Stable population structure in Europe since the Iron Age, despite high mobility.

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000-3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire's mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history.

Amyloidosis: a rare cause of severe acute liver failure.

Gastrointestinal amyloidosis can be primary, more associated with monoclonal plasma cell dyscrasia, or secondary, usually secondary to a tissue-destructive, chronic inflammatory process (such as inflammatory bowel disease, for example) and long-term dialysis. The rare presentation of severe acute liver failure in systemic amyloidosis can make this diagnosis/ management more difficult. Hepatomegaly with signs of diffuse infiltrative disease and periportal involvement associated with thoracic and other abdominal radiological findings in the appropriate clinical context may constitute a diagnostic imaging clue in this challenge.

EARLY BLOOD LACTATE AS A BIOMARKER FOR CARDIOVASCULAR COLLAPSE IN EXPERIMENTAL SEPSIS.

ABSTRACT: Cecal ligation and puncture (CLP) is the gold standard model for studying septic shock, which is characterized by hypotension and hyporeactivity to vasoconstrictors. However, approximately 30% of CLP animals do not exhibit cardiovascular changes, requiring more replicates because of the high variability of the model. Therefore, biomarkers enabling the early prediction of cardiovascular collapse in sepsis would greatly benefit sepsis nonclinical studies, refining experimental models and improving clinical translation. Thus, this study aimed to test whether the early increase in lactate levels could predict hypotension and hyporesponsiveness to vasoconstrictors in a rat model of sepsis. Male and female Wistar rats were subjected to CLP or sham procedure. Tail blood lactate was measured 6, 12, and 24 h after surgery. Then, inflammatory, biochemical, and hemodynamic parameters were evaluated. Rats subjected to CLP developed hypotension, hyporesponsiveness to vasoconstrictors, an intense inflammatory process, and increased plasma markers of organ dysfunction. By using receiver operating characteristics curve analysis, we have established that a lactate value of 2.45 mmol/L can accurately discriminate between a rat exhibiting a normal vasoconstrictive response and a vasoplegic rat with 84% accuracy (area under the curve: 0.84; confidence interval [CI]: 0.67-1.00). The sensitivity, which is the ability to identify a diseased rat (true positive), was 75% (CI: 41-95), and the true negative rate was 81% (CI: 57-93). Therefore, early measurement of lactate levels in sepsis could serve as a valuable biomarker for distinguishing vasoplegic rats from those exhibiting normal vasoconstrictive responses.

A genetic history of continuity and mobility in the Iron Age central Mediterranean.

The Iron Age was a dynamic period in central Mediterranean history, with the expansion of Greek and Phoenician colonies and the growth of Carthage into the dominant maritime power of the Mediterranean. These events were facilitated by the ease of long-distance travel following major advances in seafaring. We know from the archaeological record that trade goods and materials were moving across great distances in unprecedented quantities, but it is unclear how these patterns correlate with human mobility. Here, to investigate population mobility and interactions directly, we sequenced the genomes of 30 ancient individuals from coastal cities around the central Mediterranean, in Tunisia, Sardinia and central Italy. We observe a meaningful contribution of autochthonous populations, as well as highly heterogeneous ancestry including many individuals with non-local ancestries from other parts of the Mediterranean region. These results highlight both the role of local populations and the extreme interconnectedness of populations in the Iron Age Mediterranean. By studying these trans-Mediterranean neighbours together, we explore the complex interplay between local continuity and mobility that shaped the Iron Age societies of the central Mediterranean.

Does response to preoperative intra-articular anesthetic injections predict outcomes of femoroacetabular impingement syndrome?

INTRODUCTION: Some patients with femoroacetabular impingement syndrome (FAIS) who undergo surgery do not show satisfactory outcomes. Reliable tests that can inform prognosis of FAIS surgery are needed for optimized indications and contraindications to surgery. We aimed to review and critically appraise available literature on the capability of patient response to preoperative intra-articular anesthetic injections (PIAI) to predict post-surgical outcomes in patients with FAIS. MATERIALS AND METHODS: This study was conducted in accordance with the PRISMA statement. Studies that assessed the patient pain response to PIAI and post-surgical outcomes in patients with FAIS were considered eligible. Study selection and data collection were performed by three independent reviewers. Main outcomes evaluated were those measured by hip outcome scales often used in assessing postoperative pain and functional recovery, such as the modified Harris Hip Score (mHHS) and international Hip Outcome Tool (iHOT). The likelihood ratio of achieving satisfactory postoperative outcomes at the mHHS (LHR) was extracted or calculated-for patients with significant response to PIAI and for those without a significant response to PIAI. The risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool. RESULTS: Six studies were considered eligible for analysis. Five studies indicated that patient response to PIAI are associated to surgical outcomes for patients with FAIS, with a greater reduction in pain typically indicating a better surgical outcome. Additionally, the LHR ranged from 1.15 to 1.92 for patients with significant response to PIAI (I2 = 90.6%). For patients without a significant response, the LHR ranged from 0.18 to 0.65 (I2 = 87.5). An overall high risk of bias was observed for all studies included in the analysis. Study attrition, the prognostic factor measurement and the presence of confounding factors were the main sources of bias. CONCLUSIONS: Greater reductions in pain with preoperative intra-articular anesthetic injections were found to be associated to better outcomes after FAIS surgery, but all available studies contain a high risk of bias.

Exploring biomarkers and prognostic factors in uterine carcinosarcoma: An insight into L1CAM, CDX2, p53, and MSI status.

BACKGROUND: Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers. METHODS AND FINDINGS: The internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively). CONCLUSION: The strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival.

Intestinal pneumatosis as a manifestation of systemic sclerosis.

A 60-year-old female patient was admitted to the emergency room for a 7-day history of abdominal bloating, nausea, vomiting, constipation, and lack of flatus. She had been diagnosed with systemic sclerosis (SSc) 10 years ago and had been using methotrexate, sildenafil, and prednisone. She did not present any signs of instability, but physical examination showed malnourishment status and abdominal tenderness and distention. Plain abdominal radiography was suggestive of sigmoid volvulus, confirmed and successfully resolved after endoscopic decompression therapy. Eight months later, the patient developed a new episode of abdominal obstruction. Computed Tomography (CT) scan identified a distended sigmoid colon due to its torsion with gas areas within the bowel wall. This time, endoscopic decompression had failed to treat, so exploratory laparotomy was performed. Colonic distention and sigmoid volvulus were identified during the procedure, after which sigmoidectomy followed by primary anastomosis was performed. Neither perforation nor masses were found. Furthermore, the anatomopathological study was inconsistent with vascular, inflammatory, or neoplastic diseases.

Budd-Chiari syndrome in Behçet's disease.

A 36-year-old man was admitted to the emergency department due to a 30-day history of abdominal distention and epigastralgia. He had described a non-intentional 10kg weight loss, dry cough, and fever 6 months before his admission. He had a history of tobacco and cocaine abuse and reported recurrent oral and genital ulcers. Physical examination showed an extensive area of venous collateral circulation on the abdominal wall, hepatomegaly, signs of a moderate ascites, and lower limb edema. Liver and renal function tests were normal. The ascitic fluid analysis did not show an inflammatory or infectious pattern. Upper flexible endoscopy revealed esophageal fine-caliber varices and colonoscopy showed an isolated terminal ileal ulcer. Abdominal imaging revealed hepatomegaly, voluminous ascites, and thrombosis of hepatic veins, inferior and superior vena cava (Figure 1). Infections and coagulation or lymphoproliferative disorders were excluded. Thereafter, the diagnosis of Budd-Chiari Syndrome in Behçet disease was established and immunosuppression treatment was started with good initial clinical evolution.

Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on abdominal manifestations.

Von Hippel-Lindau (VHL) disease is a monogenic autosomal dominant disorder with germline mutations of the VHL anti-oncogene on the short arm of chromosome 3 (3p25-26). It affects 1:36,000-50,000 individuals, with a penetrance greater than 90% at 65 years of age. Although of variable onset and presentation, with pleiotropism even among members of the same family who share a specific mutation, VHL disease usually manifests initially in young adults. It predisposes to the development of benign and malignant tumors of the central nervous system (CNS) and visceral organs. The clinical diagnosis of VHL disease can be made in the following circumstances: a) in patients with a family history of the disease and at least one of the tumors characteristic of it (e.g., retinal or CNS hemangioblastomas, clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, and endolymphatic sac tumors); b) in patients with two or more CNS hemangioblastomas; c) or in patients with a retinal or CNS hemangioblastoma plus at least one visceral tumor characteristic of the disease, excluding renal and epididymal cysts. Imaging plays an important role in the diagnosis and follow-up of patients with VHL disease. This pictorial essay presents characteristic images of abdominal manifestations of VHL disease-related tumors that all radiologists should be aware of.

A doença de von Hippel-Lindau (VHL) é uma desordem autossômica dominante monogênica com mutações na linha germinativa do antioncogene VHL, no braço curto do cromossomo três (3p25-26). Afeta 1:36.000-50.000 indivíduos, com penetrância superior a 90% aos 65 anos de idade. Embora tenha início e apresentação variáveis, com pleiotropismo mesmo entre membros da mesma família que partilham uma mutação específica, usualmente manifesta-se de início em adultos jovens e predispõe ao desenvolvimento de tumores benignos e malignos no sistema nervoso central (SNC) e órgãos viscerais. Clinicamente, o diagnóstico pode ser realizado em uma das seguintes circunstâncias: a) em pacientes com história familiar de doença de VHL e pelo menos um dos tumores característicos relacionados à síndrome (como hemangioblastomas retinianos ou do SNC, carcinoma de células renais de células claras, tumores neuroendócrinos pancreáticos e tumores do saco endolinfático); b) dois ou mais hemangioblastomas do SNC; c) um hemangioblastoma retiniano ou do SNC mais pelo menos um tumor característico visceral relacionado à síndrome, excluindo-se cistos renais e epididimários. Nesse contexto, a imagem ocupa importante papel no diagnóstico e acompanhamento desses pacientes. Este ensaio iconográfico apresenta imagens características de manifestações abdominais de tumores relacionados à doença de VHL que todos os radiologistas devem conhecer.

Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on abdominal manifestations / Manifestações de imagem da doença de von Hippel-Lindau: um guia ilustrado das manifestações abdominais

Abstract Von Hippel-Lindau (VHL) disease is a monogenic autosomal dominant disorder with germline mutations of the VHL anti-oncogene on the short arm of chromosome 3 (3p25-26). It affects 1:36,000-50,000 individuals, with a penetrance greater than 90% at 65 years of age. Although of variable onset and presentation, with pleiotropism even among members of the same family who share a specific mutation, VHL disease usually manifests initially in young adults. It predisposes to the development of benign and malignant tumors of the central nervous system (CNS) and visceral organs. The clinical diagnosis of VHL disease can be made in the following circumstances: a) in patients with a family history of the disease and at least one of the tumors characteristic of it (e.g., retinal or CNS hemangioblastomas, clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, and endolymphatic sac tumors); b) in patients with two or more CNS hemangioblastomas; c) or in patients with a retinal or CNS hemangioblastoma plus at least one visceral tumor characteristic of the disease, excluding renal and epididymal cysts. Imaging plays an important role in the diagnosis and follow-up of patients with VHL disease. This pictorial essay presents characteristic images of abdominal manifestations of VHL disease-related tumors that all radiologists should be aware of.

Resumo A doença de von Hippel-Lindau (VHL) é uma desordem autossômica dominante monogênica com mutações na linha germinativa do antioncogene VHL, no braço curto do cromossomo três (3p25-26). Afeta 1:36.000-50.000 indivíduos, com penetrância superior a 90% aos 65 anos de idade. Embora tenha início e apresentação variáveis, com pleiotropismo mesmo entre membros da mesma família que partilham uma mutação específica, usualmente manifesta-se de início em adultos jovens e predispõe ao desenvolvimento de tumores benignos e malignos no sistema nervoso central (SNC) e órgãos viscerais. Clinicamente, o diagnóstico pode ser realizado em uma das seguintes circunstâncias: a) em pacientes com história familiar de doença de VHL e pelo menos um dos tumores característicos relacionados à síndrome (como hemangioblastomas retinianos ou do SNC, carcinoma de células renais de células claras, tumores neuroendócrinos pancreáticos e tumores do saco endolinfático); b) dois ou mais hemangioblastomas do SNC; c) um hemangioblastoma retiniano ou do SNC mais pelo menos um tumor característico visceral relacionado à síndrome, excluindo-se cistos renais e epididimários. Nesse contexto, a imagem ocupa importante papel no diagnóstico e acompanhamento desses pacientes. Este ensaio iconográfico apresenta imagens características de manifestações abdominais de tumores relacionados à doença de VHL que todos os radiologistas devem conhecer.

A problematização como método: pistas para uma política do pensamento / Problematization as a method: clues for a politics of thought

Este artigo apresenta a problematização como método para a pesquisa inspirada na perspectiva da filosofia da diferença, que implica uma posição crítica ao pensamento representacional. Emerge de uma experiência acadêmica de pós-graduação (um aluno de mestrado, uma aluna de doutorado e a professora orientadora) que aposta em uma política metodológica, afirmando o potencial produtivo de um pensar problemático na duração. Desenvolvemos a discussão a partir das ideias de Michel Foucault, Gilles Deleuze, Henri Bergson e René Lourau para pensar a operação da problematização enquanto método que pode produzir rupturas. Percorremos os seguintes eixos: intuição e pensamento enquanto problemáticos, análise de implicação como motor de pesquisa (retomando sua radicalidade) e, finalmente, ensaiamos uma discussão crítica acerca de modulações do objeto de pesquisa (como objeto problemático) e da ética em pesquisa, como efeitos deste exercício.

Hepatobiliary phases in magnetic resonance imaging using liver-specific contrast for focal lesions in clinical practice.

BACKGROUND: Challenging lesions, difficult to diagnose through non-invasive methods, constitute an important emotional burden for each patient regarding a still uncertain diagnosis (malignant x benign). In addition, from a therapeutic and prognostic point of view, delay in a definitive diagnosis can lead to worse outcomes. One of the main innovative trends currently is the use of molecular and functional methods to diagnosis. Numerous liver-specific contrast agents have been developed and studied in recent years to improve the performance of liver magnetic resonance imaging (MRI). More recently, one of the contrast agents introduced in clinical practice is gadoxetic acid (gadoxetate disodium). AIM: To demonstrate the value of the hepatobiliary phases using gadoxetic acid in MRI for the characterization of focal liver lesions (FLL) in clinical practice. METHODS: Overall, 302 Lesions were studied in 136 patients who underwent MRI exams using gadoxetic acid for the assessment of FLL. Two radiologists independently reviewed the MRI exams using four stages, and categorized them on a 6-point scale, from 0 (lesion not detected) to 5 (definitely malignant). The stages were: stage 1- images without contrast, stage 2- addition of dynamic phases after contrast (analogous to usual extracellular contrasts), stage 3- addition of hepatobiliary phase after 10 min (HBP 10'), stage 4- hepatobiliary phase after 20 min (HBP 20') in addition to stage 2. RESULTS: The interobserver agreement was high (weighted Kappa coefficient: 0.81- 1) at all stages in the characterization of benign and malignant FLL. The diagnostic weighted accuracy (Az) was 0.80 in stage 1 and was increased to 0.90 in stage 2. Addition of the hepatobiliary phase increased Az to 0.98 in stage 3, which was also 0.98 in stage 4. CONCLUSION: The hepatobiliary sequences improve diagnostic accuracy. With growing potential in the era of precision medicine, the improvement and dissemination of the method among medical specialties can bring benefits in the management of patients with FLL that are difficult to diagnose.

ICOS-Fc as innovative immunomodulatory approach to counteract inflammation and organ injury in sepsis.

Inducible T cell co-stimulator (ICOS), an immune checkpoint protein expressed on activated T cells and its unique ligand, ICOSL, which is expressed on antigen-presenting cells and non-hematopoietic cells, have been extensively investigated in the immune response. Recent findings showed that a soluble recombinant form of ICOS (ICOS-Fc) can act as an innovative immunomodulatory drug as both antagonist of ICOS and agonist of ICOSL, modulating cytokine release and cell migration to inflamed tissues. Although the ICOS-ICOSL pathway has been poorly investigated in the septic context, a few studies have reported that septic patients have reduced ICOS expression in whole blood and increased serum levels of osteopontin (OPN), that is another ligand of ICOSL. Thus, we investigated the pathological role of the ICOS-ICOSL axis in the context of sepsis and the potential protective effects of its immunomodulation by administering ICOS-Fc in a murine model of sepsis. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in five-month-old male wild-type (WT) C57BL/6, ICOS-/-, ICOSL-/- and OPN-/- mice. One hour after the surgical procedure, either CLP or Sham (control) mice were randomly assigned to receive once ICOS-Fc, F119SICOS-Fc, a mutated form uncapable to bind ICOSL, or vehicle intravenously. Organs and plasma were collected 24 h after surgery for analyses. When compared to Sham mice, WT mice that underwent CLP developed within 24 h a higher clinical severity score, a reduced body temperature, an increase in plasma cytokines (TNF-α, IL-1ß, IL-6, IFN-γ and IL-10), liver injury (AST and ALT) and kidney (creatinine and urea) dysfunction. Administration of ICOS-Fc to WT CLP mice reduced all of these abnormalities caused by sepsis. Similar beneficial effects were not seen in CLP-mice treated with F119SICOS-Fc. Treatment of CLP-mice with ICOS-Fc also attenuated the sepsis-induced local activation of FAK, P38 MAPK and NLRP3 inflammasome. ICOS-Fc seemed to act at both sides of the ICOS-ICOSL interaction, as the protective effect was lost in septic knockout mice for the ICOS or ICOSL genes, whereas it was maintained in OPN knockout mice. Collectively, our data show the beneficial effects of pharmacological modulation of the ICOS-ICOSL pathway in counteracting the sepsis-induced inflammation and organ dysfunction.

Peripheral artery disease: a comparison of urgent open and endovascular revascularizations on the public health system in Brazil, from 2010 to 2020.

Background: Peripheral artery disease (PAD) has high prevalence and is associated with high risk of cardiovascular events. Surgical or endovascular intervention is necessary in chronic limb-threatening ischemia. Objectives: To evaluate the distribution of open and endovascular revascularizations in different regions of Brazil, analyzing the health system costs and mortality related to these procedures. Methods: A descriptive, cross-sectional, observational, epidemiological study was carried out to evaluate open and endovascular surgeries performed on the SUS public healthcare system in Brazil, from 2010 to 2020. Data were collected from the SUS Department of Informatics (Datasus). Results: Over the period analyzed, 83,218 admissions for open and endovascular surgeries were registered, with a total cost of R$ 333,989,523.17. There were more hospital admissions for percutaneous procedures (56,132) than for conventional surgery (27,086). Most of the procedures (83%) were performed in the country's Southeast and South regions, while the North region had the lowest number of procedures. Over the period evaluated, there was a decreasing trend for open procedures and an increasing trend for endovascular procedures. The average hospital stay was shorter for endovascular procedures (5.3 days) than for open surgery (10.2 days). The analysis of mortality related to these procedures revealed a higher rate of in-hospital mortality associated with open revascularization than with endovascular (5.24% vs. 1.56%). Conclusions: Endovascular techniques constituted the primary approach for revascularization treatment in critical limb-threatening ischemia, with a lower in-hospital mortality rate and shorter hospital stay when compared to open surgeries.

Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on the central nervous system.

Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant inherited syndrome that affects the germline of the VHL gene, a tumor suppressor gene. VHL disease is characterized by the multisystemic development of a variety of benign and malignant tumors, especially in the central nervous system (CNS). Such tumors include retinal and CNS hemangioblastomas, as well as endolymphatic sac tumors. The various tumor sites are responsible for the diversity of signs and symptoms related to the disease. The mean age at symptom onset is 33 years. Despite medical advances, the average life expectancy of patients with VHL disease is 49 years. Imaging plays a pivotal role in the clinical diagnosis and is essential to the follow-up of patients with VHL disease. This pictorial essay describes characteristic CNS manifestations of VHL disease-related tumors that all radiology residents should be aware of.

A doença de von Hippel-Lindau (VHL) é uma síndrome hereditária autossômica dominante rara que afeta a linha germinativa do gene VHL, um gene supressor tumoral. A doença de VHL é caracterizada pelo desenvolvimento multissistêmico de uma variedade de tumores benignos e malignos, especialmente no sistema nervoso central (SNC). Dentre eles, destacam-se hemangioblastomas retinianos e do SNC, e o tumor do saco endolinfático. Os diferentes locais dos tumores justificam a diversidade de sinais e sintomas relacionados à doença, que usualmente se manifestam com a idade média de 33 anos. Apesar dos avanços da medicina, a expectativa de vida média desses pacientes é de 49 anos. Exames de imagem têm papel fundamental no diagnóstico e são essenciais no seguimento dos pacientes com doença de VHL. Este ensaio iconográfico descreve as manifestações características dos tumores do SNC relacionados à doença de VHL que todos os residentes de radiologia devem saber.

The Affective Dimension of Pain Appears to Be Determinant within a Pain-Insomnia-Anxiety Pathological Loop in Fibromyalgia: A Case-Control Study.

BACKGROUND: Fibromyalgia (FM) is a chronic pain disease characterized by multiple symptoms whose interactions and implications in the disease pathology are still unclear. This study aimed at investigating how pain, sleep, and mood disorders influence each other in FM, while discriminating between the sensory and affective pain dimensions. METHODS: Sixteen female FM patients were evaluated regarding their pain, while they underwent-along with 11 healthy sex- and age-adjusted controls-assessment of mood and sleep disorders. Analysis of variance and correlations were performed in order to assess group differences and investigate the interactions between pain, mood, and sleep descriptors. RESULTS: FM patients reported the typical widespread pain, with similar sensory and affective inputs. Contrary to controls, they displayed moderate anxiety, depression, and insomnia. Affective pain (but neither the sensory pain nor pain intensity) was the only pain indicator that tendentially correlated with anxiety and insomnia, which were mutually associated. An affective pain-insomnia-anxiety loop was thus completed. High ongoing pain strengthened this vicious circle, to which it included depression and sensory pain. CONCLUSIONS: Discriminating between the sensory and affective pain components in FM patients disclosed a pathological loop, with a key role of affective pain; high ongoing pain acted as an amplifier of symptoms interaction. This unraveled the interplay between three of most cardinal FM symptoms; these results contribute to better understand FM determinants and pathology and could help in orienting therapeutic strategies.

Grey wolf genomic history reveals a dual ancestry of dogs.

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1-8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.

Manifestações de imagem da doença de von Hippel-Lindau: um guia ilustrado com foco no sistema nervoso central / Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on the central nervous system

Abstract A doença de von Hippel-Lindau (VHL) é uma síndrome hereditária autossômica dominante rara que afeta a linha germinativa do gene VHL, um gene supressor tumoral. A doença de VHL é caracterizada pelo desenvolvimento multissistêmico de uma variedade de tumores benignos e malignos, especialmente no sistema nervoso central (SNC). Dentre eles, destacam-se hemangioblastomas retinianos e do SNC, e o tumor do saco endolinfático. Os diferentes locais dos tumores justificam a diversidade de sinais e sintomas relacionados à doença, que usualmente se manifestam com a idade média de 33 anos. Apesar dos avanços da medicina, a expectativa de vida média desses pacientes é de 49 anos. Exames de imagem têm papel fundamental no diagnóstico e são essenciais no seguimento dos pacientes com doença de VHL. Este ensaio iconográfico descreve as manifestações características dos tumores do SNC relacionados à doença de VHL que todos os residentes de radiologia devem saber.

Abstract Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant inherited syndrome that affects the germline of the VHL gene, a tumor suppressor gene. VHL disease is characterized by the multisystemic development of a variety of benign and malignant tumors, especially in the central nervous system (CNS). Such tumors include retinal and CNS hemangioblastomas, as well as endolymphatic sac tumors. The various tumor sites are responsible for the diversity of signs and symptoms related to the disease. The mean age at symptom onset is 33 years. Despite medical advances, the average life expectancy of patients with VHL disease is 49 years. Imaging plays a pivotal role in the clinical diagnosis and is essential to the follow-up of patients with VHL disease. This pictorial essay describes characteristic CNS manifestations of VHL disease-related tumors that all radiology residents should be aware of.

Effect of pentoxifylline and α-tocopherol on medication-related osteonecrosis of the jaw in rats: Before and after dental extraction.

OBJECTIVE: Evaluate the effect of pentoxifylline and α-tocopherol administration in the prevention or treatment of medication-related jaw osteonecrosis (MRONJ). METHODOLOGY: Sixty Wistar rats were divided into three prevention (C-prev, BP-prev and BP/PT-prev) and three treatment groups (C-treat, BP-treat and BP/PT-treat), n = 10. The animals in the BP-prev, BP/PT-prev, BP-treat and BP/PT-treat groups received zoledronic acid (0.1 mg/kg) for 12 weeks, while the animals in the C-prev and C-treat groups received saline solution. At week 6, all animals underwent tooth extraction. Between week 5 and week 12, the BP/PT-prev group was treated with pentoxifylline (50 mg/kg/day) and α-tocopherol (80 mg/kg/day), with euthanasia at the end of week 12. The BP/PT-treat group received the same drug protocol, but it was performed between week 12 and week 16, with euthanasia at the end of week 16. Afterwards, the presence of osteonecrosis was evaluated by clinical analysis, radiographic and histological. RESULTS: BP/PT-treat group showed a reduction in the histological incidence of osteonecrosis by 50%, decrease the percentage of empty osteocyte gaps and the necrotic area, decrease the presence of bone sequestration and increase the number of osteocytes and alveolar blood flow (p < 0.05). However, BP/PT-prev group showed only a reduction in the necrotic area percentage when compared to BP-prev (p < 0.05). CONCLUSIONS: Pentoxifylline and α-tocopherol administration before tooth extraction was not effective in preventing MRONJ. However, this drug protocol was able to reduce MRONJ manifestation when administrate after discontinuation of bisphosphonate, thus it can be considered as a viable strategy for the treatment of this pathological condition.