Biocontrol implications of multiparasitism by Trissolcus mitsukurii and Trissolcus japonicus on the invasive brown marmorated stink bug

The egg parasitoids Trissolcus japonicus (Ashmead) and Trissolcus mitsukurii (Ashmead) (Hymenoptera: Scelionidae) are the most effective biocontrol agents of the invasive agricultural pest Halyomorpha halys (Stål) (Heteroptera: Pentatomidae) in its native range (east Asia). Trissolcus japonicus and T. mitsukurii are sympatric in the native areas. In northern Italy, where H. halys is a major pest of fruit orchards, adventive populations of both species are spreading, and T. japonicus is artificially released under a classical biocontrol program against H. halys. This laboratory study aimed to assess the outcome of competition when both species share the same resource and possible implications for the biocontrol of the invasive stink bug. Egg masses of H. halys were offered to each parasitoid after previous parasitization by the other species. Parasitoid behaviour, number of ovipositions, and successfully developed parasitoids were recorded. Additionally, contest behaviour was assessed when both species were released simultaneously on the same egg mass. Results showed that both T. japonicus and T. mitsukurii were able to parasitize an egg mass already parasitized by the other species. Competition occurred within the host eggs and each species outperformed the other when it was the first to oviposit. Importantly, the overall contribution to H. halys mortality was not affected by the interaction between parasitoids, as non-parasitized eggs were 4–6% in the absence of competition and <8% in its presence, respectively. When simultaneously released on the egg mass, T. mitsukurii was more aggressive, engaging in chase-off events in 71% of cases compared to 50% of T. japonicus

A step towards a holistic assessment of soil degradation in Europe: Coupling on-site erosion with sediment transfer and carbon fluxes

Soil degradation due to erosion is connected to two serious environmental impacts: (i) on-site soil loss and (ii) off-site effects of sediment transfer through the landscape. The potential impact of soil erosion processes on biogeochemical cycles has received increasing attention in the last two decades. Properly designed modelling assumptions on effective soil loss are a key pre-requisite to improve our understanding of the magnitude of nutrients that are mobilized through soil erosion and the resultant effects. The aim of this study is to quantify the potential spatial displacement and transport of soil sediments due to water erosion at European scale. We computed long-term averages of annual soil loss and deposition rates by means of the extensively tested spatially distributed WaTEM/SEDEM model. Our findings indicate that soil loss from Europe in the riverine systems is about 15% of the estimated gross on-site erosion. The estimated sediment yield totals 0.164 ± 0.013 Pg yr−1 (which corresponds to 4.62 ± 0.37 Mg ha−1 yr−1 in the erosion area). The greatest amount of gross on-site erosion as well as soil loss to rivers occurs in the agricultural land (93.5%). By contrast, forestland and other semi-natural vegetation areas experience an overall surplus of sediments which is driven by a re-deposition of sediments eroded from agricultural land. Combining the predicted soil loss rates with the European soil organic carbon (SOC) stock, we estimate a SOC displacement by water erosion of 14.5 Tg yr−1 . The SOC potentially transferred to the riverine system equals to 2.2 Tg yr−1 (~15%). Integrated sediment delivery-biogeochemical models need to answer the question on how carbon mineralization during detachment and transport might be balanced or even off-set by carbon sequestration due to dynamic replacement and sediment burial

The Role of Acetyl-Carnitine and Rehabilitation in the Management of Patients with Post-COVID Syndrome: Case-Control Study

Post-COVID syndrome is characterized by the persistence of nonspecific disabling symptoms, even several months after the resolution of the infection, with clinical characteristics similar to fibromyalgia (FM) and a prevalence of 31%. We evaluated the effectiveness of physical exercise, in association with L-acetyl-carnitine (ALC) therapy, in patients with Post-COVID syndrome, on musculoskeletal pain, dyspnea, functional capacity, quality of life, and depression. We conducted an observational case-control study on patients with Post-COVID syndrome. The patients were randomly divided into two groups: a treatment group that received rehabilitation treatment in combination with ALC 500 mg therapy; a control group that received only rehabilitation treatment. Patients were assessed at the time of recruitment (T0) and one month after the end of therapy (T1), with the administration of rating scales: NRS, Barthel Dyspnea Index (NPI), 12-Item Short Form Survey (SF-12) scale, Fibromyalgia Impact Questionnaire (FIQ), and Patient Health Questionnaire (PHQ-9). The treatment group showed statistically higher variations in pain scores, quality of life, and depression. No statistically significant differences between the two groups emerged regarding changes in dyspnea and functional capacity scores. Combining exercise with ALC is a promising and effective treatment in the management of Post-COVID syndrome, especially for musculoskeletal pain, depression, and quality of life

A Drone-Based Application for Scouting Halyomorpha Halys Bugs in Orchards with Multifunctional Nets

In this work, we consider the problem of using a drone to collect information within orchards in order to scout insect pests, i.e., the stink bug Halyomorpha halys. An orchard can be modeled as an aisle-graph, which is a regular and constrained data structure formed by consecutive aisles where trees are arranged in a straight line. For monitoring the presence of bugs, a drone flies close to the trees and takes videos and/or pictures that will be analyzed offline. As the drone\u27s energy is limited, only a subset of locations in the orchard can be visited with a fully charged battery. Those places that are most likely to be infested should be selected to promptly detect the pest. We implemented the proposed approach on a DJI drone and evaluated its performance in the real-world environment

Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasis in a xenograft model of breast cancer.

Triple-negative breast cancers (TNBCs) are clinically aggressive forms associated with a poor prognosis. We evaluated the cytotoxic effect exerted on triple-negative MDA-MB231 breast cancer cells both by parthenolide and its soluble analogue dimethylamino parthenolide (DMAPT) and explored the underlying molecular mechanism. The drugs induced a dose- and timedependent decrement in cell viability, which was not prevented by the caspase inhibitor z-VAD-fmk. In particular in the first hours of treatment (1–3 h), parthenolide and DMAPT strongly stimulated reactive oxygen species (ROS) generation. The drugs induced production of superoxide anion by activating NADPH oxidase. ROS generation caused depletion of thiol groups and glutathione, activation of c-Jun N-terminal kinase (JNK) and downregulation of nuclear factor kB (NF-kB). During this first phase, parthenolide and DMAPT also stimulated autophagic process, as suggested by the enhanced expression of beclin-1, the conversion of microtubule-associated protein light chain 3-I (LC3-I) to LC3-II and the increase in the number of cells positive to monodansylcadaverine. Finally, the drugs increased RIP-1 expression. This effect was accompanied by a decrement of pro-caspase 8, while its cleaved form was not detected and the expression of c-FLIPS markedly increased. Prolonging the treatment (5–20 h) ROS generation favoured dissipation of mitochondrial membrane potential and the appearance of necrotic events, as suggested by the increased number of cells positive to propidium iodide staining. The administration of DMAPT in nude mice bearing xenografts of MDA-MB231 cells resulted in a significant inhibition of tumour growth, an increment of animal survival and a marked reduction of the lung area invaded by metastasis. Immunohistochemistry data revealed that treatment with DMAPT reduced the levels of NF-kB, metalloproteinase-2 and -9 and vascular endothelial growth factor, while induced upregulation of phosphorylated JNK. Taken together, our data suggest a possible use of parthenolide for the treatment of TNBCs

Evaluation of the in vitro and in vivo antineoplastic effects of Parthenolide on MDA-MB231 breast cancer cells

Triple-negative breast cancer refers to an aggressive subtype of breast cancer in which the tumor cells lack receptors for estrogen, progesterone and the HER2 protein on their surfaces. This type of breast cancer does not respond to treatments such as hormone therapy, like tamoxifen and aromatase inhibitors, or drugs that target HER2, like Herceptin. It is important, therefore, the identification of new selective drugs for the treatment of these tumors. Parthenolide (PN), a sesquiterpene lactone extracted from the medical plant Tanacetum parthenium, exerts anticancer activity on several tumor cell lines in culture, acting through diverse molecular mechanisms. Our previous studies have shown that the PN exerts strong cytotoxic effects on MG63 osteosarcoma and SK-Mel28 melanoma cells, through a caspase-independent mechanism which is associated with production of oxidative stress. Recently, we have undertaken a study in order to investigate the antineoplastic activity of PN on MDA-MB231 cells, a triple-negative breast cancer cell line. Our results demonstrated that this compound reduced the viability of MDA-MB231 cells in a dose- and time- dependent manner. This effect was not prevented by the addition of z-VAD-fmk, a general inhibitor of caspase, thus suggesting a caspase-independent cell death. Time-course experiments provided evidence that the cytotoxic effect of PN occurs in two different phases. In the first phase of treatment (8h) cells resulted positive to monodansylcadaverine (MDC), a fluorochrome that binds to autophagic vacuoles. Prolonging the treatment (16h) MDC-positive cells lowered, and an increase of PI-positive population was found, suggesting the appearance of necrotic events. The study of the mode of PN action provided evidence that treatment with parthenolide induces ROS generation, activation of JNK and inhibition of NF-kB activity. All these effects were prevented by the addition of NAC, thus suggesting the involvement of oxidative stress. The antineoplastic activity of PN has been also assayed in vivo employing diamminoparthenolide (DMAPT), a soluble analogue of PN. Nude mice bearing breast carcinoma MDA-MB231 xenografts were treated daily with DMAPT (50 mg/Kg). It was observed that DMAPT increased survival of MDA-MB231 xenograft-bearing nude mice as well as reduced MDA-MB231 xenografts tumor growth. Moreover, immunohistochemical studies showed that DMAPT was able to decrease the expression of MMP-2, MMP-9 and VEGF, all factors involved in metastatic events. These data suggest a possible use of parthenolide for the treatment of triple negative breast cancers

Refining Pheromone Lures for the Invasive Halyomorpha halys (Hemiptera: Pentatomidae) Through Collaborative Trials in the United States and Europe

Brown marmorated stink bug, Halyomorpha halys, is native to Asia and has invaded North America and Europe inflicting serious agricultural damage to specialty and row crops. Tools to monitor the spread of H. halys include traps baited with the two-component aggregation pheromone (PHER), (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol, and pheromone synergist, methyl (2E,4E,6Z)-decatrienoate (MDT). Here, an international team of researchers conducted trials aimed at evaluating prototype commercial lures for H. halys to establish relative attractiveness of: 1) low and high loading rates of PHER and MDT for monitoring tools and attract and kill tactics; 2) polyethylene lure delivery substrates; and 3) the inclusion of ethyl (2E,4E,6Z)-decatrieonate (EDT), a compound that enhances captures when combined with PHER in lures. In general, PHER loading rate had a greater impact on overall trap captures compared with loading of MDT, but reductions in PHER loading and accompanying lower trap captures could be offset by increasing loading of MDT. As MDT is less expensive to produce, these findings enable reduced production costs. Traps baited with lures containing PHER and EDT resulted in numerically increased captures when EDT was loaded at a high rate, but captures were not significantly greater than those traps baited with lures containing standard PHER and MDT. Experimental polyethylene vial dispensers did not outperform standard lure dispensers; trap captures were significantly lower in most cases. Ultimately, these results will enable refinement of commercially available lures for H. halys to balance attraction and sensitivity with production cost

Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs

Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against “self”. In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients’ life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)