of demethylation of 13C-aminopyrine in healthy dogs.

OBJECTIVE: To describe the kinetics of demethylation of 13C-aminopyrine in healthy dogs for use in determining the most appropriate time for collection of blood samples for a 13C-aminopyrine demethylation blood test for evaluation of hepatic function. ANIMALS: 9 healthy dogs. PROCEDURES: A 2-mL baseline blood sample was collected into an evacuated heparinized tube, and 13C-aminopyrine was administered to each dog (2 mg/kg, IV). Additional 2-mL blood samples were collected 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 240, 300, and 360 minutes after 13C-aminopyrine administration. The CO2 was extracted from blood samples by addition of a strong acid, and the percentage dose of 13CO2 (PCD) in the extracted gas was determined by fractional mass spectrometry. RESULTS: No dogs had gross evidence of adverse effects, and all had an increase in PCD after IV administration of 13C-aminopyrine. The PCD had the least variability among 5 variables used to evaluate hepatic demethylating capacity. Peak PCD was detected at 30 minutes in 1 dog, 45 minutes in 5 dogs, 60 minutes in 2 dogs, and 75 minutes in 1 dog. The mean PCD for the 9 dogs peaked at 45 minutes after 13C-aminopyrine administration. CONCLUSIONS AND CLINICAL RELEVANCE: PCD appears to be the preferable variable for evaluation of hepatic demethylating capacity. Intravenous administration of 13C-aminopyrine leads to a consistent increase in PCD. Mean PCD peaked 45 minutes after administration, suggesting that blood sample collection 45 minutes after 13C-aminopyrine administration may be appropriate for use in estimating hepatic demethylating capacity.

Microarray technology--the future analyses tool in exercise physiology?

Microarray analysis offers a set of analytical platforms that provide rapid, affordable and substantial information at the DNA, RNA or protein level. It enables the analysis of thousands of genes simultaneously in a parallel manner across samples derived from various biological sources and treatment regimens. This development became possible as a result of the combination of three technological advances achieved at the beginning of the 1990's, namely parallelism, miniaturization and automation. In regular physical checkups the microarray technology could be used to supplement the current spectrum of tests and therefore enhance the quality of the data obtained. Arrays for analyses of RNA expression will allow gene expression profiling also in exercise physiology. DNA chips may also be used for genetic screening and diagnostics to analyze polymorphisms and mutations which may underlie genetic diseases or interindividual variations between subjects. Using microarrays in exercise physiology will provide new insights into the complex molecular mechanisms of the exercise-induced stress response, adaptation to training and modulation of immune function. Gene expression profiling and genetic screening will probably help to characterize and predict the individually variable response to and efficiency of training.

Inheritance of pancreatic acinar atrophy in German Shepherd Dogs.

OBJECTIVE: To assess the heritability of pancreatic acinar atrophy (PAA) in German Shepherd Dogs (GSDs) in the United States. ANIMALS: 135 GSDs belonging to 2 multigenerational pedigrees. PROCEDURE: Two multigenerational pedigrees of GSDs with family members with PAA were identified. The clinical history of each GSD enrolled in the study was recorded, and serum samples for canine trypsin-like immunoreactivity (cTLI) analysis were collected from 102 dogs. Dogs with a serum cTLI concentration < or = 2.0 microg/L were considered to have exocrine pancreatic insufficiency (EPI) and were assumed to have PAA. RESULTS: Pedigree I consisted of 59 dogs and pedigree II of 76 dogs. Serum cTLI concentrations were measured in 48 dogs from pedigree I and 54 dogs from pedigree II. A total of 19 dogs (14.1%) were determined to have EPI, 9 in pedigree I (15.3%) and 10 in pedigree II (13.6%). Of the 19 dogs with EPI, 8 were male and 11 were female. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of data by complex segregation analysis is strongly suggestive of an autosomal recessive mode of inheritance for EPI in GSDs in the United States.

Preliminary studies of a canine 13C-aminopyrine demethylation blood test.

The objectives of this study were to determine whether a 13C-aminopyrine demethylation blood test is technically feasible in clinically healthy dogs, whether oral administration of 13C-aminopyrine causes a detectable increase in percent dose/min (PCD) of 13C administered as 13C-aminopyrine and recovered in gas extracted from blood, and whether gas extraction efficiency has an impact on PCD. A dose of 2 mg/kg body weight of 13C-aminopyrine dissolved in deionized water was administered orally to 6 clinically healthy dogs. Blood samples were taken from each dog 0, 30, 60, and 120 min after administration of the 13C-aminopyrine. Carbon dioxide was extracted from blood samples by addition of acid and analyzed by fractional mass spectrometry. None of the 6 dogs showed any side effects after 13C-aminopyrine administration. All 6 dogs showed a measurable increase of the PCD in gas samples extracted from blood samples at 30 min, 60 min, and 120 min after 13C-aminopyrine administration. Coefficients of variation between the triplicate samples were statistically significantly higher for the %CO2, a measure of extraction efficiency, than for PCD values (P < 0.0001). The 13C-aminopyrine demethylation blood test described here is technically feasible. Oral administration of 13C-aminopyrine did not lead to gross side effects in the 6 dogs. Clinically healthy dogs show a measurable increase of PCD in gas extracted from blood samples after oral administration of 13C-aminopyrine. Efficiency of CO2 extraction from blood samples does not have an impact on PCD determined from these blood samples. This test may prove useful to evaluate hepatic function in dogs.

Development and validation of a method for simultaneous separation and quantification of 5 different sugars in canine urine.

The objective of this project was to develop and validate a method for concurrent separation and quantification of methylglucose, rhamnose, xylose, sucrose, and lactulose in canine urine by using high pressure anion exchange liquid chromatography and pulsed amperometric detection. The method was validated by evaluating dilutional parallelism, spiking recovery, intra-assay variability, and inter-assay variability. Observed to expected ratios for 3 urine samples, and all sugars, ranged from 77.6% to 106.9% for a 1:2 dilution, 85.2% to 121.4% for a 1:4 dilution, and 91.6% to 163.7% for a 1:8 dilution. Observed to expected ratios for spiking recovery of 3 urine samples, all sugars, and 5 different spiking solutions, ranged from 85.5% to 116.7 % (mean +/- SD, 100.5 +/- 6.0%). The intra-assay coefficients of variation were 1.6%, 3.4%, and 4.7% for methylglucose; 1.6%, 2.0%, and 3.6% for rhamnose; 2.7%, 1.4%, and 1.1% for xylose; 9.8%, 3.4%, and 4.0% for sucrose; and 3.2%, 3.3%, and 3.3% for lactulose. Inter-assay coefficients of variation were 3.2%, 5.7%, and 4.2% for methylglucose; 4.3%, 5.4%, and 6.4% for rhamnose; 3.3%, 5.0%, and 4.2% for xylose; 9.4%, 9.9%, and 9.4% for sucrose; and 6.1%, 4.9%, and 2.7% for lactulose. In conclusion, a method for simultaneous separation and quantification of 5 sugars in canine urine was established and found to be linear, accurate, precise, and reproducible. This method may prove useful in the simultaneous evaluation of gastric permeability, small intestinal permeability, and small intestinal mucosal function in dogs with gastrointestinal disorders.

Development and validation of an enzyme-linked immunosorbent assay for feline trypsin-like immunoreactivity.

OBJECTIVE: To develop and validate an ELISA for quantitative analysis of feline trypsin-like immunore-activity (fTLI). SAMPLE POPULATION: Purified feline cationic trypsin (fCT) and rabbit anti-fCT antiserum; blood samples from 63 healthy cats. PROCEDURES: A sandwich capture ELISA was developed, using anti-fCT antiserum purified by affinity chromatography that underwent biotinylation. Purified fCT was used for standards. The assay was validated by determination of sensitivity, working range, linearity, accuracy, precision, and reproducibility. A reference range was established by assaying serum samples from the 63 healthy cats. RESULTS: Sensitivity was 1.23 microg/L; working range was 2 to 567 microg/L. Ratios of observed versus expected results for 4 samples tested at various dilutions ranged from 90.0 to 120.7%. Ratios of observed versus expected results for 5 samples spiked with various concentrations of fCT ranged from 82.0 to 101.8%. Intra- and inter-assay coefficients of variability ranged from 9.9 to 11.1% and from 10.2 to 21.7%, respectively. The reference range for serum fTLI measured with this ELISA was 12 to 82 microg/L. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that an ELISA can be used to measure serum fTLI in cats. The ELISA was sufficiently sensitive, linear, accurate, precise, and reproducible for clinical use.

Overlapping distribution of the 130- and 110-kDa myosin I isoforms on rat liver membranes.

The biochemical and mechanochemical properties and localization of myosin I suggest the involvement of these small members of the myosin superfamily in some aspects of intracellular motility in higher cells. We have determined by quantitative immunoblotting with isoform-specific antibodies that the 130-kDa myosin I (myr 1 gene product) and 110-kDa myosin I (myr 2 gene product) account for 0.5 and 0.4%, respectively, of total rat liver protein. Immunoblot analyses reveal that the 130- and 110-kDa myosins I are found in several purified subcellular fractions from rat liver. The membrane-associated 130-kDa myosin I is found at the highest concentration in the plasma membrane (28 ng/microg plasma membrane protein) followed by the endoplasmic reticulum-like mitochondria-associated membrane fraction (MAM; 10 ng/microg MAM protein), whereas the 110-kDa myosin I is found at the highest concentration in Golgi (50 ng/¿g Golgi protein) followed by plasma membrane (20 ng/microg) and MAM (7 ng/microg). Our analyses indicate that myosin I is peripherally associated with Golgi and MAM and its presence in these fractions is not a consequence of myosin I bound to contaminating actin filaments. Although found in relatively low concentrations in microsomes, because of the abundance of microsomes, in liver most of the membrane-associated myosin I is associated with microsomes. Neither myosin I isoform is detected in purified mitochondria. This is the first quantitative analysis addressing the cellular distribution of these mammalian class I myosins.