High seroprevalence of HCV in the Abruzzo Region,Italy: results on a large sample from opt-out pre-surgical screening

Purpose

Available estimates of the prevalence of chronic HCV infection in Italy are quite conflicting, varying from 1.5 to 22.5 %, with an apparent north to south gradient. As Direct Acting Antivirals are expensive, both National and local governmental Agencies are in urgent need of detailed and reliable estimates of HCV patients to be treated, nationwide and in each district. We investigated the prevalence of anti-HCV antibodies in a large unselected sample of surgical patients providing consent to in-hospital opt-out pre-surgical HCV screening, at two hospitals from the Abruzzo Region, Italy.

Methods

Data were retrieved for 55,533 screened patients (4.1 % of the total population in the Abruzzo Region), admitted in the Orthopedic and General Surgery wards of Pescara and Teramo Hospitals from 1999 to 2014.

Results

The prevalence of anti-HCV antibodies was 4.4 % in the total sample. HCV-positive patients had a mean age of 63.8 ± 19.9 years; 49.2 % were males. From 1999 to 2014, the prevalence of HCV antibodies decreased from 5.4 % to 4.1 %; at both sites, however, two age-related-peaks were evidenced, the first among patients aged 30–49 years, the second among those older than 70 years. Statistical analyses confirmed a significant trend to decrease over time and a higher prevalence in Pescara and among males (all p < 0.01).

Conclusions

Data retrieved from opt-out pre-surgical screening programs may allow inexpensive and easy-to-perform estimates of HCV seroprevalence from large samples of unselected patients with a well-defined provenience, which may turn useful for future treatment resource allocation.

     

Salt–water imbalance and fluid overload in hemodialysis patients: a pivotal role of corin

Clinical and Experimental Medicine - Natriuretic peptides (NP) play a key role in regulation of salt and water balance. Corin, a serine protease which activates NP, plays a key role in regulation...     

Ethosomes and organogels for cutaneous administration of crocin

The present study describes the production and characterization of phosphatidylcholine based ethosomes and organogels, as percutaneous delivery systems for crocin. Crocin presence did not influence ethosome morphology, while the drug slightly increased ethosome mean diameter. Importantly, the poor chemical stability of crocin has been found to be long controlled by organogel. To investigate the performance of phosphatidylcholine lipid formulations as crocin delivery system, in vivo studies, based on tape stripping and skin reflectance spectrophotometry, were performed. Tape stripping results suggested a rapid initial penetration of crocin exerted by the organogel, probably due to a strong interaction between the peculiar supramolecular aggregation structure of phospholipids in the vehicle and the lipids present in the stratum corneum and a higher maintenance of crocin concentration in the case of ethosomes, possibly because of the formation of a crocin depot in the stratum corneum. Skin reflectance spectrophotometry data indicated that both vehicles promoted the penetration of crocin through the skin, with a more rapid anti-inflammatory effect exploited by ethosomes, attributed to an ethanol pronounced penetration enhancer effect and to the carrier system as a whole.     

Effect of Recombinant Human Nerve Growth Factor on Cisplatin Neurotoxicity in Rats

In this study we evaluated the effect of recombinant human nerve growth factor (rhNGF) on cisplatin (CDDP)-induced sensory neuronopathy in an experimental paradigm in the rat. Young adult female Wistar rats were treated with CDDP (2 mg/kg ip twice weekly for nine times) alone or in combination with rhNGF (1 mg/kg sc on alternate days). The effect of CDDP +/- NGF treatment was evaluated with behavioral (tail-flick test) and neurophysiological (nerve conduction velocity in the tail) methods immediately after treatment and after a follow-up period of 6 weeks. Pathological and morphometrical examinations of the dorsal root ganglia (DRG) and sciatic and saphenous nerves were also performed. rhNGF treatment induced a significant reduction in the CDDP-induced decrease in nerve conduction velocity (P < 0.05), and this was associated with a significant protection against the decrease in somatic (P < 0.05), nuclear (P < 0.05), and nucleolar size (P < 0.01) caused by CDDP treatment. However, for each of the parameters examined the neuroprotection obtained with rhNGF treatment was not complete. At the follow-up examination no differences between the three groups were observed in tail-flick test and nerve conduction velocity. We conclude that rhNGF, administered according to the schedule used in this experiment, exerts a biologically significant neuroprotective effect against CDDP peripheral neurotoxicity.     

Impact of body mass index on hepatocellular carcinoma recurrence after liver transplantation through long-term follow-up

BackgroundObesity is associated with increased oncological risk and outcomes but the evidence surrounding the effect of body mass index (BMI) on increased risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is still questionable. The purpose of this retrospective study of a large cohort of adult patients transplanted for HCC was to investigate the effect of BMI on the incidence of HCC recurrence and outcome.MethodsData from 427 adult recipients transplanted for HCC between 2000 and 2017 were collected. Patients were classified at time of LT according to the World Health Organization BMI classification into 3 groups; group 1: BMI <25 (n=166), group 2: BMI 25–29.9 (n=150) and group 3: BMI ≥30 (n=111).ResultsThere were no significant changes of mean BMI overtime 26.8±5.0 kg/m2 at time of LT and 28.8±23.1 at 5 years. The recurrence rates of HCC after LT in the three groups were 19%, 16% and 17% respectively. The 5, 10 and 15-year recurrence free survival (RFS) rates were respectively 68.6%, 47.3% and 40.8% in group 1, 73.3%, 66.2% and 49.5% in group 2 and 68.8%, 57.5% and 47.7% in group 3 (log rank P=0.47).ConclusionsRecipient BMI at time of transplant and during follow-up didn’t impact the incidence of HCC recurrence nor long-term patient survival, irrespective to the status of the patients and their tumor characteristic at time of LT. The present study clearly confirms that obesity should not be considered, when selecting patients with HCC to LT, as a predictive factor of recurrence.     

Long first metacarpal in monozygotic twins with probable Baller-Gerold syndrome

We report on a pair of monozygotic twins with probable Baller-Gerold syndrome (BGS). Twin A had severe coronal craniosynostosis. Twin B had right radioulnar and ipsilateral first metacarpal hypoplasia. Both had bilateral fifth finger clinodactyly. Assuming that the twins were truly monozygotic, a single genetic disorder (i.e., BGS) could explain the variable expression. Together the twins have the typical anomalies of BGS. The diagnosis was supported by the metacarpophalangeal profile (MPP) which confirmed hypoplasia of the first right metacarpal in Twin A and bilateral fifth finger brachymesophalangy in both twins. Furthermore, the MPP showed an unexpected abnormal lengthening of the first metacarpal (unilateral in Twin A and bilateral in Twin B), a previously undetected radial ray defect in BGS. These findings suggest the possibility that the MPP may assist recognition of mild cases of BGS such as those with apparently isolated craniosynostosis or isolated upper limbs defects. Am. J. Med. Genet. 80:303–308, 1998. © 1998 Wiley-Liss, Inc.     

An ancient antimicrobial protein co-opted by a fungal plant pathogen for in planta mycobiome manipulation

Microbes typically secrete a plethora of molecules to promote niche colonization. Soil-dwelling microbes are well-known producers of antimicrobials that are exploited to outcompete microbial coinhabitants. Also, plant pathogenic microbes secrete a diversity of molecules into their environment for niche establishment. Upon plant colonization, microbial pathogens secrete so-called effector proteins that promote disease development. While such effectors are typically considered to exclusively act through direct host manipulation, we recently reported that the soil-borne, fungal, xylem-colonizing vascular wilt pathogen Verticillium dahliae exploits effector proteins with antibacterial properties to promote host colonization through the manipulation of beneficial host microbiota. Since fungal evolution preceded land plant evolution, we now speculate that a subset of the pathogen effectors involved in host microbiota manipulation evolved from ancient antimicrobial proteins of terrestrial fungal ancestors that served in microbial competition prior to the evolution of plant pathogenicity. Here, we show that V. dahliae has co-opted an ancient antimicrobial protein as effector, named VdAMP3, for mycobiome manipulation in planta. We show that VdAMP3 is specifically expressed to ward off fungal niche competitors during resting structure formation in senescing mesophyll tissues. Our findings indicate that effector-mediated microbiome manipulation by plant pathogenic microbes extends beyond bacteria and also concerns eukaryotic members of the plant microbiome. Finally, we demonstrate that fungal pathogens can exploit plant microbiome-manipulating effectors in a life stage–specific manner and that a subset of these effectors has evolved from ancient antimicrobial proteins of fungal ancestors that likely originally functioned in manipulation of terrestrial biota.

Microbes are found in a wide diversity of niches on our planet. To facilitate establishment within microbial communities, microbes secrete a multitude of molecules to manipulate each other. Many of these molecules exert antimicrobial activities and are exploited to directly suppress microbial coinhabitants in order to outcompete them for the limitedly available nutrients and space of a niche. Microbially secreted antimicrobials encompass diverse molecules including peptides and lytic enzymes but also nonproteinaceous molecules such as secondary metabolites. Soils are among the most biologically diverse and microbially competitive environments on earth. Microbial proliferation in the soil environment is generally limited by the availability of organic carbon (1), for which soil microbes continuously compete. Consequently, numerous saprophytic soil-dwelling microbes secrete potent antimicrobials that promote niche protection or colonization. Notably, these microbes are the primary source of our clinically used antibiotics (2, 3).Like free-living microbes, microbial plant pathogens also secrete a multitude of molecules into their environment to mediate niche colonization (4, 5). The study of molecules secreted by microbial plant pathogens has been largely confined to the context of binary interactions between pathogens and hosts. To establish disease, plant pathogenic microbes secrete a plethora of so-called effectors, molecules of various kinds that promote host colonization and that are typically thought to mainly deregulate host immune responses (4, 6, 7). Upon host colonization, plant pathogens encounter a plethora of plant-associated microbes that collectively form the plant microbiota, which represent a key factor for plant health. Beneficial plant-associated microbes are found in and on all organs of the plant and help to mitigate (a)biotic stresses (8–13). Plants shape their microbiota and specifically attract beneficial microbes to suppress pathogens (14–16). Hence, the plant microbiome can be considered an inherent, exogenous layer that complements the plant’s endogenous innate immune system. We previously hypothesized that plant pathogens not only utilize effectors to target components of host immunity as well as other aspects of host physiology to support host colonization but also to target the host microbiota in order to establish niche colonization (4, 5). We recently provided experimental evidence for this hypothesis by showing that the ubiquitously expressed effector VdAve1 that is secreted by the soil-borne fungal plant pathogen Verticillium dahliae acts as a bactericidal protein that promotes host colonization through the selective manipulation of host microbiomes by suppressing microbial antagonists (17, 18). Additionally, we demonstrated that VdAve1 and a further antibacterial effector named VdAMP2 are exploited by V. dahliae for microbial competition in soil and promote virulence of V. dahliae in an indirect manner (18). Collectively, these observations demonstrate that V. dahliae dedicates part of its effector catalog toward microbiota manipulation. Likely, the V. dahliae genome encodes further effectors that act in microbiome manipulation.Evidently, bacterial and fungal evolution on land preceded land plant evolution. As a consequence, fungal pathogen effectors involved in the manipulation of (host-associated) microbial communities may have evolved from ancestors that served in microbial competition in terrestrial niches hundreds of millions of years ago prior to land plant evolution. However, evidence for this hypothesis is presently lacking.V. dahliae is an asexual xylem-dwelling fungus that causes vascular wilt disease on hundreds of plant species (19). The fungus survives in the soil in the form of multicellular melanized resting structures, called microsclerotia, that offer protection against (a)biotic stresses and can persist in the soil for many years (20). Microsclerotia represent the major inoculum source of V. dahliae in nature, and their germination is triggered by carbon- and nitrogen-rich exudates from plant roots (21). Following microsclerotia germination, fungal hyphae grow through the soil and rhizosphere toward the roots of host plants. Next, V. dahliae colonizes the root cortex and crosses the endodermis, from which it invades xylem vessels. Once the fungus enters those vessels, it forms conidiospores that are transported with the water flow until they get trapped, for instance, by vessel end walls. This triggers germination of the conidiospores followed by penetration of cell walls, hyphal growth, and renewed sporulation, leading to systematic colonization of the plant (22). Once tissue necrosis commences and plant senescence occurs, host immune responses fade and V. dahliae enters a saprophytic phase in which it emerges from the xylem vessels to invade adjacent host tissues, which is accompanied by the production of microsclerotia. Upon littering and decomposition of plant tissues, these microsclerotia are released into the soil (23).     

Towards a Precision Medicine Approach and In Situ Vaccination against Prostate Cancer by PSMA-Retargeted oHSV

Prostate specific membrane antigen (PSMA) is a specific high frequency cell surface marker of prostate cancers. Theranostic approaches targeting PSMA show no major adverse effects and rule out off-tumor toxicity. A PSMA-retargeted oHSV (R-405) was generated which both infected and was cytotoxic exclusively for PSMA-positive cells, including human prostate cancer LNCaP and 22Rv1 cells, and spared PSMA-negative cells. R-405 in vivo efficacy against LLC1-PSMA and Renca-PSMA tumors consisted of inhibiting primary tumor growth, establishing long-term T immune response, immune heating of the microenvironment, de-repression of the anti-tumor immune phenotype, and sensitization to checkpoint blockade. The in situ vaccination protected from distant challenge tumors, both PSMA-positive and PSMA-negative, implying that it was addressed also to LLC1 tumor antigens. PSMA-retargeted oHSVs are a precision medicine tool worth being additionally investigated in the immunotherapeutic and in situ vaccination landscape against prostate cancers.