Residential exposure to traffic pollution and mammographic density in premenopausal women.

BACKGROUND: Mammographic density (MD) is the most important breast cancer biomarker. Ambient pollution is a carcinogen, and its relationship with MD is unclear. This study aims to explore the association between exposure to traffic pollution and MD in premenopausal women. METHODOLOGY: This Spanish cross-sectional study involved 769 women attending gynecological examinations in Madrid. Annual Average Daily Traffic (AADT), extracted from 1944 measurement road points provided by the City Council of Madrid, was weighted by distances (d) between road points and women's addresses to develop a Weighted Traffic Exposure Index (WTEI). Three methods were employed: method-1 (1dAADT), method-2 (1dAADT), and method-3 (e1dAADT). Multiple linear regression models, considering both log-transformed percentage of MD and untransformed MD, were used to estimate MD differences by WTEI quartiles, through two strategies: "exposed (exposure buffers between 50 and 200 m) vs. not exposed (>200 m)"; and "degree of traffic exposure". RESULTS: Results showed no association between MD and traffic pollution according to buffers of exposure to the WTEI (first strategy) for the three methods. The highest reductions in MD, although not statistically significant, were detected in the quartile with the highest traffic exposure. For instance, method-3 revealed a suggestive inverse trend (eßQ1 = 1.23, eßQ2 = 0.96, eßQ3 = 0.85, eßQ4 = 0.85, p-trend = 0.099) in the case of 75 m buffer. Similar non-statistically significant trends were observed with Methods-1 and -2. When we examined the effect of traffic exposure considering all the 1944 measurement road points in every participant (second strategy), results showed no association for any of the three methods. A slightly decreased MD, although not significant, was observed only in the quartile with the highest traffic exposure: eßQ4 = 0.98 (method-1), and eßQ4 = 0.95 (methods-2 and -3). CONCLUSIONS: Our results showed no association between exposure to traffic pollution and MD in premenopausal women. Further research is needed to validate these findings.

Population structure and identification of genomic regions associated with productive traits in five Italian beef cattle breeds.

Italy has a long history in beef production, with local breeds such as Marchigiana, Chianina, Romagnola, Maremmana, and Podolica which produce high-quality meat. Selection has improved meat production, precocity, growth ability and muscle development, but the genetic determinism of such traits is mostly unknown. Using 33K SNPs-data from young bulls (N = 4064) belonging to these five Italian breeds, we demonstrated that the Maremmana and Podolica rustic breeds are closely related, while the specialised Marchigiana, Chianina, and Romagnola breeds are more differentiated. A genome-wide association study for growth and muscle development traits (average daily gain during the performance test, weight at 1 year old, muscularity) was conducted in the five Italian breeds. Results indicated a region on chromosome 2, containing the myostatin gene (MSTN), which displayed significant genome-wide associations with muscularity in Marchigiana cattle, a breed in which the muscle hypertrophy phenotype is segregating. Moreover, a significant SNP on chromosome 14 was associated, in the Chianina breed, to muscularity. The identification of diverse genomic regions associated with conformation traits might increase our knowledge about the genomic basis of such traits in Italian beef cattle and, eventually, such information could be used to implement marker-assisted selection of young bulls tested in the performance test.

Telomeres and aging: on and off the planet!

Improving human healthspan in our rapidly aging population has never been more imperative. Telomeres, protective "caps" at the ends of linear chromosomes, are essential for maintaining genome stability of eukaryotic genomes. Due to their physical location and the "end-replication problem" first envisioned by Dr. Alexey Olovnikov, telomeres shorten with cell division, the implications of which are remarkably profound. Telomeres are hallmarks and molecular drivers of aging, as well as fundamental integrating components of the cumulative effects of genetic, lifestyle, and environmental factors that erode telomere length over time. Ongoing telomere attrition and the resulting limit to replicative potential imposed by cellular senescence serves a powerful tumor suppressor function, and also underlies aging and a spectrum of age-related degenerative pathologies, including reduced fertility, dementias, cardiovascular disease and cancer. However, very little data exists regarding the extraordinary stressors and exposures associated with long-duration space exploration and eventual habitation of other planets, nor how such missions will influence telomeres, reproduction, health, disease risk, and aging. Here, we briefly review our current understanding, which has advanced significantly in recent years as a result of the NASA Twins Study, the most comprehensive evaluation of human health effects associated with spaceflight ever conducted. Thus, the Twins Study is at the forefront of personalized space medicine approaches for astronauts and sets the stage for subsequent missions. We also extrapolate from current understanding to future missions, highlighting potential biological and biochemical strategies that may enable human survival, and consider the prospect of longevity in the extreme environment of space.

Oncology nursing specialty across Latin America: struggle and achievements past and present.

BACKGROUND: Latin America (LATAM) is a large region from Mexico to southern Patagonia in Chile and includes most islands in the Caribbean where Spanish is an official language. Efforts to address nursing specialization in the care of patients with cancer throughout the cancer continuum are described in narratives of oncology nursing struggles and achievements from eight Latin American countries. METHODS: Contributions by authors from Mexico, Costa Rica, Ecuador, Brazil and Chile are complemented by interview data (in Spanish by a bilingual medical anthropologist) to share the history and present status in the Dominican Republic, Peru and Argentina. RESULTS: We present stories of the pioneers of oncology nursing and a brief description of health systems in several of the included countries to show the disparate approaches towards cancer control and the context in which the oncology nurses work. We include key demographics and cancer data from the highlighted countries. We follow with descriptions of the formation and importance of oncology nursing associations/societies and share the history of oncology nursing education efforts, scopes of practice and recommendations for improvement in oncology nursing. CONCLUSIONS: Despite the challenges, oncology nurse leaders across LATAM are determined to raise the standards of care with structured specialization education/training, and to create advanced practice oncology nursing roles. It is critical that the achievements of oncology nurses are nationally acknowledged and appropriately compensated by governments and national and local authorities. The future is now for oncology nursing to be recognized as a critical specialized healthcare workforce to effectively address the growing threat of cancer and to ensure optimal control of this public health crisis across the region.

Landscape of global urban environmental resistome and its association with local socioeconomic and medical status.

Antimicrobial resistance (AMR) poses a critical threat to global health and development, with environmental factors-particularly in urban areas-contributing significantly to the spread of antibiotic resistance genes (ARGs). However, most research to date has been conducted at a local level, leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments. To address this issue, we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples, which were collected by the MetaSUB International Consortium involving diverse urban environments in 60 cities of 27 countries, utilizing a deep-learning based methodology. Our findings demonstrated the strong geographical specificity of urban environmental resistome, and their correlation with various local socioeconomic and medical conditions. We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters (BGCs) across different countries, and discovered that the urban environment represents a rich source of novel antibiotics. Our study provides a comprehensive overview of the global urban environmental resistome, and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.

The landscape of long non-coding RNA expression in the goat brain.

The brain regulates multiple metabolic processes, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue, which are fundamental for the maintenance of energy and glucose homeostasis during lactation and pregnancy. Besides, brain expression has a fundamental impact on the development of maternal behavior. Although brain functions are partly regulated by long non-coding RNAs (lncRNAs), their expression profiles have not been characterized in depth in any ruminant species. We have sequenced the transcriptome of 12 brain tissues from 3 1-mo pregnant and 4 non-pregnant goats to investigate their lncRNA expression patterns. Between 4,363 (adenohypophysis) and 4,604 (olfactory bulb) lncRNAs were expressed in brain tissues, leading to establish a set of 794 already annotated lncRNAs and 5,098 novel lncRNA candidates. The detected lncRNAs shared features with those of other mammals, and tissue-specific lncRNAs were enriched in brain development-related terms. Differential expression analyses between 1 mo-pregnant and non-pregnant goats showed that the lncRNA expression profiles of certain brain regions experience substantial changes associated with early pregnancy (238 lncRNAs are differentially expressed in the olfactory bulb), while others do not. Enrichment analysis showed that differentially expressed lncRNAs from the olfactory bulb are co-expressed with genes previously linked to behavioral changes related to pregnancy. These findings provide a first characterization of the landscape of lncRNA expression in the goat brain and provides valuable clues to understand the molecular events triggered by early pregnancy in the central nervous system.

Single and longitudinal genome-wide association studies for dairy traits available in goats with three recorded lactations.

Milk yield and composition phenotypes are systematically recorded across several lactations in goats, but the majority of genome-wide association studies (GWAS) performed so far have rather ignored the longitudinal nature of such data. Here, we have used two different GWAS approaches to analyse data from three lactations recorded in Murciano-Granadina goats. In Analysis 1, independent GWAS have been carried out for each trait and lactation, while a single longitudinal GWAS, jointly considering all data, has been performed in Analysis 2. In both analyses, genome-wide significant QTL for lactose percentage on chromosome 2 (129.77-131.01 Mb) and for milk protein percentage on the chromosome 6 (74.8-94.6 Mb) casein gene cluster region were detected. In Analysis 1, several QTL were not replicated in all three lactations, possibly due to the existence of lactation-specific genetic determinants. In Analysis 2, we identified several genome-wide significant QTL related to milk yield and protein content that were not uncovered in Analysis 1. The increased number of QTL identified in Analysis 2 suggests that the longitudinal GWAS is particularly well suited for the genetic analysis of dairy traits. Moreover, our data confirm that variability within or close to the casein complex is the main genetic determinant of milk protein percentage in Murciano-Granadina goats.

Palmar midcarpal instability a narrative review of the literature: Have we reached a consensus on a treatment?

Palmar midcarpal instability (PMCI) is a wrist condition that requires treatment through non-surgical rehabilitation programs or surgical stabilization. This condition's natural history is poorly understood, and the optimal treatment approach remains unknown. Non-surgical treatments are initially implemented, followed by surgical stabilization if necessary. Arthrodesis and soft tissue stabilization are the two main surgical options for PMCI, with no established gold standard for treatment. A systematic review of 12 articles comparing arthrodesis and soft tissue stabilization was conducted to identify the optimal treatment approach for PMCI. Arthrodesis techniques, such as lunotriquetral arthrodesis, showed high functional outcomes but also high reintervention rates due to nonunion. Soft tissue stabilization techniques showed superior functional outcomes with less mobility loss and lower reintervention rates compared to arthrodesis. However, more studies are required to determine the optimal soft tissue technique. Based on this review we created a treatment algorithm for PMCI starting with non-surgical treatment first, followed by surgical stabilization if needed. Soft tissue stabilization techniques are preferred over arthrodesis due to better functional outcomes and lower reintervention rates. However, each patient's treatment approach should be individualized and evaluated independently to determine the best course of action. PMCI is a rare wrist condition, and further research is needed to better understand its natural history and establish a gold standard for treatment. The lack of literature comparing the two surgical options underscores the need for further research to determine the optimal treatment approach. Nonetheless, the current evidence suggests that soft tissue stabilization is a promising alternative to arthrodesis, providing superior functional outcomes and lower reintervention rates.

Development and Implementation of Educational Material by Nurses for Parents/Caregivers of Children With Cancer: A Peruvian National Study.

Background: Education for parents and caregivers of children with cancer is one of the fundamental roles of nurses to avoid complications, provide quality care, promote adherence to treatment and maintain basic standards of care. This study aimed to design educational material for parents and caregivers of children with cancer in Peru on general information about childhood cancer and its care. Method: Within the framework of the WHO Global Initiative for Childhood Cancer in Peru, a multicenter working group was convened by the Peruvian Ministry of Health. A comprehensive needs assessment of parents and caregivers of children with cancer was performed through a survey in June and July 2020. The survey was conducted online (via Google Forms) and in person at nine hospitals to examine the preferred method of delivery and content of information. Results: Based on the findings from the parent needs assessment, a national nursing working group developed Spanish-language audiovisual materials (i.e., diagnosis and treatment videos for nurses to educate parents and caregivers). A total of 365 parents and caregivers were included. Most respondents (56.9%) were parents of children receiving treatment. Main topics were childhood cancer overview and side effects (85%), food and nutrition (75%), and palliative care (67%); most (70.9%) preferred information through talks and videos (64.7%). Twenty-three videos were developed with support by the Pan American Health Organization and the Ministry of Health. Discussion: Assessing the educational needs of parents and caregivers of children with cancer provides a starting point in the design of targeted strategies.

A Profile of Adult Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia Patients According to Pneumococcal Vaccination Status.

Certain patient profile characteristics, such as preexisting medical conditions, can modify the risk of developing SARS-CoV-2 pneumonia among adults vaccinated and not vaccinated against pneumococcal disease. This retrospective cohort study aimed to quantify the risk of pneumonia caused by SARS-CoV-2 among individuals from 15 to 64 years old with and without pneumococcal vaccination in Spain during the 2020-2021 influenza season and establish a risk profile of patients more likely to develop SARS-CoV-2 pneumonia. Data (demographic information, patient medical history, and lifestyle habits) were gathered both directly from the patient via personal interview and by reviewing electronic medical records. In an adjusted analysis for pneumococcal vaccinated patients, visits to hospital outpatient clinics were protective while visits to primary health care services, being widowed, obese, and not using masks in outdoor open spaces were identified as risk factors. For patients who had not received a pneumococcal vaccine, visits to hospital outpatient clinics were protective, while being overweight or obese, alcohol consumption, and not using masks in outdoor open spaces were identified as risk factors. Concerning comorbidities, in the pneumococcal vaccinated group none were found to be protective but having diabetes or other respiratory diseases were identified as risk factors. In the unvaccinated group, undergoing immunosuppressive treatment and having metastatic tumors were protective factors, while cerebrovascular disease and obesity with a BMI ≥ 40 were risk factors. A similar risk profile for developing SARS-CoV-2 pneumonia in pneumococcal vaccinated and non-vaccinated individuals was found. Generally, vaccinated individuals had a lower risk of developing SARS-CoV-2. The findings suggest that vaccination against S. pneumoniae could prevent and reduce SARS-CoV-2 pneumonia. Additionally, this study has identified individuals with other medical conditions, such as obesity, underweight, diabetes, and a history of respiratory diseases, who are at an increased risk of developing SARS-CoV-2 pneumonia and could benefit from vaccination and supervision.

Spatial analysis for risk assessment of dengue in Spain.

INTRODUCTION: The establishment of Aedes albopictus in new areas in Europe has changed the risk of local dengue transmission represented by imported human cases. The risk of transmission is determined by the distribution of travelers arriving from dengue-endemic areas and the distribution of Ae. albopictus as potential vectors of dengue in Spain. METHODS: Environmental, entomological, epidemiological, demographic, tourism and travel data were analyzed to produce a series of maps to represent: the distribution of Ae. albopictus across municipalities; the risk of expansion of Ae. albopictus based on a species distribution model; the calculated index of travelers from dengue-endemic areas (IDVZE) per province; the percentage contribution of each municipality to the total number of cases in Spain. The maps were then added using map algebra, to profile the spatial risk of autochthonous dengue in Spain at a municipal level from 2016 to 2018. RESULTS: Ae. albopictus was detected in 983 municipalities. The calculated IDVZE varied from 0.23 to 10.38, with the highest IDVZE observed in Madrid. The overall risk of autochthonous cases oscillated between 0.234 and 115, with the very high risk and high risk areas detected in the Mediterranean region, mainly in the Levantine coast and some parts of the Balearic Islands. Most of the interior of the peninsula was characterized as low risk. CONCLUSION: Prevention and control measures to mitigate the risk of autochthonous dengue should be prioritized for municipalities in the high risk areas integrating early detection of imported dengue cases and vector control.

Viral activation and ecological restructuring characterize a microbiome axis of spaceflight-associated immune activation.

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes, which play a role in some space-derived health disorders. However, documenting the response of microbiota to spaceflight has been difficult thus far due to mission constraints that lead to limited sampling. Here, we executed a six-month longitudinal study centered on a three-day flight to quantify the high-resolution microbiome response to spaceflight. Via paired metagenomics and metatranscriptomics alongside single immune profiling, we resolved a microbiome "architecture" of spaceflight characterized by time-dependent and taxonomically divergent microbiome alterations across 750 samples and ten body sites. We observed pan-phyletic viral activation and signs of persistent changes that, in the oral microbiome, yielded plaque-associated pathobionts with strong associations to immune cell gene expression. Further, we found enrichments of microbial genes associated with antibiotic production, toxin-antitoxin systems, and stress response enriched universally across the body sites. We also used strain-level tracking to measure the potential propagation of microbial species from the crew members to each other and the environment, identifying microbes that were prone to seed the capsule surface and move between the crew. Finally, we identified associations between microbiome and host immune cell shifts, proposing both a microbiome axis of immune changes during flight as well as the sources of some of those changes. In summary, these datasets and methods reveal connections between crew immunology, the microbiome, and their likely drivers and lay the groundwork for future microbiome studies of spaceflight.

Knowledge about COVID-19 between Children and Adolescents with and without High Intellectual Abilities.

Among the characteristics within people with high intellectual abilities, some that stand out are a better handling of information, asynchronous development, high awareness, and sensibility. Therefore, our goal was to learn if, due to these characteristics, the children and adolescents with high intellectual abilities have a better understanding and comprehension about COVID-19 compared to those with average intellectual abilities. A qualitative study was conducted at the beginning of the lockdown with 649 children with and without high intellectual abilities. An online questionnaire was used and three open questions were analyzed with the ALCESTE software. The results showed that both groups had a similar handling of the information regarding COVID-19. Despite this, in the high ability group there is a greater social concern, which coincides with some characteristics associated with a more developed moral conscience. The results are then discussed in terms of the importance of designing actions that allow us to adequately follow the control and intervention strategies, as well as to propose improvements in the communication of relevant information before diverse crises to which the child population may be exposed.

Intra-host variation in the spike S1/S2 region of a feline coronavirus type-1 in a cat with persistent infection.

Feline coronavirus type 1 (FCoV-1) is widely known for causing feline infectious peritonitis (FIP), a systemic infection that is often fatal, with the virus known as the FIPV biotype. However, subclinical disease also occurs, in which cats may not show signs and intermittently shed the virus, including in feces, possibly for long periods of time. This virus is known as the FECV biotype. Progression of FECV to FIPV has been linked to several genomic changes, however a specific region of the viral spike protein at the interface of the spike S1 and S2 domains has been especially implicated. In this study, we followed a cat (#576) for six years from 2017, at which time FCoV-1 was detected in feces and conjunctival swabs, until 2022, when the animal was euthanized based on a diagnosis of alimentary small cell lymphoma. Over this time period, the cat was clinically diagnosed with inflammatory bowel disease and chronic rhinitis, and cardiac problems were also suspected. Using hybridization capture targeting the spike (S) gene of FCoV followed by next-generation sequencing, we screened 27 clinical samples. We detected FCoV-1 in 4 samples taken in 2017 (intestine and nasal tissue, feces, and conjunctiva), and 3 samples taken in 2022 (feces, and intestinal and heart tissue), but not in fecal samples taken in 2019 and 2020. Next, we focused on the S1/S2 region within S, which contains the furin cleavage site (FCS), a key regulator of viral transmission and pathogenesis. We show that the FCoV-1 variants obtained from feces in 2017 and 2022 were identical, while the ones from conjunctiva (2017), heart (2022), and intestine (2017 and 2022) were distinct. Sequence comparison of all the variants obtained showed that most of the non-synonymous changes in the S1/S2 region occur within the FCS. In the heart, we found two variants that differed by a single nucleotide, resulting in distinct FCS motifs that differ in one amino acid. It is predicted that one of these FCS motifs will down-regulate spike cleavability. The variant from the conjunctiva (2017) had a 6-nucleotide in-frame insertion that resulted in a longer and more exposed S1/S2 loop, which is predicted to be more accessible to the furin protease. Our studies indicate that FCoV-1 can independently persist in the gastrointestinal tract and heart of a cat over a long period of time without evidence of typical FIP signs, with intermittent viral shedding from the gastrointestinal and respiratory tracts.

Evaluation of rRNA depletion methods for capturing the RNA virome from environmental surfaces.

OBJECTIVE: Metatranscriptomic analysis of RNA viromes on built-environment surfaces is hampered by low RNA yields and high abundance of rRNA. Therefore, we evaluated the quality of libraries, efficiency of rRNA depletion, and viral detection sensitivity using a mock community and a melamine-coated table surface RNA with levels below those required (< 5 ng) with a library preparation kit (NEBNext Ultra II Directional RNA Library Prep Kit). RESULTS: Good-quality RNA libraries were obtained from 0.1 ng of mock community and table surface RNA by changing the adapter concentration and number of PCR cycles. Differences in the target species of the rRNA depletion method affected the community composition and sensitivity of virus detection. The percentage of viral occupancy in two replicates was 0.259 and 0.290% in both human and bacterial rRNA-depleted samples, a 3.4 and 3.8-fold increase compared with that for only bacterial rRNA-depleted samples. Comparison of SARS-CoV-2 spiked-in human rRNA and bacterial rRNA-depleted samples suggested that more SARS-CoV-2 reads were detected in bacterial rRNA-depleted samples. We demonstrated that metatranscriptome analysis of RNA viromes is possible from RNA isolated from an indoor surface (representing a built-environment surface) using a standard library preparation kit.

A protein-coding gene expression atlas from the brain of pregnant and non-pregnant goats.

Background: The brain is an extraordinarily complex organ with multiple anatomical structures involved in highly specialized functions related with behavior and physiological homeostasis. Our goal was to build an atlas of protein-coding gene expression in the goat brain by sequencing the transcriptomes of 12 brain regions in seven female Murciano-Granadina goats, from which three of them were 1-month pregnant. Results: Between 14,889 (cerebellar hemisphere) and 15,592 (pineal gland) protein-coding genes were expressed in goat brain regions, and most of them displayed ubiquitous or broad patterns of expression across tissues. Principal component analysis and hierarchical clustering based on the patterns of mRNA expression revealed that samples from certain brain regions tend to group according to their position in the anterior-posterior axis of the neural tube, i.e., hindbrain (pons and medulla oblongata), midbrain (rostral colliculus) and forebrain (frontal neocortex, olfactory bulb, hypothalamus, and hippocampus). Exceptions to this observation were cerebellum and glandular tissues (pineal gland and hypophysis), which showed highly divergent mRNA expression profiles. Differential expression analysis between pregnant and non-pregnant goats revealed moderate changes of mRNA expression in the frontal neocortex, hippocampus, adenohypophysis and pons, and very dramatic changes in the olfactory bulb. Many genes showing differential expression in this organ are related to olfactory function and behavior in humans. Conclusion: With the exception of cerebellum and glandular tissues, there is a relationship between the cellular origin of sampled regions along the anterior-posterior axis of the neural tube and their mRNA expression patterns in the goat adult brain. Gestation induces substantial changes in the mRNA expression of the olfactory bulb, a finding consistent with the key role of this anatomical structure on the development of maternal behavior.

Instrument-based anterolateral rotatory laxity assessment of the knee has a high intra-observer and inter-observer reliability: a systematic review.

IMPORTANCE: A reliable evaluation of anterolateral rotatory instability in the anterior cruciate ligament (ACL) deficient knee is important to help surgeons determine which patients might need concurrent anterolateral augmentation procedures. OBJECTIVE: The purpose of this study was to systematically review studies that assess the intra-observer and inter-observer reliability of instruments used to measure anterolateral rotatory laxity of the knee. EVIDENCE REVIEW: A comprehensive literature review was conducted according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, using PubMed, Embase, Scopus, and Google Scholar databases for original, English-language studies evaluating the reliability of objective or instrument-based anterolateral rotatory laxity of the knee until October 31, 2022. Reliability data were extracted from text, tables, and figures. FINDINGS: Twelve studies, with patients between the ages of 14-63 years, were included. The instruments used to measure anterolateral rotatory knee laxity included inertial sensors (n â€‹= â€‹9), magnetic resonance imaging (n â€‹= â€‹1), and navigation systems (n â€‹= â€‹2). The global intra-observer intraclass correlation coefficient for these devices was between 0.63 and 0.97, and the global inter-observer reliability was between 0.63 and 0.99. CONCLUSION AND RELEVANCE: Instrument-based anterolateral rotatory knee laxity assessment has moderate to good intra- and inter-observer reliability. Evaluating anterolateral instability in ACL-deficient knees with these devices could help in decision-making when considering anterolateral augmentation. LEVEL OF EVIDENCE: IV.

C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, by infecting cells via the interaction of its spike protein (S) with the primary cell receptor angiotensin-converting enzyme (ACE2). To search for inhibitors of this key step in viral infection, we screened an in-house library of multivalent tryptophan derivatives. Using VSV-S pseudoparticles, we identified compound 2 as a potent entry inhibitor lacking cellular toxicity. Chemical optimization of 2 rendered compounds 63 and 65, which also potently inhibited genuine SARS-CoV-2 cell entry. Thermofluor and microscale thermophoresis studies revealed their binding to S and to its isolated receptor binding domain (RBD), interfering with the interaction with ACE2. High-resolution cryoelectron microscopy structure of S, free or bound to 2, shed light on cell entry inhibition mechanisms by these compounds. Overall, this work identifies and characterizes a new class of SARS-CoV-2 entry inhibitors with clear potential for preventing and/or fighting COVID-19.

Nosocomial outbreak caused by Serratia marcescens in a neonatology intensive care unit in a regional hospital. Analysis and improvement proposals.

OBJECTIVES: Serratia marcescens (SM) may cause nosocomial outbreaks in Neonatal Intensive Care Units (NICU). We describe an outbreak of SM in a NICU and propose additional prevention and control recommendations. METHODS: Between March 2019 and January 2020, samples were taken from patients in the NICU (rectal, pharyngeal, axillary and other locations) and from 15 taps and their sinks. Control measures were implemented including thorough cleaning of incubators, health education to staff and neonates'relatives, and use of single-dose containers. PFGE was performed in 19 isolates from patients and in 5 environmental samples. RESULTS: From the first case in March 2019 to the detection of the outbreak, a month elapsed. Finally, 20 patients were infected and 5 colonized. 80% of infected neonates had conjunctivitis, 25% bacteremia, 15% pneumonia, 5% wound infection, and 5% urinary tract infection. Six neonates had two foci of infection. Among the 19 isolates studied, 18 presented the same pulsotype and only one of the isolates from the sinkhole showed a clonal relationship with those of the outbreak. Initial measures established were ineffective to control de outbreak and were implemented with exhaustive cleaning, use of individual eye drops, environmental sampling and changing sinks. CONCLUSION: This outbreak presented a high number of neonates affected due to its late detection and torpid evolution. The microorganisms isolated from the neonates were related to an environmental isolate. Additional prevention and control measures are proposed, including routine weekly microbiological sampling.