Mucor germinans, a novel dimorphic species resembling Paracoccidioides in a clinical sample: questions on ecological strategy.

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous Mucorales. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as Mucor germinans sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains Mucor circinelloides and Mucor kunryangriensis as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells in vitro. Multilateral yeast cells emerge in all three Mucor species at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of Paracoccidioides. The ecological role of yeast forms in Mucorales is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for Candida or Paracoccidioides. We demonstrate that the dimorphic transition is common in Mucor species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.

Production of a bacterial secretome highly efficient for the deconstruction of xylans.

Bacteria within the Paenibacillus genus are known to secrete a diverse array of enzymes capable of breaking down plant cell wall polysaccharides. We studied the extracellular xylanolytic activity of Paenibacillus xylanivorans and examined the complete range of secreted proteins when grown on carbohydrate-based carbon sources of increasing complexity, including wheat bran, sugar cane straw, beechwood xylan and sucrose, as control. Our data showed that the relative abundances of secreted proteins varied depending on the carbon source used. Extracellular enzymatic extracts from wheat bran (WB) or sugar cane straw (SCR) cultures had the highest xylanolytic activity, coincidently with the largest representation of carbohydrate active enzymes (CAZymes). Scaling-up to a benchtop bioreactor using WB resulted in a significant enhancement in productivity and in the overall volumetric extracellular xylanase activity, that was further concentrated by freeze-drying. The enzymatic extract was efficient in the deconstruction of xylans from different sources as well as sugar cane straw pretreated by alkali extrusion (SCRe), resulting in xylobiose and xylose, as primary products. The overall yield of xylose released from SCRe was improved by supplementing the enzymatic extract with a recombinant GH43 ß-xylosidase (EcXyl43) and a GH62 α-L-arabinofuranosidase (CsAbf62A), two activities that were under-represented. Overall, we showed that the extracellular enzymatic extract from P. xylanivorans, supplemented with specific enzymatic activities, is an effective approach for targeting xylan within lignocellulosic biomass.

Epigenetic control of SOX9 gene by the histone acetyltransferase P300 in human Sertoli cells.

Background: The transcription factor SOX9 is a key regulator of male sexual development and Sertoli cell differentiation. Altered SOX9 expression has been implicated in the pathogenesis of disorders of sexual development (DSD) in mammals. However, limited information exists regarding the epigenetic mechanisms governing its transcriptional control during sexual development. Methods: This study employed real-time PCR (qPCR), immunofluorescence (IIF), and chromatin immunoprecipitation (ChIP) assays to investigate the epigenetic mechanisms associated with SOX9 gene transcriptional control in human and mouse Sertoli cell lines. To identify the specific epigenetic enzymes involved in SOX9 epigenetic control, functional assays using siRNAs for P300, GCN5, and WDR5 were performed. Results: The transcriptional activation of SOX9 was associated with selective deposition of active histone modifications, such as H3K4me3 and H3K27ac, at its enhancer and promoter regions. Importantly, the histone acetyltransferase P300 was found to be significantly enriched at the SOX9 enhancers, co-localizing with the H3K27ac and the SOX9 transcription factor. Silencing of P300 led to decreased SOX9 expression and reduced H3K27ac levels at the eSR-A and e-ALDI enhancers, demonstrating the crucial role of P300-mediated histone acetylation in SOX9 transcriptional activation. Interestingly, another histone lysine acetyltransferases like GNC5 and methyltransferases as the Trithorax/COMPASS-like may also have a relevant role in male sexual differentiation. Conclusions: Histone acetylation by P300 at SOX9 enhancers, is a key mechanism governing the transcriptional control of this essential regulator of male sexual development. These findings provide important insights into the epigenetic basis of sexual differentiation and the potential pathogenesis of DSDs.

Assessment of performance and comparison of three commercial HDV RNA detection assays: implications for diagnosis and treatment monitoring.

Objectives: Precise HDV-RNA detection and quantification are pivotal for diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three HDV RNA detection and quantification assays. Methods: Hepatitis Delta RT-PCR system kit, EurobioPlex HDV assay, and RoboGene HDV RNA Quantification kit 2.0 were used for testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. All HDV-RNA positive samples were genotyped using a next-generation sequencing strategy. Results: Qualitative results indicated a 100% concordance between tests. Quantitative results correlated well, r2 = 0.703 (Vircell-vs-Eurobio), r2 = 0.833 (Vircell-vs-RoboGene), r2 = 0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results for correlation and bias. Conclusion: This study underscores the necessity of using reliable HDV-RNA detection and quantification assays, as evidenced by the high concordance rates in qualitative detection and the observed variability in quantitative results. These findings highlight the importance of consistent assay use in clinical practice to ensure accurate diagnosis and effective treatment monitoring of HDV infection.

Assessing Telemental Health Uptake and Associated Health Care Resource Implications among Mississippi Medicaid Enrollees with Major Depression.

Objective: Investigate the association between Telemental Health (TMH) uptake and sociodemographic characteristics, and how TMH uptake relates to health care resource utilization and Medicaid expenditures among Mississippi Medicaid enrollees with major depression. Methods: A retrospective cohort study was conducted (2019-2020), comparing those who utilized TMH and those who did not. Results: Among the 21,239 identified enrollees, 806 (3.79%) utilized TMH. The TMH cohort was more likely to be of older age, non-Hispanic White, comprehensive managed care organization enrollees, rural residents, and from areas with a higher area deprivation index, and have higher Charlson comorbidity index scores. The TMH cohort also exhibited higher mental health-related and all-cause outpatient and emergency department utilization, along with higher Medicaid expenditures. Conclusion: As the first study investigating telehealth utilization among Mississippi Medicaid enrollees, this study highlights sociodemographic disparities in telehealth adoption. Addressing barriers hindering telehealth adoption among vulnerable populations and ensuring the availability of quality data are vital for future research.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for head and neck cancer: A phase 1 clinical trial.

BACKGROUND AND PURPOSE: Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates pro-apoptotic pathways and enhances radiation-induced tumour cell death. This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for head and neck cancers (HN). MATERIALS AND METHODS: This prospective phase 1 clinical trial included patients with newly diagnosed or recurrent HN cancer (except nasopharynx malignancies) for whom locoregional radiotherapy with radical- or palliative-intent as deemed appropriate. Patients with contraindications for microbubble administration or contrast-enhanced MR were excluded. MR-coupled focussed ultrasound sonicated intravenously administered microbubbles within the MR-guided target volume. Patients receiving 5-10 and 33-35 radiation fractions were planned for 2 and 3 MRgFUS-MB treatments, respectively. Primary endpoint was toxicity per CTCAEv5.0. Secondary endpoint was tumour response at 3 months per RECIST 1.1 criteria. RESULTS: Twelve patients were enrolled between Jun/2020 and Nov/2023, but 1 withdrew consent. Eleven patients were included in safety analysis. Median follow-up was 7 months (range, 0.3-38). Most patients had oropharyngeal cancer (55 %) and received 20-30 Gy/5-10 fractions (63 %). No systemic toxicity or MRgFUS-MB-related adverse events occurred. The most severe acute adverse events were radiation-related grade 3 toxicities in 6 patients (55 %; dermatitis in 3, mucositis in 1, dysphagia in 6). No radiation necrosis or grade 4/5 toxicities were reported. 8 patients were included in the 3-month tumour response assessment: 4 had partial response (50 %), 3 had complete response (37.5 %), and 1 had progressive disease (12.5 %). CONCLUSIONS: MRgFUS-MB treatment was safe and associated with high rates of tumour response at 3 months.

The incidence of HIV-2 infection in Spain is declining - a registry data analysis.

OBJECTIVES: HIV-2 infection is a neglected disease caused by a human retrovirus that causes AIDS more slowly than HIV-1. Infection with HIV-2 is endemic in West Africa. Given its differential features, guidelines recommend ruling out HIV-2 infection in all newly diagnosed HIV-seropositive individuals. METHODS: A national registry of HIV-2 cases was created in Spain in 1989, following the first report of three HIV-2+ individuals in Barcelona. The main demographics, clinical, and virological data are reported up to December 2023. RESULTS: A total of 424 individuals with HIV-2 infection were recorded in the Spanish registry. After a peak in 2009 when 31 cases were reported, new HIV-2 diagnoses steadily decreased. Less than 10 cases/year have been notified since the COVID-19 pandemic. In 2023, only eight cases were reported. Mean age at HIV-2 diagnosis was 44 years old, ranging from birth to 83 years. A total of 265 (62.5%) were male. Migrants predominated, being 322 (76%) Sub-Saharan Africans; however, 60 (14.2%) were native Spaniards. Heterosexual exposure was the most likely route of infection in at least 287 (67.7%) cases. A few cases could be traced to transfusions (n = 4), vertical infection (n = 2), or injection drug use (n = 7). In addition, 15 individuals (3.5%) were men who had sex with men. Coinfection with HIV-1 was recognized in 39 (9.2%) individuals. Molecular characterization of HIV-2 subtypes was performed in 139 individuals, 121 being infected with subtype A and 18 with subtype B. CONCLUSION: The annual incidence of HIV-2 infection in Spain has decreased after peaking 15 years ago, being the current number of cases below 10 per year. Three-quarters are African migrants, and two-thirds are male. Circulation of HIV-2 in Spain is limited and steadily decreasing.

Did the organization of primary care practices during the COVID-19 pandemic influence quality and safety? - an international survey.

BACKGROUND: Changes in demographics with an older population, the illness panorama with increasing prevalence of non-communicable diseases, and the shift from hospital care to home-based care place demand on primary health care, which requires multiprofessional collaboration and team-based organization of work. The COVID-19 pandemic affected health care in various ways, such as heightened infection control measures, changing work practices, and increased workload. OBJECTIVES: This study aimed to investigate the association between primary care practices' organization, and quality and safety changes during the COVID-19 pandemic. DESIGN: Data were collected from 38 countries in a large online survey, the PRICOV-19 study. For this paper, the participating practices were categorized as "Only GPs", comprising practices with solely general practitioners (GPs) and/or GP trainees, without any other health care professionals (n = 1,544), and "Multiprofessional," comprising practices with at least one GP or GP trainee and one or more other health professionals (n = 3,936). RESULTS: Both categories of practices improved in infection control routines when compared before and during the COVID-19 pandemic. A larger proportion of the multiprofessional practices changed their routines to protect vulnerable patients. Telephone triage was used in more "Multiprofessional" practices, whereas "Only GPs" were more likely to perform video consultations as an alternative to physical visits. Both types of practices reported that the time to review new guidelines and scientific literature decreased during the pandemic. However, both had more meetings to discuss directives than before the pandemic. CONCLUSIONS: Multiprofessional teams were keener to introduce changes to the care organization to protect vulnerable patients. However, practices with only GPs were found to be more aligned with video consultations, perhaps reflecting the close patient-doctor relationship. In contrast, telephone triage was used more in multiprofessional teams.

Patient Safety Incidents in Primary Care: Comparing APEAS-2007 (Spanish Patient Safety Adverse Events Study in Primary Care) with Data from a Health Area in Catalonia (Spain) in 2019.

The initial APEAS study, conducted in June 2007, examined adverse events (AEs) in Spanish Primary Healthcare (PHC). Since then, significant changes have occurred in healthcare systems. To evaluate these changes, a study was conducted in the Camp de Tarragona PHC region (CTPHC) in June 2019. This cross-sectional study aimed to identify AEs in 20 PHC centres in Camp de Tarragona. Data collection used an online questionnaire adapted from APEAS-2007, and a comparative statistical analysis between APEAS-2007 and CTPHC-2019 was performed. The results revealed an increase in nursing notifications and a decrease in notifications from family doctors. Furthermore, fewer AEs were reported overall, particularly in medication-related incidents and healthcare-associated infections, with an increase noted in no-harm incidents. However, AEs related to worsened clinical outcomes, communication issues, care management, and administrative errors increased. Concerning severity, there was a decrease in severe AEs, coupled with an increase in moderate AEs. Despite family doctors perceiving a reduction in medication-related incidents, the overall preventability of AEs remained unchanged. In conclusion, the reporting patterns, nature, and causal factors of AEs in Spanish PHC have evolved over time. While there has been a decrease in medication-related incidents and severe AEs, challenges persist in communication, care management, and clinical outcomes. Although professionals reported reduced severity, the perception of preventability remains an area that requires attention.

The polymorphism Val158Met in the COMT gene: disrupted dopamine system in fibromyalgia patients?

ABSTRACT: The single-nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase gene ( COMT ) is a missense variant (Val158Met) associated with altered activity of the COMT enzyme and suggested as a predictive feature for developing some chronic pain conditions. However, there are controversial results on its role in fibromyalgia (FM). Here, the SNP Val158Met was analyzed in 294 FM patients (without comorbidities) and 209 healthy controls (without chronic pain). The concurrent impact of Val158Met genotypes and FM comorbid disorders (depression and sleep impairment) on FM risk were tested. In addition, the genotypic distribution of FM patients in relation to pain intensity was evaluated. The G allele (Val) resulted in being more represented in the FM group (57.8%) compared with the control group (48.8%; P = 0.037). Logistic regression highlighted that having the G/G (Val/Val) homozygous genotype was associated with 2 times higher risk of having FM compared with the A/A (Met/Met) carriers ( P = 0.038), whereas depression and sleep impairment increased FM risk by 12 and 8 times, respectively ( P < 0.001). However, considering only the FM patient group, the A/A homozygous genotype was significantly associated with severe pain intensity ( P = 0.007). This study highlighted associations between the SNP Val158Met and both FM and pain intensity, suggesting a link between dopaminergic dysfunction and vulnerability to chronic pain. Further studies should explore this SNP in FM patients in conjunction with COMT enzymatic activity and other symptoms connected with the dopaminergic system such as depression or sleep impairment.

Temporal summation of second pain is affected by cognitive load.

This work attempted to clarify the interaction of cognition and pain sensitization during a paradigm of Temporal Summation of Second Pain (TSSP). We analyzed pain ratings and electroencephalographic (EEG) activity obtained from 21 healthy participants during the presentation of four experimental conditions that differed in the manipulation of attention to painful stimuli or working memory load (Attention to hand & TSSP; 0-back & TSSP (low cognitive load); 2-back & TSSP (high cognitive load); 2-back (without pain)). We found that the TSSP was reduced when the attention was diverted and the cognitive load increased, and this reduction was accompanied by higher midfrontal theta activity and lower posterior alpha and central beta activity. Although it is well established that TSSP is a phenomenon that occurs at the spinal level, here we show that it is also affected by supraspinal attentional mechanisms. Delivery of painful repeated stimuli did not affect the performance of the 2-back task but was associated with smaller amplitudes of attentional event-related potentials (ERPs) after standard stimuli (not the target). The study of brain activity during TSSP allowed to clarify the role of top-down attentional modulation in pain sensitization processes. Results contribute to a better understanding of cognitive dysfunction in pain conditions and reinforce the use of therapeutic strategies based on distracting attention away from pain.

Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections.

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy.

Introduction: Therapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit cytotoxic responses against malignant B cells. However, efficacy is often compromised due to a suppressive microenvironment that interferes with cellular immune responses. To overcome this suppression, agonists of pattern recognition receptors have been studied which promote direct cytotoxicity or elicit anti-tumoral immune responses. NOD2 is an intracellular pattern recognition receptor that participates in the detection of peptidoglycan, a key component of bacterial cell walls. This detection then mediates the activation of multiple signaling pathways in myeloid cells. Although several NOD2 agonists are being used worldwide, the potential benefit of these agents in the context of antibody therapy has not been explored. Methods: Primary cells from healthy-donor volunteers (PBMCs, monocytes) or CLL patients (monocytes) were treated with versus without the NOD2 agonist L18-MDP, then antibody-mediated responses were assessed. In vivo, the Eµ-TCL1 mouse model of CLL was used to test the effects of L18-MDP treatment alone and in combination with anti-CD20 antibody. Results: Treatment of peripheral blood mononuclear cells with L18-MDP led to activation of monocytes from both healthy donors and CLL patients. In addition, there was an upregulation of activating FcγR in monocytes and a subsequent increase in antibody-mediated phagocytosis. This effect required the NF-κB and p38 signaling pathways. Treatment with L18-MDP plus anti-CD20 antibody in the Eµ-TCL model of CLL led to a significant reduction of CLL load, as well as to phenotypic changes in splenic monocytes and macrophages. Conclusions: Taken together, these results suggest that NOD2 agonists help overturn the suppression of myeloid cells, and may improve the efficacy of antibody therapy for CLL.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial.

BACKGROUND: Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer. METHODS AND FINDINGS: This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial. CONCLUSIONS: MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials. TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT04431674.

Variceal hemorrhage in a patient with cirrhosis and congenital hemophilia A: A therapeutic challenge.

We describe the case of a 61-year-old male patient with a history of hemophilia A and previous hepatitis C virus infection with sustained virological response and no previous documentation of cirrhosis, who was admitted for variceal bleeding. He was taken for endoscopic evaluation with evidence of active variceal hemorrhage requiring rubber band ligation. Patients with congenital coagulation disorders, such as hemophilia A, are excluded from international guidelines for gastrointestinal bleeding, making their management and counseling challenging. In this article, we describe the specific interventions to be performed in patients with hemophilia A and upper gastrointestinal tract bleeding, specifically variceal bleeding, focusing on pre-endoscopic and endoscopic management.

Quality and safety actions in primary care practices in COVID-19 pandemic: the PRICOV-19 study in Spain.

BACKGROUND: Primary Health Care (PHC) has been key element in detection, monitoring and treatment of COVID-19 cases in Spain. We describe how PHC practices (PCPs) organized healthcare to guarantee quality and safety and, if there were differences among the 17 Spanish regions according to the COVID-19 prevalence. METHODS: Cross-sectional study through the PRICOV-19 European Online Survey in PCPs in Spain. The questionnaire included structure and process items per PCP. Data collection was due from January to May 2021. A descriptive and comparative analysis and a logistic regression model were performed to identify differences among regions by COVID-19 prevalence (low < 5% or high ≥5%). RESULTS: Two hundred sixty-six PCPs answered. 83.8% of PCPs were in high prevalence regions. Over 70% PCPs were multi-professional teams. PCPs attended mainly elderly (60.9%) and chronic patients (53.0%). Regarding structure indicators, no differences by prevalence detected. In 77.1% of PCPs administrative staff were more involved in providing recommendations. Only 53% of PCPs had a phone protocol although 73% of administrative staff participated in phone triage. High prevalence regions offered remote assessment (20.4% vs 2.3%, p 0.004) and online platforms to download administrative documents more frequently than low prevalence (30% vs 4.7%, p < 0.001). More backup staff members were hired by health authorities in high prevalence regions, especially nurses (63.9% vs 37.8%, p < 0.001. OR:4.20 (1.01-8.71)). 63.5% of PCPs provided proactive care for chronic patients. 41.0% of PCPs recognized that patients with serious conditions did not know to get an appointment. Urgent conditions suffered delayed care in 79.1% of PCPs in low prevalence compared to 65.9% in high prevalence regions (p 0.240). A 68% of PCPs agreed on having inadequate support from the government to provide proper functioning. 61% of high prevalence PCPs and 69.5% of low ones (p: 0.036) perceived as positive the role of governmental guidelines for management of COVID-19. CONCLUSIONS: Spanish PCPs shared a basic standardized PCPs' structure and common clinical procedures due to the centralization of public health authority in the pandemic. Therefore, no relevant differences in safety and quality of care between regions with high and low prevalence were detected. Nurses and administrative staff were hired efficiently in response to the pandemic. Delay in care happened in patients with serious conditions and little follow-up for mental health and intimate partner violence affected patients was identified. Nevertheless, proactive care was offered for chronic patients in most of the PCPs.

Interface entre valorização, reconhecimento e satisfação do trabalho de enfermeiros da Atenção Primária à Saúde / Interface between valorization, recognition, and satisfaction of nurses' work in Primary Health Care / Interfaz entre valorización, reconocimiento y satisfacción del trabajo de enfermeras en Atención Primaria de Salud

Objetivo:identificar a interface entre valorização, reconhecimento e satisfação advindas das percepções de enfermeiros no desenvolvimento do trabalho na Atenção Primária à Saúde. Método:estudo qualitativo, descritivo e exploratório, realizado com 132 enfermeiros de 23 municípios de Minas Gerais. Os dados foram coletados por meio de formulário on-line e analisados conforme pressupostos da análise de conteúdo, com amparo do software IraMuteQ.Resultados: a maioria dos participantes eram do sexo feminino, idade média de 36 anos, carga horária semanal de 40 horas e recebiam entre dois e quatro salários-mínimos. Os dados foram organizados em uma categoria denominada: Interface entre a valorização, o reconhecimento e a satisfação, advindas das percepções de enfermeiros no desenvolvimento do trabalho na atenção primária em saúde. Conclusões:a interface entre os fenômenos evidenciou os que permeiam o salário, a carga horária, o reconhecimento de terceiros, o valor social, a importância da profissão e a autonomia.

Objective:to identify the interfaces between appreciation, recognition, and satisfaction arising from the perceptions of nurses in the development of work in Primary Health Care. Method: this qualitative, descriptive, and exploratory study was conducted with 132 nurses from 23 municipalities in Minas Gerais. Data were collected using an online form and analyzed according to content analysis assumptions, supported by the IraMuteQsoftware. Results:the majority of participants were female, with an average age of 36 years, worked 40 hours per week, and received between two and four minimum wages. The data were organized into a category called: Interfaces between appreciation, recognition, and satisfaction arising from the perceptions of nurses in the development of work in primary health care. Conclusions: the interface between the phenomena showed that points of convergence permeate salary, working hours, recognition from third parties, social value, the importance of the profession, and autonomy.

Objetivo: identificar interfaces entre apreciación, reconocimiento y satisfacción surgidos de percepciones de enfermeras en el desarrollo del trabajo en Atención Primaria de Salud. Método: estudio cualitativo que se realizó con 132 enfermeras de 23 municipios en Minas Gerais. Los datos se recopilaron mediante formulario en línea y por análisis de contenido, con el apoyo del software IraMuteQ. Resultados: La mayoría de los participantes eran mujeres, con una edad promedio de 36 años, trabajaban 40 horas por semana y recibían entre dos y cuatro salarios mínimos. Los datos se organizaron en una categoría denominada: Interfaces entre apreciación, reconocimiento y satisfacción surgidos de las percepciones de las enfermeras en el desarrollo del trabajo en atención primaria de salud. Conclusiones: La interfaz entre los fenómenos mostró que los puntos de convergencia permeaban el salario, las horas de trabajo, elreconocimiento de terceros, el valor social, la importancia de la profesión y la autonomía.

Molecular Characterization of Juxtaglomerular Cell Tumors: Evidence of Alterations in MAPK-RAS Pathway.

Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.