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.

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.

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.

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 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.

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.

Misregulation of poly(ADP-ribose) polymerase-1 activity and cell type-specific loss of poly(ADP-ribose) synthesis in the cerebellum of aged rats.

Protein modification by ADP-ribose polymers is a common regulatory mechanism in eukaryotic cells and is involved in several aspects of brain physiology and physiopathology, including neurotransmission, memory formation, neurotoxicity, ageing and age-associated diseases. Here we show age-related misregulation of poly(ADP-ribose) synthesis in rat cerebellum as revealed by: (i) reduced poly(ADP-ribose) polymerase-1 (PARP-1) activation in response to enzymatic DNA cleavage, (ii) altered protein poly(ADP-ribosyl)ation profiles in isolated nuclei, and (iii) cell type-specific loss of poly(ADP-ribosyl)ation capacity in granule cell layer and Purkinje cells in vivo. In particular, although PARP-1 could be detected in virtually all granule cells, only a fraction of them appeared to be actively engaged in poly(ADP-ribose) synthesis and this fraction was reduced in old rat cerebellum. NAD(+), quantified in tissue homogenates, was essentially the same in the cerebellum of young and old rats suggesting that in vivo factors other than PARP-1 content and/or NAD(+) levels may be responsible for the age-associated lowering of poly(ADP-ribose) synthesis. Moreover, PARP-1 expression was substantially down-regulated in Purkinje cells of senescent rats.

Microstructure of sleep in eating disorders: preliminary results.

Attempts to analyse the sleep structure of patients with eating disorders have so far led to conflicting results. Polygraphic findings suggest that patients with bulimia nervosa are not easily distinguishable from age-matched controls, whereas anorexic patients show some abnormalities in sleep efficiency and sleep architecture. Nevertheless, both bulimic and anorexic patients complain of poor quality sleep. The aim of this study was to evaluate the microstructure of sleep in anorexia and bulimia by analysing arousal (following the rules of the American Sleep Disorders Association) and the cyclic alternating pattern (CAP). The results confirmed the presence of sleep disturbances in eating disordered patients: an increase in arousal length and the CAP rate. They also seem to confirm the findings of previous studies suggesting that altered sleep in eating disordered patients may be related to their body mass index (BMI) and psychopathological status.

Pesquisa de ambliopía en preescolares del Centro de Salud familiar Bernardo Leighton / Screening for amblyopia in pre-school children in the Family Health Centre, Bernardo Leighton

Introducción: La ambliopía corresponde a una disminución de la agudeza visual sin causa orgánica conocida y tiene una prevalencia estimada entre 1 a 5 por ciento de la población general. Objetivos: Cuantificar la prevalencia y determinar las causas de ambliopía en preescolares de 4 a 5 años. Material y Métodos: Se realizó examen oftalmológico completo a 94 niños derivados en forma aleatoria desde el programa control de niño sano del Centro de Salud Familiar Bernardo Leighton y se registraron la agudeza visual y refracción con mejor visión corregida, determinándose la existencia de ambliopía. Resultados: Se encontró ambliopía en 9,6 por ciento, siendo bilateral en 5,3 por ciento y asociándose principalmente a astigmatismo. El 93,3 por ciento de los ojos con agudeza visual sin corrección menor o igual a 0,5 tenían ambliopía. Conclusiones:La alta prevalencia de ambliopía encontrada hace necesario instaurar programas de screening visual para su detección precoz. Presentar agudeza visual sin corrección de 0,5 o inferior sería un factor de riesgo de esta patología.

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.

A phantom with tissue-like optical properties in the visible and near infrared for use in photomedicine.

BACKGROUND AND OBJECTIVE: Modeling of light transport in tissue requires development of theoretical models and experimental procedures, as well as tissue-simulating phantoms. Our purpose was to develop a phantom that matches the optical characteristics of human skin in the visible and near infrared spectral range. STUDY DESIGN/MATERIALS AND METHODS: The phantom consists of a transparent silicone rubber in which Al(2)O(3) particles and a cosmetic powder are embedded. Layers with thickness as thin as 0.1 mm can be made. The optical properties of Al(2)O(3) particles and cosmetic powder, i.e., total attenuation, absorption and scattering coefficients, and phase function, have been determined in the visible and near infrared spectral range, by using direct and indirect techniques. RESULTS: By varying the concentration of scattering and absorbing particles, tissue-like layers can be produced with predictable optical properties. In particular, mixing at suitable concentration Al(2)O(3) particles and cosmetic powder with the silicone rubber, the optical properties of human skin have been simulated over a range of wavelengths from 400 to 1,000 nm. The comparison between the phantom diffuse reflectance spectrum and that of human skin, averaged over a sample of 260 patients, showed a good agreement. CONCLUSION: The proposed technique allows to produce a stable and reproducible phantom, with accurately predictable optical properties, easy to make and to handle. This phantom is a useful tool for numerous applications involving light interaction with biologic tissue.

Metabolic changes in the poly(ADP-ribosyl)ation pathway of differentiating rat germinal cells.

Endogenous levels of poly(ADP-ribose) and betaNAD+ have been determined in rat male germinal cells at different stages of differentiation. The levels of both metabolites decreased progressively from primary spermatocytes to secondary spermatocytes and especially in spermatids. We have also determined the size and complexity of the ADP-ribose polymers synthesized in permeabilized germ cells. Polymers of different chain length and complexity were observed in cells incubated with different concentrations of [32P]betaNAD+; short polymers characterized primary spermatocytes incubated with low betaNAD+ concentration. In all cell fractions, polymers of over 20 residues in size were observed at high betaNAD+ levels. Long polymers were associated with the sulfuric acid-insoluble proteins (nonhistone proteins such as PARP itself). By contrast, oligomers of 20 ADP-ribose units or less were found in the sulfuric acid-soluble proteins (histone proteins). We have also identified the main ADP-ribose protein acceptors formed in each cell type. In all cells examined, PARP appears to be extensively automodified. However, by far, the H1t variant of histone H1 appeared to be the preferred ADP-ribose target among the acid-soluble proteins separated by reverse-phase HPLC. Therefore, we conclude that an active protein-poly(ADP-ribosyl)ation system is concentrated in primary spermatocytes, based on a high level of PARP automodification accompanied by the preferential heteromodification of the histone H1 variant specifically expressed in the cells undergoing the pachytene phase of the meiotic division.

Radioguided surgery of breast cancer: radiation protection survey.

The aim of this study was to estimate the radioactive risk for surgical staff performing radioguided sentinel lymph node (SN) biopsy and to calculate the contamination level in the operating room for assessment of the possible need for specific radiation protection procedures. We studied 20 patients who were selected for quadrantectomy and SN biopsy. The day before surgery a volume of 0.15 mL of 99mTc-nanocoll was injected: the activity was 3.11 +/- 0.85 MBq in group A (15 pts) and 11.6 +/- 0.6 MBq in group B (5 pts). External radiation to staff was evaluated by measuring the exposure rate in air one hour after radiopharmaceutical administration. The air KERMA rate during surgery was estimated considering the physical decay of 99mTc. Contamination of disposable materials and surgical instruments in the operating room was measured using a contamination monitor, whereas the residual activity in the SN and the injection site was measured with a gamma probe. The exposure rate at 20 cm from the injection site was 0.75 microSv/h when the most radioactive patients (group B) were treated. Contamination in the operating room proved to be negligible. Considering the number of radioguided treatments carried out by a surgeon in one year, an equivalent effective dose of 0.075 mSv was estimated; the recommended dose limit according to the relevant Italian law, DL 230/95, is 1 mSv/yr. Surgical staff therefore do not require a classification of "exposed workers" and there is no need to supply the operating room with special containers for radioactive waste.

Comparison of the ADP-ribosylating thermozyme from Sulfolobus solfataricus and the mesophilic poly(ADP-ribose) polymerases.

The poly(ADP-ribose) polymerase-like thermozyme purified from Sulfolobus solfataricus was characterised with respect to some physico-chemical properties. The archaeal protein exhibited a scarce electrophoretic mobility at both pH 2.9 and pH 7.5. Determination of the isoelectric point (pI=7.0-7.2) allowed us to understand the reason for the limited migration at pH 7.5, while amino acid composition analysis showed a moderate content of basic residues, which reduced mobility at pH 2.9. With respect to the charge, the archaeal enzyme behaved differently from the eukaryotic thermolabile poly(ADP-ribose) polymerase, described as a basic protein (pI=9.5). Well known inhibitors of the mesophilic polymerase like Zn(2+), nicotinamide and 3-aminobenzamide exerted a smaller effect on the enzyme from S. solfataricus, reducing the activity by at most 50%. Mg(2+) was a positive effector, although in a dose-dependent manner. It influenced the fluorescence spectrum of the archaeal protein, whereas NaCl had no effect.

Characterization of SNP, a novel tissue- and phase-specific nuclear protein expressed during the proliferative phase in the oviduct of the lizard Podarcis sicula Raf.

The amino acid sequence of a novel tissue-and phase-specific nuclear protein (SNP) has been determined, after purification from the nuclei of the oviduct of the lizard Podarcis sicula Raf. during the reproductive period of the seasonal growth. SNP has a pI of 9.0 and contains 81 amino acid residues with a molecular weight of 9211.88 +/- 0.09. It shows a bipartite organization as the first 40 amino acids contain all 8 cysteinyl residues, while the last 41 amino acids contain 16 prolyl residues. Two more components have also been identified and characterized, with the first 79 amino acids matching SNP and missing one or two residues at the C-terminus. They have thus been named [des-(Ala81) SNP1] and [des-(Lys80-Ala81) SNP2], respectively. The molecular weights are 9140.21 +/- 0.83 for [des-(Ala81) SNP1] and 9011 +/- 0.09 for [des-(Lys80-Ala81) SNP2].

In vitro induction of H1-H1 histone cross-linking by adenosine diphosphate-ribose polymers.

It is well-known that H1-H1 interactions are very important for the induction of 30 nm chromatin fiber and that, among all posttranslational modifications, poly(ADP-ribosyl)ation is one of those capable of modifying chromatin structure, mainly through H1 histone. As this protein can undergo both covalent and noncovalent modifications by poly(ADP-ribosyl)ation, our aim was to investigate whether and how ADP-ribose polymers, by themselves, are able to affect the formation of H1-H1 oligomers, which are normally present in a condensed chromatin structure. The results obtained in our in vitro experimental system indicate that ADP-ribose polymers are involved in chromatin decondensation. This conclusion was reached as the result of two different observations: (a) H1 histone molecules can be hosted in clusters on ADP-ribose polymers, as shown by their ability to be chemically cross-linked, and (b) H1 histone has a higher affinity for ADP-ribose polymers than for DNA; ADP-ribose polymers compete, in fact, with DNA for H1 histone binding.