Immunogenicity and safety of live attenuated and recombinant/inactivated varicella zoster vaccines in people living with HIV: A systematic review.

Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.

Effect of Intravitreal Brolucizumab in the Treatment of Polypoidal Choroidal Vasculopathy With Foveal Lipid Exudation.

A 71-year-old woman with a history of blurred vision in her right eye for nearly two months came to our attention. A complete ophthalmological evaluation, including best-corrected visual acuity measurement, fundus examination, spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography, was performed. Multimodal imaging showed the presence of a polypoidal choroidal vasculopathy (PCV) lesion surrounded by diffuse hard exudates in the macular area. Our patient received three monthly intravitreal injections of brolucizumab during the loading phase, followed by an intravitreal injection every eight weeks for a total of 48 weeks of follow-up. The therapy appeared to be effective for improving both visual and anatomical outcomes revealing an important regression of the PCV and an almost complete reabsorption of lipid exudates. Intravitreal brolucizumab could be considered an effective treatment in the management of lipid exudation in PCV patients.

Bacterial and fungal superinfections are detected at higher frequency in critically ill patients affected by SARS CoV-2 infection than negative patients and are associated to a worse outcome.

Patients with viral infections are at higher risk to acquire bacterial and fungal superinfections associated with a worse prognosis. We explored this critical point in the setting of patients with severe COVID-19 disease. The study included 1911 patients admitted to intensive care unit (ICU) during a 2-year study period (March 2020-March 2022). Of them, 713 (37.3%) were infected with SARS-CoV-2 and 1198 were negative (62.7%). Regression analysis was performed to determine risk factors associated with the presence of bacterial and/or fungal superinfections in SARS-CoV-2 patients and to evaluate predictors of ICU mortality. Of the 713 patients with SARS-CoV-2 infection, 473 (66.3%) had respiratory and/or bloodstream bacterial and/or fungal superinfections, while of the 1198 COVID-19-negative patients, only 369 (30%) showed respiratory and/or bloodstream bacterial and/or fungal superinfections (p < 0.0001). Baseline characteristics of COVID-19 patients included a median age of 66 (interquartile range [IQR], 58-73), a predominance of males (72.7%), and the presence of a BMI higher than 24 (median 26; IQR, 24.5-30.4). Seventy-four percent (527, 73.9%) had one or more comorbidities and 135 (18.9%) of them had received previous antibiotic therapy. Furthermore, most of them (473, 66.3%) exhibited severe radiological pictures and needed invasive mechanical ventilation. Multivariate logistic regression analysis showed that 1 unit increment in BMI rises the risk of bacterial and/or fungal superinfections acquisition by 3% and 1-day increment in ICU stays rises the risk of bacterial and/or fungal superinfections acquisition by 11%. Furthermore, 1-day increment in mechanical ventilation rises the risk of bacterial and/or fungal superinfection acquisition by 2.7 times. Furthermore, patients with both bacterial and fungal infections had a significantly higher mortality rate than patients without superinfections (45.8% vs. 26.2%, p < 0.0001). Therefore, bacterial and fungal superinfections are frequent in COVID-19 patients admitted to ICU and their presence is associated with a worse outcome. This is an important consideration for targeted therapies in critically ill SARS-CoV-2 infected patients to improve their clinical course.

Two-port dry vitrectomy for rhegmatogenous retinal detachment: a pilot study.

OBJECTIVE: To evaluate the safety and efficacy of a new surgical technique for the management of primary rhegmatogenous retinal detachment (RRD), consisting of localized PPV near the retinal break(s), without infusion line, associated with a drainage of subretinal fluid and cryoretinopexy. METHODS: Multicentric prospective study conducted at the University Hospital of Cagliari and IRCCS Fondazione Policlinico Universitario A. Gemelli, Roma. Twenty eyes affected by RRD with the causative retinal break(s) in the superior meridians were enrolled between February 2022 and June 2022. Patients with cataract ≥3, aphakia, significant posterior capsule opacification, giant retinal tears, retinal dialysis, history of trauma and PVR ≥C2 were excluded. All eyes underwent a two-port 25-gauge PPV with localized removal of the vitreous surrounding retinal break(s), followed by 20% SF6 injection and cryopexy. The surgical time was recorded for each procedure. Best-corrected visual acuity (BCVA) was measured at baseline and postoperative 6 months. RESULTS: Primary anatomic success at 6 months was achieved by 85% of patients. No complications occurred, except for three (15%) retinal re-detachments. The average surgical time was 8.61 ± 2.16 min. Overall, the difference between pre- and last postoperative mean BCVA was statistically significant (p = 0.02). CONCLUSIONS: Two-port dry PPV demonstrated safety and efficacy for the treatment of RRD, reaching an 85% of anatomical success rate. Although further studies are necessary to confirm the efficacy and long-term benefit of this treatment, we believe that this surgical technique could be considered a valid and safe alternative for the management of primary RRD.

Varicella-Zoster Virus Prevalence among Pregnant Women: A European Epidemiological Review.

Europe has faced a massive spread of the varicella-zoster virus through the years. Since the introduction of an effective vaccine, complications and severe forms of chickenpox have been restricted. Nevertheless, among the population, some categories need specific care, such as pregnant women, who present one of the most fragile conditions facing this infection, both for the mother and the fetus. In this review, we highlight how the varicella-zoster virus can be dangerous during pregnancy, underlining the problem of treatment and vaccination, and collect information about the European epidemiology among this particular category of women.

Detection of Hepatitis A Virus and Norovirus in Different Food Categories: A 6-Year Survey in Italy.

To observe the prevalence of contamination by hepatitis A virus (HAV) and norovirus (NoV) in different food types, 9242 samples were analyzed over a 6-year period (January 2014-December 2019). Samples were from routine official activities by Competent Authorities (CAs) and Food Business Operators, according to Hazard Analysis and Critical Control Points plans. Analyses were performed in accordance with European and Italian regulations. Food types were obtained from different production areas of Italy, and ranged from mollusks, ready-to-eat (RTE) and packaged vegetables, frozen berries, tap water, fruit and RTE fruit salads, and processed and preserved foods. No risk management plans were set by the authors' laboratory, because they were still adopted by conferring customers. Analyses were conducted according to ISO/TS 15216-2:2013 (ISO in Part 2: Method for Qualitative Detection. International Organization for Standardization, Geneva, 2013). The data showed that 2.25% (95% CI: 2.0-2.6) of samples were contaminated by at least one virus type, and that the most detected pathogen was NoV GII (89.50% of all positives). Mollusks (filter-feeding animals) were the most contaminated category (92.31% of all positives) not only by NoV or HAV individually, but also by multiple HAV/NoV contaminations consisting of 22.59% of all positives. For NoV, there was a significant correlation between shellfish positivity and season, with the autumn-winter period being the most associated with risk. Conversely, berries, drinking water and RTE vegetables, previously linked to several outbreaks, showed a low rate of contamination. These results from data collection have implications for the improvement of sampling plans for HAV and NoV by Italian CAs, and by food-producing and distribution operators. Moreover, these findings obtained by a standardized qualitative method contribute the collection of data aimed at establishing new microbiological criteria not yet foreseen (but advocated) by current European rules.

One-Day Molecular Detection of Salmonella and Campylobacter in Chicken Meat: A Pilot Study.

Salmonella and Campylobacter ssp. are bacterial pathogens responsible for most foodborne infections in EU countries. Poultry serves as a reservoir for these pathogens, and its important role in the meat industry makes it essential to develop a rapid detection assay able to provide results in one day. Indeed, the rapid identification of foodborne pathogens is an important instrument for the monitoring and prevention of epidemic outbreaks. To date, Salmonella and Campylobacter screening is mainly conducted through molecular methods (PCR or real-time PCR) performed after 18-24 h long enrichments. In this study, we evaluated short enrichments (0, 2, 4, and 6 h) combined with a colorimetric loop-mediated isothermal AMPlification (LAMP) or real-time PCR to detect Salmonella and Campylobacter in poultry meat contaminated at different concentration levels (101, 103, and 105 CFU/g). Our results show that real-time PCR allows the detection of Salmonella and Campylobacter, even after shorter enrichment times than prescribed by ISO references; particularly, it detected Salmonella down to 101 CFU/g since T0 and Campylobacter from 103 CFU/g since T0. Detection with LAMP was comparable to real-time PCR without the requirement of a thermal cycler and with shorter execution times. These characteristics make colorimetric LAMP a valid alternative when one-day results are needed, improving the timely identification of positive meat batches, even in the absence of specialized instrumentation.

Hepatitis E Virus (HEV) Spread and Genetic Diversity in Game Animals in Northern Italy.

Hepatitis E virus (HEV) is the causative agent of hepatitis E, an emerging public health infection which has an increasing incidence across Europe. Because of the apparent lack of species barriers, HEV was characterized as a zoonotic agent. Swine are recognized as the main reservoir, but HEV is also found in wild animals such as ungulates, lagomorphs, and bats. Our work aimed at detecting the HEV presence in wild fauna in two hunting areas of Northern Italy (Parma and Sondrio areas) with different environmental and anthropic characteristics to investigate its possible role as reservoir. Liver samples were collected from wild boars, red deer, roe deer and chamois, and viral identification was carried out by One-Step RT Real-time PCR. Positive samples were genotyped, and phylogenetic analysis was performed. The virus was found only in the wild boar population, with different prevalence and subtypes in the two areas (14% HEV3a and 1.2% close to HEV3f in Parma and Sondrio, respectively). Wild ruminants seem otherwise to pose a marginal risk. Given the high pig farm density in the Parma area, and expansion of the wild boar population, continuous monitoring of the strains circulating in wildlife is crucial.

Geographical restriction of Hepatitis E virus circulation in wild boars (Sus scrofa) in Emilia-Romagna region, Northern Italy.

Hepatitis E virus (HEV) is a singlestrand RNA virus that causes an acute viral hepatitis in humans. Among its eight recognized genotypes, HEV-3 and HEV-4 are zoonotic, infecting humans, pigs and wild boars. Recently, HEV-3 has been also detected in red deer, which represents another reservoir of HEV. Consumption of raw pork products (mainly liver sausages), undercooked wild boar meat, raw wild boar liver and deer meat has been responsible for foodborne HEV human worldwide. From November 2018 to March 2019, liver samples collected from 97 wild boars hunted in Emilia-Romagna region (Northern Italy) were tested for HEV RNA. The hunting area included two territories for an extension of 33 km2, named A (about 13 km2,natural park, deciduous wood) and B (about 20 km2, cultivated fields in proximity of a river) areas. Distance between the two areas ranged between 8 to 10 km. A total of 73 wild boars were hunted in area A, and 24 in area B. HEV RNA was detected by Real-time RT- PCR in 23/73 liver samples of wild boars living in area A only (31.5% - 95% CI: 22.0-42.8%). The HEV sequences (n=13) clustered within genotype 3. The majority of positives belonged to animals < 12 months (12/25; 48%), followed by subadults (13-24 months) (7/16; 43.8%) and adults (4/32; 12.5%). This difference was found to be statistically significant (p=0.0024). In absence of pig farms, the restriction of HEV-positive animals to a well-defined territory of 13 km2 (Boschi di Carrega Regional Park) could hypothetically be related to the presence of red deer (Cervus elaphus), which lived in area A at the beginning of the hunting season. Further studies are needed to confirm or deny our hypothesis.

Time-scaled phylogeography of complete Zika virus genomes using discrete and continuous space diffusion models.

Zika virus (ZIKV), a vector-borne infectious agent that has recently been associated with neurological diseases and congenital microcephaly, was first reported in the Western hemisphere in early 2015. A number of authors have reconstructed its epidemiological history using advanced phylogenetic approaches, and the majority of Zika phylogeography studies have used discrete diffusion models. Continuous space diffusion models make it possible to infer the possible origin of the virus in real space by reconstructing its ancestral location on the basis of geographical coordinates deduced from the latitude and longitude of the sampling locations. We analysed all the ZIKV complete genome isolates whose sampling times and localities were available in public databases at the time the study began, using a Bayesian approach for discrete and continuous phylogeographic reconstruction. The discrete phylogeographic analysis suggested that ZIKV emerged to become endemic/epidemic in the first decade of the 1900s in the Ugandan rainforests, and then reached Western Africa and Asia between the 1930s and 1950s. After a long period of about 40 years, it spread to the Pacific islands and reached Brazil from French Polynesia. Continuous phylogeography of the American epidemic showed that the virus entered in north-eastern Brazil in late 2012 and started to spread in early 2013 from two high probability regions: one corresponding to the entire north-east Brazil and the second surrounding the city of Rio de Janeiro, in a mainly northwesterly direction to Central America, the north-western countries of south America and the Caribbean islands. Our data suggest its cryptic circulation in both French Polynesia and Brazil, thus raising questions about the mechanisms underlying its undetected persistence in the absence of a known animal reservoir, and underline the importance of continuous diffusion models in making more reliable phylogeographic reconstructions of emerging viruses.

Reconstructing the recent West Nile virus lineage 2 epidemic in Europe and Italy using discrete and continuous phylogeography.

West Nile virus lineage 2 (WNV-2) was mainly confined to sub-Saharan Africa until the early 2000s, when it was identified for the first time in Central Europe causing outbreaks of human and animal infection. The aim of this study was to reconstruct the origin and dispersion of WNV-2 in Central Europe and Italy on a phylodynamic and phylogeographical basis. To this aim, discrete and continuous space phylogeographical models were applied to a total of 33 newly characterised full-length viral genomes obtained from mosquitoes, birds and humans in Northern Italy in the years 2013-2015 aligned with 64 complete sequences isolated mainly in Europe. The European isolates segregated into two highly significant clades: a small one including three sequences and a large clade including the majority of isolates obtained in Central Europe since 2004. Discrete phylogeographical analysis showed that the most probable location of the root of the largest European clade was in Hungary a mean 12.78 years ago. The European clade bifurcated into two highly supported subclades: one including most of the Central/East European isolates and the other encompassing all of the isolates obtained in Greece. The continuous space phylogeographical analysis of the Italian clade showed that WNV-2 entered Italy in about 2008, probably by crossing the Adriatic sea and reaching a central area of the Po Valley. The epidemic then spread simultaneously eastward, to reach the region of the Po delta in 2013, and westward to the border area between Lombardy and Piedmont in 2014; later, the western strain changed direction southward, and reached the central area of the Po valley once again in 2015. Over a period of about seven years, the virus spread all over an area of northern Italy by following the Po river and its main tributaries.

A pentasymmetric open channel blocker for Cys-loop receptor channels.

γ-Aminobutyric acid type A receptors (GABAA receptors) are chloride ion channels composed of five subunits, mediating fast synaptic and tonic inhibition in the mammalian brain. These receptors show near five-fold symmetry that is most pronounced in the second trans-membrane domain M2 lining the Cl- ion channel. To take advantage of this inherent symmetry, we screened a variety of aromatic anions with matched symmetry and found an inhibitor, pentacyanocyclopentdienyl anion (PCCP-) that exhibited all characteristics of an open channel blocker. Inhibition was strongly dependent on the membrane potential. Through mutagenesis and covalent modification, we identified the region α1V256-α1T261 in the rat recombinant GABAA receptor to be important for PCCP- action. Introduction of positive charges into M2 increased the affinity for PCCP- while PCCP- prevented the access of a positively charged molecule into M2. Interestingly, other anion selective cys-loop receptors were also inhibited by PCCP-, among them the Drosophila RDL GABAA receptor carrying an insecticide resistance mutation, suggesting that PCCP- could serve as an insecticide.

Azo-propofols: photochromic potentiators of GABA(A) receptors.

Shine and rise! GABA(A) receptors are ligand-gated chloride ion channels that respond to γ-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter of the mammalian central nervous system. Azobenzene derivatives of propofol, such as compound 1 (see scheme), increase GABA-induced currents in the dark form and lose this property upon light exposure and thus function as photochromic potentiators. Compound 1 can be employed as a light-dependent general anesthetic in translucent tadpoles.

TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development.

TRPM channels have emerged as key mediators of diverse physiological functions. However, the ionic permeability relevant to physiological function in vivo remains unclear for most members. We report that the single Drosophila TRPM gene (dTRPM) generates a conductance permeable to divalent cations, especially Zn(2+) and in vivo a loss-of-function mutation in dTRPM disrupts intracellular Zn(2+) homeostasis. TRPM deficiency leads to profound reduction in larval growth resulting from a decrease in cell size and associated defects in mitochondrial structure and function. These phenotypes are cell-autonomous and can be recapitulated in wild-type animals by Zn(2+) depletion. Both the cell size and mitochondrial defect can be rescued by extracellular Zn(2+) supplementation. Thus our results implicate TRPM channels in the regulation of cellular Zn(2+) in vivo. We propose that regulation of Zn(2+) homeostasis through dTRPM channels is required to support molecular processes that mediate class I PI3K-regulated cell growth.

Responses to environmental enrichment differ with sex and genotype in a transgenic mouse model of Huntington's disease.

BACKGROUND: Environmental enrichment (EE) in laboratory animals improves neurological function and motor/cognitive performance, and is proposed as a strategy for treating neurodegenerative diseases. EE has been investigated in the R6/2 mouse model of Huntington's disease (HD), where increased social interaction, sensory stimulation, exploration, and physical activity improved survival. We have also shown previously that HD patients and R6/2 mice have disrupted circadian rhythms, treatment of which may improve cognition, general health, and survival. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects of EE on the behavioral phenotype and circadian activity of R6/2 mice. Our mice are typically housed in an "enriched" environment, so the EE that the mice received was in addition to these enhanced housing conditions. Mice were either kept in their home cages or exposed daily to the EE (a large playground box containing running wheels and other toys). The "home cage" and "playground" groups were subdivided into "handling" (stimulated throughout the experimental period) and "no-handling" groups. All mice were assessed for survival, body weight, and cognitive performance in the Morris water maze (MWM). Mice in the playground groups were more active throughout the enrichment period than home cage mice. Furthermore, R6/2 mice in the EE/no-handling groups had better survival than those in the home cage/no-handling groups. Sex differences were seen in response to EE. Handling was detrimental to R6/2 female mice, but EE increased the body weight of male R6/2 and WT mice in the handling group. EE combined with handling significantly improved MWM performance in female, but not male, R6/2 mice. CONCLUSIONS/SIGNIFICANCE: We show that even when mice are living in an enriched home cage, further EE had beneficial effects. However, the improvements in cognition and survival vary with sex and genotype. These results indicate that EE may improve the quality of life of HD patients, but we suggest that EE as a therapy should be tailored to individuals.