Acknowledging and citing core facilities: Key contributions to data lifecycle should be recognised in the scientific literature: Key contributions to data lifecycle should be recognised in the scientific literature.

Core facilities play a central role in the life sciences by generating data and ensuring quality standards. Their contributions to research should be appropriately acknowledged or cited in research papers.

Pharmacist's Role and Pharmaceutical Care During the COVID-19 Pandemic.

Pharmacists play a vital role in public health during the COVID-19 pandemic. In this chapter, we present the most significant contributions that pharmacists could make to communitarian and hospital settings. It includes the provision of essential services, such as continuous access to medication and supplies, support to medical services, education and information to the population and the health team to reduce the misuse of medications, patient monitoring and follow-up, and the detection and referral of suspected cases of COVID-19. The chapter ends with a discussion over certain elements related to innovation needs, such as telepharmacy services.

The Role of Ultrasound for Detecting Occult Penetrating Cardiac Wounds in Hemodynamically Stable Patients.

BACKGROUND: There is evidence in favor of using the ultrasound as the primary screening tool in looking for an occult cardiac injury. We report on a prospective single-center study to determine the diagnostic accuracy of chest ultrasound for the diagnosis of occult penetrating cardiac wounds in a low-resource hospital from a middle-income country. METHODS: Data were collected prospectively. We included all consecutive patients 14 years and older who presented to the Emergency Trauma Unit with (1) penetrating injuries to the precordial area and (2) a systolic blood pressure ≥ 90 mmHg (hemodynamically stable). The main outcome measures were sensitivity, specificity, and positive and negative predictive values of ultrasound compared with those of the pericardial window, which was the standard test. RESULTS: A total of 141 patients met the inclusion criteria. Our results showed that for diagnosing an occult cardiac injury, the sensitivity of the chest ultrasonography was 79.31%, and the specificity was 92.86%. Of the 110 patients with a normal or negative ultrasound, six had a positive pericardial window. All of these patients had left hemothoraces. None of them required further cardiac surgical interventions. CONCLUSION: We found that ultrasound was 79% sensitive and 92% specific for the diagnosis of occult penetrating cardiac wounds. However, it should be used with caution in patients with injuries to the cardiac zone and simultaneous left hemothorax.

Discovery of novel N-hydroxy-2-arylisoindoline-4-carboxamides as potent and selective inhibitors of HDAC11.

N-Hydroxy-2-arylisoindoline-4-carboxamides are potent and selective inhibitors of HDAC11. The discovery, synthesis, and structure activity relationships of this novel series of inhibitors are reported. An advanced analog (FT895) displays promising cellular activity and pharmacokinetic properties that make it a useful tool to study the biology of HDAC11 and its potential use as a therapeutic target for oncology and inflammation indications.

Bisphenol A (BPA) modulates the expression of endocrine and stress response genes in the freshwater snail Physa acuta.

Bisphenol A (BPA), a known endocrine disrupting chemical (EDC) that can mimic the action of oestrogens by interacting with hormone receptors, is potentially able to influence reproductive functions in vertebrates and invertebrates. The freshwater pulmonate Physa acuta is a sensitive organism to xenobiotics appropriate for aquatic toxicity testing in environmental studies. This study was conducted to explore the effects of BPA on the Gastropoda endocrine system. The effects following a range of exposure times (5-96h) to BPA in P. acuta were evaluated at the molecular level by analysing changes in the transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), as well as in genes involved in the stress response, such as hsp70 and hsp90. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that BPA induced a significant increase in the mRNA levels of ER, ERR, and RXR, suggesting that these receptors could be involved in similar pathways or regulation events in the endocrine disruptor activity of this chemical at the molecular level in Gastropoda. Additionally, the hsp70 expression was upregulated after 5 and 72h of BPA exposures, but hsp90 was only upregulated after 5h of BPA exposure. Finally, we assessed the glutathione-S-transferase (GST) activity after BPA treatment and found that it was affected after 48h. In conclusion, these data provide, for the first time, evidences of molecular effects produced by BPA in the endocrine system of Gastropoda, supporting the potential of ER, ERR and RXR as biomarkers to analyse putative EDCs in ecotoxicological studies. Moreover, our results suggest that P. acuta is an appropriate sentinel organism to evaluate the effect of EDCs in the freshwater environment.

Endocrine-related genes are altered by antibacterial agent triclosan in Chironomus riparius aquatic larvae.

Triclosan (TCS) is an antibacterial agent widely used in personal care and consumer products and commonly detected in aquatic ecosystems. In the present study, the effects of TCS on endocrine-related genes of Chironomus riparius aquatic larvae, a reference organism in aquatic toxicology, were evaluated. Twenty-four-hour in vivo exposures at 10µg/L, 100µg/L, and 1000µg/L TCS revealed that this xenobiotic was able to alter the transcriptional activity of ecdysone receptor gene (EcR), the ultraspiracle gene (usp), the estrogen-related receptor gene (ERR), and the E74 early ecdysone-inducible gene, as measured by real-time RT-PCR. Moreover, the hsp70 gene, a heat shock protein gene, was upregulated after exposure to TCS. The results of the present work provide the first evidence of the potential disruptive effects of TCS in endocrine-related genes suggesting a mode of action that mimics ecdysteroid hormones in insects.

Mucormycosis in a Non-Hodgkin Lymphoma Patient Caused by Syncephalastrum racemosum: Case Report and Review of Literature.

Mucormycosis is a rare opportunistic fungal infection caused by saprophytic zygomycetes. These fungal infections are caused by members of the mucorales. The clinical importance of zygomycosis, an emerging and frequently fatal mycotic disease, has increased during recent years, due to several risk factors such as (a) the use of broad-spectrum antibiotic, (b) use of empirical antifungal treatment (mainly triazoles), and (c) aggressive chemotherapy and sustained leucopenia (i.e., peripheral stem cell transplantation). An almost fulminant pneumonia caused by Syncephalastrum racemosum in an immunocompromised patient with an aggressive non-Hodgkin lymphoma (NHL) is described. Despite treatment with amphotericin B, deoxycholate, caspofungin, and surgical resection of fungal bodies from both lungs, and survival of 10 months without relapsing from fungal infection, the patient died due to hematological complications from an unresponsive disease. Herein is the description of the first case of pulmonary infection caused by Syncephalastrum racemosum.

[Vaginal colonization by Candida spp. Frequency and description of the species isolated in asymptomatic women]. / Colonización vaginal por Candida spp. Frecuencia y descripción de las especies aisladas en mujeres asintomáticas.

BACKGROUND: During reproductive age 75% of women experience at least one episode of vulvovaginal candidiasis, approximately 6% to 55% of healthy women are asymptomatic carriers. In Mexico there are no current data of the frequency of vaginal colonization by Candida in the general population. OBJECTIVE: To determine the frequency of the colonization by Candida species in asymptomatic women. MATERIAL AND METHODS: A descriptive, open, observational, prospective, cross sectional study was carried out in adult women attending the cervical cytology department at Hospital General Dr. Manuel Gea González in Mexico City. The study was conducted from January to May 2013. RESULTS: There were a total of 150 samples of asymptomatic women between 15 and 77 years (mean 43 years). We obtained positive culture for Candida in 19 samples (12.6 %). 47% of the species corresponded to C. albicans, however, it was isolated other species such as C. krusei in 26%, C. glabrata (21%) and C. tropicalis by 15%. CONCLUSIONS: Our findings are consistent with data reported in the literature. It is relevant the isolation of non-albicans Candida species. These findings may be caused by an increase of inappropriate therapies.

Anatomical factors of the maxillary tuberosity that influence molar distalization.

Objective: To examine the areas of the maxillary tuberosity (MT) (coronal, apical, width, and height) with respect to the presence or absence of the third molar to establish possible anatomical limitations for molar distalization. Methods: A total of 277 tuberosities were evaluated through sagittal computed tomography (CT) images, divided for measurement into coronal (free of bone), apical (area of influence of the maxillary sinus), and tuberosity (bony area) zones, and stratified by the presence or absence of the third molar, sex, and two age subgroups. Mann-Whitney U test was used to compare the groups considering the third molar. Results: The medians of the width and height of the tuberosity decreased significantly in the absence of the third molar (P < 0.001). The apical area also showed differences, with negative values in the absence of the third molar and positive values in the presence of the third molar (P < 0.001). However, no differences were observed for the coronal area (P > 0.05). Conclusions: In the absence of the third molar, the size of the MT, represented by its width and height, was smaller and negative values (decrease) were observed for the maxillary sinus. The sagittal CT provides useful information regarding the amount of bone tissue available for distalization and relationship of the second molar with respect to the maxillary sinus, which allows individualizing each case in relation to the amount and type of movement expected.

Molecular effects of polystyrene nanoplastics on human neural stem cells.

Nanoplastics (NPs) have been found in many ecological environments (aquatic, terrestrial, air). Currently, there is great concern about the exposition and impact on animal health, including humans, because of the effects of ingestion and accumulation of these nanomaterials (NMs) in aquatic organisms and their incorporation into the food chain. NPs´ mechanisms of action on humans are currently unknown. In this study, we evaluated the altered molecular mechanisms on human neural stem cell line (hNS1) after 4 days of exposure to 30 nm polystyrene (PS) NPs (0.5, 2.5 and 10 µg/mL). Our results showed that NPs can induce oxidative stress, cellular stress, DNA damage, alterations in inflammatory response, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases.

DNA damage and molecular level effects induced by polystyrene (PS) nanoplastics (NPs) after Chironomus riparius (Diptera) larvae.

In this work, we analyzed the early molecular effects of polystyrene (PS) nanoplastics (NPs) on an aquatic primary consumer (larvae of Chironomus riparius, Diptera) to evaluate their potential DNA damage and the transcriptional response of different genes related to cellular and oxidative stress, endocrine response, developmental, oxygen transport, and immune response. After 24-h exposures of larvae to doses of PS NPs close to those currently found in the environment, the results revealed a large genotoxic effect. This end was evidenced after significant increases in DNA strand breaks of C. riparius larvae quantified by the comet assay, together with results obtained when analyzing the expression of four genes involved in DNA repair (xrrc1, ATM, DECAY and NLK) and which were reduced in the presence of these nanomaterials. Consequently, this reduction trend is likely to prevent the repair of DNA damage caused by PS NPs. In addition, the same tendency to reduce the expression of genes involved in cellular stress, oxidative stress, ecdysone pathway, development, and oxygen transport was observed. Taken together, these results suggest that PS NPs reduce the expression of hormonal target genes and a developmental gene. We show, for the first time, effects of PS NPs on the endocrine system of C. riparius and suggest a possible mechanism of blocking ecdysteroid hormones in insects. Moreover, the NPs were able to inhibit the expression of hemoglobin (Hb C), a protein involved in oxygen transport, and activate a gene of the humoral immune system. These data reveal for the first time the genomic effects of PS NPs in the aquatic invertebrate C. riparius, at the base of the food chain.

Internalization and toxicity of polystyrene nanoplastics on inmortalized human neural stem cells.

Global plastic production has increased exponentially in recent decades, and a significant part of it persists in the environment, where it degrades into microplastics and nanoplastics (MPs and NPs). These can enter in humans by ingestion, inhalation, and dermal routes, and there is scientific evidence that they are able to reach the systemic circulation and penetrate and accumulate in various tissues and organs. Neurodevelopmental toxicity of NPs is one of the most worrying effects, as they can cross the blood-brain barrier. In the following study, we analyzed, by transmission electron microscopy, the in vitro uptake of 30-nm polystyrene nanoplastics (PS-NPs) into human neural stem cells (NSCs), their accumulation and subcellular localization within the cell. Furthermore, we studied the effects of different concentrations of PS-NPs on cell death, proliferation, and cell differentiation using immunocytochemistry and quantitative real time PCR for specific markers. This study demonstrated that PS-NPs were able to enter the cell, probably by endocytosis, accumulate, and aggregated in human NSCs, without being detected in the nucleus, causing cell death by apoptosis and decreased cell proliferation. This study provides new insights into the interaction and effects of PS-NPs in human NSC and supports the scientific evidence for the involvement of nanoplastic in neurodevelopmental disorders.

Update on the management of older patients with pancreatic adenocarcinoma: a perspective from medical oncology.

In the context of pancreatic cancer, surgical intervention is typically recommended for localized tumours, whereas chemotherapy is the preferred approach in the advanced and/or metastatic setting. However, pancreatic cancer is closely linked to ageing, with an average diagnosis at 72 years. Paradoxically, despite its increased occurrence among older individuals, this population is often underrepresented in clinical studies, complicating the decision-making process. Age alone should not determine the therapeutic strategy but, given the high comorbidity and mortality of this disease, a comprehensive geriatric assessment (CGA) is necessary to define the best treatment, prevent toxicity, and optimize older patient care. In this review, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours (Grupo Español de Tratamiento de los Tumores Digestivos, TTD), and the Multidisciplinary Spanish Group of Digestive Cancer (Grupo Español Multidisciplinar en Cáncer Digestivo, GEMCAD) have assessed the available scientific evidence and propose a series of recommendations on the management and treatment of the older population with pancreatic cancer.

[Repeatability of spirometrys expiratory flows]. / Repetitividad de los flujos espiratorios de la espirometría.

Background: The quality of the spirometry is estimated with criteria of acceptability and repeatability. The repeatability criteria accepted by consensus is < 0.150 L. Objective: To know the repeatability in quality A spirometry. Material and methods: Analytical cross-sectional design. The demographic variables and the 3 best spirometry curves with normal, suggestive of restriction and bronchial obstruction profiles were obtained from consecutive subjects of both genders from 18 to 80 years of age. The repeatability was analyzed with the mean difference (bias) and the intraclass correlation coefficient. Results: 630 curves from 210 subjects were accepted. Group age 60 ± 15 years. Female predominance 113 (53.8%), occupation: domestic services 61 (29%), and diagnosed with chronic obstructive pulmonary disease: 70 (33.4%). The differences in the curves were < 0.150 L. The mean difference (bias) and the intraclass correlation coefficient (95% confidence interval, 95% CI) of the forced expiratory volume in the first second were 1 vs. 2 maneuver: -0.01 (0.13, -0.14), 0.997 (95% CI 0.996, 0.998); 2 vs. 3 maneuver: 0.00 (0.13, -0.13), 0.997 (95% CI 0.996, 0.998), and maneuver 1 vs. 3: -0.00 (0.16, -0.17), 0.995 (95% CI 0.994, 0.996). Forced vital capacity: 1 vs. 2 maneuver: -0.01 (0.17, -0.18), 0.996 (95% CI 0.995, 0.997); 2 vs. 3 maneuver: 0.01 (0.17, -0.16), 0.997 (95% CI 0.0.996, 0.998), and maneuver 1 vs. 3: -0.00 (0.18, -0.19), 0.996 (95% CI 0.995, 0.997). Conclusion: The repeatability obtained in spirometry with quality A validates the use of the repeatability criterion of 0.150 L.

Introducción: la calidad de la espirometría se estima con criterios de aceptabilidad y repetitividad. La repetitividad aceptada por consenso es < 0.150 L. Objetivo: conocer la repetitividad en espirometrías de calidad A. Material y métodos: diseño transversal analítico. Se obtuvieron las variables demográficas y las 3 mejores curvas de espirometría con perfil normal, que sugiriera restricción y obstrucción bronquial de sujetos consecutivos de ambos géneros de 18 a 80 años. La repetitividad se analizó con la diferencia de medias (sesgo) y el coeficiente de correlación intraclase. Resultados: se aceptaron 630 curvas de 210 sujetos. Edad grupal 60 ± 15 años. Predominio femenino 113 (53.8%), ocupación: servicios domésticos 61 (29%) y con enfermedad pulmonar obstructiva crónica 70 (33.4%). Las diferencias en las curvas fueron < 0.150 L. Las diferencias medias (sesgo) y el coeficiente de correlación intraclase (intervalo de confianza al 95%, IC 95%) del volumen espiratorio forzado en el primer segundo fueron: maniobra 1 frente a 2: −0.01 (0.13, −0.14), 0.997 (IC 95% 0.996, 0.998); maniobra 2 frente a 3: 0.00 (0.13, −0.13), 0.997 (IC 95% 0.996, 0.998), y maniobra 1 frente a 3: −0.00 (0.16, −0.17), 0.995 (IC 95% 0.994, 0.996). La capacidad vital forzada: maniobra 1 frente a 2: −0.01 (0.17, −0.18), 0.996 (IC 95% 0.995, 0.997); maniobra 2 frente a 3: 0.01 (0.17, −0.16), 0.997 (IC 95% 0.0.996, 0.998), y maniobra 1 frente a 3: −0.00 (0.18, −0.19), 0.996 (IC 95% 0.995, 0.997). Conclusión: la repetitividad obtenida en espirometrías con calidad A valida el uso del criterio de repetitividad de 0.150 L.

Identification of NOG as a specific breast cancer bone metastasis-supporting gene.

Metastasis requires numerous biological functions that jointly provide tumor cells from a primary site to seed and colonize a distant organ. Some of these activities are selected for in the primary site, whereas others are acquired at the metastatic niche. We provide molecular evidence showing that the BMP inhibitor, NOG, provides metastatic breast cancer cells with the ability to colonize the bone. NOG expression is acquired during the late events of metastasis, once cells have departed from the primary site, because it is not enriched in primary tumors with high risk of bone relapse. On the contrary, breast cancer bone metastatic lesions do select for high levels of NOG expression when compared with metastasis to the lung, liver, and brain. Pivotal to the bone colonization functions is the contribution of NOG to metastatic autonomous and nonautonomous cell functions. Using genetic approaches, we show that when NOG is expressed in human breast cancer cells, it facilitates bone colonization by fostering osteoclast differentiation and bone degradation and also contributes to metastatic lesions reinitiation. These findings reveal how aggressive cancer cell autonomous and nonautonomous functions can be mechanistically coupled to greater bone metastatic potential.

Genotoxic effects of environmental endocrine disruptors on the aquatic insect Chironomus riparius evaluated using the comet assay.

Genotoxicity is one of the most important toxic endpoints in chemical toxicity testing and environmental risk assessment. The aim of this study was to evaluate the genotoxic potential of various environmental pollutants frequently found in aquatic environments and characterized by their endocrine disrupting activity. Monitoring of DNA damage was undertaken after in vivo exposures of the aquatic larvae of the midge Chironomus riparius, a model organism that represents an abundant and ecologically relevant macroinvertebrate, widely used in freshwater toxicology. DNA-induced damage, resulting in DNA fragmentation, was quantified by the comet assay after short (24 h) and long (96 h) exposures to different concentrations of the selected toxicants: bisphenol A (BPA), nonylphenol (NP), pentachlorophenol (PCP), tributyltin (TBT) and triclosan (TCS). All five compounds were found to have genotoxic activity as demonstrated by significant increases in all the comet parameters (%DNA in tail, tail length, tail moment and Olive tail moment) at all tested concentrations. Persistent exposure did not increase the extent of DNA damage, except for TCS at the highest concentration, but generally there was a reduction in DNA damage thought to be associated with the induction of the detoxification processes and repairing mechanisms. Comparative analysis showed differences in the genotoxic potential between the chemicals, as well as significant time and concentration-dependent variations, which most likely reflect differences in the ability to repair DNA damage under the different treatments. The present report demonstrates the sensitivity of the benthic larvae of C. riparius to these environmental genotoxins suggesting its potential as biomonitor organism in freshwater ecosystems. The results obtained about the DNA-damaging potential of these environmental pollutants reinforce the need for additional studies on the genotoxicity of endocrine active substances that, by linking genotoxic activity to other biological responses, could provide further understanding of adverse effects in aquatic environments.

The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex.

The MRE11 complex (MRE11, RAD50 and NBS1) and the ataxia-telangiectasia mutated (ATM) kinase function in the same DNA damage response pathway to effect cell cycle checkpoint activation and apoptosis. The functional interaction between the MRE11 complex and ATM has been proposed to require a conserved C-terminal domain of NBS1 for recruitment of ATM to sites of DNA damage. Human Nijmegen breakage syndrome (NBS) cells and those derived from multiple mouse models of NBS express a hypomorphic NBS1 allele that exhibits impaired ATM activity despite having an intact C-terminal domain. This indicates that the NBS1 C terminus is not sufficient for ATM function. We derived Nbs1(DeltaC/DeltaC) mice in which the C-terminal ATM interaction domain is deleted. Nbs1(DeltaC/DeltaC) cells exhibit intra-S-phase checkpoint defects, but are otherwise indistinguishable from wild-type cells with respect to other checkpoint functions, ionizing radiation sensitivity and chromosome stability. However, multiple tissues of Nbs1(DeltaC/DeltaC) mice showed a severe apoptotic defect, comparable to that of ATM- or CHK2-deficient animals. Analysis of p53 transcriptional targets and ATM substrates showed that, in contrast to the phenotype of Chk2(-/-) mice, NBS1(DeltaC) does not impair the induction of proapoptotic genes. Instead, the defects observed in Nbs1(DeltaC/DeltaC) result from impaired phosphorylation of ATM targets including SMC1 and the proapoptotic factor, BID.

Graphene Oxides (GOs) with Different Lateral Dimensions and Thicknesses Affect the Molecular Response in Chironomus riparius.

Graphene oxide (GO) materials possess physicochemical properties that facilitate their application in the industrial and medical sectors. The use of graphene may pose a threat to biota, especially aquatic life. In addition, the properties of nanomaterials can differentially affect cell and molecular responses. Therefore, it is essential to study and define the possible genotoxicity of GO materials to aquatic organisms and their ecosystems. In this study, we investigated the changes in the expression of 11 genes in the aquatic organism Chironomus riparius after 96 h of exposure to small GOs (sGO), large GOs (lGO) and monolayer GOs (mlGO) at 50, 500 and 3000 µg/L. Results showed that the different genes encoding heat shock proteins (hsp90, hsp70 and hsp27) were overexpressed after exposure to these nanomaterials. In addition, ATM and NLK-the genes involved in DNA repair mechanisms-were altered at the transcriptional level. DECAY, an apoptotic caspase, was only activated by larger size GO materials, mlGO and lGO. Finally, the gene encoding manganese superoxide dismutase (MnSOD) showed higher expression in the mlG O-treated larvae. The lGO and mlGO treatments indicated high mRNA levels of a developmental gene (FKBP39) and an endocrine pathway-related gene (DRONC). These two genes were only activated by the larger GO materials. The results indicate that larger and thicker GO nanomaterials alter the transcription of genes involved in cellular stress, oxidative stress, DNA damage, apoptosis, endocrine and development in C. riparius. This shows that various cellular processes are modified and affected, providing some of the first evidence for the action mechanisms of GOs in invertebrates. In short, the alterations produced by graphene materials should be further studied to evaluate their effect on the biota to show a more realistic scenario of what is happening at the molecular level.