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Autophagy has been proposed to play a dual role in cancer—as a tumor suppressor in early stages and oncogenic in late stages of tumorigenesis. This study investigated the role of autophagy in oral carcinogenesis using the model of oral squamous cell carcinoma (OSCC) induced by carcinogen 4-nitroquinoline 1-oxide (4NQO), mimicking molecular and histopathologic aspects of human OSCC. The induction of autophagy by spermidine (SPD) treatment reduced the severity of lesions and the incidence of OSCC in mice exposed to 4NQO. On the other hand, autophagy inhibition by chloroquine treatment had no protection. The comet assay indicated that SPD reduced 4NQO-induced DNA damage, likely related to the activation of DNA repair and the decrease of reactive oxygen species. As sphingolipid alterations have been reported in OSCC, sphingolipids in the tongue and plasma of animals were analyzed and plasma C16 ceramide levels were shown to increase proportionally to lesion severity, indicating its potential as a biomarker. Mice exposed to 4NQO plus SPD had lower levels of C16 ceramide than the 4NQO group, which indicated SPD's ability to prevent the 4NQO-induced carcinogenesis. Together, these data indicate that activation of autophagy has a tumor suppressor role during the early stages of oral carcinogenesis. Because of its ability to induce autophagy accompanied by reduced oxidative stress and DNA damage, SPD may have a protective action against chemically induced oral cancer.

Executive functions include functions such as planning, working memory, inhibition, mental flexibility, and action monitoring and initiation, and are essential to carry out an independent everyday life. Individuals suffering from brain injury, such as a stroke, very commonly experience executive deficits that reduce the capacity to regain functional independence. In recent years, there has been a growing interest in developing tablet computer-based cognitive training programs for stroke patients and healthy aging adults since such programs can be included in non-supervised environments. In this respect, we described and evaluated the usability of a novel tablet application (app) for executive function training, developed in the context of the MEMORI-net project, a cross-border Italy-Slovenia program for the rehabilitation of stroke patients. We conducted a pilot study with a non-clinical sample of 16 participants to obtain information about the usability of the sFEra APP. Our descriptive analyses suggest that most users were satisfied with the overall experience and the app was highly usable, and instructions were clear, even with little previous experience with tablet applications. Acceptability and effectiveness will need to be evaluated in a clinical randomized controlled study.

ABSTRACTIn 2015, the world witnessed the resurgence and global spread of Zika virus (ZIKV). This arbovirus infection is associated with Guillain-Barré syndrome in adults and with devastating congenital malformations during pregnancy. Despite scientific efforts, the development of a vaccine capable of inducing long-term protection has been challenging. Without a safe and efficacious licensed vaccine, control of virus transmission is based on vector control, but this strategy has been shown to be inefficient. An effective and protective vaccine relies on several requirements, which include: (i) induction of specific immune response against immunodominant antigens; (ii) selection of adjuvant-antigen formulation; and (iii) assessment of safety, effectiveness, and long-term protection. In this commentary, we provide a brief overview about the current efforts for the development of an efficacious ZIKV vaccine, covering the most important preclinical trials up to the formulations that are now being evaluated in clinical trials.

Background: Hip fractures (HF) are a major issue worldwide. We aimed at evaluating the practices in delivering care to patients with HF among several Italian Orthogeriatric centers. Methods: The study took place from February 2016 to July 2018. Seven performance indicators (pre-surgical cognitive assessment, surgery performed ≤ 48 h from fracture, removal of urinary catheter/absence of delirium/start of physiotherapy on the first post-operative day, prescription of bone protection at discharge, and discharge toward rehabilitation) were collected. Results: The 14 participating hospitals totally recruited 3.017 patients. Patients were old (median age 86 years; Inter Quartile Range [IQR] 80–90), mostly females (77%). Nearly 55% of them were already impaired in mobility and about 10% were nursing home residents. Median time-to-surgery was 41 h (IQR 23–62). Models of care greatly varied among centers, only 49.3% of patients being co-managed by geriatricians and orthopedics. There was high variability across centers in four indicators (“pre-surgical cognitive assessment”, “bone protection prescription”, “use of urinary catheter” and “start of physiotherapy”), moderate in two indicators (“surgery performed ≤ 48 h from fracture” and “discharge toward rehabilitation” and low in one (“absence of delirium on day following surgery”). Comparison with international studies suggests very different ways of providing care to HF Italian patients. Conclusions: The study results suggest high inter-center variability in the key-performance indicators, and different approaches in providing care to our HF patients in comparison to other countries. A National debate on the topic is required in Italy to harmonize practices of orthogeriatric care.

The Upland Goose (Chloephaga picta picta) is a migratory species of South America, which breeds from September to April in Patagonia (Argentina and Chile) and winters from May to September in the southern Pampas (Argentina). Despite some protection in both countries, this species is still persecuted and large numbers are killed by unregulated hunting. Therefore, precise knowledge of their migratory routes is vital to ensure protection of necessary resources and sites throughout the year. We deployed five miniaturised satellite transmitters on adult Upland Geese to gather data about breeding, wintering and stopover sites all along their migratory routes. We aimed to identify important areas in the wintering and breeding grounds through kernel density analyses, and to match these sites along the migration routes with protected areas. Tracked birds exhibited different migration routes and reached different breeding grounds. Two individuals travelled from their wintering grounds in Buenos Aires province to their presumed breeding areas in southern Patagonia. However, we also found different stopover sites from another bird in northern Patagonia, from the ones postulated before, and evidence that some Upland Geese are not large-scale migrants. Our results highlight a considerable amount of plasticity in Upland Geese migratory behaviour. This study represents an essential first step towards identifying important stopover sites along the Upland Geese flyways and it also highlights the lack of protected habitats along most of their migration routes.

•This is the first multicenter study to assess the prevalence of motor subtypes of delirium in older patients admitted to acute hospital and rehabilitation settings.•The most frequent delirium subtype was the hypoactive delirium followed by the mixed, hyperactive and non-motor subtype of delirium.•All three delirium motor subtypes were associated with pre-existing dementia.•Atypical antipsychotics were statistically less likely to be prescribed for patients identified with hypoactive delirium.•Mixed delirium was associated with an increased number of intravenous lines.

In the natural products research, a valuable approach is the prospection of uncommon sources and unexplored habitat. Special attention has been given to endophytic fungi because of their ability to produce new and interesting secondary metabolites, which have several biological applications. The endophytes establish exclusive symbiotic relationships with plants and the metabolic interactions may support the synthesis of some similar valuables compounds. Among secondary metabolites, phenol-derived structures are responsible for several bioactivities such as antioxidant, cytotoxic, antimicrobial, among others. Phenolic compounds might be biosynthesized from the shikimate pathway. Although shikimic acid is a common precursor in plants, it is described as rare in microorganisms. To the best of our knowledge, this is the first review about phenolic compounds produced by endophytic fungi and a comparison has been made with those produced by the plant host. This review covers 124 phenolic secondary metabolites produced by endophytic fungi. Considering the data analyzed by us, only seven of such compounds were isolated from fungi and from their hosts. These observations claim for more attention to phenolic compounds produced by endophytic fungi with a view to understand the real importance of these compounds to endophytes survival.

Thyroid hormones (THs) have a relevant action on brain development and maintenance. By using an acute treatment to induce a hyperthyroid animal model, we aimed at investigating the effect of an altered THs levels on learning and memory and on the activity of Na+, K+-ATPase in the rat brain. Our results have shown that the acute treatment with L-T4 did not alter the retrieval of the inhibitory avoidance task, but had a significant effect on the elevated plus maze and on open-field performance in rats. We suggest that animals subjected to L-T4 administration improved the habituation to a novel environment as well as a better evaluation of a dangerous environment, respectively. Na+, K+-ATPase activity is increased in parietal cortex (30%), but it is not altered in hippocampus in L-T4 treated group. These both brain structures are involved in memory processing and it was previously demonstrated that there is a double dissociation between them for spatial location information, perceptual and episodic memory. We propose the hypothesis that this increase of Na+, K+- ATPase activity in parietal cortex may be correlated to our results in behavior tests, which suggest a role of THs as well as of the Na+, K+-ATPase in the cognitive process.

Many studies indicate a dissociation between two forms of orientation: allocentric orientation, in which an organism orients on the basis of cues external to the organism, and egocentric spatial orientation (ESO) by which an organism orients on the basis of proprioceptive information. While allocentric orientation is mediated primarily by the hippocampus and its afferent and efferent connections, ESO is mediated by the prefronto-striatal system. Striatal lesions as well as classical neuroleptics, which block dopamine receptors, act through the prefronto-striatal system and impair ESO. The purpose of the present study was to determine the effects of the atypical antipsychotics clozapine, olanzapine and risperidone which are believed to exert its antipsychotic effects mainly by dopaminergic, cholinergic and serotonergic mechanisms. A delayed-two-alternative-choice-task, under conditions that required ESO and at the same time excluded allocentric spatial orientation was used. Clozapine and olanzapine treated rats made more errors than risperidone treated rats in the delayed alternation in comparison with the controls. Motor abilities were not impaired by any of the drugs. Thus, with regard to the delayed alternation requiring ESO, clozapine and olanzapine but not risperidone affects the prefronto-striatal system in a similar way as classical neuroleptics does.

Thyroid hormones (THs), including triiodothyronine (T3) and tetraiodothyronine (T4), are recognized as key metabolic hormones of the body. THs are essential for normal maturation and function of the mammalian central nervous system (CNS) and its deficiency, during a critical period of development, profoundly affects cognitive function. Sodiumpotassium adenosine 5'-triphosphatase (Na+, K+-ATPase) is a crucial enzyme responsible for the active transport of sodium and potassium ions in the CNS necessary to maintain the ionic gradient for neuronal excitability. Studies suggest that Na+, K+-ATPase might play a role on memory formation. Moreover, THs were proposed to stimulate Na+, K+-ATPase activity in the heart of some species. In this work we investigated the effect of a chronic administration of L-thyroxine (LT4) or propylthiouracil (PTU), an antithyroid drug, on some behavioral paradigms: inhibitory avoidance task, open field task, plus maze and Y-maze, and on the activity of Na+, K+-ATPase in the rat parietal cortex and hippocampus. By using treatments which have shown to induce alterations in THs levels similar to those found in hyperthyroid and hypothyroid patients, we aimed to understand the effect of an altered hyperthyroid and hypothyroid state on learning and memory and on the activity of Na+, K+-ATPase. Our results showed that a hyper and hypothyroid state can alter animal behavior and they also might indicate an effect of THs on learning and memory.

In the present paper we report the performance on object use and on semantic tasks of two patients, D.L. with probable semantic dementia, and A.M. with an atypical onset of dementia of Alzheimer, assessed twice two years apart. In particular, we investigated whether the patients' ability to use objects degraded as a function of their semantic knowledge about those objects. Results from the two assessments in 2002 and in 2004 confirmed that both patients had a selective loss of the lexical-semantic knowledge, despite a relative preservation of the other cognitive abilities including object use. This pattern of results suggests that semantic knowledge is not necessarily involved in the correct use of objects.

Abstract.: Objective and design: Chronic glucocorticoid treatment is associated with pharmacological resistance. We investigated the auxiliary effects of fructose-1,6-bisphosphate (FBP) on dexamethasone (DEX)-related modulation of inflammation and T-cell proliferation.

The records of 92 pluviometric stations located in the Trentino Province (Italian Eastern Alps) were analyzed in order to find significant features in their spatial and temporal distribution. Differentiation of climatic regimes was detected, as well as the influence of many topographic-geographic parameters. Analyses of the data from the 20 stations with the best continuity of records indicate some periodic trends, with a major influence of those having a wavelength of ca. 26.7, 36.9 and 13.5 years. Also non strictly periodic Mediterranean oscillations influences the precipitation in the study area.

Plasmablastic lymphoma (PBL) is a rare B-cell lymphoma occurring mainly in HIV patients. The tumor frequently involves extranodal sites such as the oral cavity, nasal cavity, gastrointestinal tract, skin, and lungs. The neoplastic cells are characterized by a plasmablastic appearance and typical immunophenotype that indicates plasma cell differentiation. Herein, we report a case of intraocular involvement by plasmablastic lymphoma in a HIV patient with a long history of cytomegalovirus retinitis and loss of vision. After an evisceration performed to control the blind, painful eye a diagnosis of PBL was made by examining the eye contents. Two months later, a biopsy of cervical lymph node revealed nodal lymphoma of the same type. To the best of our knowledge, this is the second case of intraocular PBL reported in English literature.

The antidepressant-like effects of phloroglucinol and seven synthetic related derivatives were investigated using the tail suspension test (TST) in mice. Compounds 2-methyl-1-[2,4,6-trihydroxy-3-(2-methylpropanoyl)phenyl] propan-1-one (5), 1-(2,4,6-trihydroxyphenyl)ethan-1-one (6), 1-(3-acetyl-2,4,6-trihydroxyphenyl)ethan-1-one (7), 2-methyl-1-[2,4,6-trihydroxy-3-(2-methylpropanoyl)-5-{[2,4,6-trihydroxy-3,5-bis(2-methylpropanoyl)phenyl]methyl} phenyl] propan-1-one (9) and 1-{3-acetyl-5-[(3,5-diacetyl-2,4,6-trihydroxyphenyl)methyl]-2,4,6-trihydroxyphenyl}ethan-1-one (10), containing acyl groups, decreased the immobile behavior of mice treated orally with equimolar doses of imipramine 20 mg/kg, with no alterations in locomotor activity as assessed by the open-field test. These results suggest that these phloroglucinol derivatives could represent a new molecular model in the search for antidepressant drugs.