Maleimide-bearing nanogels as novel mucoadhesive materials for drug delivery

Novel maleimide-functionalised nanogels have been synthesised via the polymerisation of 2,5-dimethylfuran-protected 3-maleimidoethyl butylacrylate in the presence of presynthesised poly(N-vinylpyrrolidone) (PVP) nanogel scaffolds using surfactant-free emulsion polymerisation techniques. The protected maleimide nanogels were subsequently deprotected to generate the reactive maleimide group via a retro-Diels-Alder reaction. These activated nanogels were found to exhibit excellent mucoadhesive properties on ex vivo conjunctival tissue when compared to the known mucoadhesive chitosan. In order to determine the viability of the materials as drug carriers, nanogels were loaded with a model drug compound and the in vitro release kinetics were analysed. The nanogels could sustain the release of a model drug compound over several hours owing to the swellable hydrophilic nanogel structure, exhibiting first order release kinetics. As a consequence, these findings support the potential of these maleimide-bearing nanogels as a novel platform for sustained ocular drug delivery

Persistence of Cyprinid Herpesvirus 3 in Infected Cultured Carp Cells▿

Cyprinid herpesvirus 3 (CyHV-3), previously designated carp interstitial nephritis and gill necrosis virus or koi herpesvirus, is the cause of a worldwide mortal disease of koi and carp. Morphologically, the virus resembles herpesviruses, yet it bears a genome of 277 to 295 kbp, which is divergent from most of the genomic sequences available in GenBank. The disease afflicts fish in the transient seasons, when the water temperature is 18 to 28°C, conditions which permit virus propagation in cultured cells. Here we report that infectious virus is preserved in cultured cells maintained for 30 days at 30°C. CyHV-3-infected vacuolated cells with deformed morphology converted to normal, and plaques disappeared following shifting up of the temperature and reappeared after transfer to the permissive temperature. Viral propagation and viral gene transcription were turned off by shifting cells to the nonpermissive temperature. Upon return of the cells to the permissive temperature, transcription of viral genes was reactivated in a sequence distinguished from that occurring in naïve cells following infection. Our results show that CyHV-3 persists in cultured cells maintained at the nonpermissive temperature and suggest that viruses could persist for long periods in the fish body, enabling a new burst of infection upon a shift to a permissive temperature

Detection of Carp Interstitial Nephritis and Gill Necrosis Virus in Fish Droppings

Carp interstitial nephritis and gill necrosis virus (CNGV) is an unclassified large DNA virus that morphologically resembles members of the Herpesviridae but contains a large (ca. ∼280-kbp) linear double-stranded DNA. This virus has also been named koi herpesvirus, koi herpes-like virus, and cyprinid herpesvirus 3. CNGV is the cause of a lethal disease that afflicts common carp and koi. By using immunohistochemistry, molecular analysis, and electron microscopy we previously demonstrated that this virus is present mainly in the intestine and kidney of infected fish. Based on these observations, we postulated that viruses and/or viral components may appear in droppings of infected carp. Here we report that (i) by using PCR we demonstrated that fish droppings contain viral DNA, (ii) fish droppings contain viral antigens which are useful for CNGV diagnosis, and (iii) fish droppings contain active virus which can infect cultured common carp brain cells and induce the disease in naïve fish following inoculation. Thus, our findings show that CNGV can be identified by using droppings without taking biopsies or killing fish and that infectious CNGV is present in the stools of sick fish. The possibility that fish droppings preserve viable CNGV during the nonpermissive seasons is discussed

Invasive Disease Due to <i>Neisseria meningitidis</i>: Surveillance and Trends in Israel Prior to and during the COVID-19 Pandemic

Invasive meningococcal disease (IMD) is a devastating disease with significant mortality and long-term morbidity. The COVID-19 pandemic and containment measures have affected the epidemiology of infectious pathogens. This study’s aim was to assess IMD trends in Israel prior to and during the COVID-19 pandemic. The Neisseria meningitidis invasive infection is a notifiable disease in Israel. Laboratory analysis includes serogrouping and molecular characterization. The overall national IMD incidence rate (1998–2022) was 0.8/100,000 population. The IMD incidence rates declined during the pandemic years (0.3/100,000 in 2020–2022 vs. 0.9/100,000 in 1998–2019). The number of notified IMD cases declined by 65% in 2020–2022. The case fatality rate among laboratory-confirmed IMD cases was 9% (47/521, 2007–2022). Mortality risk markers included cases’ age (older) and socio-economic status (lower). Overall, most Neisseria meningitidis isolates were of serogroup B (62.6%), and the most prevalent clonal complex (CC) was CC32 (24.2%). Serogroup B prevailed in cases aged 0–9 years (74.5%) and less in cases aged 10 years and above (39%). Neisseria meningitidis serogroups and CC distribution altered recently with a decline in serogroup B fraction, an increase in serogroup Y, and a decline in CC32. Ongoing IMD surveillance is necessary to assess trends in circulating strains and support decision-making on meningococcal vaccination programs

Trends in the Epidemiology of Non-Typhoidal Salmonellosis in Israel between 2010 and 2021

Non-typhoidal salmonellosis (NTS) is one of the most common foodborne diseases worldwide. In this study, we aimed to analyze trends in the epidemiology of NTS in the last decade in Israel. Laboratory-confirmed cases of NTS at eight sentinel laboratories were reported to the Israel Sentinel Laboratory-Based Surveillance Network, integrated with the serotype identification performed at the Salmonella National Reference Laboratory of the Ministry of Health. The decrease in NTS incidence since 1999 continued between 2010 and 2014 (16.1 per 100,000 in 2014) and was interrupted by a rise between 2015 and 2017 (39.1 per 100,000 in 2017) associated with outbreaks of Salmonella Enteritidis. The incidence of NTS dropped again thereafter (21.4 per 100,000 in 2021). The 0–4 age group was the most affected by NTS (55.5% of the cases) throughout the surveillance period. The age-adjusted incidence rates were consistently high in the summer months (June-September) and low in the winter months (December–February). The overall decrease in the incidence of NTS in Israel since 1999 was temporarily interrupted in the last decade by country-wide outbreaks involving emerging or re-emerging Salmonella serotypes. Control measures should be enhanced for all risk points of food chain transmission of Salmonella spp. to further reduce the NTS morbidity in Israel

DataSheet_1_An insight into gill microbiome of Eastern Mediterranean wild fish by applying next generation sequencing.pdf

Bacterial diseases of marine fish inflict significant economic damage to fisheries and aquaculture and pose an increasing risk to public health. When addressing fish disease, an accumulating body of research suggests adding another factor to the classic epidemiological triangle of host-environment-pathogen: the microbiome. The gills, being a gateway into the fish body and bearing an important role in fish homeostasis, have been found to be a proxy of the gut microbiota as well as reflecting the microbial communities of surrounding water. In this study, 16S rRNA amplicons of bacterial DNA extracted from the gills of 89 asymptomatic specimens of three wild fish species (Pagrus caeruleostictus, Scomber colias and Saurida lessepsianus) were sequenced using Next Generation Sequencing methodology (NGS). Data analyses revealed the presence of 41 potentially pathogenic species, including several zoonotic agents. Five genera known to include widespread and potentially pathogenic species were chosen for further investigation: Photobacterium, Shewanella, Staphylococcus, Streptococcus and Vibrio. Of these, Photobacterium and Shewanella proved the most prevalent and abundant, making up 30.2% and 11.3% of the Bluespotted seabream (P. caeruleostictus) gill microbiome alone. Photobacterium damselae and Shewanella baltica were most common at the species level. The remaining genera - Vibrio, Staphylococcus and Streptococcus – were less prevalent, and at a species level were comprised of only 1−4% potentially pathogenic representatives. Gill microbiomes exhibited host species specificity, with strong correlations between certain bacterial taxonomic groups. No definite obligatory pathogenic bacteria were found in this study, and it was suggested that pathogenic species are present as either covert pathobionts or as opportunists of the fish found to host them.</p