Avian orthoavulaviruses type-1 (AOaV-1) have recently transitioned from animal vaccine vector to a bona fide vaccine delivery vehicle in human. Owing to induction of robust innate and adaptive immune responses in mucus membranes in both birds and mammals, AOaVs offer an attractive vaccine against respiratory pathogens. The unique features of AOaVs include over 50 years of safety profile, stable expression of foreign genes, high infectivity rates in avian and mammalian hosts, broad host spectrum, limited possibility of recombination and lack of pre-existing immunity in humans. Additionally, AOaVs vectors allow the production of economical and high quantities of vaccine antigen in chicken embryonated eggs and several GMP-grade mammalian cell lines. In this review, we describe the biology of AOaVs and define protocols to manipulate AOaVs genomes in effectively designing vaccine vectors. We highlighted the potential and established portfolio of AOaV-based vaccines for multiple respiratory and non-respiratory viruses of veterinary and medical importance. We comment on the limitations of AOaV-based vaccines and propose mitigations strategies. The exploitation of AOaVs vectors is expanding at an exciting pace; thus, we have limited the scope to their use as vaccines against viral pathogens in both animals and humans.

The sequestration of elevated atmospheric CO2 levels in seawater results in increasing acidification of oceans and it is unclear what the consequences of this will be on seaweed ecophysiology and ecological services they provide in the coastal ecosystem. In the present study, we examined the physiological and biochemical response of intertidal green seaweed Ulva compressa to elevated pCO2 induced acidification. The green seaweed was exposed to control (pH 8.1) and acidified (pH 7.7) conditions for 2 weeks following which net primary productivity, pigment content, oxidative status and antioxidant enzymes, primary and secondary metabolites, and mineral content were assessed. We observed an increase in primary productivity of the acidified samples, which was associated with increased levels of photosynthetic pigments. Consequently, primary metabolites levels were increased in the thalli grown under lowered pH conditions. There was also richness in various minerals and polyunsaturated fatty acids, indicating that the low pH elevated the nutritional quality of U. compressa. We found that low pH reduced malondialdehyde (MDA) content, suggesting reduced oxidative stress. Consistently we found reduced total antioxidant capacity and a general reduction in the majority of enzymatic and non-enzymatic antioxidants in the thalli grown under acidified conditions. Our results indicate that U. compressa will benefit from seawater acidification by improving productivity. Biochemical changes will affect its nutritional qualities, which may impact the food chain/food web under future acidified ocean conditions.

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial clearance, but the effect on BPD remains to be determined.

A concise and modular total synthesis of the highly potent N-desacetoxytubulysin H () has been accomplished in 18 steps in an overall yield of up to 30%. Our work highlights the complexity-augmenting and route-shortening power of diastereoselective multicomponent reaction (MCR) as well as the role of bulky ligands to perfectly control both the regioselective and diastereoselective synthesis of tubuphenylalanine in just two steps. The total synthesis not only provides an operationally simple and step economy but will also stimulate major advances in the development of new tubulysin analogues.

The objective of this study was to determine the immediate source of Escherichia coli on beef trimmings produced at a large
packing plant by analyzing the E. coli on trimmings at various locations of a combo bin filled on the same day and of bins filled
on different days. Ten 2,000-lb (907-kg) combo bins (B1 through B10) of trimmings were obtained from a large plant on 6 days
over a period of 5 weeks. Thin slices of beef with a total area of approximately 100 cm2 were excised from five locations (four
corners and the center) at each of four levels of the bins: the top surface and 30, 60, and 90 cm below the top. The samples were
enriched for E. coli in modified tryptone soya broth supplemented with 20 mg/liter novobiocin. The positive enrichment cultures,
as determined by PCR, were plated on E. coli/coliform count plates for recovery of E. coli. Selected E. coli isolates were
genotyped using multiple-locus variable-number tandem repeat analysis (MLVA). Of the 200 enrichment cultures, 43 were
positive by PCR for E. coli, and 32 of these cultures yielded E. coli isolates. Two bins did not yield any positive enrichment
cultures, and three PCR-positive bins did not yield any E. coli isolates. MLVA of 165 E. coli isolates (30, 62, 56, 5, and 12 from
B6 through B10, respectively) revealed nine distinct genotypes. MLVA types 263 and 89 were most prevalent overall and on
individual days, accounting for 49.1 and 37.6% of the total isolates, respectively. These two genotypes were also found at
multiple locations within a bin. All nine genotypes belonged to the phylogenetic group A0 of E. coli, suggesting an animal origin.
The finding that the trimmings carried very few E. coli indicates an overall effective control over contamination of beef with E.
coli at this processing plant. The lack of strain diversity of the E. coli on trimmings suggests that most E. coli isolates may have
come from common sources, most likely equipment used in the fabrication process.

The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more complications. Nine independent variables were included in the investigation as predictors. Logistic regression models were used for Group A [transfusion-dependent thalassaemia (TDT)], Group B [transfused non-TDT (NTDT)] and Group C (non-transfused NTDT). Statistically significant predictors included age (years), haemoglobin levels, hepatic transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase] and left-ventricular ejection fraction (LVEF) for Group A; age (years), age at first chelation (months), ALT and LVEF for Group B; and age (years), mean serum ferritin (SF) levels and LVEF for Group C. The area under the receiver operating characteristic curve was 84·5%, 82·1% and 80·0% for Groups A, Group B and Group C respectively, suggesting the models had good discrimination. Finally, the CoRS for each group was categorised into four risk classes (low, intermediate, high, and very high) using the centiles of its distribution. In conclusion, we have developed a CoRS for TS that can assist physicians in prospectively tailoring patients' treatment.

BACKGROUND: Heterozygous PAX2 mutations cause renal coloboma syndrome (RCS) [OMIM no. 120330]. RCS is a renal syndromic disease encompassing retinal coloboma and sensorineural hearing loss. Recently, a causative role for PAX2 was reported in adult-onset nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS). However, the prevalence of PAX2 mutations among large cohort of children with steroid-resistant nephrotic syndrome (SRNS) and FSGS has not been systematically studied.

METHODS: We employed whole-exome sequencing (WES) to identify the percentage of SRNS cases explained by monogenic mutations in known genes of SRNS/FSGS. As PAX2 mutations are not an established cause of childhood FSGS, we evaluated a cohort of 215 unrelated families with SRNS, in whom no underlying genetic etiology had been previously established.

RESULTS: Using WES, we identified 3 novel causative heterozygous PAX2 mutations in 3 out of the 215 unrelated index cases studied (1.3%). All three cases were detected in individuals from families with more than one affected and compatible with an autosomal dominant mode of inheritance (3/57 familial cases studied (5.2%)). The clinical diagnosis in three out of four pediatric index patients was done during routine medical evaluation.

CONCLUSIONS: Our findings demonstrate high frequency of PAX2 mutations in familial form of SRNS (5.2%) and further expand the phenotypic spectrum of PAX2 heterozygous mutations to include autosomal dominant childhood-onset FSGS. These results highlight the importance of including PAX2 in the list of genes known to cause FSGS in children.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease-causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1 Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease-causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management.

The family of polyhalogenated monoterpenes from Plocamium counts over a hundred known members. Using glyceraldehyde acetonide as a chiral-pool precursor, an enantioselective and divergent strategy was developed that provides a blueprint for the synthesis of many of the small yet complex acyclic members of this family. The broad applicability of this approach is demonstrated with the short, eight-step synthesis of four natural products and three analogues. These syntheses are the first of any members of the acyclic polyhalogenated Plocamium monoterpenes and permitted the evaluation of their selectivity against a range of tumor cell lines.

PURPOSE: We aimed to evaluate the advantages of magnetic resonance angiography (MRA)-planned prostatic artery embolization (PAE) for benign prostatic hyperplasia (BPH).

METHODS: In this retrospective study, MRAs of 56 patients (mean age, 67.23±7.73 years; age range, 47-82 years) who underwent PAE between 2017 and 2018 were evaluated. For inclusion, full information about procedure time and radiation values must have been available. To identify prostatic artery (PA) origin, three-dimensional MRA reconstruction with maximum intensity projection was conducted in every patient. In total, 33 patients completed clinical and imaging follow-up and were included in clinical evaluation.

RESULTS: There were 131 PAs with a second PA in 19 pelvic sides. PA origin was correctly identified via MRA in 108 of 131 PAs (82.44%). In patients in which MRA allowed a PA analysis, a significant reduction of the fluoroscopy time (-27.0%, p = 0.028) and of the dose area product (-38.0%, p = 0.003) was detected versus those with no PA analysis prior to PAE. Intervention time was reduced by 13.2%, (p = 0.25). Mean fluoroscopy time was 30.1 min, mean dose area product 27,749 µGy•m2, and mean entrance dose 1553 mGy. Technical success was achieved in all 56 patients (100.0%); all patients were embolized on both pelvic sides. The evaluated data documented a significant reduction in IPSS (p < 0.001; mean 9.67 points).

CONCLUSION: MRA prior to PAE allowed the identification of PA in 82.44% of the cases. MRA-planned PAE is an effective treatment for patients with BPH.

 The locoregional interventional oncological treatment approach is an accepted modality for liver neoplasms, especially for hepatocellular carcinoma (HCC) and oligonodular liver metastases.  The main aim of ablation therapies like microwave ablation (MWA) is to eradicate all malignant cells in a minimally invasive technique under imaging guidance while preserving the healthy tissue with a sufficient safety margin (at least 5 mm) surrounding the ablated lesion.  Ablation therapy can be performed via a percutaneous, laparoscopic or intraoperative approach under ultrasound, MRI or CT guidance for adequate localization and monitoring of the ablation process.  Ablation is the method of choice for oligonodular HCCs ≤ 3 cm. The technical success rate varies from 88 % to 98 % and progression-free survival (PFS) at 3 years from 27 % to 91.7 %. The same criteria apply to the therapy of liver metastases.   · Careful selection of patients proves to be essential for optimum results of MWA. · Interventionists should be familiar with all aspects of complication and rapid assessment of imaging methods in order to evaluate induced damage by thermal ablation. · MWA seems to have some advantages over radiofrequency ablation, like shorter ablation time, less pain, less heat sink effect; however, scientific proof is needed. · Vogl TJ, Nour-Eldin A, Hammerstingl RM et al. Microwave Ablation (MWA): Basics, Technique and Results in Primary and Metastatic Liver Neoplasms - Review Article. Fortschr Röntgenstr 2017; 189: 1055 - 1066.

IF: 2.240