The origin of the Acheulean: the 1.7 million-year-old site of FLK West, Olduvai Gorge (Tanzania)

The appearance of the Acheulean is one of the hallmarks of human evolution. It represents the emergence of a complex behavior, expressed in the recurrent manufacture of large-sized tools, with standardized forms, implying more advance forethought and planning by hominins than those required by the precedent Oldowan technology. The earliest known evidence of this technology dates back to c. 1.7 Ma. and is limited to two sites (Kokiselei [Kenya] and Konso [Ethiopia]), both of which lack fauna. The functionality of these earliest Acheulean assemblages remains unknown. Here we present the discovery of another early Acheulean site also dating to c. 1.7 Ma from Olduvai Gorge. This site provides evidence of the earliest steps in developing the Acheulean technology and is the oldest Acheulean site in which stone tools occur spatially and functionally associated with the exploitation of fauna. Simple and elaborate large-cutting tools (LCT) and handaxes co-exist at FLK West, showing that complex cognition was present from the earliest stages of the Acheulean. Here we provide a detailed technological study and evidence of the use of these tools on the butchery and consumption of fauna, probably by early Homo erectus sensu lato

Use of Placental MSCs and their exosomes as theragnostic agents for cancer treatment and diagnostic

P117 INTRODUCTION: The Na/ I symporter gene (hNIS) is expressed in the thyroid and allows the accumulation of iodine from the diet, to form T3 and T4 hormones. Moreover, it is widely used (i) as a reporter gene for molecular imaging (when the positron emitter isotope is I124 for PET or Tc99 for SPECT) or (ii) as a therapeutic gene for cancer therapy, mediated by the accumulation of I131. An unresolved challenge is how to direct this gene specifically to the tumoral area. Previously, our group demonstrated the migratory capacity of placental mesenchymal stem cells (MSCs), carrying an adenovirus-hNIS to tumors, with good results as theragnostic tool. However, as hNIS is expressed at the placental tissue (because transfers iodine to the foetus from the maternal blood), here we decided to study whether placental MSCs and their exosomes (1) express hNIS endogenously and therefore transfers the imaging and therapeutic potentials when administered with radioactive iodine (2) are capable to reach tumoral areas when they are intravenously injected due to the tumoral tissues extravasation. RESULTS/ SUMMARY We proved that human placenta MSCs and their exosomes have endogenous expression of NIS, migrate specifically to the tumour and their endogenous expression of NIS is enough to image both cells or exosomes in vivo, and their accumulation caused significant therapeutic effect combined with 131I. This highlight the use of endogenous NIS expression as therapy but also to trace new metastatic nodules

Combination of exosomes and near-infrared responsive gold nanoparticles: new selective and specific therapeutic vehicle

P602 Exosomes are extracellular vesicles (50 -150 nm of diameter) considered key elements for the intercellular communication. Although they are proposed to be ideal vehicles for the targeting of novel therapies, very little is known about the selectiveness and specificity of the transference processes involving exosomes released from different cells. PEGylated Hollow gold nanoparticles (PEG-HGNs) are near-infrared (NIR) responsive nanoparticles (NPs) which are able to generate localized heat by the use of NIR light leading to cell death when applying optical hyperthermia. In this study, we demonstrate the selectivity of in vitro exosomal transfer between certain cell types and how this phenomenon can be exploited to develop new specific vectors for advanced therapies. Firstly, PEG-HGNs were successfully incorporated in the exosome biogenesis pathway of placental stem cells (MSCs) and they were released as PEG-HGNs-loaded exosomes (PEGHGNs_ MSCs_EXOs). Exosomes were characterized by confocal microscopy, western blot, nanosight, zeta potential and electronic microscopy. Afterwards, time lapse microscopy and atomic emission spectroscopy demonstrated the selective transfer of the ..

Human breast milk exosomes accelerate mouse wound healing

P543 The healing of cutaneous wounds is a very efficient process despite being very complex. Under certain pathological conditions healing may be impaired, prolonging the healing process and eventually leading to medical intervention and the chronicity of the wound. Exosomes are secreted extracellular vesicles present in biological fluids where they play a key role in intercellular communication at the tissue, organ and organismal levels. Given that human breast milk contains abundant maternal extracellular vesicles (MEVs) with pro-regenerative and immunomodulatory properties, the aim of the present study was to evaluate if topical application ofMEVs into open wounds would be beneficial for healing. Full-thickness excision wounds of 4-mm diameter were created in the dorsal skin of C57BL/6 mice and topical application of 20 micrograms of human MEV isolated at weeks 9, 11, 12 and 15 postpartum of breastfeeding were placed onto the open wounds. Control wounds were vehicle-treated. Macroscopic measurements up to 7 days postwounding revealed that the area of the wound treated with MEV significantly decreased compared with controls. Histological analyses at day 7 post-wounding showed no differences in the granulation tissue area between groups. ..

Nitrogen-doped carbon nanodots deposited on titania nanoparticles: unconventional near-infrared active photocatalysts for cancer therapy

Cancer represents a major public health issue and a primary cause of death for the mankind and the search for alternative cancer treatments that assist or alleviate the drawbacks of current cancer therapies remains imperative. Nanocatalytic medicine represents a new discipline that aims at exploiting the unique response of heterogeneous catalysts exposed to unconventional conditions such as those encountered in the tumor microenvironment (TME). Photo-triggered cancer therapies using light-activable catalytic materiales can stimulate and activate multiple biological processes and represent a very promising field of study. Herein, we evaluate the use of carbon nanodots with different composition (CNDs) retrieved by laser pyrolysis as potential near-infrared (NIR) photosensitizers able to activate P25 semiconductor nanostructured photocatalysts. We describe the enhanced photocatalytic response towards glucose conversion and reactive oxygen species (ROS) generation upon irradiation with NIR-LEDs when CNDs doped with heteroatoms were tested. The most active photocatalysts were evaluated in the presence of cancer cells and revealed a promising photodynamic effect under NIR irradiation. This work represents one of the scarce examples of a conventional inorganic photocatalyst containing TiO2 that is translated into a biomedical application with a successful outcome

Public health failures in the 20th century

Introdução: O século XX é caracterizado por avanços consideráveis na área da saúde pública. Não obstante os importantes feitos, esta revisão pretende retratar os insucessos deste período. Material e métodos: Foi realizada uma revisão narrativa da literatura, orientada por temas e consulta de fontes de informação fornecidas por peritos em saúde pública. Na inclusão, seleção e análise da evidência coletada foi utilizada a técnica de grupo nominal pelos autores. Resultados e discussão: Distinguem-se cinco esferas consideradas fundamentais para uma prática adequada em saúde pública: evidência, avaliação, apreciação do risco, políticas de saúde e planeamento. Os insucessos da saúde pública no século XX identificados traduzem-se pela carência de decisão informada em evidência e avaliações de impacto; da apreciação do risco, com o duplo peso de doenças transmissíveis e não-transmissíveis; de políticas de saúde, orientadas para os determinantes de saúde; e do planeamento sustentável. Transversalmente, a ausência de comunicação efetiva dificultou a identificação precoce dos insucessos no século XX. Destaca-se a desarticulação entre planeamento, políticas de saúde e os diversos setores sociais, sobretudo o político-económico. O processo de tomada de decisão e as respostas aos problemas de saúde pública caracterizaram-se pela reatividade e ações ad hoc, agravado pela escassa evidência já existente. Conclusões: A falta de financiamento para planos e programas focados na promoção da saúde, e de investimento no desenvolvimento de com-petências de salutogénese e no combate às iniquidades no acesso à saúde adiaram e impediram o alcance das metas delineadas para o século XX e serão alguns dos maiores desafios da saúde pública para o futuro. Introduction: the 20th century is characterized for its considerable developments in the public health sector. Notwithstanding those important accomplishments, this review aims to depict the unsuccessful endeavours of that period. Materials and method: a narrative review of the literature was carried, organised by topics and by the consultation of informative sources provided by experts in public health. Nominal group technique was applied by the authors in the inclusion, selection and analysis of collected evidence. Results and discussion: five domains can be identified in order to achieve an adequate practice of public health: evidence, evaluation, risk assessment, health policies and planning. The failures in public health identified across the 20th century can be explained by the lack of informed decisions made on evidence and impact assessment; on risk assessment, with double burden on communicable and non-communicable diseases; on health policies, oriented toward health determinants; and on sustainable planning.Transversely, the absence of effective communication hampered the early identification of failures in the 20th century. The miscommunication between planning, health policies and several social sectors can be highlighted, particularly in the political-economic sector. The process of decision making and the answers to public health issues were by reaction and ad hoc actions, aggravated by the scarce evidence available at the time. Conclusion: the lack of financing for plans and programs focused in health promotion, and of investment in the development of salutogenesis competences and the fight against iniquities in access to health delayed and prevented the objectives outlined for the 20th century. Those will be some of the biggest challenges for public health in the futurepublishersversionpublishe

A targeted likelihood estimation comparing cefepime and piperacillin/tazobactam in critically ill patients with community-acquired pneumonia (CAP)

Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01–1.27], p = 0.03), (OR 1.14 95% CI [1.03–1.26], p = 0.009), (OR 1.1 95% CI [1.01–1.22], p = 0.039) and (OR 1.13 95% CI [1.03–1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

When urban modernisation entails service delivery co-production: a glance from Medellin

International audienceThrough the example of Ciudadela Nuevo Occidente, a large social housing district in Medellín, this article describes a process that primarily involves co-learning and micro-negotiations that help produce the cognitive alignment necessary to the management of services. The hypothesis put forward in this article is that the frictions caused by the residents' difficulties in adapting to the socioeconomic , cultural and cognitive frameworks of their new environment, imposed by urban modernisation running processes, engender forms of service co-production that ultimately strengthen the utility's capacity to extend and adapt its delivery model while enhancing the quality of services