Archaeogenomic distinctiveness of the Isthmo-Colombian area.

The recently enriched genomic history of Indigenous groups in the Americas is still meager concerning continental Central America. Here, we report ten pre-Hispanic (plus two early colonial) genomes and 84 genome-wide profiles from seven groups presently living in Panama. Our analyses reveal that pre-Hispanic demographic events contributed to the extensive genetic structure currently seen in the area, which is also characterized by a distinctive Isthmo-Colombian Indigenous component. This component drives these populations on a specific variability axis and derives from the local admixture of different ancestries of northern North American origin(s). Two of these ancestries were differentially associated to Pleistocene Indigenous groups that also moved into South America, leaving heterogenous genetic footprints. An additional Pleistocene ancestry was brought by a still unsampled population of the Isthmus (UPopI) that remained restricted to the Isthmian area, expanded locally during the early Holocene, and left genomic traces up to the present day.

Spatiotemporally controlled generation of NTPs for single-molecule studies.

Many essential processes in the cell depend on proteins that use nucleoside triphosphates (NTPs). Methods that directly monitor the often-complex dynamics of these proteins at the single-molecule level have helped to uncover their mechanisms of action. However, the measurement throughput is typically limited for NTP-utilizing reactions, and the quantitative dissection of complex dynamics over multiple sequential turnovers remains challenging. Here we present a method for controlling NTP-driven reactions in single-molecule experiments via the local generation of NTPs (LAGOON) that markedly increases the measurement throughput and enables single-turnover observations. We demonstrate the effectiveness of LAGOON in single-molecule fluorescence and force spectroscopy assays by monitoring DNA unwinding, nucleosome sliding and RNA polymerase elongation. LAGOON can be readily integrated with many single-molecule techniques, and we anticipate that it will facilitate studies of a wide range of crucial NTP-driven processes.

The genomic landscape across 474 surgically accessible epileptogenic human brain lesions.

Understanding the exact molecular mechanisms involved in the aetiology of epileptogenic pathologies with or without tumour activity is essential for improving treatment of drug-resistant focal epilepsy. Here, we characterize the landscape of somatic genetic variants in resected brain specimens from 474 individuals with drug-resistant focal epilepsy using deep whole-exome sequencing (>350×) and whole-genome genotyping. Across the exome, we observe a greater number of somatic single-nucleotide variants in low-grade epilepsy-associated tumours (7.92 ± 5.65 single-nucleotide variants) than in brain tissue from malformations of cortical development (6.11 ± 4 single-nucleotide variants) or hippocampal sclerosis (5.1 ± 3.04 single-nucleotide variants). Tumour tissues also had the largest number of likely pathogenic variant carrying cells. low-grade epilepsy-associated tumours had the highest proportion of samples with one or more somatic copy-number variants (24.7%), followed by malformations of cortical development (5.4%) and hippocampal sclerosis (4.1%). Recurring somatic whole chromosome duplications affecting Chromosome 7 (16.8%), chromosome 5 (10.9%), and chromosome 20 (9.9%) were observed among low-grade epilepsy-associated tumours. For germline variant-associated malformations of cortical development genes such as TSC2, DEPDC5 and PTEN, germline single-nucleotide variants were frequently identified within large loss of heterozygosity regions, supporting the recently proposed 'second hit' disease mechanism in these genes. We detect somatic variants in 12 established lesional epilepsy genes and demonstrate exome-wide statistical support for three of these in the aetiology of low-grade epilepsy-associated tumours (e.g. BRAF) and malformations of cortical development (e.g. SLC35A2 and MTOR). We also identify novel significant associations for PTPN11 with low-grade epilepsy-associated tumours and NRAS Q61 mutated protein with a complex malformation of cortical development characterized by polymicrogyria and nodular heterotopia. The variants identified in NRAS are known from cancer studies to lead to hyperactivation of NRAS, which can be targeted pharmacologically. We identify large recurrent 1q21-q44 duplication including AKT3 in association with focal cortical dysplasia type 2a with hyaline astrocytic inclusions, another rare and possibly under-recognized brain lesion. The clinical-genetic analyses showed that the numbers of somatic single-nucleotide variant across the exome and the fraction of affected cells were positively correlated with the age at seizure onset and surgery in individuals with low-grade epilepsy-associated tumours. In summary, our comprehensive genetic screen sheds light on the genome-scale landscape of genetic variants in epileptic brain lesions, informs the design of gene panels for clinical diagnostic screening and guides future directions for clinical implementation of epilepsy surgery genetics.

Real-time measurements of aminoglycoside effects on protein synthesis in live cells.

The spread of antibiotic resistance is turning many of the currently used antibiotics less effective against common infections. To address this public health challenge, it is critical to enhance our understanding of the mechanisms of action of these compounds. Aminoglycoside drugs bind the bacterial ribosome, and decades of results from in vitro biochemical and structural approaches suggest that these drugs disrupt protein synthesis by inhibiting the ribosome's translocation on the messenger RNA, as well as by inducing miscoding errors. So far, however, we have sparse information about the dynamic effects of these compounds on protein synthesis inside the cell. In the present study, we measured the effect of the aminoglycosides apramycin, gentamicin, and paromomycin on ongoing protein synthesis directly in live Escherichia coli cells by tracking the binding of dye-labeled transfer RNAs to ribosomes. Our results suggest that the drugs slow down translation elongation two- to fourfold in general, and the number of elongation cycles per initiation event seems to decrease to the same extent. Hence, our results imply that none of the drugs used in this study cause severe inhibition of translocation.

Opioids and fibromyalgia: frequency of use and factors associated with increased consumption in patients remitted to a tertiary care center.

BACKGROUND: Opioids are not recommended for fibromyalgia. OBJECTIVE: To investigate the frequency of opioid use in a large cohort of fibromyalgia patients and to identify factors associated with opioid consumption. METHODS: A retrospective, observational study of a large fibromyalgia cohort in a tertiary care center. We assessed fibromyalgia severity, functional capacity, anxiety, depression, drugs consumption and the patient's impression of change. We compared strong opioid consumers (SOC) and non-SOC. Inferential statistical and logistic regression analysis were used to identify factors associated with opioid consumption, and ANOVA for repeated measurements. RESULTS: We found a prevalence of 9.2% of SOC (100 patients) among 1087 patients in the cohort. During the last four years there was a significant increase on the incidence of SOC up to 12.8% (p = 0.004). There were no differences in demographic variables between SOC and non-SOC. Clinical variables were significantly more severe in SOC, and they consumed more non-opioid drugs (p < 0.0001). Opioid consumption was independently associated with other non-opioid drugs (Odds ratio 1.25, CI: 1.13-1.38), but not with the fibromyalgia severity. At three months, 62% of the patients had opioid withdrawal. There were no statistical differences in the fibromyalgia severity at the initial evaluation, or the patient's impression of change compared with those patients who continued opioids. Coping strategies were better in those patients who withdrew opioids (p = 0.044). CONCLUSIONS: We observed an increase in opioid prescriptions during the last four years. Opioid consumption was associated with concomitant use of non-opioid drugs, but it was not associated with fibromyalgia severity.

Ganglioglioma with adverse clinical outcome and atypical histopathological features were defined by alterations in PTPN11/KRAS/NF1 and other RAS-/MAP-Kinase pathway genes.

Exome-wide sequencing studies recently described PTPN11 as a novel brain somatic epilepsy gene. In contrast, germline mutations of PTPN11 are known to cause Noonan syndrome, a multisystem disorder characterized by abnormal facial features, developmental delay, and sporadically, also brain tumors. Herein, we performed a deep phenotype-genotype analysis of a comprehensive series of ganglioglioma (GG) with brain somatic alterations of the PTPN11/KRAS/NF1 genes compared to GG with common MAP-Kinase signaling pathway alterations, i.e., BRAFV600E. Seventy-two GG were submitted to whole exome sequencing and genotyping and 84 low grade epilepsy associated tumors (LEAT) to DNA-methylation analysis. In 28 tumours, both analyses were available from the same sample. Clinical data were retrieved from hospital files including disease onset, age at surgery, brain localization, and seizure outcome. A comprehensive histopathology staining panel was available in all cases. We identified eight GG with PTPN11 alterations, copy number variant (CNV) gains of chromosome 12, and the commonality of additional CNV gains in NF1, KRAS, FGFR4 and RHEB, as well as BRAFV600E alterations. Histopathology revealed an atypical glio-neuronal phenotype with subarachnoidal tumor spread and large, pleomorphic, and multinuclear cellular features. Only three out of eight patients with GG and PTPN11/KRAS/NF1 alterations were free of disabling-seizures 2 years after surgery (38% had Engel I). This was remarkably different from our series of GG with only BRAFV600E mutations (85% had Engel I). Unsupervised cluster analysis of DNA methylation arrays separated these tumours from well-established LEAT categories. Our data point to a subgroup of GG with cellular atypia in glial and neuronal cell components, adverse postsurgical outcome, and genetically characterized by complex alterations in PTPN11 and other RAS-/MAP-Kinase and/or mTOR signaling pathways. These findings need prospective validation in clinical practice as they argue for an adaptation of the WHO grading system in developmental, glio-neuronal tumors associated with early onset focal epilepsy.

Oral or pulse glucocorticoid use at the onset of giant cell arteritis and its influence on the risk of relapse: a retrospective study.

The objective is to investigate whether initial therapy with intravenous methylprednisolone pulses (ivMTP) or oral glucocorticoid (OG) influences the relapse rate in giant cell arteritis (GCA) patients. This is a retrospective observational study of patients with GCA from 2004 to 2021. Demographics, clinical and laboratory variables, cumulative glucocorticoid dose and relapse rate at 6-month follow-up defined according to EULAR recommendations were recorded. Univariate and multivariate logistic regression models were used to determine possible risk factors for relapse. A total of 74 GCA patients were included for analysis (54 (73%) female, mean (SD) age 77.2 (7.4) years). Overall, 47 (63.5%) patients received ivMTP at disease onset and 27 (36.5%) OG. Mean (SD) cumulative prednisone dose (mg) at 6-month follow-up was 3790.7 (1832.7) for patients with ivMTP vs 4298.1 (2930.6) for the OG group, p = 0.37. A total of 15 (20.3%) relapses occurred at 6-month follow-up. Relapse rates did not differ according to the initial therapy (19.1 vs 22.2%, respectively, p = 0.75). In the multivariate analysis, fever at disease onset (OR 4.837; CI 1.1-21.6) and dyslipidemia (OR 5.651; CI 1.1-28.4) were independent predictors for relapse. Initial therapy with ivMTP or OG does not influence the relapse rate of GCA patients. Fever at disease onset and dyslipidemia are independent predictors of disease relapse.

Co-occurrence of heterogeneous Flavobacterium psychrophilum isolates within the same Chilean farm and during the same infectious outbreak.

Flavobacterium psychrophilum is a pathogenic bacterium affecting Chilean salmonid farms. High antigenic and genetic diversity exists among Chilean F. psychrophilum isolates, but the distribution thereof among farms is poorly understood. These epidemiological data are key for developing isolate-specific vaccines. The present study isolated F. psychrophilum in diseased Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) from five freshwater farms between 2018 and 2019. Each farm only raised one salmonid species and was geographically separated from and did not share culturing water with the other farms. Antigenic and genetic analyses were conducted to shed light on the possibility of isolates coexisting within the same farm during outbreaks. A total of 68 Chilean F. psychrophilum isolates were recovered from skin lesions, gills, fins, kidney and spleen of moribund and live fish. Among the 68 Chilean isolates, mPCR-serotyping indicated three major serotypes (i.e. 23.5% type 0; 47.1% type 2; and 26.5% type 4) and, to a lesser degree, serotype 1 (2.9%). Sixteen antigenic groups were detected by slide agglutination. Genetic characterizations by 16S rRNA alleles identified 71% of the isolates as the virulent genogroup CSF259-93 allele. A predominant serotype was associated with each farm, with types 0 and 4 related to Atlantic salmon and types 1 and 2 to rainbow trout. Notwithstanding, several antigenic groups coexisted within some farms. Likewise, the experimental intramuscular challenges (n = 20) demonstrated that the type-2 isolates from rainbow trout were the most pathogenic among isolates recovered from infectious outbreaks in Atlantic salmon, especially as compared to those from types-0 and -4. These results allow us to suggest that prevention measures, specifically vaccines, should be developed according to dominant isolates and with specificity to each farm, that is the use of autogenous or site-specific vaccines.

The role of ultrasound and FDG-PET/CT to detect extracranial artery involvement in patients with suspected large vessel vasculitis.

OBJECTIVE: To assess the accuracy of ultrasound (US) versus fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) to identify extracranial involvement in large vessel vasculitis (LVV). METHODS: A retrospective observational study of patients with suspected LVV. All patients underwent US exam within 24 h per protocol. FDG-PET/CT was performed according to clinician criteria. The gold standard for LVV diagnosis was clinical confirmation after 6 months. RESULTS: Of the 113 patients included (74.3% female, mean age 74 years), 37 (32.7%) were diagnosed with LVV after 6 months. The sensitivity and specificity of US were 86.5% and 96.1%, respectively. Only 12 (42.9%) of 28 patients undergoing a FDG-PET/CT per clinician criteria showed positive findings. The sensitivity and specificity of FDG-PET/CT for LVV were 61.1% and 90%, respectively. Taking FDG-PET/CT as the reference, US showed extracranial inflammation in 10/12 (83.3%) and detected 2 (12.5%) additional cases of extracranial involvement with negative FDG-PET/CT. Conversely, FDG-PET/CT was positive in two patients with negative US (one isolated aortitis and one aortoiliac involvement). CONCLUSIONS: US and FDG-PET/CT are both valid tools to detect extracranial involvement. The presence of US extracranial artery inflammation is consistent with FDG-PET/CT examination, although a negative US scan does not rule out extracranial involvement.

Angiogenesis in adipose tissue and obesity.

While most tissues exhibit their greatest growth during development, adipose tissue is capable of additional massive expansion in adults. Adipose tissue expandability is advantageous when temporarily storing fuel for use during fasting, but becomes pathological upon continuous food intake, leading to obesity and its many comorbidities. The dense vasculature of adipose tissue provides necessary oxygen and nutrients, and supports delivery of fuel to and from adipocytes under fed or fasting conditions. Moreover, the vasculature of adipose tissue comprises a major niche for multipotent progenitor cells, which give rise to new adipocytes and are necessary for tissue repair. Given the multiple, pivotal roles of the adipose tissue vasculature, impairments in angiogenic capacity may underlie obesity-associated diseases such as diabetes and cardiometabolic disease. Exciting new studies on the single-cell and single-nuclei composition of adipose tissues in mouse and humans are providing new insights into mechanisms of adipose tissue angiogenesis. Moreover, new modes of intercellular communication involving micro vesicle and exosome transfer of proteins, nucleic acids and organelles are also being recognized to play key roles. This review focuses on new insights on the cellular and signaling mechanisms underlying adipose tissue angiogenesis, and on their impact on obesity and its pathophysiological consequences.

Prevalence of post-COVID-19 in patients with fibromyalgia: a comparative study with other inflammatory and autoimmune rheumatic diseases.

OBJECTIVES: To determine the prevalence and characteristics of post-COVID-19 (PC) in fibromyalgia (FM) patients. METHODS: Retrospective, multi-centric, observational study, comparing a group of FM patients (FM group) with another group of patients with other rheumatic diseases (RD group). COVID-19 diagnosis was established by positive polymerase chain reaction or antigen during acute infection or by positive antibodies thereafter. We considered PC diagnosis when symptoms remain after COVID-19. We collected the principal characteristics of COVID-19, the severity of fatigue, waking unrefreshed and cognitive impairment, and persistent symptoms. The American College of Rheumatology (ACR) criteria and the Combined Index of Severity in Fibromyalgia (ICAF) were collected in the FM group. RESULTS: RD group (n = 56) had more pneumonia (p = 0.001) and hospital admissions (p = 0.002), but the FM group (n = 78) had a higher number of symptoms (p = 0.002). The percentage of patients with PC was similar between groups (FM group 79.5%; RD group 66.1%, p = 0.081). FM group had more PC symptoms (p = 0.001), more impairment after COVID-19 (p = 0.002) and higher severity of fatigue, waking unrefreshed and cognitive impairment (p <  0.0001). Only loss of smell was more frequent in the FM group (p = 0.005). The FM group with PC (n = 29) showed more severity of the Combined Index of Severity in Fibromyalgia (ICAF) total score and physical factor after COVID-19, while emotional, coping factors and the ACR criteria did not change. CONCLUSIONS: The prevalence of PC in FM patients is similar to RD patients. In FM patients, the presence of PC does not appear to impact the severity of FM.

A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors.

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

Author Correction: tRNA tracking for direct measurements of protein synthesis kinetics in live cells.

In the version of this article originally published, the values on the y axis of Fig. 6d were incorrect. They should be 0.00, 0.02, 0.04, 0.06 and 0.08 instead of the previous 0.00, 0.04, 0.08 and 0.12. The error has been corrected in the HTML and PDF versions of this paper.

Clinical impact of confinement due to the COVID-19 pandemic on patients with fibromyalgia: a cohort study.

OBJECTIVES: To our knowledge, the impact of the COVID-19 pandemic on fibromyalgia (FM) patients has not been studied before. FM patients often experience clinical impairment with stress. The aim of this study was to determine whether severity of FM increases because of confinement by the COVID-19 pandemic. METHODS: This prospective study includes patients from the Combined Index of Severity of Fibromyalgia (ICAF) cohort who met the 2010 ACR FM criteria. In this cohort, all patients have a periodical evaluation of their quality of life through two questionnaires, the ICAF, which assesses the ability to perform daily living activities, anxiety and depression, and through the Patient Global Impression of Change (PGIC), which assesses overall change after a therapeutical intervention. Pre- and post-confinement measurements were analysed. Inferential statistical analysis and ANOVA for repeated measurements were used. RESULTS: A total of 93 patients received a phone consultation, (95.5% females), mean (SD) age of 48.23 (8.38) years. Four patients were excluded as presenting COVID-19 and 51 (57%) completed the post-confinement ICAF. Following confinement, 25 (49%) patients got worse (group-worse) and 26 (51%) patients experienced no change or improved (group-stable). Comparisons between pre- and post-confinement ICAF did not show significant differences in both groups. Passive coping was significantly different in group-worse in pre-confinement evaluation. In the 80% of patients with passive coping predominance there were no changes in coping strategy. CONCLUSIONS: No clinical impairment due to COVID-19 confinement occurred. The perceived worsening among FM patients relies primarily on how patients cope with their disease, without a real impact on clinical manifestations.

A catalogue of new incidence estimates of monogenic neurodevelopmental disorders caused by de novo variants.

A large fraction of rare and severe neurodevelopmental disorders are caused by sporadic de novo variants. Epidemiological disease estimates are not available for the vast majority of these de novo monogenic neurodevelopmental disorders because of phenotypic heterogeneity and the absence of large-scale genomic screens. Yet, knowledge of disease incidence is important for clinicians and researchers to guide health policy planning. Here, we adjusted a statistical method based on genetic data to predict, for the first time, the incidences of 101 known de novo variant-associated neurodevelopmental disorders as well as 3106 putative monogenic disorders. Two corroboration analyses supported the validity of the calculated estimates. First, greater predicted gene-disorder incidences positively correlated with larger numbers of pathogenic variants collected from patient variant databases (Kendall's τ = 0.093, P-value = 6.9 × 10-6). Second, for six of seven (86%) de novo variant associated monogenic disorders for which epidemiological estimates were available (SCN1A, SLC2A1, SALL1, TBX5, KCNQ2, and CDKL5), the predicted incidence estimates matched the reported estimates. We conclude that in the absence of epidemiological data, our catalogue of 3207 incidence estimates for disorders caused by de novo variants can guide patient advocacy groups, clinicians, researchers, and policymakers in strategic decision-making.

Pain is not the major determinant of quality of life in fibromyalgia: results from a retrospective "real world" data analysis of fibromyalgia patients.

OBJECTIVE: To identify correlates of quality of life (QoL) measured with the Quality of Life Scale (QOLS) in participants of a multidisciplinary day hospital treatment program for fibromyalgia (FM). METHODS: In this cross-sectional, observational study, "real world" data from 480 FM patients including socio-demographics, pain variables and questionnaires such as the SF-36, Beck Depression Inventory (BDI), Multiphasic Pain Inventory (MPI), SCL-90-R and others were categorized according to the components (body structure and function, activities and participation, personal factors, environmental factors) of the International Classification of Functioning (ICF). For every ICF component, a linear regression analysis with QOLS as the dependent variable was computed. A final comprehensive model was calculated on the basis of the results of the five independent analyses. RESULTS: The following variables could be identified as main correlates for QoL in FM, explaining 56% of the variance of the QOLS (subscale/questionnaire and standardized beta in parenthesis): depression (- 0.22), pain-related interference with everyday life (- 0.19), general activity (0.13), general health perception (0.11), punishing response from others (- 0.11), work status (- 0.10), vitality (- 0.11) and cognitive difficulties (- 0.12). Pain intensity or frequency was not an independent correlate. CONCLUSIONS: More than 50% of QoL variance could be explained by distinct self-reported variables with neither pain intensity nor pain frequency playing a major role. Therefore, FM treatment should not primarily concentrate on pain but should address multiple factors within multidisciplinary therapy.

tRNA tracking for direct measurements of protein synthesis kinetics in live cells.

Our ability to directly relate results from test-tube biochemical experiments to the kinetics in living cells is very limited. Here we present experimental and analytical tools to directly study the kinetics of fast biochemical reactions in live cells. Dye-labeled molecules are electroporated into bacterial cells and tracked using super-resolved single-molecule microscopy. Trajectories are analyzed by machine-learning algorithms to directly monitor transitions between bound and free states. In particular, we measure the dwell time of tRNAs on ribosomes, and hence achieve direct measurements of translation rates inside living cells at codon resolution. We find elongation rates with tRNAPhe that are in perfect agreement with previous indirect estimates, and once fMet-tRNAfMet has bound to the 30S ribosomal subunit, initiation of translation is surprisingly fast and does not limit the overall rate of protein synthesis. The experimental and analytical tools for direct kinetics measurements in live cells have applications far beyond bacterial protein synthesis.

Self-forgiveness in fibromyalgia patients and its relationship with acceptance, catastrophising and coping.

OBJECTIVES: Forgiveness influences health through numerous mechanisms, but commonly it is thought to reduce stress, increase healthy behaviour, and promote social support, thereby positively impacting health and wellbeing. Self-forgiveness has been given considerable attention in relation to health and wellbeing. Fibromyalgia (FM) patients had lower forgiveness of others and self-forgiveness as compared to controls. The aim of this study is to explore the relationship of self-forgiveness (FS) with the impact and severity of FM, acceptance, catastrophising, and coping. METHODS: We evaluated 228 FM female patients who completed the Mauger Forgiveness Scale, the Combined Index of Severity in Fibromyalgia (ICAF) survey, the Chronic Pain Acceptance Questionnaire (CPAQ), and the Pain Catastrophising Scale (PCS). RESULTS: High self-forgiveness is related to high levels of active coping (r=.41) and acceptation (r=.38), and low self-forgiveness is related to emotional negative factors and catastrophising (r=-.56). Two factors (physical and emotional) were obtained. Lower FS is an emotional factor with negative emotion, catastrophising and a deficit in active coping. A decision-tree analysis showed a first node with ICAF Emotional scores and a second level with CPAQ and PCS scores as predictors. CONCLUSIONS: A notable lack of FS indicates a problem (distress and catastrophising) with the health aspects related to this syndrome. Acceptance could require a low negative emotional status. People with high FS were likely to increase acceptation as the positive component of acceptance in FS. This finding does not indicate an interest in maintaining problematic behaviours.

Coronavirus disease 2019 (COVID-19) in autoimmune and inflammatory conditions: clinical characteristics of poor outcomes.

OBJECTIVE: To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization. METHODS: We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization. RESULTS: A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization. CONCLUSION: Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.

Relationship between Night Shifts and Risk of Breast Cancer among Nurses: A Systematic Review.

BACKGROUND AND OBJECTIVES: The incidence of breast cancer worldwide has increased in recent decades, accounting for 1 in 3 neoplasms in women. Besides, nurses are mainly represented by the female collective, most of them, undertaking working conditions with intensive rotative and night shifts due to the 24-h pace of work of this profession. The objective of this study was to assess the possible relationship between shift work, especially night-time work, and the development of breast cancer among nurses. MATERIALS AND METHODS: A systematic review of the literature was carried out through the consultation of the following databases: Cochrane Plus Library, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, ScienceDirect, Scopus, and Dialnet. Records were selected between 2010 and 2020, in Spanish and English, which covered the association between breast cancer diagnosed among nursing professionals and rotating night shifts. RESULTS: A total of 12 studies were identified after critical reading. Most of the studies found an association between breast cancer and consecutive rotating night shifts prolonged over time. Among the associated factors, the alteration of the circadian rhythm influenced the expression of peripheral clock genes, which was the same as reproductive hormones. The risk of breast cancer in nurses increased during early adulthood and after 5 or more years with 6 or more consecutive nights. CONCLUSIONS: The different studies of this review show significant associations between breast cancer and prolonged rotating night shifts. Similarly, there is a relationship between the alterations in certain circadian rhythm markers (such as melatonin), epigenetic markers (such as telomeres), and breast cancer that would require more studies in order to corroborate these findings.