New objects in old structures: The Iron Age hoard of the Palacio III megalithic funerary complex (Almadén de la Plata, Seville, Spain)

Cultural contact, exchange and interaction feature high in the list of challenging topics of current research on European Prehistory. Not far off is the issue of the changing role of monuments in the making and maintaining of key cultural devices such as memory and identity. Addressing both these highly-debated issues from a science-based perspective, in this paper we look at an unusual case study set in southern Iberia and illustrate how these archaeological questions can benefit from robust materials-science approaches.We present the contextual, morphological and analytical study of an exceptional Early Iron Age hoard composed of a number of different (and mostly exotic) materials such as amber, quartz, silver and ceramic. This hoard, found under the fallen orthostat of a megalithic structure built at least 2000 years earlier, throws new light on long-distance exchange networks and the effect they could have had on the cultural identities and social relations of local Iberian Early Iron Age communities. Moreover, the archaeometric study reveals how diverse and distant the sources of these item are (Northern Europe to Eastern and Western Mediterranean raw materials, as well as local and eastern technologies), therefore raising questions concerning the social mechanisms used to establish change and resistance in contexts of colonial encounter

Systemic Treatment of Metastatic Conjunctival Melanoma.

Conjunctival melanoma (CM) is an exceptionally rare tumor, with a propensity for local and distant recurrence, with the lungs, skin, liver, and brain being the most common sites of metastasis. Recent progress in systemic treatments, with checkpoint inhibitors and targeted therapies blocking BRAF and MEK, has redefined the standard of care of advanced unresectable and metastatic melanoma. Although most trials did not include patients with conjunctival melanoma, its close molecular and genetic relationship to cutaneous melanoma might suggest a similar response to these novel agents. The authors describe two uncommon cases of metastatic conjunctival melanomas with distinct genetic profiles and, as such, submitted to different systemic treatments.info:eu-repo/semantics/publishedVersio

¿Sigue siendo útil medir el GC mediante el Catéter de Arteria Pulmonar en pacientes críticos?

Koo et al analizan el uso del Catéter de Arteria Pulmonar (CAP) en un estudio longitudinal multicéntrico realizado en las UCIs de la región de Hamilton (Canadá). Para ello incluyen en el estudio todos los pacientes ingresados en las UCIs a los que se les implantó un CAP en los primeros 2 días de ingreso. El estudio abarca un periodo de 5 años. La variable dependiente fue el uso precoz del CAP (inserción en los 2 primeros días de ingreso), lo cual representó el 96,7% de todas las inserciones. Se estudiaron las variables predictoras del uso precoz del CAP que se agruparon en 3 grupos: - Tipo de UCI: UCI-J (incluye pacientes en diálisis crónica, transplante renal e intervenciones de cabeza, cuello y cirugía torácica), UCI-M (pacientes con enfermedades hematológicas y de alto riesgo obstétrico), UCI-H (centro regional del cáncer) y UCI-G (pacientes de neurocirugía, trauma y enfermedades vasculares). - Especialidad básica del médico intensivista: Con respecto a los médicos se incluyeron 24 médicos con experiencia en cuidados críticos y se dividieron en especialidad médica, especialidad quirúrgica, anestesiólogos y “otros intensivistas” (en éste último estaban incluidos médicos que atendían esporádicamente a los pacientes) así como sus años de experiencia. - Tipo de paciente: datos demográficos (edad, sexo, año de ingreso en UCI), tipo de paciente (médico, quirúrgico emergente y quirúrgico electivo), diagnóstico (cardiovascular, respiratorio, séptico, gastrointestinal, neurológico, politrauma, renal, metabólico/tóxico, hematológico y “otros”), variables fisiológicas (APACHE II), criterios de daño renal agudo (Cr sérica > 350 mmol/l o diuresis menor de 21 ml/h por lo menos durante 24 horas) y “otras intervenciones” (ventilación mecánica, tratamiento con vasopresores). No se incluyó a los pacientes a los que se les realizaron intervenciones de cirugía cardíaca y reparaciones de aneurismas de la aorta torácica, ya que en estos casos el CAP fue el estándar de cuidados

Intestinal colonization due to Escherichia coli ST131: Risk factors and prevalence

Background Escherichia coli sequence type 131 (ST131) is a successful clonal group that has dramatically spread during the last decades and is considered an important driver for the rapid increase of quinolone resistance in E. coli. Methods Risk factors for rectal colonization by ST131 Escherichia coli (irrespective of ESBL production) were investigated in 64 household members (18 were colonized) and 54 hospital contacts (HC; 10 colonized) of 34 and 30 index patients with community and nosocomial infection due to these organisms, respectively, using multilevel analysis with a p limit of < 0.1. Result Colonization among household members was associated with the use of proton-pump inhibitors (PPI) by the household member (OR = 3.08; 95% CI: 0.88–10.8) and higher age of index patients (OR = 1.05; 95% CI; 1.01–1.10), and among HC, with being bed-ridden (OR = 21.1; 95% CI: 3.61–160.0) and having a urinary catheter (OR = 8.4; 95% CI: 0.87–76.9). Conclusion Use of PPI and variables associated with higher need of person-to-person contact are associated with increased risk of rectal colonization by ST131. These results should be considered for infection control purposes.Plan Nacional de I + D + i 2013-2016Ministerio de Economía y Competitividad (España)European Development Regional Fund REIPI RD12/0015/0010 REIPI RD16/0016/0001Instituto de Salud Carlos III 070190 AC16/000076-MODERN AC16/AC16/00072-ST131TSJunta de Andalucía CTS5259 CTS21

Randomized pilot study on the effects of sarcocornia as a salt substitute in arterial blood pressure and vascular function in healthy young adults

Previous studies have shown that excessive salt intake is strongly associated with high blood pressure (HT), vascular dysfunction, and the overall risk of cardiovascular diseases. The aim of this study was to evaluate Sarcocornia effectiveness as a salt substitute, addressing its effect on cardiovascular function in healthy young individuals. Thirty healthy participants, aged 18 to 26 years, were randomized into two groups: the control group (CG) and the intervention group (IG). The IG used Sarcocornia powder as a salt substitute for cooking, and the CG used regular salt, during a period of 1 month. A baseline evaluation was performed before the participants started the intervention phase, and was repeated after a 30-day intervention period. Each evaluation included blood pressure (BP) measurement, carotid-femoral pulse wave velocity (PWV), and carotid pulse wave analysis (PWA), and blood samples were also collected for analysis. Sodium excretion was measured at baseline and after intervention through spot urine collection and analysis, a method suitable for this population but with known limitations. Baseline parameters were similar between groups and were within the normal range. Sodium excretion remained unchanged in the two evaluations in the CG, but significantly decreased after intervention in the IG. The reduction in sodium excretion in the IG was followed by a significant reduction in brachial and aortic systolic (SBP) and diastolic blood pressure (DBP), and also in PWV. No significant changes were observed in the CG in terms of cardiovascular parameters. This preliminary study conveys positive results in favor of Sarcocornia as a dietary substitute for regular salt, providing added evidence of the negative cardiovascular effects of high salt intake in young and healthy adults.info:eu-repo/semantics/publishedVersio

p27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor–positive breast cancer

Biomarker; Hormone receptor-positive; Breast cancerBiomarcador; Cáncer de mama; Receptor hormonal positivoBiomarcador; Càncer de mama; Receptor hormonal positiuCDK4/6 inhibitors benefit a minority of patients who receive them in the breast cancer adjuvant setting. p27Kip1 is a protein that inhibits CDK/Cyclin complexes. We hypothesized that single-nucleotide polymorphisms that impaired p27Kip1 function could render patients refractory to endocrine therapy but responsive to CDK4/6 inhibitors, narrowing the patient subpopulation that requires CDK4/6 inhibitors. We found that the p27Kip1 V109G single-nucleotide polymorphism is homozygous in approximately 15% of hormone-positive breast cancer patients. Polymorphic patients experience rapid failure in response to endocrine monotherapy compared with wild-type or heterozygous patients in the first-line metastatic setting (progression-free survival: 92 vs 485 days, P < .001); when CDK4/6 inhibitors are added, the differences disappear (progression-free survival: 658 vs 761 days, P = .92). As opposed to wild-type p27Kip1, p27Kip1 V109G is unable to suppress the kinase activity of CDK4 in the presence of endocrine inhibitors; however, palbociclib blocks CDK4 kinase activity regardless of the p27Kip1 status. p27Kip1 genotyping could constitute a tool for treatment selection.MM is supported by the Spanish Ministry of Science and Innovation (RTI2018-095582-B-100; PLEC2021-007892 and RED2018-102723-T), AES (DTS21/00132) and Comunidad de Madrid (B2017/BMD-3884 and Y2020/BIO-6519). MQF is a recipient of the following grants: AES—PI 19/00454 funded by the ISCIII and co-funded by the European Regional Development Fund (ERDF), and B2017/BMD3733 (Immunothercan-CM) – Call for Coordinated Research Groups from the Madrid Region—Madrid Regional Government—ERDF funds. This study was also funded by a donation from CRIS Contra El Cancer Foundation

Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

Rule reactivation and capture errors in goal directed behaviour

In everyday life people may act automatically, following "unwanted" lines of action which are triggered by contextual cues and may interfere with current goals. Such occurrences are known as "capture errors" in reference to errors that occur when a more salient behaviour takes place when a similar, but less salient, action was intended. Clinical neuropsychological studies suggest that reactivation of previous rules may play an important role in behavioural interference, but such reactivation has been little studied in normal subjects and simple experimental tasks. In the present study we develop this theme, presenting data on 4 subjects who spontaneously showed capture errors in verbal fluency tasks, and developing a new experimental paradigm specifically designed to elicit such interference in normal subjects. In the new paradigm, 101 normal subjects performed a simple series of working memory tasks, including occasional stimuli whose answer matched both the current and the previous rule. We found that normal controls indeed tend to commit more mistakes after the presentation of a stimulus whose answer is consistent with a current and preceding rule. In this case, however, the errors produced are not necessarily associated with a shift back to the old rule, suggesting that rule reactivation leads to a more general interference effect. We discuss the importance of our data from both theoretical and clinical perspectives

Rational Design of Pathogen-Mimicking Amphiphilic Materials as Nanoadjuvants

An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The value of using polyanhydride nanovaccines was demonstrated by the induction of long-lived protection against a lethal challenge of Yersinia pestis following a single administration ten months earlier. This approach has the tantalizing potential to catalyze the development of next generation vaccines against diseases caused by emerging and re-emerging pathogens

Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted