Granulomatous Folliculotropic Secondary Syphilis: An Unusual Histopathological Clue.

ABSTRACT: Syphilis is a sexually transmitted disease that can present a wide variety of clinical and histopathological manifestations. We present the case of a 75-year-old patient with a persistent maculopapular rash on the trunk and extremities, in which the biopsy showed an exclusively perifollicular granulomatous infiltrate. In the immunohistochemical staining with anti-Treponema pallidum antibodies, spirochetes scattered within the perifollicular inflammatory infiltrate were identified. These findings together with the serological analysis allowed the diagnosis of secondary syphilis. Folliculotropic nonalopecic syphilis is rare, and the pathogenic mechanisms that cause this specific tropism are unknown. On the other hand, granulomatous inflammation is a pattern typically described in tertiary syphilis but also occasionally found in secondary syphilis. We present a case of secondary syphilis with the combination of both histopathological findings, an uncommon constellation for dermatopathologists to consider.

Influence of menstrual pain and symptoms on activities of daily living and work absenteeism: a cross-sectional study.

OBJECTIVE: To examine the prevalence of menstrual pain among women of reproductive age and its impact on their daily lives and professional responsibilities. METHODS: A cross-sectional and descriptive study was conducted in July and August 2022. Phone interviews were carried out using a random system to select women aged between 15 and 49 years old. The questionnaire included sociodemographic variables, contraception method used, characteristics of the menstrual pattern (pain and bleeding amount), its influence on their working life, and if they would need to resort to sick leaves due to the impairments arising from the menstrual symptoms. RESULTS: A total of 1800 women representative of the Spanish population took part in this study. 72.6% of them report menstrual pain, with 45.9% requiring medication. 35.9% identify their menstrual bleeding as intense or very intense. 38.8% assert that menstrual discomforts affect their everyday life. 34.3% would have required not attending their work activities or having requested sick leave due to the discomforts, although only 17.3% of the women finally requested so, mainly because 58.4% considered that it might imply consequences in their professional environment, especially those with Higher Education. The women who report more discomfort are the youngest ones and those who resort to condoms as a contraceptive method (p < 0.001). CONCLUSIONS: Menstrual pain is a prevalent problem among women of reproductive age and can affect their everyday life and professional environment, requiring work leaves on some occasions.

This study is a starting point to know the prevalence of menstrual discomforts among Spanish women of reproductive age and their effect on the professional environment, to enable an assessment of the possible impact of the menstrual leave legislation recently implemented in Spain.

Intracranial investigation of piriform cortex epilepsy during odor presentation.

The piriform cortex (PC) is part of the olfactory system, principally receiving input from the lateral olfactory tract and projecting to downstream components of the olfactory network, including the amygdala. Based on preclinical studies, PC is vulnerable to injury and can be easily kindled as an onset site for seizures. While the role of PC in human epilepsy has been studied indirectly and the subject of speculation, cases of demonstrated PC seizure onset from direct intracranial recording are rare. We present a pediatric patient with drug-resistant focal reflex epilepsy and right mesial temporal sclerosis with habitual seizures triggered by coconut aroma. The patient underwent stereoelectroencephalography with implantation of olfactory cortices including PC, through which we identified PC seizure onset, mapped high-frequency activity associated with presentation of olfactory stimuli and performance on cognitive tasks, and reproduced habitual seizures via cortical stimulation of PC. Coconut odor did not trigger seizures in our work with the patient. Surgical workup resulted in resection of the patient's right amygdala, PC, and mesial temporal pole, following which she has been seizure free for 20 months without functional decline in cognition or smell. Histological findings from resected tissue showed astrogliosis and subpial gliosis.

One-lung ventilation with a bronchial blocker in thoracic patients.

BACKGROUND: Lung isolation is a technique used in a multitude of surgeries to ensure single-lung ventilation with collapse of the contralateral lung, as to achieve improved access and visualization of relevant anatomical structures. Despite being accepted and having favorable outcomes, bronchial blockers (BBs) are not to this day the main device of choice among anaesthesiologists. METHODS: In this retrospective and descriptive study, we analyzed the safety and efficacy of a BB in all types of thoracic surgeries in our centre between 2015 and 2022, excluding patients with massive hemoptysis or empyema, or who had undergone a prior pneumonectomy. RESULTS: One hundred and thirty-four patients were intervened due to lung cancer (67.9%), respiratory disease (23.9%), and non-respiratory disease (8.2%) undergoing lung surgeries (65.7%), pleural and mediastinal surgeries (29.9%), chest wall surgeries (3.0%) and other surgeries (1.5%). In most cases, lung collapse was considered excellent (63.9%) or good (33.1%) with only 4 cases (3.0%) of poor lung collapse. More than 90% of patients did not present intraoperative or immediate postoperative complications. No statistically significant differences were found between lung collapse and the demographic, clinical or BB-related variables (p > 0.05). However, we found a significatively higher proportion of excellent lung collapses in VATS surgeries and lateral decubitus positioning, as well as a significatively less proportion of poor lung collapses (p < 0.05). Moreover, there was a significantly higher proportion of excellent lung collapses when the BB was placed in the left bronchus (p < 0.05). CONCLUSIONS: With these results, in our experience BBs constitute an effective alternative, capable of achieving pulmonary collapse in all kinds of thoracic procedures with satisfactory safety rates due to their minimal complications.

In Vitro Bioaccessibility of Bioactive Compounds of Freeze-Dried Orange Juice Co-Product Formulated with Gum Arabic and Modified Starch.

The large amount of waste generated by the orange juice industry has sparked the interest of many researchers in incorporating recycling systems and following a much more sustainable circular economy model. This work proposes the valorization of the co-product generated in the orange juice extraction industry after freeze-drying for its subsequent reuse as a natural ingredient in the food industry. In addition, the possible protective effect of gum Arabic and corn starch esterified with octenyl succinic groups, in proportions optimised in previous studies 0.25 and 0.45 g/g orange co-product dry solutes, on the main bioactive compounds of orange peel during the freeze-drying process has been studied. The samples were characterised for their content of vitamin C (ascorbic and dehydroascorbic acids), flavonoids (hesperidin and narirutin), total phenols and total carotenoids, as well as their antioxidant capacity (DPPH and FRAP assays). In addition, samples were digested, mimicking the human enzymatic oral gastro-intestinal digestion process, and the bioaccessibility of the bioactive compounds was evaluated. It was observed that the addition of both biopolymers improved the stability of the hydrophilic compounds during freeze-drying. This conservative effect was more remarkable for higher biopolymer concentrations. However, no protective effect on carotenoid compounds was observed. This trend was reflected in the antioxidant activity of the different samples. In addition, the incorporation of biopolymers improved the bioaccessibility of the bioactive compounds studied. In conclusion, the results supported the feasibility of the freeze-dried orange juice co-product as a natural, sustainable source of health-promoting compounds.

Bioavailability of Bioactive Compounds from Reconstituted Grapefruit Juice as Affected by the Obtention Process.

Much attention has been paid to the health benefits of including fruits and vegetables in the diet. However, for the compounds responsible for this beneficial effect to be effective at the level of the human organism, they must be available for absorption after digestion. In this sense, in vivo studies are needed to demonstrate the bioavailability of these compounds and their physiological activity. In order to provide information in this regard, this study collects data on the levels of vitamin C (VC) and naringenin (NAG) in the blood serum of the 11 volunteer participants in this trial, before and after consuming two different grapefruit juices. The juices were prepared by rehydrating the grapefruit powder obtained by freeze-drying (FD) the fruit puree or by spray-drying (SD) the liquefied grapefruit. No significant differences (p > 0.05) neither by juice nor by participant were observed in any case. The mean relative increase of VC, NAG and the radical scavenging ability (RSA) in blood serum due to grapefruit juices intake was 12%, 28% and 26%, respectively. Just VC showed a positive and significant Pearson's correlation with RSA. The mean bioavailability of VC was quantified as 1.529 ± 0.002 mg VC/L serum per 100 mg of VC ingested.

Coenzyme B12 -dependent and independent photoregulation of carotenogenesis across Myxococcales.

Light-induced carotenogenesis in Myxococcus xanthus is controlled by the B12 -based CarH repressor and photoreceptor, and by a separate intricate pathway involving singlet oxygen, the B12 -independent CarH paralogue CarA and various other proteins, some eukaryotic-like. Whether other myxobacteria conserve these pathways and undergo photoregulated carotenogenesis is unknown. Here, comparative analyses across 27 Myxococcales genomes identified carotenogenic genes, albeit arranged differently, with carH often in their genomic vicinity, in all three Myxococcales suborders. However, CarA and its associated factors were found exclusively in suborder Cystobacterineae, with carA-carH invariably in tandem in a syntenic carotenogenic operon, except for Cystobacter/Melittangium, which lack CarA but retain all other factors. We experimentally show B12 -mediated photoregulated carotenogenesis in representative myxobacteria, and a remarkably plastic CarH operator design and DNA binding across Myxococcales. Unlike the two characterized CarH from other phyla, which are tetrameric, Cystobacter CarH (the first myxobacterial homologue amenable to analysis in vitro) is a dimer that combines direct CarH-like B12 -based photoregulation with CarA-like DNA binding and inhibition by an antirepressor. This study provides new molecular insights into B12 -dependent photoreceptors. It further establishes the B12 -dependent pathway for photoregulated carotenogenesis as broadly prevalent across myxobacteria and its evolution, exclusively in one suborder, into a parallel complex B12 -independent circuit.

The impact of ABCDE bundle implementation on patient outcomes: A nationwide cohort study.

BACKGROUND: The ABCDE bundle is a set of evidence-based practices to systematically reduce the risks of sedation, delirium, and immobility in intensive care patients. Implementing the bundle improves clinical outcome. AIMS AND OBJECTIVES: To investigate the association between patient outcomes and compliance with bundle components ABC (analgosedation algorithms), D (delirium protocol), and E (early mobilization protocol). DESIGN: A Spanish multicentre cohort study of adult patients receiving invasive mechanical ventilation (IMV) for ≥48 h until extubation. METHODS: The primary outcome was pain level, cooperation to permit Medical Research Council Scale administration, patient days of delirium, and mobility. The secondary outcome was cumulative drug dosing by IMV days. Tertiary outcomes (ICU days, IMV days, bed rest days, ICU mortality, ICUAW) and independent variables (analgosedation, delirium, early mobilization protocols) were also studied. RESULTS: Data were collected from 605 patients in 80 ICUs and 5214 patient days with IMV. Two-thirds of the ICUs studied applied no protocols. Pain was not assessed on 83.6% of patient days. Patient cooperation made scale administration feasible on 20.7% of days. Delirium and immobility were found on 4.2% and 69.9% of days, respectively. Patients had shorter stays in ICUs with bundle protocols and fewer days of IMV in ICUs with delirium and mobilization bundle components (P = 0.006 and P = 0.03, respectively). Analgosedation protocols were associated with more opioid dosing (P = 0.02), and delirium and early mobilization protocols with more propofol (P = 0.001), dexmedetomidine (P = 0.001), and lower benzodiazepine dosing (P = 0.008). CONCLUSIONS: The implementation rate of ABCDE bundle components was very low in our Spanish setting, but when implemented, patients had a shorter ICU stay, more analgesia dosing, and lighter sedation. RELEVANCE TO CLINICAL PRACTICE: Applying some but not all the bundle components, there is increased analgesia and light sedation drug use, decreased benzodiazepines, and increased patient cooperation and mobility, resulting in a shorter ICU stay and fewer days of IMV.

Variables associated with mobility levels in critically ill patients: A cohort study.

BACKGROUND: Early mobilization in the intensive care unit (ICU) helps improve patients' functional status at discharge. However, many barriers hinder this practice. AIM AND OBJECTIVES: To identify mobility levels acquired by critically ill patients and their variables. DESIGN: A multi-centre cohort study was conducted in adult patients receiving invasive mechanical ventilation for at least 48 hours. METHODS: The primary outcome was level of mobility according to the ICU mobility scale. The secondary outcome was human resource availability and existence of ABCDEF bundle guidelines. A logistic regression was performed, based on days 3 to 5 of the ICU stay and significant association with active mobility. RESULTS: Six hundred and forty-two patients were included from 80 ICUs. Active moving in and out of bed was found on 9.9% of patient-days from day 8 of the ICU stay. Bed exercises, or passive transfers, and immobility were observed on 45.6% and 42.2% of patient-days, respectively. Patients achieving active mobility (189/642, 29.4%) were in ICUs with more physiotherapist hours. Active mobility was more likely with a 1:4 nurse-patient ratio (odds ratio [OR] 3.7 95% confidence interval [CI] [1.2-11.2]), high MRC sum-score (OR 1.05 95% CI [1.04-1.06]) and presence of delirium (OR 1.01 95% CI [1.00-1.02]). By contrast, active mobility was hindered by higher BMI (OR 0.92 95% CI [0.88-0.97]), a 1:3 nurse-patient ratio (OR 0.54 95% CI [0.32-0.93]), or a shift-dependent nurse-patient ratio (OR 0.27 95% CI [0.12-0.62]). CONCLUSIONS: Immobility and passive mobilization were prevalent. A high MRC sum-score and presence of delirium are protective factors of mobilization. A 1:4 nurse-patient ratio shows a stronger association with active mobility than a 1:3 ratio. RELEVANCE TO CLINICAL PRACTICE: Severity-criteria-based nurse-patient ratios hinder mobilization. Active mobilization may be enhanced by using nursing-intervention-based ratios, increasing physiotherapist hours, and achieving wider application of the ABCDEF bundle, resulting in more awake, cooperative patients.

Association between clinical and IVF laboratory parameters and miscarriage after single euploid embryo transfers.

BACKGROUND: The goal of this study was to investigate which factors, excluding embryo aneuploidies, are associated with miscarriage in patients who have undergone a single euploid blastocyst transfer. METHODS: Retrospective, observational and multicenter study with 2832 patients undergoing preimplantational genetic testing for aneuploidies (PGT-A) due to repeated implantation failure, recurrent pregnancy loss, advanced maternal age or severe male factor were transferred one single euploid embryo. RESULTS: One of the main findings was a significant relationship between body mass index (BMI) and miscarriage rates (13.4% in underweight women, 12.1% in normal weight, 14.5% in overweight, and 19.2% in obese women, odds ratio [OD] 1.04; 95% confidence interval [CI], 1.01-1.07 p = 0.006). Endometrial thickness (OD 0.65; 95%, 0.52-0.77 p = 0.04) and type of endometrial preparation (natural cycle or hormone replacement cycle) (OD 0.77; 95%, 0.52-0.77, p = 0.04) were also associated with miscarriage rates. CONCLUSIONS: BMI was strongly associated to miscarriage rates. We also observed a weaker association with endometrial thickness and with the type of endometrial preparation (natural cycle or hormone replacement cycle). None of the other studied variables (biopsy day, maternal and male age, duration of infertility, cycle length, previous miscarriages, previous live births, previous In Vitro Fertilization (IVF) cycles, endometrial pattern and/or diagnosis) were associated with miscarriage rates.

Self-rated health among people living with HIV in Spain in 2019: a cross-sectional study.

BACKGROUND: HIV infection has become a chronic disease and well-being of people living with HIV (PLHIV) is now of particular concern. The objectives of this paper were to describe self-rated health among PLHIV, on ART and on ART virally suppressed and to analyse its determinants. METHODS: Data were obtained from a second-generation surveillance system based on a cross-sectional one-day survey in public hospitals. Epidemiological and clinical data were collected among HIV-infected inpatients and outpatients receiving HIV-related care the day of the survey in 86 hospitals in 2019. Self-rated health was measured using a question included in the National Health Survey: "In the last 12 months, how would you rate your health status?" an ordinal variable with five categories (very good, good, moderate, bad and very bad). For the analysis, these responses were dichotomized into two categories: 1 = very good/good and 0 = moderate, bad or very bad health status. Factors associated with very good/good self-rated health were estimated using logistic regression. RESULTS: Of 800 PLHIV, 67.5% perceived their health as very good/good, 68.4% among PLHIV on ART and 71.7% of those virally suppressed. Having university education (adjusted odds ratio (aOR):2.1), being unemployed (aOR:0.3) or retired (aOR:0.2), ever being diagnosed of AIDS (aOR:0.6), comorbidities (aOR:0.3), less than 2 year since HIV diagnosis (aOR:0.3) and not receiving ART (aOR:0.3) were associated with good self-rated health. Moreover, among PLHIV on ART, viral load less than 200 copies (aOR:3.2) were related to better perceived health. Bad adherence was inversely associated with good self-rated health among PLHIV on ART (aOR:0.5) and of those virally suppressed (aOR:0.4). CONCLUSIONS: Nearly seven in 10 PLHIV in Spain considered their health status as very good/good, being higher among virally suppressed PLHIV. Both demographic and clinical determinants affect quality of life.

Clear Cell Proliferations of the Skin: A Histopathologic Review.

ABSTRACT: Cutaneous clear cell proliferations encompass a heterogenous group of several primary cutaneous neoplasms and metastatic tumors with different histogenesis. Many of these clear cell proliferations may seem strikingly similar under the microscope resulting in challenging diagnosis. In many of these clear cell lesions, the reason for the clear or pale appearance of proliferating cells is unknown, whereas in other ones, this clear cell appearance is due to intracytoplasmic accumulation of glycogen, mucin, or lipid. Artifacts of tissue processing and degenerative phenomenon may also be responsible for the clear cell appearance of proliferating cells. Awareness of the histopathologic findings as well as histochemical and immunohistochemical techniques are crucial to the accurate diagnosis. This review details the histopathologic features of clear cell cutaneous proliferations, classifying them according their type of differentiation and paying special attention to the histopathologic differential diagnosis among them.

Knowledge of dental trauma among dental students. Lecture intervention protocol and follow-up over four academic courses.

BACKGROUND AND AIMS: A study was made to evaluate knowledge of dental trauma among first-year dental students at the start of the career; assess the knowledge gained immediately after a lecture intervention; and evaluate persisting knowledge on an annual basis until the fourth year of the career. MATERIAL AND METHODS: The study involved 29 volunteers from the first year of dentistry (School of Dentistry, Madrid Complutense University, Madrid, Spain). All the participants completed a previously validated questionnaire including questions referred to the management of dental trauma at the site of the accident, and other related aspects. This was followed by a brief lecture on the subject, and then the same questionnaire was administered again. Completion of the original questionnaire was subsequently repeated on an annual basis up until the fourth year of the career. Repeated measures analysis was used to assess the evolution of student knowledge. RESULTS: Knowledge of the subject was seen to be lacking at the start of the career, but increased significantly as a result of the lecture intervention (P < .001). Over the subsequent courses, although the notions referred to dental trauma were seen to decrease with respect to the first evaluation, they remained high. All of the participants agreed on the need for informative campaigns referred to dental trauma targeted to students in the first courses of the health sciences. CONCLUSIONS: It is necessary to impart knowledge on the prevention and immediate management of dental traumatisms in order to improve their prognosis. This learning is especially relevant to students in the first courses of the health sciences.

[Patient safety in nursing homes. The experience of the Autonomous Community of the Region of Murcia]. / La seguridad del paciente en las residencias sociosanitarias. La experiencia de la Comunidad Autónoma de la Región de Murcia.

The pandemic has exposed the vulnerability of residential centers and the fragility of the population that lives there. In the Region of Murcia, care for this population group became a priority and a regional plan was drawn up to attend the needs of residents from the ethical framework of procedural justice. The immediacy imposed by the health crisis has meant that all this intervention is not without risks. Based on the Reason model, we have carried out a root cause analysis of the contributing factors that led the nursing homes to suffer a devastating impact, categorizing the security failures at three levels: infection control, social health environment and health-clinical environment. The pandemic has shown the urgency of strengthening the care model that we offer to our elders. A model that guarantees the coverage of the needs of extremely fragile patients that go beyond health and biomedical care and that considers their preferences and values.

Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by medically unexplained debilitating fatigue with suggested altered immunological state. Our study aimed to explore peripheral blood mononuclear cells (PBMCs) for microRNAs (miRNAs) expression in ME/CFS subjects under an exercise challenge. The findings highlight the immune response and inflammation links to differential miRNA expression in ME/CFS. The present study is particularly important in being the first to uncover the differences that exist in miRNA expression patterns in males and females with ME/CFS in response to exercise. This provides new evidence for the understanding of differential miRNA expression patterns and post-exertional malaise in ME/CFS. We also report miRNA expression pattern differences associating with the nutritional status in individuals with ME/CFS, highlighting the effect of subjects' metabolic state on molecular changes to be considered in clinical research within the NINDS/CDC ME/CFS Common Data Elements. The identification of gender-based miRNAs importantly provides new insights into gender-specific ME/CFS susceptibility and demands exploration of sex-suited ME/CFS therapeutics.

The anterior caudate nucleus supports impulsive choices triggered by pramipexole.

BACKGROUND: Pramipexole is a dopamine agonist used as a treatment in PD and restless legs syndrome to reduce motor symptoms, but it often induces impulse control disorders. In particular, patients with impulse control disorders tend to make more impulsive choices in the delay discounting task, that is, they choose small immediate rewards over larger delayed ones more often than patients without impulse control disorders and healthy subjects do. Yet the site of action of pramipexole that produces these impulsive choices remains unknown. Based on the heterogeneity of corticostriatal projections and the massive dopamine innervation of the striatum, we hypothesized that impulsive choices triggered by dopamine treatments may be supported by a specific striatal territory. OBJECTIVES: This study aims to determine by which anteriorstriatum territory the Pramipexole trigger impulsive choices; the caudate nucleus, the ventral striatum or the putamen. METHODS: We compared pramipexole intramuscular injections to intracerebral microinjections within the three striatal territories in healthy monkeys trained to execute the delay discounting task, a behavioral paradigm typically used to evaluate impulsive choices. RESULTS: We found that pramipexole intramuscular injections induced impulsive choices in all monkeys. Local microinjections were performed inside the anterior caudate nucleus, ventral striatum, and anterior putamen and reproduced those impulsive choices when pramipexole was directly injected into the caudate nucleus, whereas injections into the ventral striatum or putamen had no effect on monkeys' choices. CONCLUSIONS: These results, consistent with clinical studies, suggest that impulsive choices triggered by pramipexole are supported by the caudate nucleus, allowing us to emphasize the importance of dopamine modulation inside this striatal territory in decision processes underlying impulsive behaviors. © 2019 International Parkinson and Movement Disorder Society.

Methylene blue-treated plasma, versus quarantine fresh frozen plasma, for acute thrombotic thrombocytopenic purpura treatment: Comparison between centres and critical review on longitudinal data.

INTRODUCTION: Therapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP). Methylene blue-plasma (MBP) has been used for over 20 years, but its efficacy in this setting remains controversial. PATIENTS AND METHODS: this is a comparative analysis of the experience of two Centres, with different plasma products, to evaluate their efficacy in TTP. One centre used quarantine plasma (QP), and MBP the other. We performed a retrospective longitudinal study, analysing the clinical files of TTP patients of a 13-year data evaluation period. Duration of treatment and transfusion parameters, medical record, laboratory testing, concomitant medication, and survival rate, were assessed for every episode. RESULTS: During the study period, 12 (55.5 %) and 10 (45.5 %) new cases were treated with QP and MBP, respectively. There were no significant differences between the mean numbers of TPE processes, days elapsed from diagnosis to TPE, and plasma volume transfused. The QP TPE episodes of treatment were significantly associated with an increased time to recovery compared with MBP episodes of treatment (p = 0.004). CONCLUSION: MBP was as effective as QP in the treatment of TTP patients. Since recovery was more favourable when MBP was used, we consider MBP remains a suitable alternative to treat TTP patients.

Delphi-based recommendations for the management of cardiovascular comorbidities in patients with psoriatic arthritis and moderate-to-severe psoriasis.

The aim of this study was to generate practical recommendations to assist rheumatologists and dermatologists in the management of cardiovascular (CV) comorbidities in patients with moderate-to-severe psoriasis (MS-PSO) and psoriatic arthritis (PsA). A two-round Delphi study was conducted. A panel of experts rated their agreement with a set of statements (n = 52) on a nine-point Likert scale (1 = totally disagree; 9 = totally agree). Statements were classified as inappropriate (median 1-3), irrelevant (median 4-6) or appropriate (median 7-9). Consensus was established when at least two-thirds of the panel responded with a score within any one range. A total of 25 experts, 60% rheumatologists and 40% dermatologists, participated in two consultation rounds. There was overall unanimity on the appropriateness of an initial assessment for CV risk factors in all patients with MS-PSO and PsA. Most panelists (88.0%) also supported the evaluation of patients' psychological and physical status. Additionally, most panelists (72.2%) agreed on a novel sequential approach for the management of CV comorbidities. This sequence starts with the assessment of hypertension, diabetes and dyslipidemia along with the identification of depression and anxiety disorders. Once these factors are under control, smoking cessation programs might be initiated. Finally, if patients have not met weight loss goals with lifestyle modifications, they should receive specialized treatment for obesity. This study has drawn up a set of practical recommendations that will facilitate the management of CV comorbidities in patients with MS-PSO and PsA.

Multifactorial control of the expression of a CRISPR-Cas system by an extracytoplasmic function σ/anti-σ pair and a global regulatory complex.

Expression of CRISPR-Cas systems is a prerequisite for their defensive role against invading genetic elements. Yet, much remains unknown about how this crucial step is regulated. We describe a new mechanism controlling CRISPR-cas expression, which requires an extracytoplasmic function (ECF) σ factor (DdvS), its membrane-bound anti-σ (DdvA) and a global regulatory complex (CarD-CarG). Transcriptomic analyses revealed that the DdvS/CarD/CarG-dependent regulon comprises a type III-B CRISPR-Cas system in Myxococcus xanthus. We mapped four DdvS-driven CarD/CarG-dependent promoters, with one lying immediately upstream of the cas cluster. Consistent with direct action, DdvS and CarD-CarG localize at these promoters in vivo. The cas genes are transcribed as a polycistronic mRNA that reads through the leader into the CRISPR array, a putative σA-dependent promoter in the leader having negligible activity in vivo. Consequently, expression of the entire CRISPR-Cas system and mature CRISPR-RNA (crRNA) production is DdvS/CarD/CarG-dependent. DdvA likely uses its large C-terminal domain to sense and transduce the extracytoplasmic signal triggering CRISPR-cas expression, which we show is not starvation-induced multicellular development. An ECF-σ/anti-σ pair and a global regulatory complex provide an effective mechanism to coordinate signal-sensing with production of precursor crRNA, its processing Cas6 endoribonuclease and other Cas proteins for mature crRNA biogenesis and interference.

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients.

Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary. Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS. The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-ß and INF-γ) but unchanged levels of TNF-α. The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.