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During the investigations on ticks and tick-borne pathogens (TBP) range expansion in the Northern Apennines, we captured 107 Podarcis muralis lizards. Sixty-eight animals were infested by immature Ixodes ricinus, Haemaphysalis sulcata and H. punctata. Borrelia burgdorferi s.l. was detected in 3.7% of I. ricinus larvae and 8.0% of nymphs. Together with the species-specific B. lusitaniae, we identified B. garinii, B. afzelii and B. valaisiana. Rickettsia spp . (18.1% larvae, 12.0% nymphs), namely R. monacensis, R. helvetica and R. hoogstraalii, were also found in I. ricinus. R. hoogstraalii was detected in H. sulcata nymphs as well, while the two H. punctata did not harbour any bacteria. One out of 16 lizard tail tissues was positive to R. helvetica. Our results support the hypothesis that lizards are involved in the epidemiological cycles of TBP. The heterogeneity of B. burgdorferi genospecies mirrors previous findings in questing ticks in the area, and their finding in attached I. ricinus larvae suggests that lizards may contribute to the maintenance of different genospecies. The rickettsiae are new findings in the study area, and R. helvetica infection in a tail tissue indicates a systemic infection. R. hoogstraalii is reported for the first time in I. ricinus ticks. Lizards seem to favour the bacterial exchange among different tick species, with possible public health consequences. [ABSTRACT FROM AUTHOR]

This study aimed to determine the impact of a novel formulation of a supplement composed of the natural ingredients, bromelain, quercetin, and Lentinula edodes , on the gut microbiota of healthy adult dogs. Adult healthy female dogs were administered either a placebo (CTR, n = 15) or the supplement (TRT, n = 15) over 28 days. Stool samples were collected for 16S rRNA sequencing before supplement administration (T0), at completion of supplement administration (T28), and one week after the end of supplement administration (T35) to characterize changes in the gut microbial communities. QIIME was used to determine both alpha- and beta-diversity, and ANCOM-BC was used to identify differences in taxonomic abundances before and after supplementation. We found a significant decrease in overall diversity in the CTR group but no significant differences in overall diversity in the TRT group over time. Furthermore, we found differences in the abundance of several taxa in both the CTR and TRT groups, but differences in the abundance of beneficial bacteria were more pronounced in the TRT group. Specifically, we found increases in the abundance of sequences belonging to the genera Bifidobacterium , Lactobacillus , and Pediococcus at T28 in the TRT group with significant increases in Bifidobacterium and Lactobacillus persisting at T35 when compared to T0. Importantly, members of these genera are considered important for their anti-inflammatory properties, vital for fostering a balanced and robust gut microbiota in dogs. The results of our study show the potential of our supplement to selectively enhance specific beneficial bacterial taxa, offering a targeted approach to modulating the gut microbiome without causing disruptions to the overall equilibrium., Competing Interests: The authors declare no conflicts of interest.

Overweight and obese dogs can develop metabolic dysfunction, characterized by an inflammatory response and involvement of liver functions. If a modulation of the gut microbiome and its interaction with the gut-liver axis is implicated in the development of metabolic dysfunction, exploration becomes necessary. Over the past decade, diverse therapeutic approaches have emerged to target pathogenic factors involved in metabolic dysfunction. This study investigated the impact of a supplement with hepatoprotective activity, containing extracts of Silybum marianum , prebiotics, probiotics, n-3 polyunsaturated fatty acids, vitamins, and minerals on hematological markers of liver functions and inflammation, as well as on the intestinal microbiota of 10 overweight adult dogs over a 35-day time span. Animals underwent clinical and laboratory evaluations every 7 days, both before the administration of the supplement (T0) and after 7, 14, 21, 28, and 35 days (T1, T2, T3, T4, and T5). In comparison to T0, a significant ( p < 0.05) decrease in ALP, glucose, direct bilirubin, and CRP was observed from T3 to T5. The alpha diversity of the fecal microbiota significantly decreased ( p < 0.05) only at T1, with high variability observed between dogs. Total short-chain fatty acid and lactic acid were also lower at T1 ( p < 0.05) compared to the other times of sampling. The beta diversity of the fecal microbiota failed to show a clear pattern in relation to the sampling times. These results of blood parameters in overweight dogs show a reduction of the inflammation and an improvement of metabolic status during the study period, but the effective contribution of the supplement in this clinical outcome deserves further investigation. Furthermore, the considerable individual variability observed in the microbiome hinders the confident detection of supplement effects.

Food supplements are a category of products perceived safe and therefore commonly used by different categories of consumers without any particular attention or precaution. However, health risks associated with the consumption of supplements containing undeclared substances cannot be excluded. A variety of analytical methods are used to control supplement quality composition, but usually, these procedures are complex and time-consuming. Here, we report the results of a simple and fast liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, to detect and quantify simultaneously different categories of active molecules, such as biogenic ammines and natural alkaloids that at high doses can produce negative health effect in consumers. Three categories of products intended for body weight loss, energy boosting, and erectile dysfunction treatment, purchased through e-commerce sites and from local supermarkets, were analyzed (n = 91). The caffeine, synephrine, agmatine sulfate, yohimbine, phenethylamine, and icariin were correctly separated and identified with good precision (RSD < 20%) and recovery (89-109%). The identification and quantification of the analytes in real samples highlighted that the 26% of the samples were not compliant with labeling, confirming that frauds are very common also in the natural supplements market. This LC-MS/MS method could be easily used to test natural supplements in order to check the correct labeling and to protect consumers from potential health risks and food frauds., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Oxidative stress causes several pathological conditions in humans and animals, including gastrointestinal disorders. The aim of this study was to analyze the antioxidant capacity of three natural powdered raw materials containing quercetin, bromelain, and Lentinula edodes and develop a new feed supplement for dogs using a combination of them. The total phenolic content (TPC), antioxidant activity, DPPH (2,2-diphenyl-1-picrylhydrazyl), and ABTS (2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) of the extracts, either individually or in combination, were evaluated colorimetrically. The effects of this supplement on healthy adult dogs' nutritional, inflammatory, and stress status were evaluated. American Staffordshire Terrier adult female dogs ( n = 30) were randomly assigned to a control ( n = 15) or a treated ( n = 15) group. The supplement was added as powder to the food of the treated dogs once daily for 28 days. There was no significant difference in the body weight and body condition scores between the initial and final phases of the experiment. At the end of our study, a significant decrease in fecal calprotectin, cortisol, indole/skatole, and N-methylhistamine and a significant increase in short-chain fatty acids were observed as compared to the control group. In conclusion, this natural feed supplement can be used to improve gastrointestinal health and psycho-physical conditions in dogs.

Dogs are commonly affected by Osteoarthritis (OA). Different approaches can be used to alleviate animals' symptoms. In this randomised, placebo-controlled and double-blind clinical trial, we performed a three months follow-up study assessing the efficacy of a food supplement containing natural ingredients ( Cannabis sativa oil, Boswellia serrata Roxb. Phytosome ® and Zingiber officinale extract) in dogs with OA after the interruption of physiotherapy that was performed during the previous three months. Inflammation and oxidative stress were reduced in the treated group (higher glutathione (GSH) and lower C-reactive protein [CRP] levels in blood) as well as chronic pain.

Non-Hermitian two-site dimers serve as minimal models in which to explore the interplay of gain and loss in dynamical systems. In this paper, we experimentally and theoretically investigate the dynamics of non-Hermitian dimer models with nonreciprocal hoppings between the two sites. We investigate two types of non-Hermitian couplings; one is when asymmetric hoppings are externally introduced, and the other is when the nonreciprocal hoppings depend on the population imbalance between the two sites, thus introducing the non-Hermiticity in a dynamical manner. We engineer the models in our synthetic mechanical setup comprised of two classical harmonic oscillators coupled by measurement-based feedback. For fixed nonreciprocal hoppings, we observe that, when the strength of these hoppings is increased, there is an expected transition from a PT-symmetric regime, where oscillations in the population are stable and bounded, to a PT-broken regime, where the oscillations are unstable and the population grows/decays exponentially. However, when the non-Hermiticity is dynamically introduced, we also find a third intermediate regime in which these two behaviors coexist, meaning that we can tune from stable to unstable population dynamics by simply changing the initial phase difference between the two sites. As we explain, this behavior can be understood by theoretically exploring the emergent fixed points of a related dimer model in which the nonreciprocal hoppings depend on the normalized population imbalance. Our study opens the way for the future exploration of non-Hermitian dynamics and exotic lattice models in synthetic mechanical networks.

Oxidative stress is often involved in liver disease progression. Liver is the primary site for the synthesis of glutathione (GSH), the major intracellular antioxidant. GSH erythrocyte concentration can decrease in case of liver damage. So, the use of food supplements with antioxidant capacity has been reported in the veterinary literature. In this case-control study, we tested a new supplement containing S-acetyl-glutathione (SAG), silybin, and other antioxidant ingredients in dogs affected by liver disease. After two weeks of supplement administration, we were able to report a significant increase in the level of erythrocyte GSH in the treated (TRT) group, nearly reaching the physiological limit at the end of the study. In addition, most of the key liver parameters are significantly reduced in the TRT group by the end of the trial. The results of this study support the effectiveness of the tested complementary feed, which may be helpful in managing dogs with liver conditions.

Background: Larval source management (LSM) may help reduce Plasmodium parasite transmission in malaria-endemic areas. LSM approaches include habitat modification (permanently or temporarily reducing mosquito breeding aquatic habitats); habitat manipulation (temporary or recurrent change to environment); or use of chemical (e.g. larviciding) or biological agents (e.g. natural predators) to breeding sites. We examined the effectiveness of habitat modification or manipulation (or both), with and without larviciding. This is an update of a review published in 2013., Objectives: 1. To describe and summarize the interventions on mosquito aquatic habitat modification or mosquito aquatic habitat manipulation, or both, on malaria control. 2. To evaluate the beneficial and harmful effects of mosquito aquatic habitat modification or mosquito aquatic habitat manipulation, or both, on malaria control., Search Methods: We used standard, extensive Cochrane search methods. The latest search was from January 2012 to 30 November 2021., Selection Criteria: Randomized controlled trials (RCT) and non-randomized intervention studies comparing mosquito aquatic habitat modification or manipulation (or both) to no treatment or another active intervention. We also included uncontrolled before-after (BA) studies, but only described and summarized the interventions from studies with these designs. Primary outcomes were clinical malaria incidence, malaria parasite prevalence, and malaria parasitaemia incidence., Data Collection and Analysis: We used standard Cochrane methods. We assessed risk of bias using the Cochrane RoB 2 tool for RCTs and the ROBINS-I tool for non-randomized intervention studies. We used a narrative synthesis approach to systematically describe and summarize all the interventions included within the review, categorized by the type of intervention (habitat modification, habitat manipulation, combination of habitat modification and manipulation). Our primary outcomes were 1. clinical malaria incidence; 2. malaria parasite prevalence; and 3. malaria parasitaemia incidence. Our secondary outcomes were 1. incidence of severe malaria; 2. anaemia prevalence; 3. mean haemoglobin levels; 4. mortality rate due to malaria; 5. hospital admissions for malaria; 6. density of immature mosquitoes; 7. density of adult mosquitoes; 8. sporozoite rate; 9. entomological inoculation rate; and 10., Harms: We used the GRADE approach to assess the certainty of the evidence for each type of intervention., Main Results: Sixteen studies met the inclusion criteria. Six used an RCT design, six used a controlled before-after (CBA) study design, three used a non-randomized controlled design, and one used an uncontrolled BA study design. Eleven studies were conducted in Africa and five in Asia. Five studies reported epidemiological outcomes and 15 studies reported entomological outcomes. None of the included studies reported on the environmental impacts associated with the intervention. For risk of bias, all trials had some concerns and other designs ranging from moderate to critical. Ten studies assessed habitat manipulation (temporary change to the environment). This included water management (spillways across streams; floodgates; intermittent flooding; different drawdown rates of water; different flooding and draining regimens), shading management (shading of drainage channels with different plants), other/combined management approaches (minimal tillage; disturbance of aquatic habitats with grass clearing and water replenishment), which showed mixed results for entomological outcomes. Spillways across streams, faster drawdown rates of water, shading drainage canals with Napier grass, and using minimal tillage may reduce the density of immature mosquitoes (range of effects from 95% reduction to 1.7 times increase; low-certainty evidence), and spillways across streams may reduce densities of adult mosquitoes compared to no intervention (low-certainty evidence). However, the effect of habitat manipulation on malaria parasite prevalence and clinical malaria incidence is uncertain (very low-certainty evidence). Two studies assessed habitat manipulation with larviciding. This included reducing or removal of habitat sites; and drain cleaning, grass cutting, and minor repairs. It is uncertain whether drain cleaning, grass cutting, and minor repairs reduces malaria parasite prevalence compared to no intervention (odds ratio 0.59, 95% confidence interval (CI) 0.42 to 0.83; very low-certainty evidence). Two studies assessed combination of habitat manipulation and permanent change (habitat modification). This included drainage canals, filling, and planting of papyrus and other reeds for shading near dams; and drainage of canals, removal of debris, land levelling, and filling ditches. Studies did not report on epidemiological outcomes, but entomological outcomes suggest that such activities may reduce the density of adult mosquitoes compared to no intervention (relative risk reduction 0.49, 95% CI 0.47 to 0.50; low-certainty evidence), and preventing water stagnating using drainage of canals, removal of debris, land levelling, and filling ditches may reduce the density of immature mosquitoes compared to no intervention (ranged from 10% to 55% reductions; low-certainty evidence). Three studies assessed combining manipulation and modification with larviciding. This included filling or drainage of water bodies; filling, draining, or elimination of rain pools and puddles at water supply points and stream bed pools; and shoreline work, improvement and maintenance to drainage, clearing vegetation and undergrowth, and filling pools. There were mixed effect sizes for the reduction of entomological outcomes (moderate-certainty evidence). However, filling or draining water bodies probably makes little or no difference to malaria parasite prevalence, haemoglobin levels, or entomological inoculation rate when delivered with larviciding compared to no intervention (moderate-certainty evidence)., Authors' Conclusions: Habitat modification and manipulation interventions for preventing malaria has some indication of benefit in both epidemiological and entomological outcomes. While the data are quite mixed and further studies could help improve the knowledge base, these varied approaches may be useful in some circumstances., (Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Tick-borne encephalitis (TBE) is an infection caused by the Tick-borne encephalitis virus (TBEv) and it is common in Europe. The virus is predominantly transmitted by ticks, but other non-vectorial modes of transmission are possible. This systematic review synthesises the epidemiological impact of non-vectorial modes of TBEv transmission in Europe. 41 studies were included comprising of 1308 TBE cases. Alimentary (36 studies), handling infected material (3 studies),  blood-borne (1 study), solid organ transplant (1 study) were identified as potential routes of TBEv transmission; however, no evidence of vertical transmission from mother to offspring was reported (2 studies). Consumption of unpasteurised milk/milk products was the most common vehicle of transmission and significantly increased the risk of TBE by three-fold (pooled RR 3.05, 95% CI 1.53 to 6.11; 4 studies). This review also confirms handling infected material, blood-borne and solid organ transplant as potential routes of TBEv transmission. It is important to tracing back to find the vehicle of the viral infection and to promote vaccination as it remains a mainstay for the prevention of TBE., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The aim of this study was to evaluate the effect of the administration of Saccharomyces boulardii on the nutritional, immunological, inflammatory, and stress status and on the composition of the gut microbiota and mycobiota in healthy adult dogs. A total of 25 American Staffordshire Terrier dogs were selected and randomly assigned to two groups: control (CTR, n = 12) and treated (TRT, n = 13) groups. No significant differences were found between the two groups regarding body weight, body condition score, and fecal score. No significant differences in microbiota/mycobiota, short chain fatty acids, indole/skatole, histamine, zonulin, or lactoferrin were detected. Indeed, supplementation with S. boulardii significantly decreased fecal calprotectin Immunoglobulin A, indicating an improvement in the gut well-being. Interestingly, fecal cortisol significantly decreased in dogs belonging to the TRT group compared to the CTR, suggesting both an improvement of the intestinal status and a reduction of stress, a common condition affecting animals managed in a breeding environment.

This study aimed to investigate whether cranberry extract could reduce lower urinary tract (LUT) and gastro-intestinal (GI) signs in feline idiopathic cystitis (FIC). Twenty-one client-owned cats were randomly allocated to two groups: a treated group (T, n = 10) receiving daily an oral nutritional supplement containing cranberry extract and a control group (C, n = 11). Owners were trained to recognise daily LUT and GI signs. Physical examination, urinalysis and bladder ultrasonography were performed at day 0 (T0), 15 (T15), 30 (T30), 60 (T60). Both groups showed an improvement for dysuria and periuria from T0 to T30 ( p  < 0.05), but only in cats of the T group, LUT signs disappeared at T60. A significant improvement in the T group was also observed for GI signs and bladder ultrasonography at T60 ( p  = 0.03). Urinalysis did not show any significant differences. This preliminary study suggests that cranberry could be effective in reducing LUT and GI signs in FIC.

Chronic intestinal disorders (CID) are characterized by persistent, or recurrent gastrointestinal (GI) signs present for at least three weeks. In human medicine, inflammatory bowel disease (IBD) is a group of chronic GI diseases and includes Crohn's disease (CD) and ulcerative colitis (UC). On the other hand, the general term chronic enteropathies (CE) is preferred in veterinary medicine. Different therapeutic approaches to these diseases are used in both humans and pets. This review is focused on the use of traditional therapies and nutraceuticals with specific antioxidant properties, for the treatment of CID in humans and animal patients. There is strong evidence of the antioxidant properties of the nutraceuticals included in this review, but few studies report their use for treating CID in humans and none in animals. Despite this fact, the majority of the nutraceuticals described in the present article could be considered as promising alternatives for the regular treatment of CID in human and veterinary medicine.

This study is a randomized, placebo-controlled, double-blinded trial performed to investigate the effects of a dietary supplement containing a mixture of Boswellia serrata Roxb., chlorophyll, green tea extract, glucosamine, chondroitin sulfate, hyaluronic acid, and further in the manuscript: non-hydrolised type II collagen in dogs with osteoarthritis (OA). A total of 40 dogs were enrolled in the study, they were randomly divided in control (CTR) and treatment (TRT) groups. The TRT group received the dietary supplement for 60 days. The CTR group received a placebo for the same number of days. All the subjects had veterinary evaluations during the trial and owners were requested to fill in questionnaires on chronic pain using the Helsinki Chronic Pain Index. The product was easy to administer and no side effects were reported. Combining results from veterinarian and owner evaluations, the tested product proved to be significantly beneficial in alleviating pain and in reducing the clinical signs in dogs with OA., Competing Interests: EM and MB were paid as consultants of Candioli Pharma Srl, and RA and NB as employees of the Candioli Pharma Srl. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Antibiotic resistance is a global problem, searching for new antimicrobial agents is an urgent need. In this study, in vitro antibacterial and antimicrobial effects of milk-derived antimicrobial agents, lactoferrin-derived peptides, lactoferricin (Lfc) and lactoferrampin (Lfa) (alone or in combination) and their association with natural extracts have been explored. The assessment of antimicrobial activity was based on two measurements: Minimum Inhibitory Concentration and Fractional Inhibitory Concentration indexes. Lfc alone is more suitable for inhibiting Staphylococcus intermedius and Malassezia pachydermatis, while Lfa against Candida albicans , a synergistic effect of the two peptides against all the three pathogens has been detected. A strong synergy of all the natural extracts with Lfc and Lfa solution against selected microorganisms in vitro was pointed out. Our results suggest that natural-derived compounds, such as milk peptides and vegetal extracts could be promising tools to treat moderate fungal and bacterial infections.

Chronic kidney disease (CKD) causes an irreversible loss of kidney functioning in dogs. This double-blind case-control study evaluates the efficacy of a dietary supplement, which contains calcium carbonate, calcium lactate-gluconate, chitosan, sodium bicarbonate, Lactobacillus acidophilus D2/CSL, Olea europaea L. extract, and fructooligosaccharides, in dogs in advanced CKD stage. Thirty dogs were enrolled in the study; half were administered the new dietary supplementation for 90 days, while the others were used as controls. Hematologic, biochemical, and urinalysis were performed. This novel dietary supplement mainly reported a good control of uremia, phosphate, acid-base balance, blood pressure, inflammation, and oxidative stress in dogs with advanced stages of CKD.

Mosquito-borne viruses cause diseases of great public health concern. Arboviral disease case distributions have complex relationships with socioeconomic and environmental factors. We combined information about socio-economic (population, and poverty rate) and environmental (precipitation, and land use) characteristics with reported human cases of arboviral disease in the counties of Alabama, USA, from 2007-2017. We used county level data on West Nile virus (WNV), dengue virus (DENV), chikungunya virus (CHIKV), Zika virus (ZIKV), California serogroup virus, Eastern equine encephalitis virus, and Saint Louis encephalitis virus to provide a detailed description of their spatio-temporal pattern. We found a significant spatial convergence between incidence of WNV and poverty rate clustered in the southern part of Alabama. DENV, CHIKV and ZIKV cases showed a different spatial pattern, being mostly located in the northern part, in areas of high socioeconomic status. The results of our study establish that poverty-driven inequities in arboviral risk exist in the southern USA, and should be taken into account when planning prevention and intervention strategies., Competing Interests: The authors have declared that no competing interests exist.

Chronic kidney disease (CKD) is a common disease in elderly dogs. The present study aims to evaluate the efficacy of a dietary supplement containing calcium carbonate, calcium-lactate gluconate, chitosan and sodium bicarbonate in dogs with IRIS stage 3 of CKD. Twenty dogs were enrolled in the study, ten were administered the new dietary supplementation for 180 days (T group) while the others were used as control group (C group). Haematologic, biochemical and urinalysis were performed every 30 days. A significant reduction in the T group compared to the C group in serum phosphorus level and increase in serum bicarbonate and ionized calcium values were recorded. The urine protein-to-creatinine ratio (UPC) was significantly lower in the T group at the end of the study compared to the C group. The tested supplement could be considered as a supportive treatment for dogs with advanced CKD., Competing Interests: Candioli Pharma S.r.l. is a company that may be affected by the research reported. Candioli Pharma S.r.l. provided the tested supplement, contributed in planning the study and writing the manuscript and gave financial support for publication., (©2020 Martello et al.)

Importance: The incidence and geographic range of Lyme disease continues to increase in the United States because of the expansion of Ixodes scapularis, the species of tick that is the main Lyme disease vector. Currently, no dynamic model for the disease spread exists that integrates information of both acarological and human case surveillance data., Objective: To characterize the spatiotemporal spread of Lyme disease in humans among counties in US endemic regions., Design, Setting, and Participants: This cross-sectional study modeled the spread of Lyme disease county-level case reporting, accounting for county-level demographic factors, environmental factors associated with tick presence and human exposure, and the spatiotemporal association between counties. The analyses were conducted between January and August 2019. The setting was 1405 counties in the following regions of the United States: West North Central, East North Central, New England, Middle Atlantic, and the South. Assessments were based on publicly available Lyme disease case data reported to the US Centers for Disease Control and Prevention (CDC) between January 2000 and December 2017., Main Outcomes and Measures: Probability of reporting the first case of Lyme disease by county by year., Results: Between 2000 and 2017, a total of 497 569 Lyme disease cases were reported to the CDC in the study area. Reporting a first case of Lyme disease was associated with a county's and county's neighbors' forest coverage, elevation, percentage of population living in the wildland-urban interface, tick presence, county's population size, proportion of neighbors reporting cases, and neighbors' years since first reporting. The model that included these variables showed high predictive power, with a mean area under the receiver operating characteristic curve of 81.1 (95% CI, 68.5-86.2). The model predicted the first reported Lyme disease case a mean (SD) of 5.5 (3.5) years earlier than was reported to the CDC, with a mean spread velocity estimated at 27.4 (95% CI, 13.6-54.4) km per year. Among 162 counties without reported cases, 47 (29.0%) had a high probability of reporting Lyme disease by 2018. The estimated mean time lag between the first reported case in a neighboring county and any county was 7 (95% CI, 3-8) years., Conclusions and Relevance: This study's findings suggest that, if updated regularly and expanded geographically, this predictive model could enable states and counties to develop more specific Lyme disease prevention and control plans, including improved sensitization of the general population and medical community.

3-hydroxy-3-methyl glutaryl-CoA reductase, also known as HMGR, plays a crucial role in regulating cholesterol biosynthesis and represents the main pharmacological target of statins. In mammals, this enzyme localizes to the endoplasmic reticulum membrane. HMGR includes different regions, an integral N-terminal domain connected by a linker-region to a cytosolic C-terminal domain, the latter being responsible for enzymatic activity. The aim of this work was to design a simple strategy for cloning, expression, and purification of the catalytic C-terminal domain of the human HMGR (cf-HMGR), in order to spectrophotometrically test its enzymatic activity. The recombinant cf-HMGR protein was heterologously expressed in Escherichia coli, purified by Ni + -agarose affinity chromatography and reconstituted in its active form. MALDI mass spectrometry was adopted to monitor purification procedure as a technique orthogonal to the classical Western blot analysis. Protein identity was validated by MS and MS/MS analysis, confirming about 82% of the recombinant sequence. The specific activity of the purified and dialyzed cf-HMGR preparation was enriched about 85-fold with respect to the supernatant obtained from cell lysate. The effective, cheap, and easy method here described could be useful for screening statin-like molecules, so simplifying the search for new drugs with hypocholesterolemic effects.

Strongyloides stercoralis , a worldwide-distributed soil-transmitted helminth, causes chronic infection which may be life threatening. Limitations of diagnostic tests and nonspecificity of symptoms have hampered the estimation of the global morbidity due to strongyloidiasis. This work aimed at assessing S. stercoralis -associated morbidity through a systematic review and meta-analysis of the available literature. MEDLINE, Embase, CENTRAL, LILACS, and trial registries (WHO portal) were searched. The study quality was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) of the association between symptoms and infection status and frequency of infection-associated symptoms were calculated. Six articles from five countries, including 6,014 individuals, were included in the meta-analysis-three were of low quality, one of high quality, and two of very high quality. Abdominal pain (OR 1.74 [CI 1.07-2.94]), diarrhea (OR 1.66 [CI 1.09-2.55]), and urticaria (OR 1.73 [CI 1.22-2.44]) were associated with infection. In 17 eligible studies, these symptoms were reported by a large proportion of the individuals with strongyloidiasis-abdominal pain by 53.1% individuals, diarrhea by 41.6%, and urticaria by 27.8%. After removing the low-quality studies, urticaria remained the only symptom significantly associated with S. stercoralis infection (OR 1.42 [CI 1.24-1.61]). Limitations of evidence included the low number and quality of studies. Our findings especially highlight the appalling knowledge gap about clinical manifestations of this common yet neglected soil-transmitted helminthiasis. Further studies focusing on morbidity and risk factors for dissemination and mortality due to strongyloidiasis are absolutely needed to quantify the burden of S. stercoralis infection and inform public health policies.

Ticks and ear biopsies were collected from wild small rodents in 2011 and 2012 in the northern Apennines (Italy), up to 1650 m above sea level. Apodemus spp. (n = 83) and Myodes glareolus (n = 22) were infested by Ixodes ricinus (192 larvae and two nymphs), Dermacentor marginatus (179 larvae and 29 nymphs), and Ixodes trianguliceps (three larvae and two nymphs). We detected several Borrelia burgdorferi sensu lato (s.l.) genospecies (B. afzelii, B. burgdorferi sensu stricto, B. garinii, B. lusitaniae, B. valaisiana) in I. ricinus and skin biopsies. The most common genospecies found in I. ricinus was B. valaisiana, while it was B. lusitaniae in tissues. Spotted fever group (SFG) rickettsiae (Rickettsia monacensis, R. slovaca and R. raoultii) infected I. ricinus, D. marginatus and rodent tissues. Rickettsia slovaca was the Rickettsia species most frequently found in our samples. Coinfections by B. burgdorferi s.l. and SFG rickettsiae indicate an overlap of transmission cycles and potential risk for humans to be infected by multiple pathogens, resulting in more severe symptoms. The findings of B. lusitaniae and R. slovaca in bank voles, and of B. valaisiana in small rodents, open new questions about host-pathogen interactions. In addition, our results highlight the importance of small rodents as data sources for studying tick-borne pathogens., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

The objective of the present study was the identification of farming practices in the production of turkeys for human consumption, and their ranking in terms of the occupational probability of exposure to antimicrobial resistant (AMR) bacteria, for farm workers. We gathered evidence and data from scientific literature, on risk factors for AMR in farmers, and on the prevalence of those hazards across farming phases. We administered semi-structured interviews to public and private veterinarians in Northern Italy, to obtain detailed information on turkey farming phases, and on working practices. Data were then integrated into a semi-quantitative Failure Modes and Effect Analysis (FMEA). Those working practices, which are characterized by direct contact with numerous animals, and which are carried out frequently, with rare use of personal protection devices resulted as associated with the greatest probability of exposure to AMR. For methicillin resistant Staphylococcus aureus (MRSA), these included vaccination and administration of any individual therapy, and removal and milling of litter, given the exposure of farmers to high dust level. Indeed, levels of occupational exposure to MRSA are enhanced by its transmission routes, which include direct contact with animal, as well as airborne transmission. Level of exposure to extended spectrum beta lactamase (ESBL) is more strictly associated with direct contact and the oral-fecal route. Consequently, exposure to ESBL resulted and associated with the routinely tipping over of poults turned on their back, and with the individual administration of therapies.

Several ATP-depending reactions take place in the endoplasmic reticulum (ER). Although in Saccharomyces cerevisiae ER the existence of a Sac1p-dependent ATP transport system was already known, its direct involvement in ATP transport was excluded. Here we report an extensive biochemical characterization of a partially purified adenine nucleotide transport system (ANTS) not dependent on Sac1p. Highly purified ER membranes from the wild-type and Δsac1 yeast strains reconstituted into liposomes transported ATP with the same efficiency. A chromatography on hydroxyapatite was used to partially purify ANTS from Δsac1 ER extract. The two ANTS-enriched transport activity eluted fractions showed essentially the presence of four bands, one having an apparent MW of 56 kDa, similar to that observed for ANTS identified in rat liver ER. The two fractions reconstituted into liposomes efficiently transported, by a strict counter-exchange mechanism, ATP and ADP. ATP transport was saturable with a Km of 0.28 mM. The ATP/ADP exchange mechanism and the kinetic constants suggest that the main physiological role of ANTS is to catalyse the transport of ATP into ER, where it is used in several energy-requiring reactions and to export back to the cytosol the ADP produced.

Background: Transfusion-transmitted malaria (TTM) is an accidental Plasmodium infection caused by whole blood or a blood component transfusion from a malaria infected donor to a recipient. Infected blood transfusions directly release malaria parasites in the recipient's bloodstream triggering the development of high risk complications, and potentially leading to a fatal outcome especially in individuals with no previous exposure to malaria or in immuno-compromised patients. A systematic review was conducted on TTM case reports in non-endemic areas to describe the epidemiological characteristics of blood donors and recipients., Methods: Relevant articles were retrieved from Pubmed, EMBASE, Scopus, and LILACS. From each selected study the following data were extracted: study area, gender and age of blood donor and recipient, blood component associated with TTM, Plasmodium species, malaria diagnostic method employed, blood donor screening method, incubation period between the infected transfusion and the onset of clinical symptoms in the recipient, time elapsed between the clinical symptoms and the diagnosis of malaria, infection outcome, country of origin of the blood donor and time of the last potential malaria exposure., Results: Plasmodium species were detected in 100 TTM case reports with a different frequency: 45% Plasmodium falciparum, 30% Plasmodium malariae, 16% Plasmodium vivax, 4% Plasmodium ovale, 2% Plasmodium knowlesi, 1% mixed infection P. falciparum/P. malariae. The majority of fatal outcomes (11/45) was caused by P. falciparum whilst the other fatalities occurred in individuals infected by P. malariae (2/30) and P. ovale (1/4). However, non P. falciparum fatalities were not attributed directly to malaria. The incubation time for all Plasmodium species TTM case reports was longer than what expected in natural infections. This difference was statistically significant for P. malariae (p = 0.006). A longer incubation time in the recipient together with a chronic infection at low parasite density of the donor makes P. malariae a subtle but not negligible risk for blood safety aside from P. falciparum., Conclusions: TTM risk needs to be taken into account in order to enhance the safety of the blood supply chain from donors to recipients by means of appropriate diagnostic tools.

Host-seeking ticks were collected in the Northern Apennines, Italy, by dragging at 35 sites, at altitudes ranging from 680 and 1670 m above sea level (asl), from April to November, in 2010 and 2011. Ixodes ricinus (4431 larvae, 597 nymphs and 12 adults) and Haemaphysalis punctata (11,209 larvae, 313 nymphs, and 25 adults) were the most abundant species, followed by Haemaphysalis sulcata (20 larvae, five nymphs, and 13 adults), Dermacentor marginatus (42 larvae and two adults) and Ixodes hexagonus (one nymph). Greatest numbers of ticks were collected at locations characterised by southern exposure and limestone substratum, at altitudes <1400 m asl; I. ricinus was most abundant in Turkey oak (Quercus cerris) wood, whereas H. punctata was mostly collected in hop hornbeam (Ostrya carpinifolia) wood and on exposed rocks. Ixodes ricinus was also found up to 1670 m asl, in high stand beech (Fagus sylvatica) wood. The overall prevalence of Borrelia burgdorferi sensu lato (sl) in 294 host-seeking I. ricinus nymphs was 8.5 %. Borrelia garinii was the most frequently identified genospecies (64.0 % of positive nymphs), followed by B. valaisiana, B. burgdorferi sensu stricto, B. afzelii, and B. lusitaniae. Based upon the comparison with the results of previous studies at the same location, these research findings suggest the recent invasion of the study area by the tick vector and the agents of Lyme borreliosis.

Immature ticks (Ixodes ricinus and Dermacentor marginatus) were collected from small rodents (Apodemus spp. and Myodes glareolus), in the Northern Apennines, Italy, at an altitude up to 1650 m above sea level (a.s.l.), from 2009 through 2012. While D. marginatus had been found at the same location in studies carried out in 1994, I. ricinus was very rare or absent. Prevalence (95% confidence interval) of infestation by I. ricinus larvae on Apodemus spp. was 54.4% (47.5, 61.2), and it was greater than prevalence of D. marginatus larvae on the same hosts (23.3%, 17.8, 29.5). The mean (standard deviation) numbers of I. ricinus and D. marginatus larvae per individual Apodemus spp. were similar: 2.3 (4.1) and 2.1 (9.8), respectively. The monthly infestation pattern of the two tick species on Apodemus spp. were different. I. ricinus larvae were more frequent in June and September, than in July-August. I. ricinus nymphs were generally rare, and were most frequently found in July. The prevalence of D. marginatus larvae peaked in July-August, whereas nymphs were mostly active in August-September. Increasing population densities of roe deer (Capreolus capreolus), and increasing temperatures, in the last decades, in the Apennine area might have contributed to the observed range expansion of I. ricinus., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Immature Dermacentor marginatus ticks and tissues from small rodents were tested for infection with Rickettsia slovaca in the northern Apennines, Lucca Province, where tick-borne lymphadenopathy (TIBOLA) was previously reported in people. Prevalence of infestation with D. marginatus was 30.5% (n=131, 95% CI: 22.8-39.2%) in Apodemus spp. and 26.5% (n=34, 95% CI: 12.9-44.4%) in Myodes glareolus, which were captured during 1980 trap nights in 2009 and 2010. Rickettsia slovaca was identified by polymerase chain reaction, targeting the gltA and OmpA genes, in ear biopsies from 8 out of 37 tested Apodemus (22%, 95% CI: 9.8-38.2%), but not from 9 M. glareolus. The prevalence of R. slovaca in D. marginatus feeding on Apodemus spp. was 53% in larvae (n=51, 95% CI: 38.5-67.1%) and 47.5% in nymphs (n=59, 95% CI: 34.3-60.9%). No larvae (0.0%, 95% CI: 0-36.9%), but one nymph removed from M. glareolus was positive (10%, 95% CI: 0.3-44.5%). Prevalence of R. slovaca in host-seeking D. marginatus larvae, collected in the same area, was 42% (n=38; 95% CI: 26.3-59.2%). Prevalence of R. slovaca was greater in larvae feeding on PCR-positive Apodemus than in those feeding on negative mice (78.6% vs. 37.1%). Furthermore, levels of infestation with D. marginatus larvae were greater for R. slovaca-positive mice. The infection of Apodemus spp. was probably the result of repeated bites by transovarially infected larvae. On the other hand, the finding of R. slovaca in mice tissues would be compatible with transmission from these hosts to feeding D. marginatus. Based on such a hypothesis, the most heavily infested Apodemus might play a role as amplifiers of the infection., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

The mitochondrial carriers are members of a family of transport proteins that mediate solute transport across the inner mitochondrial membrane. Two isoforms of the glutamate carriers, GC1 and GC2 (encoded by the SLC25A22 and SLC25A18 genes, respectively), have been identified in humans. Two independent mutations in SLC25A22 are associated with severe epileptic encephalopathy. In the present study we show that two genes (CG18347 and CG12201) phylogenetically related to the human GC encoding genes are present in the D. melanogaster genome. We have functionally characterized the proteins encoded by CG18347 and CG12201, designated as DmGC1p and DmGC2p respectively, by overexpression in Escherichia coli and reconstitution into liposomes. Their transport properties demonstrate that DmGC1p and DmGC2p both catalyze the transport of glutamate across the inner mitochondrial membrane. Computational approaches have been used in order to highlight residues of DmGC1p and DmGC2p involved in substrate binding. Furthermore, gene expression analysis during development and in various adult tissues reveals that CG18347 is ubiquitously expressed in all examined D. melanogaster tissues, while the expression of CG12201 is strongly testis-biased. Finally, we identified mitochondrial glutamate carrier orthologs in 49 eukaryotic species in order to attempt the reconstruction of the evolutionary history of the glutamate carrier function. Comparison of the exon/intron structure and other key features of the analyzed orthologs suggests that eukaryotic glutamate carrier genes descend from an intron-rich ancestral gene already present in the common ancestor of lineages that diverged as early as bilateria and radiata., (© 2013.)

The citrate carrier (CIC), a nuclear-encoded protein located in the mitochondrial inner membrane, plays an important metabolic role in the transport of acetyl-CoA from the mitochondrion to the cytosol in the form of citrate for fatty acid and cholesterol synthesis. Citrate has been reported to be essential for fibroblast differentiation into fat cells. Because peroxisome proliferator-activated receptor-gamma (PPARγ) is known to be one of the master regulators of adipogenesis, we aimed to study the regulation of CIC by the PPARγ ligand rosiglitazone (BRL) in 3T3-L1 fibroblasts and in adipocytes. We demonstrated that BRL up-regulated CIC mRNA and protein levels in fibroblasts, while it did not elicit any effects in mature adipocytes. The enhancement of CIC levels upon BRL treatment was reversed using the PPARγ antagonist GW9662, addressing how this effect was mediated by PPARγ. Functional experiments using a reporter gene containing rat CIC promoter showed that BRL enhanced CIC promoter activity. Mutagenesis studies, electrophoretic-mobility-shift assay and chromatin-immunoprecipitation analysis revealed that upon BRL treatment, PPARγ and Sp1 are recruited on the Sp1-containing region within the CIC promoter, leading to an increase in CIC expression. In addition, mithramycin, a specific inhibitor for Sp1-DNA binding activity, abolished the PPARγ-mediated up-regulation of CIC in fibroblasts. The stimulatory effects of BRL disappeared in mature adipocytes in which PPARγ/Sp1 complex recruited SMRT corepressor to the Sp1 site of the CIC promoter. Taken together, our results contribute to clarify the molecular mechanisms by which PPARγ regulates CIC expression during the differentiation stages of fibroblasts into mature adipocytes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Fosfomycin is widely used to treat urinary tract and pediatric gastrointestinal infections of bacteria. It is supposed that this antibiotic enters cells via two transport systems, including the bacterial Glycerol-3-phosphate Transporter (GlpT). Impaired function of GlpT is one mechanism for fosfomycin resistance., Methods: The interaction of fosfomycin with the recombinant and purified GlpT of Escherichia coli reconstituted in liposomes has been studied. IC(50) and the half-saturation constant of the transporter for external fosfomycin (K(i)) were determined by transport assay of [(14)C]glycerol-3-phosphate catalyzed by recombinant GlpT. Efficacy of fosfomycin on growth rates of GlpT defective bacteria strains transformed with recombinant GlpT was measured., Results: Fosfomycin, externally added to the proteoliposomes, poorly inhibited the glycerol-3-phosphate/glycerol-3-phosphate antiport catalyzed by the reconstituted transporter with an IC(50) of 6.4mM. A kinetic analysis revealed that the inhibition was completely competitive, that is, fosfomycin interacted with the substrate-binding site and the K(i) measured was 1.65mM. Transport assays performed with proteoliposomes containing internal fosfomycin indicate that it was not very well transported by GlpT. Complementation study, performed with GlpT defective bacteria strains, indicated that the fosfomycin resistance, beside deficiency in antibiotic transporter, could be due to other gene defects., Conclusions: The poor transport observed in a reconstituted system together with the high value of K(i) and the results of complementation study well explain the usual high dosage of this drug for the treatment of the urinary tract infections., General Significance: This is the first report regarding functional analysis of interaction between fosfomycin and GlpT., (2011 Elsevier B.V. All rights reserved.)