Differential Uptake of Gold Nanoparticles by 2 Species of Tadpole, the Wood Frog (Lithobates Sylvaticus) and the Bullfrog (Lithobates Catesbeianus)

Engineered nanoparticles are aquatic contaminants of emerging concern that exert ecotoxicological effects on a wide variety of organisms. We exposed cetyltrimethylammonium bromide–capped spherical gold nanoparticles to wood frog and bullfrog tadpoles with conspecifics and in combination with the other species continuously for 21 d, then measured uptake and localization of gold. Wood frog tadpoles alone and in combination with bullfrog tadpoles took up significantly more gold than bullfrogs. Bullfrog tadpoles in combination with wood frogs took up significantly more gold than controls. The rank order of weight-normalized gold uptake was wood frogs in combination \u3e wood frogs alone \u3e bullfrogs in combination \u3e bullfrogs alone \u3e controls. In all gold-exposed groups of tadpoles, gold was concentrated in the anterior region compared with the posterior region of the body. The concentration of gold nanoparticles in the anterior region of wood frogs both alone and in combination with bullfrogs was significantly higher than the corresponding posterior regions. We also measured depuration time of gold in wood frogs. After 21 d in a solution of gold nanoparticles, tadpoles lost \u3e83% of internalized gold when placed in gold-free water for 5 d. After 10 d in gold-free water, tadpoles lost 94% of their gold. After 15 d, gold concentrations were below the level of detection. Our finding of differential uptake between closely related species living in similar habitats with overlapping geographical distributions argues against generalizing toxicological effects of nanoparticles for a large group of organisms based on measurements in only one species

Putative role of circulating human papillomavirus DNA in the development of primary squamous cell carcinoma of the middle rectum: A case report

Here we present the case of a patient affected by rectal squamous cell carcinoma in which we demonstrated the presence of Human Papillomavirus (HPV) by a variety of techniques. Collectively, the virus was detected not only in the tumor but also in some regional lymph nodes and in non-neoplastic mucosa of the upper tract of large bowel. By contrast, it was not identifiable in its common sites of entry, namely oral and ano-genital region. We also found HPV DNA in the plasma-derived exosome. Next, by in vitro studies, we confirmed the capability of HPV DNA-positive exosomes, isolated from the supernatant of a HPV DNA positive cell line (CaSki), to transfer its DNA to human colon cancer and normal cell lines. In the stroma nearby the tumor mass we were able to demonstrate the presence of virus DNA in the stromal compartment, supporting its potential to be transferred from epithelial cells to the stromal ones. Thus, this case report favors the notion that human papillomavirus DNA can be vehiculated by exosomes in the blood of neoplastic patients and that it can be transferred, at least in vitro, to normal and neoplastic cells. Furthermore, we showed the presence of viral DNA and RNA in pluripotent stem cells of non-tumor tissue, suggesting that after viral integration (as demonstrated by p16 and RNA in situ hybridization positivity), stem cells might have been activated into cancer stem cells inducing neoplastic transformation of normal tissue through the inactivation of p53, p21, and Rb. It is conceivable that the virus has elicited its oncogenic effect in this specific site and not elsewhere, despite its wide anatomical distribution in the patient, for a local condition of immune suppression, as demonstrated by the increase of T-regulatory (CD4/CD25/FOXP3 positive) and T-exhausted (CD8/PD-1positive) lymphocytes and the M2 polarization (high CD163/CD68 ratio) of macrophages in the neoplastic microenvironment. It is noteworthy that our findings depicted a static picture of a long-lasting dynamic process that might evolve in the development of tumors in other anatomical sites

Phase Ib study of poly-epitope peptide vaccination to thymidylate synthase (TSPP) and GOLFIG chemo-immunotherapy for treatment of metastatic colorectal cancer patients

ABSTRACT: Thymidylate synthase (TS) is a tumor-associated enzyme critical for DNA replication and main 5′-fluorouracil (5′-FU) target. TSPP/VAC1 is a multi-arm trial phase-Ib trial program aimed to investigate the toxicity and biomodulatory activity of a poly-epitope-peptide vaccine to TS (TSPP) in cancer patients (pts). Here, we present the results of the TSPP/VAC1/arm C trial aimed to evaluate TSPP in combination with chemo-immunotherapy in pretreated metastatic colo-rectal cancer (mCRC) pts. Twenty-nine pts, 14 males and 15 females, received poly-chemotherapy with gemcitabine [GEM; 1,000 mg/sqm, day-1], oxaliplatin [OX; 80 mg/sqm, day-2], levofolinate [100 mg/sqm, days 1–2], bolus/infusional 5′-FU [400 mg/800 mg/sqm, days 1–2], sargramostim [50 μg, days 3–7/q30], and interleukin-2 [sc. 0.5 MIU twice a day, days 8–14/18–30] [GOLFIG-regimen]. Seventeen pts received sc. TSPP injections at escalating dosage [3 pts, 100 µg (DL-1); 3 pts, 200 µg (DL-2) and 11pts, 300 µg (DL-3)] one week after each chemotherapy cycle (concomitant module), while 10 out 12 pts received TSPP (300 µg) after 12 GOLFIG courses [dose level (DL)-0] (sequential module). TSPP MTD was not achieved. Adverse events consisted in swelling/erythema at injection sites (17 cases), G1–2 haematological (16 cases) and gastro-enteric events (12), fever, rhinitis, conjunctivitis, and poly-arthralgia and rise in auto-antibodies [ANA, ENA, c-ANCA, p-ANCA in the DL1–3 pts]. Both treatment-modules showed immunomodulating and antitumor activity (disease-control-rate, DL1–3 and DL0 were 70.6% and 83.3%, respectively) with a better survival recorded in the second group [median OS DL1–3 vs. DL0 = 8 vs. 16 mo, p = 0.049]. The promising long-term survival produced by the sequential treatment module deserves further phase II evaluation

Growing Opportunities for Equitable, Interdisciplinary Undergraduate Food Systems Education: A Review of Food Systems Education at Land-Grant Institutions and Development of Open-Access Materials

Post-secondary coursework related to agriculture and the food supply has been at the core of the United States' land-grant system for more than 150 years. However, as the complexity of food systems has grown, so too have critiques that the education provided in these programs is too narrow to adequately prepare graduates to address pressing food systems issues. In response, some higher education institutions have developed degrees in food systems. To support development of this burgeoning field, we created, tested, and refined four evidence-informed, interdisciplinary, equity-oriented, open-access teaching modules. These modules are based on our experience conducting a multi-site, multi-year transdisciplinary investigation of subsidized, or “cost-offset”, community supported agriculture and a survey asking instructors at land-grant institutions (n = 66) about topic offerings and current unmet needs for instructional materials. Our collaboration illuminated the potential and challenges of food systems research; underscored the value of transdisciplinary research teams; and identified several equity-oriented topics related to the design, implementation, and evaluation of local food initiatives suitable for advancing sustainable foods systems education. Instructors reported that the most helpful teaching aids would be case studies, lesson plans with active learning components, and reference lists with relevant peer-reviewed publications. The final modules seek to shed light on the complexity of food systems projects and build knowledge, vocabularies, and skills across disciplines engaged with food systems. Per instructor-defined needs, each module features a case study, active-learning activities, and references. We anticipate that the adaptable modules will be suitable for a wide range of students and courses

Summary of investigations of entrance effects in circular thrust bearings

Pressure distribution near single axial supply hole of externally pressurized circular thrust bearing - investigation of entrance effect

[Restaging brain computerized tomography after treatment of non-operable lung neoplasms]

PURPOSE: To assess the role of CT brain scans as a routine restaging procedure after primary, aggressive, drug or radiation therapy of unresectable lung cancer. If early, asymptomatic brain metastases are detected and treated, survival could be improved relative to the patients showing brain involvement in a later CT scan performed during the follow-up, at the onset of neurological symptoms. MATERIAL AND METHODS: One hundred patients affected with lung cancer, unresectable on account of histology (small-cell carcinoma) or advanced stage (III, IV) were submitted to chemo- and/or radiotherapy, after a clinical staging including brain CT, which was negative in all patients. Brain CT was also repeated at the end of therapy (restaging), in the absence of any neurological symptom. Further scans were obtained during the subsequent follow-up only when clinical symptoms occurred, suggesting metastases to the brain. Survival values were analyzed in the patients whose brain involvement was detected during restaging, vs those showing symptomatic brain metastases during the follow-up. RESULTS: Only 4 patients had asymptomatic metastases, diagnosed with the restaging brain CT scan. Their survival rate was significantly lower than that of the 20 patients whose brain involvement was shown by a follow-up CT scan, performed after the onset of neurological symptoms. However, death was rarely a consequence of brain metastases: primary or other metastatic sites were involved in the terminal events, in the greatest majority of these cases. DISCUSSION AND CONCLUSIONS: The sudden, asymptomatic brain involvement, detected at restaging CT scan after primary therapy for unresectable lung cancer, does not correlate with a better prognosis than symptomatic metastases, diagnosed later with a follow-up CT obtained performed for clinical suspicion. Therefore the use of restaging CT scan is not warranted, as a routine procedure, except for the clinical trials intended to define optimal treatment schedules