Automated Prediction of Bacterial Exclusion Areas on SEM Images of Graphene-Polymer Composites.

To counter the rising threat of bacterial infections in the post-antibiotic age, intensive efforts are invested in engineering new materials with antibacterial properties. The key bottleneck in this initiative is the speed of evaluation of the antibacterial potential of new materials. To overcome this, we developed an automated pipeline for the prediction of antibacterial potential based on scanning electron microscopy images of engineered surfaces. We developed polymer composites containing graphite-oriented nanoplatelets (GNPs). The key property that the algorithm needs to consider is the density of sharp exposed edges of GNPs that kill bacteria on contact. The surface area of these sharp exposed edges of GNPs, accessible to bacteria, needs to be inferior to the diameter of a typical bacterial cell. To test this assumption, we prepared several composites with variable distribution of exposed edges of GNP. For each of them, the percentage of bacterial exclusion area was predicted by our algorithm and validated experimentally by measuring the loss of viability of the opportunistic pathogen Staphylococcus epidermidis. We observed a remarkable linear correlation between predicted bacterial exclusion area and measured loss of viability (R2 = 0.95). The algorithm parameters we used are not generally applicable to any antibacterial surface. For each surface, key mechanistic parameters must be defined for successful prediction.

Precontrolled Alignment of Graphite Nanoplatelets in Polymeric Composites Prevents Bacterial Attachment.

Graphene coatings composed of vertical spikes are shown to mitigate bacterial attachment. Such coatings present hydrophobic edges of graphene, which penetrate the lipid bilayers causing physical disruption of bacterial cells. However, manufacturing of such surfaces on a scale required for antibacterial applications is currently not feasible. This study explores whether graphite can be used as a cheaper alternative to graphene coatings. To examine this, composites of graphite nanoplatelets (GNP) and low-density polyethylene (LDPE) are extruded in controlled conditions to obtain controlled orientation of GNP flakes within the polymer matrix. Flakes are exposed by etching the surface of GNP-LDPE nanocomposites and antibacterial activity is evaluated. GNP nanoflakes on the extruded samples interact with bacterial cell membranes, physically damaging the cells. Bactericidal activity is observed dependent on orientation and nanoflakes density. Composites with high density of GNP (≥15%) present two key advantages: i) they decrease bacterial viability by a factor of 99.9999%, which is 10 000-fold improvement on the current benchmark, and ii) prevent bacterial colonization, thus drastically reducing the numbers of dead cells on the surface. The latter is a key advantage for longer-term biomedical applications, since these surfaces will not have to be cleaned or replaced for longer periods.

Antibacterial effect of boron nitride flakes with controlled orientation in polymer composites.

Boron nitride (BN) is a stable 2D material with physiochemical properties similar to graphene-based nanomaterials. We have recently demonstrated that vertically aligned coatings of graphene-based nanomaterials provide strong antibacterial effects on various surfaces. Here we investigated whether BN, a nanomaterial with extensive similarities to graphene, might exhibit similar antibacterial properties. To test this, we developed a novel composite material using BN and low density polyethylene (LDPE) polymer. The composite was extruded under controlled melt flow conditions leading to highly structured morphology, with BN oriented in the extrusion flow direction. Nanocomposite extruded surfaces perpendicular to the flow direction were etched, thus exposing BN nanoparticles embedded in the matrix. The antimicrobial activity of extruded samples was evaluated against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus aureus by the colony forming units (CFUs) counting method. Furthermore, the bactericidal effect of oriented BN against E. coli and S. aureus was evaluated by scanning electron microscopy (SEM) and live/dead viability assay. Our results suggest that BN nanoflakes on the extruded BN/LDPE composite physically interact with the bacterial cellular envelope, leading to irreparable physical damage. Therefore, we propose that BN-polymer composites might be useful to develop polymer based biomedical devices protected against bacterial adhesion, and thus minimize device associated infections.

Pneumococcal conjugate vaccine triggers a better immune response than pneumococcal polysaccharide vaccine in patients with chronic lymphocytic leukemia A randomized study by the Swedish CLL group.

AIM: To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent pneumococcal conjugated vaccine (PCV13), Prevenar13®, compared to a 23-valent pneumococcal polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response. BACKGROUND: Streptococcus pneumoniae causes substantial morbidity in patients with CLL, a group known to respond poorly to polysaccharide vaccines. Comparative studies with conjugated vaccines are lacking. METHODS: 128 treatment naïve CLL patients from eight hematology clinics in Sweden were randomized to vaccination with PCV13 (n = 63) or PPSV23 (n = 65) after stratification by IgG level and CLL clinical stage (Rai). Blood samples for evaluation of immune response were obtained at baseline, and at one and six months after vaccination. Analyses for each of the 12 pneumococcal serotypes common for PCV13 and PPSV23 were performed by opsonophagocytic assay (OPA) and enzyme-linked immunosorbent assay (ELISA). RESULTS: PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, measured as OPA geometric mean titers (GMTs). Geometric mean concentrations of serotype-specific IgG antibodies elicited by PCV13 as measured by ELISA, were higher than those elicited by PPSV23 in half of the common serotypes, both after one and six months. PPSV23 did not trigger a better immune response than PCV13 for any of the serotypes, regardless of analysis method or time point of analysis. Negative predictive factors for vaccination response were hypogammaglobulinemia and long disease duration. Both vaccines were well tolerated. CONCLUSIONS: In patients with previously untreated CLL, the efficacy of PCV13 in terms of immune response is superior to PPSV23 for most serotypes common for the two vaccines. We therefore propose that PCV13 should be included in vaccination programs against Streptococcus pneumoniae for CLL patients and administered as early as possible during the course of the disease.

Validating microscopic colitis (MC) in Swedish pathology registers.

OBJECTIVE: Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is a diagnosis which relies on histopathologic criteria. This report examines the validity of having a diagnosis of MC in Swedish pathology registers. METHODS: We reviewed patient charts from 215 randomly selected individuals from 15 pathology departments in five healthcare regions in Sweden with a relevant histopathology code for MC on colon biopsies. Information on clinical symptoms and laboratory data were obtained from medical chart review. We obtained sufficient data on 211 individuals for calculating positive predictive values (PPVs) for MC. RESULTS: In total, 200/211 patients with a histopathology diagnosis of MC were confirmed as also having a clinical diagnosis of MC after chart review, yielding a PPV of 95% (95%CI =91-97%). The PPV for CC was 95% (95%CI =87-98%) and 85% for LC (95%CI =78-90%). The median age at biopsy was 67 years (range 17-90 years), and 72% (n = 154) were women. The most common symptoms in patients with MC histopathology were diarrhea (96% of patients), weight loss (24%) and abdominal pain (13%). Four percent (4/111) of patients with available data on stool culture were positive for gastrointestinal pathogens (none had Clostridium difficile). In 81 patients with available celiac serology, five (6%) were positive. Twenty-six percent of all patients had at least one other autoimmune disease, the most frequent being hypothyroidism (8%) and celiac disease (6%). CONCLUSIONS: This study found a high validity for MC as recorded in Swedish pathology registers.

[Biological treatments in pediatric IBD]. / Biologiska läkemedel etablerad terapi för barn med IBD i Sverige.

Biological treatments in pediatric IBD In Sweden, there are an estimated 1 500 pediatric IBD patients. We sent out a survey regarding the use of biological treatments in pediatric IBD to pediatric gastroenterologists in Sweden. Of 1 098 recorded IBD patients, 17% had ongoing treatment with biological drugs. The drugs used were almost exclusively infliximab and adalimumab, i.e. anti-TNF-alpha. Use of biologics varied among responders. Anaphylactic reactions and other types of infusion reactions were the most frequent side effects.

All-printed diode operating at 1.6 GHz.

Printed electronics are considered for wireless electronic tags and sensors within the future Internet-of-things (IoT) concept. As a consequence of the low charge carrier mobility of present printable organic and inorganic semiconductors, the operational frequency of printed rectifiers is not high enough to enable direct communication and powering between mobile phones and printed e-tags. Here, we report an all-printed diode operating up to 1.6 GHz. The device, based on two stacked layers of Si and NbSi2 particles, is manufactured on a flexible substrate at low temperature and in ambient atmosphere. The high charge carrier mobility of the Si microparticles allows device operation to occur in the charge injection-limited regime. The asymmetry of the oxide layers in the resulting device stack leads to rectification of tunneling current. Printed diodes were combined with antennas and electrochromic displays to form an all-printed e-tag. The harvested signal from a Global System for Mobile Communications mobile phone was used to update the display. Our findings demonstrate a new communication pathway for printed electronics within IoT applications.

Improved survival in myeloma patients: starting to close in on the gap between elderly patients and a matched normal population.

The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population (n = 9 340 682). Median overall survival for non-high-dose treated patients was 2·8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4·9 years) compared to conventional treatment (2·3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6·9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.

Portal vein thrombosis is a common complication following splenectomy in patients with malignant haematological diseases.

BACKGROUND: Elective laparoscopic splenectomy (LS) is performed with increasing frequency rather than open splenectomy (OS) because of reduced morbidity. LS is feasible also in patients with haematological diseases with splenomegaly, a group that is subject to more postoperative complications, such as bleeding, infections and portal vein thrombosis (PVT). METHOD: We retrospectively reviewed the medical records of 69 patients splenectomised for haematological diseases during a 5-yr period at a single centre with the aim of comparing the results and complications after LS and OS. RESULTS: Thirty-nine patients underwent LS and 30 OS. The median durations of surgery were 138 and 115 min (ns) in the LS and OS groups respectively. Three conversions (7.7%) from laparoscopic surgery to open surgery were necessary because of bleeding and/or splenomegaly. Thromboembolic complications occurred in totally seven of 69 patients. PVT was diagnosed in five of 37 (13.5%) patients with haematological malignancies (three with indolent lymphoma and two with myeloproliferative disease), one after LS and four after OS. All patients with PVT had splenomegaly and had received thromboembolic prophylaxis with low-molecular-weight heparin of short duration. Two patients were diagnosed with deep vein thromboses in the lower leg. Both had idiopathic thrombocytopenic purpura (ITP) and LS. CONCLUSIONS: Patients with malignant haematological diseases and splenomegaly seem to have a high risk of developing PVT after splenectomy why careful observation and prolonged thromboprophylaxis is recommended for these patients. Ultrasonography or computerised tomography should be considered in all patients with abdominal symptoms after splenectomy.