The latest freshwater giants: a new Peltocephalus (Pleurodira: Podocnemididae) turtle from the Late Pleistocene of the Brazilian Amazon.

Overkill of large mammals is recognized as a key driver of Pleistocene megafaunal extinctions in the Americas and Australia. While this phenomenon primarily affected mega-mammals, its impact on large Quaternary reptiles has been debated. Freshwater turtles, due to the scarcity of giant forms in the Quaternary record, have been largely neglected in such discussions. Here we present a new giant podocnemidid turtle, Peltocephalus maturin sp. nov., from the Late Pleistocene Rio Madeira Formation in the Brazilian Amazon, that challenges this assumption. Morphological and phylogenetic analyses of the holotype, a massive partial lower jaw, reveal close affinities to extant Amazonian species and suggest an omnivorous diet. Body size regressions indicate Pe. maturin possibly reached about 180 cm in carapace length and is among the largest freshwater turtles ever found. This finding presents the latest known occurrence of giant freshwater turtles, hinting at coexistence with early human inhabitants in the Amazon.

Dollo meets Bergmann: morphological evolution in secondary aquatic mammals.

Secondary transitions to aquatic environments are common among vertebrates, and aquatic lineages display several adaptations to this realm, some of which might make these transitions irreversible. At the same time, discussions about secondary transitions often focus only on the marine realm, comparing fully terrestrial with fully aquatic species. This, however, captures only a fraction of land-to-water transitions, and freshwater and semi-aquatic groups are often neglected in macroevolutionary studies. Here, we use phylogenetic comparative methods to unravel the evolution of different levels of aquatic adaptations across all extant mammals, testing if aquatic adaptations are irreversible and if they are related to relative body mass changes. We found irreversible adaptations consistent with Dollo's Law in lineages that rely strongly on aquatic environments, while weaker adaptations in semi-aquatic lineages, which still allow efficient terrestrial movement, are reversible. In lineages transitioning to aquatic realms, including semi-aquatic ones, we found a consistent trend towards an increased relative body mass and a significant association with a more carnivorous diet. We interpret these patterns as the result of thermoregulation constraints associated with the high thermal conductivity of water leading to body mass increase consistently with Bergmann's rule and to a prevalence of more nutritious diets.

Psychotropic medications sales during COVID-19 outbreak in Italy changed according to the pandemic phases and related lockdowns.

OBJECTIVES: We have investigated the psychotropic medications sales (i.e. benzodiazepines, mood stabilisers and selective serotonin reuptake inhibitors) during the COVID-19 pandemic in the period from March 2020 to February 2021 compared with the same period in the preceding year. STUDY DESIGN: This was a retrospective and observational study. METHODS: Data were obtained from five pharmacies located in a working-class zone populated by approximately 150,000 people in the urban area of Rome (Italy). RESULTS: A general slight increase in psychotropic medications sales was observed during the whole pandemic period compared with the previous year. CONCLUSION: Our data showed that (1) the percentage of sales seems to vary according to the pandemic phases and related lockdowns and (2) the sales differ between the classes of medications considered.

The human pegivirus: A new name for an "ancient" virus. Can transfusion medicine come up with something new?

Human pegivirus (HPgV, formerly called GB virus C/hepatitis G virus) is a poorly understood RNA virus of the Flaviviridae family. The HPgV infection is common worldwide and the virus is likely transmitted by blood products. At this time, no causal association between HPgV and human diseases has been identified. While waiting for new findings to better understand the Pegivirus genus, the aim of our narrative review is to discuss the currently available information on HPgV focusing on its prevalence in blood donors and its potential threat to transfusion safety.

Psychological functioning measures in patients with primary insomnia and sleep state misperception.

OBJECTIVE: Sleep state misperception (SSM) is a term used in the International Classification of Sleep Disorders to indicate people who mistakenly perceive their sleep as wakefulness. SSM is a form of primary insomnia. The aim of this study was to record psychological functioning measures (anxiety, depression, ability to feel pleasure, obsessive-compulsive traits) in a population of patients with primary insomnia and to evaluate the relationship between these measures and the patients' perception of their sleep. MATERIALS AND METHODS: Seventy-six consecutive patients with primary insomnia were enrolled: 34 men and 42 women, mean age 53.9 ± 13.1. Sleep study included the following: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Berlin's Questionnaire and home-based polysomnography. Psychometric evaluation included the following: Self-Administered Anxiety Scale, Beck's Depression Inventory, Maudsley's Obsessive Compulsive Inventory, Snaith-Hamilton Pleasure Scale, Eating Attitude Test. RESULTS: All patients with insomnia had psychometric scores higher than the general population, but very few patients, in both groups, had anxiety or depression scores consistent with severe mood or anxiety disorders. Comparisons between subjective and objective scores confirmed that most sleep parameters were underestimated. Patients with SSM had lower anxiety scores as compared to patients without SSM. CONCLUSIONS: The study did not succeed in identifying any predictor of sleep misperception. We speculate that a group of patients, rather than being extremely worried by their insomnia, may have a sort of agnosia of their sleep.

Psychological distress and coping strategies in patients attending a dermatology outpatient clinic.

BACKGROUND: Psychological distress is frequent among dermatological patients. The development of a positive attitude toward diagnosis and treatment is thought to be critical for successful coping and mental health outcomes. OBJECTIVE: The aim of this study was to assess the coping strategies and the psychological distress, due to anxiety and depression, in an unselected sample of dermatological patients. METHODS: Self-administered questionnaires (HADS, COPE) were given to 603 dermatological patients. RESULTS: Out of 567 participants, 149 (26.2%) scored positive for Anxiety, and 52 (9.2%) scored positive for Depression. Multivariate analysis, adjusting for gender, age, socio-economic status, and disease, showed that both Anxiety and Depression are associated with a less frequent use of Positive attitude coping. CONCLUSION: Our results reinforce the notion that while planning the treatment of dermatological patients, evaluating their mental health might help to provide optimal treatment. Since coping ability was found to be important for mental health status, policy implications could include emphasis on social programs to assist individuals to manage stress, as well as psychological support.

The effect of newer serotonin-noradrenalin antidepressants on cytokine production: a review of the current literature.

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.

Physical exercise activates the poly(ADP-ribosyl)ation system in rat testes.

Given the high sensitivity of the male reproductive system to oxidative stress and to temperature changes, the amount of germ cell apoptosis and the activation of the poly(ADP-ribosyl)ation system (a very sensitive index of genotoxic stress) were evaluated in the testicular tissue of adult rats which underwent a 10-wk treadmill training, according to either a mild or a strong protocol; rats were sacrificed 24 h after the last training session or after a single bout of an additional stressing exercise (30 min of swimming). Controls were untrained rats (one resting group and one group with acute exercise). Both training and acute exercise increased marginally germ cell apoptotic indexes (caspase-induced poly(ADP-ribose) polymerase fragmentation and TUNEL-positive cells), while the activity of poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase enzymes was affected in a way that suggests that acute exercise is associated with reversible genotoxic stress, and that training induces adaptive responses, as demonstrated by the activation of poly(ADP-ribose) polymerase system without subsequent increase in apoptosis.

The role of cholesterol levels in mood disorders and suicide.

The individuation of sensitive and specific biochemical markers, easily assessable on large samples of subjects and usefully employable as predictors of severe psychiatric disorders, such as mood disorders, could help clinicians to improve the diagnostic and therapeutic processes facilitating the long-term follow-up. In particular, serum cholesterol levels may potentially be optimal markers due to their relative easy sampling and low cost. The involvement of cholesterol in affective disorders such as Major Depression (MD), Seasonal Affective Disorder (SAD) and Bipolar Disorders (BD) is a debated issue in current research. However, current literature is controversial and, to date, it is still not possible to reach an agreement on its possible usefulness of cholesterol as a biological marker of affective disorders. Despite the controversial results on the relationships between cholesterol levels and affective disorders, the majority of literature seems to show a more consistent relationship between cholesterol levels and suicidal behaviour, with few studies that have found no relationships. The aim of this review is to elucidate current facts and views about the role of cholesterol levels in mood disorders as well as its involvement in suicidal behaviour.

Consenso chileno para el diagnóstico y tratamiento de gliomas del adulto / Diagnosis and treatment of glioma in adult: Chilean consensus

Resumen Los tumores cerebrales se caracterizan por su gran morbilidad y mortalidad. La gran mayoría corresponde a tumores secundarios (metástasis). Dentro de los tumores primarios del sistema nervioso central, los gliomas corresponden al 30% de éstos. En EEUU, entre el 2007-2011, se estima una incidencia aproximada de 21,4 casos por 100.000 habitantes. Los recientes avances en la comprensión molecular de la biología de estos tumores han permitido mejorar sustancialmente su clasificación, posibilitando realizar un mejor correlato con los desenlaces clínicos y el pronóstico. En esta línea, hoy en día es posible estratificar a los pacientes por riesgo y entregar tratamientos capaces de prolongar la sobrevida global entre 5-7 años, para los gliomas grado II y III. El presente consenso, elaborado por un panel multidisciplinario de expertos de diversas sociedades científicas chilenas y, por tanto, de todas las especialidades involucradas en el manejo médico-quirúrgico de las personas portadoras de gliomas cerebrales. A la luz de este nuevo conocimiento desarrollado al alero de la oncología molecular, esta propuesta ofrece un insumo de utilidad clínica real, que, articulado a una revisión actualizada en relación con el tratamiento y seguimiento de estos pacientes, permite entender la relevancia de estos biomarcadores en el manejo de precisión de la enfermedad. Cabe señalar que, este manuscrito emerge de la misma fuerza de trabajo, que elaboró el Protocolo Clínico de Gliomas del Adulto 2019, publicado por el Ministerio de Salud, y que ha diferencia de esta, que ofrece los detalles clínicos-operativos, como flujogramas y dosis, nuestra revisión intenta relevar los avances imagenológicos y moleculares y como estos impactan en el manejo actual de la enfermedad.

Brain tumors are characterized by high morbidity and mortality. The vast majority correspond to secondary tumors (metastasis). On the other hand, within the primary tumors of the central nervous system, gliomas correspond to 30% of these. In the US, between 2007-2011, an approximate incidence of 21.4 cases per 100,000 inhabitants was estimated. Recent advances in the molecular understanding of the biology of these tumors have made it possible to substantially improve their classification, allowing a better correlation with clinical outcomes and prognosis. Along these lines, today, it is possible to stratify patients by risk and deliver treatments capable of prolonging global survival between 5-7 years, for grade II and III gliomas. The present consensus, prepared by a multidisciplinary panel of experts from various Chilean scientific societies and, therefore, from all the specialties involved in the medical and surgical therapy. Enlightened from the molecular oncology, this proposal offers an input of clinical utility, which, together with an updated review in relation to the treatment and follow-up of these patients, allows us to understand the relevance of these biomarkers in precision disease management. It should be noted that this manuscript emerges from the same work force, which prepared the Clinical Protocol for Adult Gliomas 2019, published by the Ministry of Health, and that differs from it, which offers clinical-operative details, such as flowcharts and dose, our review attempts to reveal imaging and molecular advances and how they impact the current management of the disease.

Poly(ADP-ribosylation) of nuclear proteins in rat testis correlates with active spermatogenesis.

Poly(ADP-ribosylation) of nuclear proteins has been investigated in rat testis under different experimental conditions to determine whether it is associated with somatic or germinal cells. Isolated, intact nuclei were incubated with [14C]NAD and extracted sequentially with 5% HClO4 and 0.25 M HCl, and labelled soluble proteins were analysed by reverse-phase high-performance liquid chromatography and acetic acid-urea polyacrylamide gel electrophoresis (pH 2.9). Results show that in normal adult testis a major acceptor protein for poly(ADP-ribose) in HClO4 extracts is the tissue-specific histone, H1t. Core histones and three proteins (alpha, beta and gamma) with low mobility on acetic acid-urea gels were the major acceptors identified in HCl extracts. Poly(ADP-ribosylation) of all the aforementioned proteins is very low in isolated intact nuclei of testis from 8-day-old animals (only spermatogonia present in seminiferous tubules), increases significantly by 16-day (pachytene spermatocytes appear) and reaches adult proportions by 32 days (condensing spermatids present). In the nuclei from cryptorchid testes, poly(ADP-ribosylation) of nuclear proteins resembles 8-day-old testis. It is concluded that (a) poly(ADP-ribosylation) of nuclear proteins in rat testis is closely correlated with spermatogenesis and can be inferred that is particularly active in the early stages of meiosis; (b) testis-specific proteins (histone H1t and low mobility proteins, alpha, beta and gamma) are poly(ADP-ribosylated) to higher specific radioactivity than somatic histones.

Reversible inactivation of ribonucleases by ADPribosylation.

The activity of purified bovine seminal RNAase and pancreatic RNAase A (EC 3.1.27.5) has been investigated following in vitro ADPribosylation in the presence of nuclear ADPribosyltransferase (EC 2.4.2.30) and NAD+ X ADPribosylation of these enzymes was correlated with a significant decrease in their activities. Approximately three residues of ADPribose were present per mol of enzyme. Removal of the bound ADPribose restored enzyme activity to near normal levels. Similar results were obtained with nuclei isolated from bull seminal vesicles as an endogenous source of seminal RNAase and nuclear ADPribosyltransferase. The findings suggest that in vitro ADPribosylation has a reversible inactivating effect on ribonucleases.

Poly(ADP-ribose) binding properties of histone H1 variants.

Using a poly(ADP-ribose) binding assay on protein blots we examined the ability of rat testis histone H1 variants to establish non-covalent interactions with the polymer. All the H1 variants bound ADP-ribose polymers; the binding was salt resistant and highly specific, occurring even in the presence of a large excess of competitor DNA. A comparison among the H1 variants showed that H1t has the highest affinity for poly(ADP-ribose). Long and branched poly(ADP-ribose) molecules were found to be preferentially involved in the interaction with the histone variants. The results further corroborate the concept that non-covalent interactions of poly(ADP-ribose) with target proteins may constitute an important mechanism to modulate chromatin structure.

ADP-ribosylation of a specific protein from isolated intact bull testis nuclei.

ADP-ribosylation of a specific basic protein has been investigated in isolated intact bull testis nuclei incubated with NAD+. The electrophoretic mobility, molecular weight and amino-acid composition of the purified bull testis specific protein are similar to those of rat testis protein. About 1-5% of the total radioactivity incorporated in the 20% acid-insoluble fraction was associated with testis protein and was identified as ADP-ribose.

In vitro poly(ADPribosylation) of estrogen-induced proteins from the oviduct of the lizard Podarcis s. sicula Raf.

Poly(ADPribosylation) of nuclear proteins has been investigated in the nuclei from growing oviducts of intact and estrogen-treated spayed females of the lizard Podarcis s. sicula Raf. Isolated nuclei were incubated with [14C] NAD and nuclear proteins extracted in 0.2 m H2SO4. Labeled acid-soluble proteins were analysed by reverse-phase high-performance liquid chromatography (HPLC) and acetic acid-urea gel electrophoresis. The results reported here indicate that the ADPribosylation reaction is involved in modifying besides histone H2b, tissue specific proteins (SNPs and LMG-O). Moreover, comparable results have been obtained from nuclei prepared from the fully active oviduct of intact animals and spayed lizards stimulated with 17 beta-estradiol. It is concluded that the poly-(ADPribosylation) of hormone-induced proteins might play a role in the differentiation of the lizard oviduct.

ADP-ribosylation reactions in Sulfolobus solfataricus, a thermoacidophilic archaeon.

An ADP-ribosylating system was detected in a crude homogenate from Sulfolobus solfataricus, a thermophilic archaeon, optimally growing at 87 degrees C. The archaeal ADP-ribosylation reaction was time-, temperature- and NAD-dependent. It proved to be highly thermostable, with about 30% decrease of 14C incorporation from [14C]NAD on incubation at 80 degrees C for up to 24 h. The main reaction product was found to be mono-ADP-ribose. Testing both [adenine-14C(U)]NAD and [adenine-14C(U)]ADPR as substrates, it was found that acceptor proteins were modified by ADP-ribose both enzymatically, via ADP-ribosylating enzymes, and via chemical attachment of free ADP-ribose, likely produced by NAD glycohydrolase activity. The synthesis of ADP-ribose-protein complexes was shown to involve mainly acceptors with molecular masses in the 40-100 kDa range, as determined by electrophoresis on polyacrylamide gel in the presence of sodium dodecyl sulphate.

Rat germinal cells require PARP for repair of DNA damage induced by gamma-irradiation and H2O2 treatment.

The ability of rat germinal cells to recover from genotoxic stress has been investigated using isolated populations of primary spermatocytes and round spermatids. Using a comet assay at pH 10.0 to assess single strand breakage (SSB) in DNA, it was found that a high level of damage was induced by 5 Gy gamma-irradiation and acute exposure to 50 microM H2O2. This damage was effectively repaired during a subsequent recovery period of 1-3 hours culture in vitro but repair was significantly delayed in the presence of the poly(ADP-ribose)polymerase (PARP) inhibitor 3-aminobenzamide (3-ABA). Immunofluorescence detection of PARP with specific antibodies localised the protein to discrete foci within the nucleus of both spermatocytes and spermatids. Poly(ADP-ribose) (pADPR) could also be detected in spermatid nuclei following gamma-irradiation or H2O2 treatment. Moreover, PARP activation occurs both in spermatocytes and spermatids left to recover after both genotoxic stresses. The NO donors, 3-morpholino-sydnonimine (SIN-1) and S-nitrosoglutathione (SNOG), caused significant SSBs in both spermatocytes and spermatids. The effects of SIN-1 could be prevented by exogenous catalase (CAT), but not superoxide dismutase (SOD), in the cell suspensions. SNOG-induced SSBs were insensitive to both CAT and SOD. It is concluded that DNA in spermatocytes and spermatids is sensitive to damage by gamma-irradiation and H2O2 and that efficient repair of SSBs requires PARP activity.

Immunochemical detection of ADP-ribosylating enzymes in the archaeon Sulfolobus solfataricus.

Polyclonal antibodies raised against eukaryotic mono-(ADPribose)transferase and poly(ADPribose)polymerase were used to test the presence of antigenic determinants in a crude extract of Sulfolobus solfataricus, a thermophilic archaeon. Samples from eukaryotic (bull testis) and bacterial (E. coli) sources were analysed for comparison. All tested antibodies reacted with the sulfolobal sample with a specificity comparable to that of the eukaryotic preparation, as revealed by ELISA test, activity assays in the presence of antibodies and immunoblot experiments. After electrophoresis and western blot of sulfolobal proteins, a band at a mass around 50 kDa was detected by immunostaining.

Poly(ADP-ribose) polymerase activity is inhibited by 2',5'-oligoadenylates in mouse L-cells.

Down regulation of poly(ADP-ribose)polymerase (ADPRP) activity was observed in mouse LW-cells after treatment with 2'-5'oligoadenylates or with fibroblast interferon and poly(rI) poly(rC). The poly(rI) poly(rC)-induced inhibition of the enzymatic activity correlates with the observed increase of endogenous 2',5'-oligoadenylate cores which were reported to be potent inhibitors of ADPRP in vitro.