Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

The evolving pattern of the monoclonal protein improves the IMWG 2/20/20 classification for patients with smoldering multiple myeloma.

The 2/20/20 International Myeloma Working Group (IMWG) score is the most employed risk score in clinical practice to evaluate the risk of progression from smoldering multiple myeloma (SMM) to symptomatic multiple myeloma. However, it faces a serious limitation: The risk score is applied at diagnosis and cannot be reapplied. Since a dynamic accurate patient risk assessment for progression is necessary, we aimed to investigate whether the detection of an evolving pattern in serum M-protein (SMP) improves the identification of high-risk patients. Eighty-three patients diagnosed with SMM between 2011 and 2020 were included. Patients were initially classified applying the 2/20/20 IMWG score at baseline and later reclassified depending on the presence of an SMP evolving pattern into six groups. We regrouped the patients into three final risk groups: low-risk, intermediate-risk, and high-risk. The risk of progression at two years for the high-risk group was 88% and all patients had progressed at 4 years. The performance measurements were superior for the new 2/20/20-Evolving score independently for the detection of high-risk patients. We show that the sequential measurement of the SMP is a noninvasive and widely available test that improves the 2/20/20 IMWG risk score.

Prevalence and incidence of diabetic retinopathy in patients with diabetes of Latin America and the Caribbean: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to assess the prevalence and incidence of diabetic retinopathy in patients with diabetes of Latin America and the Caribbean. METHODS: We searched Web of Science (WoS)/Core Collection, WoS/MEDLINE, WoS/Scielo, Scopus, PubMed/Medline and Embase databases until January 16, 2023. We meta-analyzed prevalences according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). RESULTS: Forty-three prevalence studies (47 585 participants) and one incidence study (436 participants) were included. The overall prevalence of retinopathy in patients with T1DM was 40.6% (95% CI: 34.7 to 46.6; I2: 92.1%) and in T2DM was 37.3% (95% CI: 31.0 to 43.8; I2: 97.7), but the evidence is very uncertain (very low certainty of evidence). In meta-regression, we found that age (T1DM) and time in diabetes (T2DM) were factors associated with the prevalence. On the other hand, one study found a cumulative incidence of diabetic retinopathy of 39.6% at 9 years of follow-up. CONCLUSIONS: Two out of five patients with T1DM or T2DM may present diabetic retinopathy in Latin America and the Caribbean, but the evidence is very uncertain. This is a major public health problem, and policies and strategies for early detection and opportunely treatment should be proposed.

Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma.

PURPOSE: B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial. PATIENTS AND METHODS: We collected apheresis, final product, peripheral blood and bone marrow samples before and after infusion. We assessed BCMA, T-cell subsets, CART kinetics and antibodies, B-cell aplasia, cytokines, and measurable residual disease by next-generation flow cytometry, and correlated these to clinical outcomes. RESULTS: At cut-off date March 17, 2023, with a median follow-up of 23.1 months (95% CI, 9.2-37.1), overall response rate in the first 3 months was 95% [95% confidence interval (CI), 89.5-100]; cytokine release syndrome (CRS) was observed in 90% of patients (5% grades ≥3) and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 2 patients (3%). Median progression-free survival was 15.8 months (95% CI, 11.5-22.4). Surface BCMA was not predictive of response or survival, but soluble BCMA correlated with worse clinical outcomes and CRS severity. Activation marker HLA-DR in the apheresis was associated with longer progression-free survival and increased exhaustion markers correlated with poorer outcomes. ARI0002h kinetics and loss of B-cell aplasia were not predictive of relapse. CONCLUSIONS: Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes.

Prevalence of computer vision syndrome: A systematic review and meta-analysis

Purpose This review aimed to estimate the prevalence of computer vision syndrome (CVS) in the general population and subgroups. Methods A search was conducted in the following the databases: PubMed, SCOPUS, EMBASE, and Web of Science until February 13, 2023. We included studies that assessed the prevalence of CVS in any population. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the methodological quality. A meta-analysis of the prevalence of CVS was done using a random-effects model, assessing the sources of heterogeneity using subgroup and meta-regression analyses. Results A total of 103 cross-sectional studies with 66 577 participants were included. The prevalence of CVS was 69.0% (95% CI: 62.3 to 75.3; I2: 99.7%), ranging from 12.1 to 97.3% across studies. Point prevalence was higher in women than in men (71.4 vs. 61.8%), university students (76.1%), Africa (71.2%), Asia (69.9%), contact lens wearers (73.1% vs. 63.8%) in studies conducted before the COVID-19 pandemic (72.8%), and in those that did not use the CVS-Q questionnaire (75.4%). In meta-regression, using the CVS-Q scale was associated with a lower prevalence of CVS. Conclusion Seven out of ten people suffer from CVS. Preventive strategies and interventions are needed to decrease the prevalence of this condition which can affect productivity and quality of life. Future studies should standardize a definition of CVS. (AU)

Percutaneous coronary intervention versus optimal medical therapy for stable coronary artery disease: An umbrella review.

Background: Invasive management of stable coronary artery disease is still a controversial topic. The purpose of this umbrella review was to synthesize systematic reviews (SRs) that evaluate the benefits and harms of percutaneous coronary intervention (PCI) versus optimal medical therapy (OMT) in patients with stable coronary artery disease. Methods: We systematically searched PubMed/MEDLINE, Embase, and CENTRAL from 2018 to August 7, 2022. We included SRs with meta-analyses of randomized controlled trials (RCTs) that evaluated the question of interest. We assessed the methodological quality of the SRs with the AMSTAR-2 tool. We summarized the results of the outcomes for each SR. We calculated the degree of overlap of the RCTs included in the SRs using the corrected covered area (CCA). Results: We found 10 SRs with meta-analyses. The SRs included 3 to 15 RCTs. The degree of overlap among the SRs was very high (CCA > 15%). No SR evaluated the certainty of the evidence using the GRADE system and 9 out of 10 had critically low methodological quality. The SRs reported heterogeneous results for the outcomes of all-cause mortality, myocardial infarction, revascularization, and angina. On the other hand, for the outcomes of cardiovascular mortality and stroke, all SRs agreed that there were no differences between PCI and OMT alone. Conclusions: We found 10 SRs on the use of PCI compared to OMT alone for patients with stable coronary artery disease. However, none had high methodological quality, none evaluated the certainty of the evidence using the GRADE approach, and the results were inconsistent for several outcomes. This variability in evidence may result in divergent clinical decisions for the management of stable coronary artery disease among healthcare professionals. It is necessary to perform a high-quality SR using the GRADE approach to clarify the balance of benefits and harms of PCI.

Gene-specific RNA homeostasis revealed by perturbation of coactivator complexes.

Transcript buffering entails the reciprocal modulation of mRNA synthesis and degradation rates to maintain stable RNA levels under varying cellular conditions. Current research supports a global, non-sequence-specific connection between mRNA synthesis and degradation, but the underlying mechanisms are still unclear. In this study, we investigated changes in RNA metabolism following acute depletion of TIP60/KAT5, the acetyltransferase subunit of the NuA4 transcriptional coactivator complex, in mouse embryonic stem cells. By combining RNA sequencing of nuclear, cytoplasmic, and newly synthesised transcript fractions with biophysical modelling, we demonstrate that TIP60 predominantly enhances transcription of numerous genes, while a smaller set of genes undergoes TIP60-dependent transcriptional repression. Surprisingly, transcription changes caused by TIP60 depletion were offset by corresponding changes in RNA nuclear export and cytoplasmic stability, indicating gene-specific buffering mechanisms. Similarly, disruption of the unrelated ATAC coactivator complex also resulted in gene-specific transcript buffering. These findings reveal that transcript buffering functions at a gene-specific level and suggest that cells dynamically adjust RNA splicing, export, and degradation in response to individual RNA synthesis alterations, thereby sustaining cellular homeostasis.

Synchronization of two chaotic microresonator frequency combs.

We explore the synchronization of chaotic microresonator frequency combs, emphasizing the modulation instability state, which is known for its inherent chaotic behaviors. Our study confirms that the synchronization of two such combs is feasible by injecting the output from the lead microresonator into the next microresonator's input. We also identify the optimal parameters for this synchronization. Remarkably, even partial injection from the leader is sufficient for synchronization, paving the way for versatile future system configurations. Such systems could simultaneously utilize distinct spectral components for synchronization and transmission. This work advances our understanding of chaotic microresonator combs, showing them to be pivotal elements in next-generation optical communication systems.

Cerebrospinal fluid shunting for the management of cryptococcal meningitis: a scoping review.

Objective: This scoping review aimed to describe studies that evaluate the management of cryptococcal meningitis (CM) using cerebrospinal fluid (CSF) shunts, types of shunts used, and clinically relevant patient outcomes. Methods: We searched in the following databases: PubMed, Web of Science/Core collection, Embase, the Cochrane Library, and clinicaltrials.gov on 1 April 2022. We included two-arm and one-arm cohort studies that evaluated clinically relevant patient outcomes. Case reports were used to describe the type of CSF shunts used and the rationale behind its selection. The selection and extraction processes were independently performed by two authors. Results: This study included 20 cohort studies and 26 case reports. Only seven cohort studies compared two groups. Ventriculoperitoneal shunt was the most commonly used type of shunt (82.1%). The main indications for placing a shunt were persistently high opening pressure (57.1%) and persisting neurological symptoms or deterioration (54.3%). Cohort studies suggest that patients with shunt showed improvement in some outcomes such as neurological symptoms and hospital stay length. The most common shunt complications were post-operative fever (1-35.6%) and shunt obstruction (7-16%). Conclusion: CSF shunts may improve some clinically relevant outcomes in patients with CM, but the evidence is very uncertain.

Toxic Effects of Different Coating-Related Functionalized Nanoparticles on Aquatic Organisms.

The peculiar physico-chemical characteristics of nanomaterials (NMs) and the use of different coatings to improve their expected properties result in a huge amount of nanoforms, which vary in chemical composition, size, shape and surface characteristics. This makes it almost impossible to test all the nanoforms available, and efforts have been made to establish grouping or read-across strategies. The aim of this work was to find a behavior pattern of effect among nanoforms of different metallic core nanoparticles (NPs) (TiO2, CeO2 and Ag NP) with the same coatings (sodium citrate, poly (ethylene glycol), dodecylphosphonic acid or oleylamine). Daphnia magna, rainbow trout and two fish cell lines (PLHC-1 and RTH-149) were exposed to a range of concentrations (up to 100 mg/L) of the uncoated or coated NPs. Ag NPs were the most toxic, followed by CeO2 NPs and finally by TiO2 NPs. The results show that a clear pattern of toxicity in the studied species could not be established related to the coatings. However, it was possible to confirm different inter-species sensitivities. RTH-149 was the most sensitive cell line, and Daphnia magna was more sensitive than fish. Moreover, some differences in coating-core interactions were found between the metal oxide and the metal NPs in Daphnia magna.

Prevalence of computer vision syndrome: A systematic review and meta-analysis.

PURPOSE: This review aimed to estimate the prevalence of computer vision syndrome (CVS) in the general population and subgroups. METHODS: A search was conducted in the following the databases: PubMed, SCOPUS, EMBASE, and Web of Science until February 13, 2023. We included studies that assessed the prevalence of CVS in any population. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the methodological quality. A meta-analysis of the prevalence of CVS was done using a random-effects model, assessing the sources of heterogeneity using subgroup and meta-regression analyses. RESULTS: A total of 103 cross-sectional studies with 66 577 participants were included. The prevalence of CVS was 69.0% (95% CI: 62.3 to 75.3; I2: 99.7%), ranging from 12.1 to 97.3% across studies. Point prevalence was higher in women than in men (71.4 vs. 61.8%), university students (76.1%), Africa (71.2%), Asia (69.9%), contact lens wearers (73.1% vs. 63.8%) in studies conducted before the COVID-19 pandemic (72.8%), and in those that did not use the CVS-Q questionnaire (75.4%). In meta-regression, using the CVS-Q scale was associated with a lower prevalence of CVS. CONCLUSION: Seven out of ten people suffer from CVS. Preventive strategies and interventions are needed to decrease the prevalence of this condition which can affect productivity and quality of life. Future studies should standardize a definition of CVS.

Geographical approach analysis of the impact of air pollution on newborn intrauterine growth and cord blood DNA damage in Mexico City.

BACKGROUND: Few epidemiologic studies have focused on the specific source of ambient air pollution and adverse health effects in early life. Here, we investigated whether air pollutants from different emission sources were associated with decreased birth anthropometry parameters and increased DNA adduct formation in mother-child pairs residing in the Mexico City Metropolitan Area (MCMA). METHODS: This cross-sectional study included 190 pregnant women recruited during their last trimester of pregnancy from two hospitals at MCMA, and a Modeling Emissions Inventory (MEI) to calculate exposure to ambient air pollutants from different emissions sources (area, point, mobile, and natural) for two geographical buffers 250 and 750 m radii around the participants households. RESULTS: Contaminants were positively correlated with umbilical cord blood (UCB) adducts, but not with maternal blood (MB) adducts. PM10 emissions (area and point sources, overall emissions), PM2.5 (point sources), volatile organic compounds (VOC), total organic compounds (TOC) from point sources were positively correlated with UCB adducts. Air pollutants emitted from natural sources were correlated with a decrease in MB and UCB adducts. PM10 and PM2.5 were correlated (p < 0.05) with a decrease in birth weight (BW), birth length (BL) and gestational age at term (GA). In multivariate analyses adjusted for potential confounders, PM10 was associated with an increase in UCB adducts. PM10 and PM2.5 from overall emissions were associated with a decrease in BW, BL and GA at term. IMPACT: Results suggested higher susceptibility of newborns compared to mothers to damage related to ambient air pollution. PMs are associated with birth anthropometry parameters and DNA damage in adjusted models, highlighting the need for more strict regulation of PM emissions.

Hallazgo incidental de neoplasia primaria de pulmón: blastoma pulmonar en mujer adulta. Reporte de caso / Incidental finding of primary lung neoplasm: pulmonary blastoma in an adult woman, case report

El blastoma pulmonar es una neoplasia poco común y agresiva que se origina en el pulmón; está compuesto por tejido mesenquimal y epitelial inmaduro que imita la configuración pulmonar en etapas embrionarias. Tiene una baja incidencia y una alta tasa de mortalidad, con aproximadamente un 60 %. Este blastoma tiende a desarrollarse con mayor frecuencia entre la cuarta y quinta década de vida, siendo más prevalente en mujeres y generalmente asociado al tabaquismo. Se presenta el caso de una mujer de 23 años sin factores de riesgo conocidos, a quien se le diagnosticó incidentalmente un blastoma pulmonar primario. La paciente experimentaba dolor en la región costal izquierda, tos productiva, disnea y hemoptisis desde hace 30 días. Los hallazgos en las imágenes de rayos X y tomografías de tórax llevaron a la realización de una biopsia del pulmón izquierdo, que reveló fragmentos de tejido con una notable presencia de necrosis tumoral. Cinco días después, la paciente consultó nuevamente debido a un empeoramiento de los síntomas, incluyendo dolor torácico de tipo pleurítico. Se decidió realizar una lobectomía inferior izquierda, durante la cual se encontró un tumor sólido adherido a la pleura visceral, con masas tumorales en la pleura parietal. El estudio histopatológico final confirmó el diagnóstico de un tumor maligno de alto grado compatible con blastoma pulmonar. En conclusión, el blastoma pulmonar es una neoplasia rara que puede presentarse en diferentes etapas de la vida, aunque tiene mayor incidencia entre los 40 y 50 años. Es importante que los patólogos consideren esta enfermedad en sus diagnósticos diferenciales debido a los desafíos que implica su diagnóstico. Detectar el blastoma pulmonar en etapas tempranas es crucial para el tratamiento adecuado, aunque actualmente no se conocen marcadores predictivos confiables y el pronóstico de esta enfermedad es generalmente desfavorable.

Pulmonary blastoma is a rare and aggressive neoplasm that originates in the lung. It is composed of immature mesenchymal and epithelial tissue that mimics the embryonic configuration of the lung. It has a low incidence and a high mortality rate, of approximately 60%. Pulmonary blastoma tends to occur more frequently between the fourth and fifth decades of life, being more prevalent in women and generally associated with smoking. The case of a 23-year-old woman with no known risk factors is presented, who incidentally was diagnosed with a primary pulmonary blastoma. The patient experienced pain in the left costal region, productive cough, dyspnea, and hemoptysis for 30 days. Findings on X-ray and chest tomography led to a biopsy of the left lung, which revealed tissue fragments with significant tumor necrosis. Five days later, the patient consulted again due to worsened symptoms, including pleuritic chest pain. It was decided to perform a left lower lobectomy, during which a solid tumor attached to the visceral pleura with tumor masses in the parietal pleura was found. The final histopathological study confirmed the diagnosis of a high-grade malignant tumor compatible with pulmonary blastoma. In conclusion, pulmonary blastoma is a rare neoplasm that can occur at different stages of life, although it has a higher incidence between the ages of 40 and 50. Pathologists need to consider this disease in their differential diagnoses due to the challenges involved in its diagnosis. Detecting pulmonary blastoma at early stages is crucial for appropriate treatment, although currently there are no reliable predictive markers, and the prognosis of this disease is generally unfavorable.

Outcomes of Patients with Newly Diagnosed Transplant-Ineligible Multiple Myeloma According to Clinical Trials Enrollment: Experience of a Single Institution.

The proportion of non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients excluded from clinical trials (CTs) and their prognosis is unknown. CT results may not be generalizable to real-world practice due to strict recruitment criteria. We analyzed causes of NTE-NDMM patient exclusion form CTs and their outcomes. A total of 211 NTE-NDMM patients were included. They were divided into three periods: 2003-2007, 2008-2012, and 2013-2017. Overall, 50% received non-trial treatment (NCT), while 50% participated in a CT (20% control group (CG) and 30% experimental group (EG)). Main causes for exclusion from CTs were comorbidities, ECOG > 2, and renal insufficiency. In the first two periods, the CR rate was similar regardless of treatment type, but in the last period, the EG group showed improved CR. Median PFS was similar in the first two periods, with a benefit seen only in the EG in the last period. The median OS was significantly longer in CT-included patients compared to NCT group in the last two periods. Conclusions: The presence of comorbidities and worsened ECOG were the main reasons for CT exclusion. Patients included in CTs had a longer OS than NCT. This OS benefit may be influenced by a selection bias, making it challenging to generalize CT results to real clinical practice.

Association between weight status and migraine in the paediatric population: a systematic review and meta-analysis.

Introduction: An association between weight status and migraine has been previously reported; however, this relationship has only been studied in adults, not in the paediatric population. Objective: To evaluate the association between weight status and migraine in the paediatric population. Methods: We searched PubMed/Medline, Scopus, Web of Science, Ovid Medline, and Embase using a cut-off date of May 2023. We included observational studies that evaluated the association between weight status (underweight, overweight, obese, and excess weight) and migraine in the paediatric population (children and adolescents). Normal weight was the comparator. The outcome was migraine (all types, episodic and chronic). We performed meta-analyses using a random-effects model to estimate the pooled effects for each outcome. Sensitivity analysis was performed based on study design and risk of bias (using the Newcastle-Ottawa Scale). Certainty of evidence was assessed using the GRADE approach. Results: Eight studies (6 cross-sectional, 1 case-control and 1 cohort) covering 16,556 patients were included. The overall certainty of evidence was very low for the association between overweight, obesity, and excess weight with migraine. In the sensitivity analysis, meta-analyses of studies with a low risk of bias found that the overweight population probably had an increased odds of migraine (OR: 1.70; 95% CI: 1.14 to 2.53; I2 = 32.3%, p = 0.224) and that excess weight may increase the odds of migraine (OR: 1.58; 95% CI: 1.06 to 2.35; I2 = 83.7%, p = 0.002). Additionally, cohort and case-control studies found that obesity probably increases the odds of migraine. No studies analysed the association between underweight and migraine. Conclusion: The associations between overweight, obesity, excess weight and migraine were uncertain, but studies with better methodological quality reported increased odds. Future longitudinal studies with proper confounding control are needed to disentangle their causal relationship. Systematic review registration: PROSPERO, identifier CRD42021271533.

Sis2 regulates yeast replicative lifespan in a dose-dependent manner.

Application of microfluidic platforms facilitated high-precision measurements of yeast replicative lifespan (RLS); however, comparative quantification of lifespan across strain libraries has been missing. Here we microfluidically measure the RLS of 307 yeast strains, each deleted for a single gene. Despite previous reports of extended lifespan in these strains, we found that 56% of them did not actually live longer than the wild-type; while the remaining 44% showed extended lifespans, the degree of extension was often different from what was previously reported. Deletion of SIS2 gene led to the largest RLS increase observed. Sis2 regulated yeast lifespan in a dose-dependent manner, implying a role for the coenzyme A biosynthesis pathway in lifespan regulation. Introduction of the human PPCDC gene in the sis2Δ background neutralized the lifespan extension. RNA-seq experiments revealed transcriptional increases in cell-cycle machinery components in sis2Δ background. High-precision lifespan measurement will be essential to elucidate the gene network governing lifespan.

Corrigendum: Ring attractor bio-inspired neural network for social robot navigation.

[This corrects the article DOI: 10.3389/fnbot.2023.1211570.].

Regulatory and pathogenic mechanisms in response to iron deficiency and excess in fungi.

Iron is an essential element for all eukaryote organisms because of its redox properties, which are important for many biological processes such as DNA synthesis, mitochondrial respiration, oxygen transport, lipid, and carbon metabolism. For this reason, living organisms have developed different strategies and mechanisms to optimally regulate iron acquisition, transport, storage, and uptake in different environmental responses. Moreover, iron plays an essential role during microbial infections. Saccharomyces cerevisiae has been of key importance for decrypting iron homeostasis and regulation mechanisms in eukaryotes. Specifically, the transcription factors Aft1/Aft2 and Yap5 regulate the expression of genes to control iron metabolism in response to its deficiency or excess, adapting to the cell's iron requirements and its availability in the environment. We also review which iron-related virulence factors have the most common fungal human pathogens (Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans). These factors are essential for adaptation in different host niches during pathogenesis, including different fungal-specific iron-uptake mechanisms. While being necessary for virulence, they provide hope for developing novel antifungal treatments, which are currently scarce and usually toxic for patients. In this review, we provide a compilation of the current knowledge about the metabolic response to iron deficiency and excess in fungi.

Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid.

S. aureus is a pathogen that frequently causes severe morbidity and phage therapy is being discussed as an alternative to antibiotics for the treatment of S. aureus infections. In this in vitro and animal study, we demonstrated that the activity of anti-staphylococcal phages is severely impaired in 0.5% plasma or synovial fluid. Despite phage replication in these matrices, lysis of the bacteria was slower than phage propagation, and no reduction of the bacterial population was observed. The inhibition of the phages associated with a reduction in phage adsorption, quantified to 99% at 10% plasma. S. aureus is known to bind multiple coagulation factors, resulting in the formation of aggregates and blood clots that might protect the bacterium from the phages. Here, we show that purified fibrinogen at a sub-physiological concentration of 0.4 mg/ml is sufficient to impair phage activity. In contrast, dissolution of the clots by tissue plasminogen activator (tPA) partially restored phage activity. Consistent with these in vitro findings, phage treatment did not reduce bacterial burdens in a neutropenic mouse S. aureus thigh infection model. In summary, phage treatment of S. aureus infections inside the body may be fundamentally challenging, and more investigation is needed prior to proceeding to in-human trials.

Prevalence of hypertension in adults living at altitude in Latin America and the Caribbean: A systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to assess the prevalence of hypertension in populations living at altitude in Latin America and the Caribbean. METHODS: We conducted a systematic search from January 1, 2000 to January 10, 2023 in Web of Science (WoS)/Core Collection, WoS/Medline, WoS/Scielo, Scopus, PubMed and Embase databases. We included studies that assessed the prevalence of hypertension in altitude populations (>1500 m.a.s.l.) and these were meta-analyzed using a random-effects model. To assess the sources of heterogeneity, we performed subgroup and meta-regression analyses. RESULTS: Thirty cross-sectional studies (117 406 participants) met the inclusion criteria. Studies used different cut-off points. The prevalence of hypertension in the studies that considered the cut-off point of ≥ 140/90 mmHg in the general population was 19.1%, ≥ 130/85 mmHg was 13.1%, and ≥ 130/80 mmHg was 43.4%. There was a tendency for the prevalence of hypertension to be higher in men. In meta-regression analyses, no association was found between altitude, mean age, year of publication, risk of bias and prevalence of hypertension. CONCLUSION: The prevalence of hypertension in the altitude population of Latin America and the Caribbean is lower than that reported in populations living at sea level and lower than other altitude populations such as Tibetans. PROSPERO: CRD42021275229.