Curing Cats with Feline Infectious Peritonitis with an Oral Multi-Component Drug Containing GS-441524

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn^® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn^®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn^® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn^® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.     

Fast and accurate liver volumetry prior to hepatectomy

BackgroundVolumetric assessment of the liver is essential in the prevention of postresectional liver failure after partial hepatectomy. Currently used methods are accurate but time-consuming. This study aimed to test a new automated method for preoperative volumetric liver assessment.MethodsPatients who underwent a contrast enhanced portovenous phase CT-scan prior to hepatectomy in 2012 were included. Total liver volume (TLV) and future remnant liver volume (FRLV) were measured using TeraRecon Aquarius iNtuition^® (autosegmentation) and OsiriX^® (manual segmentation) software by two observers for each software package. Remnant liver volume percentage (RLV%) was calculated. Time needed to determine TLV and FRLV was measured. Inter-observer variability was assessed using Bland-Altman plots.ResultsTwenty-seven patients were included. There were no significant differences in measured volumes between OsiriX^® and iNtuition^®. Moreover, there were significant correlations between the OsiriX^® observers, the iNtuition^® observers and between OsiriX^® and iNtuition^® post-processing systems (all R² > 0.97). The median time needed for complete liver volumetric analysis was 18.4 ± 4.9 min with OsiriX^® and 5.8 ± 1.7 min using iNtuition^® (p < 0.001).ConclusionBoth OsiriX^® and iNtuition^® liver volumetry are accurate and easily applicable. However, volumetric assessment of the liver with iNtuition^® auto-segmentation is three times faster compared to manual OsiriX^® volumetry.     

Chitosonic? Acid as a Novel Cosmetic Ingredient: Evaluation of its Antimicrobial,Antioxidant and Hydration Activities

Chitosonic^® Acid, carboxymethyl hexanoyl chitosan, is a novel chitosan material that has recently been accepted by the Personal Care Products Council as a new cosmetic ingredient with the INCI (International Nomenclature of Cosmetic Ingredients) name Carboxymethyl Caprooyl Chitosan. In this study, we analyze several important cosmetic characteristics of Chitosonic^® Acid. Our results demonstrate that Chitosonic^® Acid is a water-soluble chitosan derivative with a high HLB value. Chitosonic^® Acid can form a nano-network structure when its concentration is higher than 0.5% and can self-assemble into a nanosphere structure when its concentration is lower than 0.2%. Chitosonic^® Acid has potent antimicrobial activities against gram-positive bacteria, gram-negative bacteria and fungus. Chitosonic^® Acid also has moderate DPPH radical scavenging activity. Additionally, Chitosonic^® Acid exhibits good hydration activity for absorbing and retaining water molecules with its hydrophilic groups. From a safety point of view, Chitosonic^® Acid has no cytotoxicity to L-929 cells if its concentration is less than 0.5%. Moreover, Chitosonic^® Acid has good compatibilities with various normal cosmetic ingredients. Therefore, we propose that Chitosonic^® Acid has the potential to be a widely used ingredient in various types of cosmetic products.     

Expanding the view of a standard colonoscope with the Third Eye? Panoramic? cap

AIM: To evaluate a new imaging device for colonoscopy that adds two side viewing CMOS lenses, the Third Eye^® Panoramic™ cap.METHODS: In this prospective observational feasibility study, 33 patients, 18 male and 15 female, underwent routine screening, surveillance or diagnostic colonoscopy with the new Third Eye^® Panoramic™ cap clipped on to the distal tip of a high definition Fuji EC530-LS Slim Colonoscope^®. All procedures were performed at the New York Presbyterian-Queens Endoscopy unit by two experienced endoscopists (Rubin M and Kim SH). Main outcome measurements included evaluation of the image quality of the Third Eye^® Panoramic™ cap, adenoma detection rate, cecal intubation rate, withdrawal time and total procedure time.RESULTS: The Third Eye^® Panoramic™ cap enabled enhanced views without affecting the quality of the colonoscope’s image or its handling characteristics through the colon. Ileal intubation was accomplished in most cases, but was more challenging. The side view lenses detected polyps and diverticula hidden behind folds and in flexures not seen on the standard view. The side view lenses were easily cleaned utilizing an Endogator^® Irrigation Pump (Medivators, Minneapolis, MN, United States) by angling the scope tip against the mucosa while washing. The cecum was reached in all 33 patients. Mean cecal intubation time was 8.19 ± 2.17 min, mean withdrawal time was 10.15 ± 5.56 min and mean total procedure time was 20.31 ± 5.14 min. The overall adenoma detection rate was 44%.CONCLUSION: The Third Eye^® Panoramic™ cap enables wide view colonoscopy with enhanced visualization utilizing standard forward view colonoscopes.     

Cytolytic Properties and Genome Analysis of Rigvir® Oncolytic Virotherapy Virus and Other Echovirus 7 Isolates

Rigvir^® is a cell-adapted, oncolytic virotherapy enterovirus, which derives from an echovirus 7 (E7) isolate. While it is claimed that Rigvir^® causes cytolytic infection in several cancer cell lines, there is little molecular evidence for its oncolytic and oncotropic potential. Previously, we genome-sequenced Rigvir^® and five echovirus 7 isolates, and those sequences are further analyzed in this paper. A phylogenetic analysis of the full-length data suggested that Rigvir^® was most distant from the other E7 isolates used in this study, placing Rigvir^® in its own clade at the root of the phylogeny. Rigvir^® contained nine unique mutations in the viral capsid proteins VP1-VP4 across the whole data set, with a structural analysis showing six of the mutations concerning residues with surface exposure on the cytoplasmic side of the viral capsid. One of these mutations, E/Q/N162G, was located in the region that forms the contact interface between decay-accelerating factor (DAF) and E7. Rigvir^® and five other isolates were also subjected to cell infectivity assays performed on eight different cell lines. The used cell lines contained both cancer and non-cancer cell lines for observing Rigvir^®’s claimed properties of being both oncolytic and oncotropic. Infectivity assays showed that Rigvir^® had no discernable difference in the viruses’ oncolytic effect when compared to the Wallace prototype or the four other E7 isolates. Rigvir^® was also seen infecting non-cancer cell lines, bringing its claimed effect of being oncotropic into question. Thus, we conclude that Rigvir^®’s claim of being an effective treatment against multiple different cancers is not warranted under the evidence presented here. Bioinformatic analyses do not reveal a clear mechanism that could elucidate Rigvir^®’s function at a molecular level, and cell infectivity tests do not show a discernable difference in either the oncolytic or oncotropic effect between Rigvir^® and other clinical E7 isolates used in the study.     

Sustainable Chitosan-Dialdehyde Cellulose Nanocrystal Film

In this study, we incorporated 2,3-dialdehyde nanocrystalline cellulose (DANC) into chitosan as a reinforcing agent and manufactured biodegradable films with enhanced gas barrier properties. DANC generated via periodate oxidation of cellulose nanocrystal (CNC) was blended at various concentrations with chitosan, and bionanocomposite films were prepared via casting and characterized systematically. The results showed that DANC developed Schiff based bond with chitosan that improved its properties significantly. The addition of DANC dramatically improved the gas barrier performance of the composite film, with water vapor permeability (WVP) value decreasing from 62.94 g·mm·m⁻²·atm⁻¹·day⁻¹ to 27.97 g·mm·m⁻²·atm⁻¹·day⁻¹ and oxygen permeability (OP) value decreasing from 0.14 cm³·mm·m⁻²·day⁻¹·atm⁻¹ to 0.026 cm³·mm·m⁻²·day⁻¹·atm⁻¹. Meanwhile, the maximum decomposition temperature (Td_max) of the film increased from 286 °C to 354 °C, and the tensile strength of the film was increased from 23.60 MPa to 41.12 MPa when incorporating 25 wt.% of DANC. In addition, the chitosan/DANC (75/25, wt/wt) films exhibited superior thermal stability, gas barrier, and mechanical strength compared to the chitosan/CNC (75/25, wt/wt) film. These results confirm that the DANC and chitosan induced films with improved gas barrier, mechanical, and thermal properties for possible use in film packaging.     

Comparison of the Dielectric Properties of Ecoflex® with L,D-Poly(Lactic Acid) or Polycaprolactone in the Presence of SWCN or 5CB

The main goal of this paper was to study the dielectric properties of hybrid binary and ternary composites based on biodegradable polymer Ecoflex^®, single walled carbon nanotubes (SWCN), and liquid crystalline 4′-pentyl-4-biphenylcarbonitrile (5CB) compound. The obtained results were compared with other created analogically to Ecoflex^®, hybrid layers based on biodegradable polymers such as L,D-polylactide (L,D-PLA) and polycaprolactone (PCL). Frequency domain dielectric spectroscopy (FDDS) results were analyzed taking into consideration the amount of SWCN, frequency, and temperature. For pure Ecoflex^®, two relaxation processes (α and β) were identified. It was shown that the SWCN admixture (in the weight ratio 10:0.01) did not change the properties of the Ecoflex^® layer, while in the case of PCL and L,D-PLA, the layers became conductive. The dielectric constant increased with an increase in the content of SWCN in the Ecoflex^® matrix and the conductive behavior was not visible, even for the greatest concentration (10:0.06 weight ratio). In the case of the Ecoflex^® polymer matrix, the conduction relaxation process at a frequency ca. several kilohertz appeared and became stronger with an increase in the SWCN admixture in the matrix. Addition of oleic acid to the polymer matrix had a smaller effect on the increase in the dielectric response than the addition of liquid crystal 5CB. Fourier transform infrared (FTIR) results revealed that the molecular structure and chemical character of the Ecoflex^® and PCL matrixes remained unchanged upon the addition of SWCN or 5CB in a weight ratio of 10:0.01 and 10:1, respectively, while molecular interactions appeared between L,D-PLA and 5CB. Moreover, adding oleic acid to pure Ecoflex^® as well as the binary and ternary hybrid layers with SWCN and/or 5CB in a weight ratio of Ecoflex^®:oleic acid equal to 10:0.3 did not have an influence on the chemical bonding of these materials.     

EVALUATION OF METHODS IN DETECTING VANCOMYCIN MIC AMONG MRSA ISOLATES AND THE CHANGES IN ACCURACY RELATED TO DIFFERENT MIC VALUES

INTRODUCTION: Methicillin-Resistant Staphylococcus aureus (MRSA) presenting reduced susceptibility to vancomycin has been associated to therapeutic failure. Some methods used by clinical laboratories may not be sufficiently accurate to detect this phenotype, compromising results and the outcome of the patient. OBJECTIVES: To evaluate the performance of methods in the detection of vancomycin MIC values among clinical isolates of MRSA. MATERIAL AND METHODS: The Vancomycin Minimal Inhibitory Concentration was determined for 75 MRSA isolates from inpatients of Mãe de Deus Hospital, Porto Alegre, Brazil. The broth microdilution (BM) was used as the gold-standard technique, as well as the following methods: E-test^® strips (BioMérieux), M.I.C.E^® strips (Oxoid), PROBAC^® commercial panel and the automated system MicroScan^® (Siemens). Besides, the agar screening test was carried out with 3 µg/mL of vancomycin. RESULTS: All isolates presented MIC ≤ 2 µg/mL for BM. E-test^® had higher concordance (40%) in terms of global agreement with the gold standard, and there was not statistical difference among E-test^® and broth microdilution results. PROBAC^® panels presented MICs, in general, lower than the gold-standard panels (58.66% major errors), while M.I.C.E.^® MICs were higher (67.99% minor errors). CONCLUSIONS: For the population of MRSA in question, E-test^® presented the best performance, although with a heterogeneous accuracy, depending on MIC values.     

Permeability of Ibuprofen in the Form of Free Acid and Salts of L-Valine Alkyl Esters from a Hydrogel Formulation through Strat-M™ Membrane and Human Skin

This paper aimed to evaluate the effect of vehicle and chemical modifications of the structure of active compounds on the skin permeation and accumulation of ibuprofen [IBU]. In vitro permeation experiments were performed using human abdominal skin and Strat-M™ membrane. The HPLC method was used for quantitative determinations. The formulations tested were hydrogels containing IBU and its derivatives and commercial gel with ibuprofen. The results obtained indicate that Celugel^® had an enhancing effect on the skin penetration of IBU. The average cumulative mass of [IBU] after 24 h permeation test from Celugel^® formulation through human skin was over 3 times higher than for the commercial product. Three ibuprofen derivatives containing [ValOiPr][IBU], [ValOPr][IBU], and [ValOBu][IBU] cation were evaluated as chemical penetration enhancers. The cumulative mass after 24 h of penetration was 790.526 ± 41.426, 682.201 ± 29.910, and 684.538 ± 5.599 μg IBU cm⁻², respectively, compared to the formulation containing unmodified IBU-429.672 ± 60.151 μg IBU cm⁻². This study demonstrates the perspective of the transdermal hydrogel vehicle in conjunction with the modification of the drug as a potential faster drug delivery system.     

Assessment of the Effect of Structural Modification of Ibuprofen on the Penetration of Ibuprofen from Pentravan® (Semisolid) Formulation Using Human Skin and a Transdermal Diffusion Test Model

The effect of transdermal vehicle (Pentravan^®) on skin permeability was examined for unmodified ibuprofen (IBU) and ion pairs of ibuprofen with new L-valine alkyl esters [ValOR][IBU]. The percutaneous permeation across the human skin and transdermal diffusion test model (Strat-M^® membranes) of ibuprofen and its structural modification were measured and compared using Franz diffusion cells. For comparison, the penetration of ibuprofen from a commercial product was also investigated. The cumulative amount of drug permeated through human skin at the end of the 24 h study was highest for ibuprofen derivatives containing propyl (C3), isopropyl (C3), ethyl (C2), and butyl (C4) esters. For Strat-M^®, the best results were obtained with the alkyl chain length of the ester from C2 to C5. The permeation profiles and parameters were appointed, such as steady-state flux, lag time, and permeability coefficient. It has been shown that L-valine alkyl ester ibuprofenates, with the propyl, butyl, and amyl chain, exhibit a higher permeation rate than ibuprofen. The diffusion parameters of analyzed drugs through human skin and Strat-M^® were similar and with good correlation. The resulting Pentravan-based creams with ibuprofen in the form of an ionic pair represent a potential alternative to other forms of the drug-containing analgesics administered transdermally. Furthermore, the Strat-M^® membranes can be used to assess the permeation of transdermal preparations containing anti-inflammatory drugs.     

Impact of being underweight or overweight on factor VIII dosing in hemophilia A patients

Since 1981, the number of factor VIII units to infuse into patients with hemophilia A in order to achieve adequate circulating factor VIII levels has been calculated using the formula: [body weight(kg)×desired factor VIII increase(%)]/2, assuming a factor VIII recovery value of 2 for all patients. This study’s aim was to evaluate the impact of several morphometric parameters and various coagulation factor concentrates on factor VIII recovery. The analysis included 201 hemophilia A adults (>18 years of age) who were carefully selected from eight pharmacokinetic clinical trials using three recombinant factor VIII concentrates (Advate^®, Kogenate^® FS, or ReFacto AF^®/Xyntha^®). Regression tree analysis was used to identify factor VIII recovery predictors. The median factor VIII recovery was 2.16 for all patients. Using regression tree analysis, patients were separated into three groups on the basis of body mass index: below 20.3 kg/m², between 20.3 and 29.5 kg/m², and 29.6 kg/m² or more. Each group had a significantly different median factor VIII recovery (P<0.001): 1.60, 2.14, and 2.70, respectively. The type of coagulation factor concentrate had no influence on recovery in the regression tree. In conclusion, factor VIII dosing should be adapted to underweight and overweight patients, as a factor VIII recovery of 2 does not apply to these patients. Ideal body weight should be considered instead of actual body weight in the dose calculations.     

Analytical Study of Porous Organosilicate Glass Films Prepared from Mixtures of 1,3,5- and 1,3-Alkoxysilylbenzenes

Organosilicate glass (OSG)-based porous low dielectric constant (low-k) films with different molar ratios of 1,3,5-tris(triethoxysilyl)benzene to 1,3-bis(triethoxysilyl)benzene bridging organic groups (1:3 and 1:7) were spin-on deposited, followed by a soft bake in air and N₂ at 150 °C and hard bake in air and N₂ at 400 °C. Non-ionic template (Brij^®30) concentrations were varied from 0 to 41 wt% to control the porosity of the films. The chemical composition of the matrix of the films was evaluated and discussed with the shrinkage of the film during the curing, refractive indices, mechanical properties, k-values, porosity and pore structure. The chemical composition of the film cured in both air and N₂-containing ambient were evaluated and compared. The benzene bridging groups containing films change their porosity (0 to 43%) but keep the pore size constant and equal to 0.81 nm when porosity is lower than 30%. The k-value decreases with increasing porosity, as expected. The films containing benzene bridge have higher a Young’s modulus than plasma-enhanced chemical vapor deposition (PECVD) methyl-terminated low-k films with the same porosity and show good hydrophobic properties after a hard bake and close to the values reported for 1,4-benzene-bridged films. The fabricated films show good stability after a long time of storage. However, the improvement of mechanical properties was lower than the values predicted by the published literature data. It was concluded that the concentration of 1,3,5-benzene bridges was below the stiffness threshold required for significant improvement of the mechanical properties. The films show UV-induced luminescence with a photon energy of 3.6 to 4.3 eV. The luminescence is related to the presence of oxygen-deficient-type defects or their combination with organic residues. The most intensive luminescence is observed in as-deposited and soft bake samples, then the intensity is reduced after a hard bake. It is assumed that the oxygen-deficient centers form because of the presence of Si–OC₂H₅ groups in the films and the concentration of these centers reduces when all these groups completely transformed into siloxane (Si–O–Si).     

Thermal Comfort and Electrostatic Properties of Socks Containing Fibers with Bio-Ceramic,Silver and Carbon Additives

Socks are an important part of our clothing used in everyday activities. In order to ensure thermal comfort during wear in cool outdoor or indoor conditions, and for health improvement, socks must have effective thermoregulation properties. Chemical far-infrared (FIR) fibers with different bio-ceramic compounds incorporated into socks’ structures can provide an improved thermoregulation effect to the wearer of the socks. Fibers with silver and carbon additives incorporated in their structures can also affect the thermoregulation properties of socks. Moreover, these conductive additives avoid the unpleasant effect of static electricity of socks. The main parts of the different investigated structures of the socks were made in a plush pattern. The plush loops were formed by using functional Resistex^® Bioceramic, Shieldex^® and two modifications of Nega-Stat^® fiber yarns. The main thermal comfort (thermal efficiency, microclimate and heat exchange temperatures, thermal resistance, water vapor permeability) and electrostatic (surface and vertical resistances, shielding factor, half time decay of charge) properties of the socks were investigated. Based on the obtained results of the thermal comfort and electrostatic characteristics of the different investigated structures of socks, the optimal static dissipative (half-time decay <0.01 s, shielding factor—0.96) plush knitting structure with 55% Resistex^® Bioceramic and 31% bicomponent Nega-Stat^® P210 fibers yarns was selected. Comparing the control sample without FIR and the knitted structure with conductive additives, we can draw the conclusion that the heat retention capability of the selected socks was improved by 1.5 °C and the temperature of their created microclimate was improved by 2 °C.     

Diagnostic Performance of an Automated System for Assaying Anti-Hepatitis E Virus Immunoglobulins M and G Compared with a Conventional Microplate Assay

To evaluate the diagnostic performance of the Liaison^® Murex anti-HEV IgM and IgG assays running on the Liaison^® instrument and compare the results with those obtained with Wantai HEV assays. We tested samples collected in immunocompetent and immunocompromised patients during the acute (HEV RNA positive, anti-HEV IgM positive) and the post-viremic phase (HEV RNA negative, anti-HEV IgM positive) of infections. The specificity was assessed by testing HEV RNA negative/anti-HEV IgG-IgM negative samples. The clinical sensitivity of the Liaison^® IgM assay was 100% for acute-phase samples (56/56) and 57.4% (27/47) for post-viremic samples from immunocompetent patients. It was 93.8% (30/32) for acute-phase (viremic) samples and 71%% (22/31) for post-viremic samples from immunocompromised patients. The clinical sensitivity of the Liaison^® IgG assay was 100% for viremic samples (56/56) and 94.6% (43/47) for post-viremic samples from immunocompetent patients. It was 84.3% (27/32) for viremic samples and 93.5% (29/31) for post-viremic samples from immunocompromised patients. Specificity was very high (>99%) in both populations. We checked the limit of detection stated for the Liaison^® IgG assay (0.3 U/mL). The clinical performance of the Liaison^® ANTI-HEV assays was good. These rapid, automated assays for detecting anti-HEV antibodies will greatly enhance the arsenal for diagnosing HEV infections.     

Surface Characteristics,Fluoride Release and Bond Strength Evaluation of Four Orthodontic Adhesives

Orthodontic adhesives have similar properties in terms of fluoride release, roughness, shear bond strength or cement debris for specific clinical conditions. Three commercial consecrated orthodontic adhesives (Opal Seal^®, Blugloo^®, Light Bond^®) were compared with an experimental orthodontic material (C1). Brackets were bonded to enamel using a self-etch technique followed by adhesive application and then de-bonded 60 days later. Share bond strength evaluation, scanning electron microscopy, atomic force microscopy and fluoride release analysis were performed. The highest amount of daily and cumulative fluoride release was obtained for the experimental material, while the lowest value was observed for Opal Seal^®. The materials evaluated in the current study presented adequate shear bond strength, with the experimental material having a mean value higher than Opal Seal and Blugloo. The atomic force microscopy measurements indicated that the smoothest initial sample is Opal Seal^® followed by Light Bond^®. Scanning electron microscopy evaluation indicated different aspects of cement debris on the enamel and/or bracket surface, according to the type of adhesive. The experimental material C1 presented adequate properties in terms of shear bond strength, fluoride release, roughness and enamel characteristics after de-bonding, compared to the commercial materials. Under these circumstances, it can be considered for clinical testing.     

Miniaturized Self-Expanding Drug-Eluting Stent in Small Coronary Arteries: Late Effectiveness

Background

Small vessels represent a risk factor for restenosis in percutaneous coronary angioplasty (PCA). The Sparrow^® self-expanding drug-eluting stent, which has a lower profile than the current systems, has never been tested in this scenario.

Objectives

To evaluate the late effectiveness of the Sparrow^® drug-eluting stent, regarding in-stent late lumen loss (LLL).

Methods

Patients with ischemia, symptomatic or documented, were submitted to PCA in vessels with reference diameter < 2.75 mm, divided into two groups regarding Sparrow^® stent type: group 1: Sparrow^® drug-eluting stent (DES), group 2: Sparrow^® bare metal stent (BMS). Clinical follow-up duration was 12 months. Evaluation using quantitative coronary angiography (QCA) was performed immediately and at 8 months. A decrease of over 65% of in-stent LLL with DES was estimated to calculate sample size. IBM^® SPSS software, release 19 (Chicago, Illinois, USA) was used for the statistical analysis.

Results

A total of 24 patients were randomized, 12 in each group. The DES and BMS groups were similar in age (63.25 ± 10.01 vs. 64.58 ± 11.54, p = 0.765), male gender (58.3% vs. 33.3%, p = 0.412), risk factors and all angiographs aspects. Immediate results were satisfactory in both groups. At 8 months in-stent late lumen loss was significantly lower in DES than in BMS group (DES vs. BMS 0.25 ± 0.16 0.97 ± 0.76, p = 0.008).

Conclusion

In small-vessel PCA, the Sparrow^® DES determined significant reduction in in-stent LLL, when compared to Sparrow^® BMS.     

Reduction in Severity of All-Cause Gastroenteritis Requiring Hospitalisation in Children Vaccinated against Rotavirus in Malawi

Rotavirus is the major cause of severe gastroenteritis in children aged <5 years. Introduction of the G1P[8] Rotarix^® rotavirus vaccine in Malawi in 2012 has reduced rotavirus-associated hospitalisations and diarrhoeal mortality. However, the impact of rotavirus vaccine on the severity of gastroenteritis presented in children requiring hospitalisation remains unknown. We conducted a hospital-based surveillance study to assess the impact of Rotarix^® vaccination on the severity of gastroenteritis presented by Malawian children. Stool samples were collected from children aged <5 years who required hospitalisation with acute gastroenteritis from December 2011 to October 2019. Gastroenteritis severity was determined using Ruuska and Vesikari scores. Rotavirus was detected using enzyme immunoassay. Rotavirus genotypes were determined using nested RT-PCR. Associations between Rotarix^® vaccination and gastroenteritis severity were investigated using adjusted linear regression. In total, 3159 children were enrolled. After adjusting for mid-upper arm circumference (MUAC), age, gender and receipt of other vaccines, all-cause gastroenteritis severity scores were 2.21 units lower (p < 0.001) among Rotarix^®-vaccinated (n = 2224) compared to Rotarix^®-unvaccinated children (n = 935). The reduction in severity score was observed against every rotavirus genotype, although the magnitude was smaller among those infected with G12P[6] compared to the remaining genotypes (p = 0.011). Each one-year increment in age was associated with a decrease of 0.43 severity score (p < 0.001). Our findings provide additional evidence on the impact of Rotarix^® in Malawi, lending further support to Malawi’s Rotarix^® programme.     

“Sticky Bone” Preparation Device: A Pilot Study on the Release of Cytokines and Growth Factors

Sticky bone, a growth factor-enriched bone graft matrix, is a promising autologous material for bone tissue regeneration. However, its production is strongly dependent on manual handling steps. In this sense, a new device was developed to simplify the confection of the sticky bone, named Sticky Bone Preparation Device (SBPD^®). The purpose of this pilot study was to investigate the suitability of the SBPD^® to prepare biomaterials for bone regeneration with autologous platelet concentrates. The SBPD^® allows the blending of particulate samples from synthetic, xenograft, or autogenous bone with autologous platelet concentrates, making it easy to use and avoiding the need of further manipulations for the combination of the materials. The protocol for the preparation of sticky bone samples using the SBPD^® is described, and the resulting product is compared with hand-mixed SB preparations regarding in vitro parameters such as cell content and the ability to release growth factors and cytokines relevant to tissue regeneration. The entrapped cell content was estimated, and the ability to release biological mediators was assessed after 7 days of incubation in culture medium. Both preparations increased the leukocyte and platelet concentrations compared to whole-blood samples (p < 0.05), without significant differences between SB and SBPD^®. SBPD^® samples released several growth factors, including VEGF, FGFb, and PDGF, at concentrations physiologically equivalent to those released by SB preparations. Therefore, the use of SBPD^® results in a similar product to the standard protocol, but with more straightforward and shorter preparation times and less manipulation. These preliminary results suggest this device as a suitable alternative for combining bone substitute materials with platelet concentrates for bone tissue regeneration.