Cholangiocarcinoma: from molecular biology to treatment

Cholangiocarcinoma is a rare tumor originating in the bile ducts, which, according to their anatomical location, is classified as intrahepatic, extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in recent decades. With respect to tumor biology, several genetic alterations correlated with resistance to chemotherapy and radiotherapy have been identified. Here, we highlight changes in KRAS and TP53 genes that are normally associated with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family appear to be involved in the resistance that the cholangiocarcinoma presents toward conventional therapies. With regard to diagnosis, tumor markers most commonly used are CEA and CA 19-9, and although its use isolated appears controversial, their combined value has been increasingly advocated. In imaging terms, various methods are needed, such as abdominal ultrasound, computed tomography and cholangiopancreatography. Regarding therapy, surgical modalities are the only ones that offer chance of cure; however, due to late diagnosis, most patients cannot take advantage of them. Thus, the majority of patients are directed to other therapeutic modalities like chemotherapy, which, in this context, assumes a purely palliative role. Thus, it becomes urgent to investigate new therapeutic options for this highly aggressive type of tumor

Influence of P53 on the radiotherapy response of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines

Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature

This is an accepted manuscript of an article published by Elsevier in Journal of Thermal Biology on 18/07/2017, available online: https://doi.org/10.1016/j.jtherbio.2017.07.006 The accepted version of the publication may differ from the final published version.© 2017 Elsevier Ltd The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n  =  24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants’ demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled “Thermographic Imaging in Sports and Exercise Medicine (TISEM)” which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.Published versio

Staphylococcus aureus reservoirs and transmission routes in a Portuguese Neonatal Intensive Care Unit: a 30-month surveillance study.

Although Staphylococcus aureus is a major cause of outbreaks in neonatal intensive care units (NICUs), there are no studies on the epidemiology of S. aureus isolates responsible for infection in Portuguese NICUs. Between July 2005 and December 2007, a total of 54 methicillin susceptible S. aureus (MSSA) isolates were recovered from 16 infected infants, parents, health care workers (HCWs), and the environment in a level III NICU. Isolates were characterized by pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing. Virulence determinants were detected by multiplex polymerase chain reaction. Three major MSSA clones were endemic in the NICU, representing 70% (n=38) of the isolates: PFGE type A-ST5 (n=17); type B-ST30 (n=12); and type C-ST1 (n=9). Leukotoxins and hemolysins were present in all isolates, although none of them carried PVL. HCWs, plastic folders protecting clinical files, and mothers' nipples were identified as potential reservoirs and/or vehicles of dissemination of S. aureus. Consequently, additional infection control measures were implemented in this NICU

A New Era in the Quest for Dark Matter

There is a growing sense of `crisis' in the dark matter community, due to the absence of evidence for the most popular candidates such as weakly interacting massive particles, axions, and sterile neutrinos, despite the enormous effort that has gone into searching for these particles. Here, we discuss what we have learned about the nature of dark matter from past experiments, and the implications for planned dark matter searches in the next decade. We argue that diversifying the experimental effort, incorporating astronomical surveys and gravitational wave observations, is our best hope to make progress on the dark matter problem.Comment: Published in Nature, online on 04 Oct 2018. 13 pages, 1 figur

Dynamics of early establishment of SARS-CoV-2 VOC Omicron lineages in Minas Gerais, Brazil

Brazil is one of the nations most affected by Coronavirus disease 2019 (COVID-19). The introduction and establishment of new virus variants can be related to an increase in cases and fatalities. The emergence of Omicron, the most modified SARS-CoV-2 variant, caused alarm for the public health of Brazil. In this study, we examined the effects of the Omicron introduction in Minas Gerais (MG), the second-most populous state of Brazil. A total of 430 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples from November 2021 to June 2022 from Belo Horizonte (BH) city were sequenced. These newly sequenced genomes comprise 72% of all previously available SARS-CoV-2 genomes for the city. Evolutionary analysis of novel viral genomes reveals that a great diversity of Omicron sublineages have circulated in BH, a pattern in-keeping with observations across Brazil more generally. Bayesian phylogeographic reconstructions indicate that this diversity is a product of a large number of international and national importations. As observed previously, São Paulo state is shown as a significant hub for viral spread throughout the country, contributing to around 70% of all viral Omicron introductions detected in MG

High prevalence of ST121 in community-associated methicillin-susceptible Staphylococcus aureus lineages responsible for skin and soft tissue infections in Portuguese children

In order to evaluate the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Portugal, we analyzed a collection of 38 S. aureus isolates recovered from 30 children attending the pediatric emergency department of a central hospital in Lisbon due to skin and soft tissue infections. Molecular characterization identified seven clonal lineages among the 35 methicillin-susceptible S. aureus (MSSA) isolates, of which the major lineage PFGE A/t159/ST121 included 63% of the isolates. The three MRSA isolates belonged to the Pediatric clone PFGE D/t535/ST5-IV (n = 2) and to the European CA-MRSA clone PFGE G/t044/ST80-IVc (n = 1). All isolates harbored several virulence factors, namely, leukocidins. Panton-Valentine leukocidin (PVL) was produced by isolates from five MSSA lineages and by the ST80 MRSA. Of interest, this is the first reported isolation of CA-MRSA ST80 in Portugal

Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis

The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis

Brazilian obstetrician-gynecologists and abortion: a survey of knowledge, opinions and practices

BACKGROUND: Abortion laws are extremely restrictive in Brazil. The knowledge, opinions of abortion laws, and abortion practices of obstetrician-gynecologists can have a significant impact on women's access to safe abortion. METHODS: We conducted a mail-in survey with a 10% random sample of obstetrician-gynecologists affiliated with the Brazilian Federation of Obstetricians and Gynecologists. We documented participants' experiences performing abortion under a range of legal and illegal circumstances, and asked about which abortion techniques they had experience with. We used chi-square tests and crude logistic regression models to determine which sociodemographic, knowledge-related, or practice-related variables were associated with physician opinion. RESULTS: Of the 1,500 questionnaires that we mailed out, we received responses from 572 (38%). Less than half (48%) of the respondents reported accurate knowledge about abortion law and 77% thought that the law should be more liberal. One-third of respondents reported having previous experience performing an abortion, and very few of these physicians reported having experience with manual vacuum aspiration (MVA) or with misoprostol with either mifepristone or methotrexate. Physicians that favored liberalization of the law were more likely to have correct knowledge about abortion law, and to be in favor of public funding for abortion services. CONCLUSION: Brazilian obstetrician-gynecologists need more information on abortion laws and on safe, effective abortion procedures