Optic disc edema and visual loss from paracentral acute middle maculopathy mimicking optic neuritis

ABSTRACT Optic neuritis is an important cause of unilateral and acute visual loss in young adults, but other differential diagnoses should be considered, especially when the disease has an atypical presentation. This report presents the case of a young woman with reduced visual acuity in her right eye, associated with optic disc edema and a relative afferent pupillary defect, that was initially misdiagnosed as optic neuritis and subsequently found to have paracentral acute middle maculopathy, possibly secondary to subtle impending central retinal vein occlusion. This case emphasizes the need to remember that retinal vascular diseases can occasionally mimic optic neuritis. Detailed anamnesis and ophthalmic examination can avoid unnecessary interventions.

Microprotein-encoding RNA regulation in cells treated with pro-inflammatory and pro-fibrotic stimuli.

BACKGROUND: Recent analysis of the human proteome via proteogenomics and ribosome profiling of the transcriptome revealed the existence of thousands of previously unannotated microprotein-coding small open reading frames (smORFs). Most functional microproteins were chosen for characterization because of their evolutionary conservation. However, one example of a non-conserved immunomodulatory microprotein in mice suggests that strict sequence conservation misses some intriguing microproteins. RESULTS: We examine the ability of gene regulation to identify human microproteins with potential roles in inflammation or fibrosis of the intestine. To do this, we collected ribosome profiling data of intestinal cell lines and peripheral blood mononuclear cells and used gene expression of microprotein-encoding transcripts to identify strongly regulated microproteins, including several examples of microproteins that are only conserved with primates. CONCLUSION: This approach reveals a number of new microproteins worthy of additional functional characterization and provides a dataset that can be queried in different ways to find additional gut microproteins of interest.

Rheumatic fever and long-term use of benzathine penicillin as possible risk factors for extensive macular atrophy with pseudodrusen in a Brazilian cohort.

BACKGROUND: Although there has been a large increase in the number of extensive macular atrophy with pseudodrusen (EMAP) cases, the basic aspects of this disease remain unknown. Brazilian patients have a common past history of rheumatic fever (RF) and/or benzathine penicillin (BP) treatment possibly related to the disease. We analyzed how RF and BP might be correlated with EMAP in Brazilian patients. DESIGN: Observational, retrospective, case-control study. METHODS: The databases of three private eye clinics in Brazil were searched for patients with an EMAP-like appearance. Each patient was asked about a previous history of RF and/or long-term use of BP. Patients underwent best-corrected visual acuity (BCVA) measurement, color fundus imaging, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT) imaging, and electroretinography (ERG). The following characteristics were analyzed: subretinal drusenoid deposits (SDD), pigment mottling, retinal pigment epithelial/basement membrane (RPE/BM) separation, outer retinal or RPE atrophy, and identification of a paving stone-like appearance. The choroidal thickness was measured using enhanced depth imaging OCT. The central atrophic area was measured manually on ultra-wide-field FAF. RESULTS: A total of 154 eyes of 77 patients (women, 66.2%; mean age, 58.6 years) with EMAP were included; 90.9% of patients were diagnosed with RF; 94.8% had been treated with BP and treatment was started at an average age of 7.3 years (mean duration, 11.8 years). The treatment duration was significant for the area of atrophy (P = 0.027) in which each 1-year increase in treatment duration led to an average reduction of 6.91 mm2 in area. The age at diagnosis of RF was significant (P = 0.026) for SDD. The increase of 1 year in the diagnosis of RF (late disease) led to a reduction of 24% in the chance of central SDD being present. On OCT, 65.5% eyes had SDD and more than 70% had a split RPE/BM and outer retinal or RPE atrophy. The choroidal thickness in patients with EMAP was significantly (P < 0.001) thinner than the control group. The ERG was abnormal in all eyes. CONCLUSION: These findings may suggest a relation between RF and EMAP in Brazilian patients. Patients with EMAP should be questioned about a history of RF.

Risk Factors, Management, and Evolution after the First Acute Myocardial Infarction: A Real-World Study Comparing Cohorts of Women and Men in the TriNetX Network. / Fatores de Risco, Manejo e Evolução após Primeiro Infarto Agudo do Miocárdio: Um Estudo de Mundo Real Comparando Coortes de Mulheres e Homens na Rede TriNetX.

BACKGROUND: International cohort studies have consistently demonstrated an unfavorable prognosis in female patients after the first acute myocardial infarction (AMI) over the past decades. However, national data on this topic are limited. OBJECTIVES: This study aims to compare national cohorts of men and women hospitalized due to the first acute myocardial infarction, examining long-term outcomes. METHODS: A retrospective, observational study using real-world data extracted from the global TriNetX platform, including patients of both sexes with a confirmed diagnosis of AMI according to the International Classification of Diseases (ICD), version 11, code I21. The level of statistical significance adopted in the analysis was 5% (0.05). The primary outcome assessed was a composite of death, new hospitalization for AMI, myocardial revascularization procedures, or heart failure after the hospital phase with a 5-year follow-up. RESULTS: Data from 29,041 patients were evaluated, of which 11,284 (38.4%) were women. The mean age of the female and male populations was 64.4 and 59.8 years, respectively. The group of women showed a higher occurrence of the composite outcome of death, new hospitalization for AMI, myocardial revascularization procedures, or heart failure after the hospital phase with a 5-year follow-up (OR 1.058; CI 1.005 - 1.113; p = 0.03). CONCLUSIONS: In this large Brazilian cohort, the female sex was associated with a higher occurrence of cardiovascular events within 5 years after hospital discharge. BACKGROUND: Real-world study comparing female and male cohorts in the TriNetX network.

Changes in muscle cross-sectional area during two menstrual cycles may not be exclusively attributed to resistance training.

This study investigated the impact of menstrual cycle (MC) phases and resistance training (RT) on muscle cross-sectional area (CSA) in two MCs utilizing a within-subject design. Twenty women with regular MCs had their legs randomly allocated to either the control (CON) or RT condition, which included 16 training sessions over two MCs. CSA, estradiol (E2), and progesterone (P4) were assessed during the menstruation (M), ovulation (O), and luteal (L) phases in the first (M1, O1, L1) and second (M2, O2, L2) MCs and at the beginning of the third MC (M3). P4 values were significantly higher during the luteal phase than during menstruation (P < 0.0001) and ovulation (P < 0.0001). No significant differences in E2 concentrations were observed between the MC phases (P = 0.08). For the RT condition, the CSA showed significant increases at O2, L2, and M3 compared to baseline (M1) (all P < 0.0001). No significant changes were observed for the CON condition during the two MCs (P > 0.05). However, RT condition showed a significant change in average CSA across two MCs. Additionally, individual analyses revealed that 19 participants showed variation in CSA above or below the minimum detectable difference during the two MCs. These findings suggest that changes in muscle CSA observed during two MCs may not be exclusively attributed to RT.

Abnormal Unilateral Dilated Perifoveal Venule Found During Observation of a Transient Vitreomacular Traction.

This case report describes a new type of perifoveal retinal vascular abnormality (RVA) incidentally discovered during a posterior vitreous detachment (PVD) investigation. A 65-year-old woman with sudden central visual loss displayed a unilateral focal telangiectatic venule in the perifoveal area. Multimodal imaging documented the vascular abnormality and associated retinal changes. Despite symptom resolution, the RVA persisted. This case represents a unique presentation of perifoveal RVA, likely an atypical form of macular telangiectasia. The sequential imaging documentation during a process of PVD with central bouquet traction provides insights into the underlying mechanisms in addition to diagnosing and monitoring perifoveal RVAs. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Optic disc edema and visual loss from paracentral acute middle maculopathy mimicking optic neuritis.

Optic neuritis is an important cause of unilateral and acute visual loss in young adults, but other differential diagnoses should be considered, especially when the disease has an atypical presentation. This report presents the case of a young woman with reduced visual acuity in her right eye, associated with optic disc edema and a relative afferent pupillary defect, that was initially misdiagnosed as optic neuritis and subsequently found to have paracentral acute middle maculopathy, possibly secondary to subtle impending central retinal vein occlusion. This case emphasizes the need to remember that retinal vascular diseases can occasionally mimic optic neuritis. Detailed anamnesis and ophthalmic examination can avoid unnecessary interventions.

Strong synergistic and antagonistic effects of quinones and metal ions in oxidative potential (OP) determination by ascorbic acid (AA) assays.

A key challenge in oxidative potential (OP) assays is to accurately assess the cumulative impact of redox-active aerosol species rather than only their individual effects. This study investigates the OP of single and combined mixtures of 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ), 9,10-phenanthrenequinone (9,10-PQ), 1,4-benzoquinone (1,4-BQ), Cu, Fe, Mn, and Zn in standard ascorbic acid (OPAA) and the synthetic respiratory tract lining fluid (OPRTLF) assays. In both OPAA and OPRTLF, binary mixtures showed additive and synergistic effects in the presence of 1,2-NQ. The mixture of Cu and Zn showed substantial synergisms in both assays, while the mixtures in the absence of 1,2-NQ primarily induced antagonistic effects. For the first time, we propose linear equations to improve the prediction of OP values by considering the impacts of synergistic and antagonistic effects. Under this approach, we observed that the potential effects caused by binary mixtures in ambient particulate matter (PM) samples could account for up to 68 % of the PM-OP values in Fez, Morocco (OPmAA: 0.34 nmol min-1 µg-1 and OPmRTLF: 0.18 nmol min-1 µg-1). The present study improves the understanding of effects of chemical interaction of potentially toxic substances that are important in the understanding of PM-induced oxidative stress in the human body.

Rp3: Ribosome profiling-assisted proteogenomics improves coverage and confidence during microprotein discovery.

There has been a dramatic increase in the identification of non-canonical translation and a significant expansion of the protein-coding genome. Among the strategies used to identify unannotated small Open Reading Frames (smORFs) that encode microproteins, Ribosome profiling (Ribo-Seq) is the gold standard for the annotation of novel coding sequences by reporting on smORF translation. In Ribo-Seq, ribosome-protected footprints (RPFs) that map to multiple genomic sites are removed since they cannot be unambiguously assigned to a specific genomic location. Furthermore, RPFs necessarily result in short (25-34 nucleotides) reads, increasing the chance of multi-mapping alignments, such that smORFs residing in these regions cannot be identified by Ribo-Seq. Moreover, it has been challenging to identify protein evidence for Ribo-Seq. To solve this, we developed Rp3, a pipeline that integrates proteogenomics and Ribosome profiling to provide unambiguous evidence for a subset of microproteins missed by current Ribo-Seq pipelines. Here, we show that Rp3 maximizes proteomics detection and confidence of microprotein-encoding smORFs.

Selective Laser Trabeculoplasty vs Medical Therapy for the Treatment of Open-angle Glaucoma or Ocular Hypertension: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

PRCIS: Selective laser trabeculoplasty (SLT) and medical therapy groups displayed comparable intraocular pressure (IOP) at most follow-ups. SLT was associated with significantly decreased rates of glaucoma surgeries, antiglaucomatous medications, and ocular adverse effects. PURPOSE: To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) compared to medical therapy in the treatment of open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: A systematic search was performed in PubMed, Embase, Cochrane Library and Web of Science databases. Randomized controlled trials (RCTs) comparing SLT with medical therapy were included. We computed mean differences (MDs) or standardized mean differences (STDs) for continuous endpoints and risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 statistics. Software R, version 4.2.1, was used for statistical analyses. Subgroup analyses were performed on treatment-naive patients and on the class of drugs in the medical therapy group. RESULTS: Fourteen RCTs comprising 1,706 patients were included, of whom 936 were submitted to SLT. Medical therapy was associated with a significantly improved IOP at 1 month and a higher proportion of patients achieving ≥20% IOP reduction. There were no significant differences between groups in IOP at 2, 3, 6, and 12 months, IOP fluctuation, rate of eyes at target IOP, visual field, and quality of life. The SLT group exhibited significantly decreased rates of glaucoma surgeries, antiglaucoma medications, and ocular adverse effects. CONCLUSION: SLT demonstrated comparable efficacy to medical therapy in IOP control at most follow-ups, along with favorable impacts on critical treatment-related factors. Our findings support SLT as a safe and effective treatment for OAG or OHT.

2023 Brazilian Society of Rheumatology guidelines for the treatment of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

Competency mapping of primary healthcare nurses on the Brazil-Paraguay border.

OBJECTIVE: To map the competencies of Primary Health Care nurses in border regions of Brazil and Paraguay. METHOD: Exploratory qualitative studyconducted between February and July 2020, with 64 nurses from six Brazilian municipalities bordering Paraguay. It was conducted in three stages: 1. Documentary study: analysis of legal documents to identify the nurse's competencies. 2. Application of instrument to the study population .3. Mapping of competencies, through the competencies expressed by nurses analyzed using the collective subject discourse technique. RESULTS: Twenty-eight general competencies were identified, categorized as assistance and management, and five specific competencies required to work in border regions: conducting a situational diagnosis of the border community; attending to foreign users with active and humanized listening; communicating appropriately with foreign users; identifying the epidemiological profile of the border; and, understanding the health policies of the neighboring country. The competencies required for the work from the participants' perspective were included in the mapping. The competence gap identified in the mapping refers to educational practices in communities. FINAL CONSIDERATIONS: The study identified the necessary competencies for nurses to work in border regions, but pointed out gaps in the training and continuing education of these professionals.

Identification of Novel Bacterial Microproteins Encoded by Small Open Reading Frames Using a Computational Proteogenomics Workflow.

Genome annotation has historically ignored small open reading frames (smORFs), which encode a class of proteins shorter than 100 amino acids, collectively referred to as microproteins. This cutoff was established to avoid thousands of false positives due to limitations of pure genomics pipelines. Proteogenomics, a computational approach that combines genomics, transcriptomics, and proteomics, makes it possible to accurately identify these short sequences by overlaying different levels of omics evidence. In this chapter, we showcase the use of µProteInS, a bioinformatics pipeline developed for the identification of unannotated microproteins encoded by smORFs in bacteria. The workflow covers all the steps from quality control and transcriptome assembly to the scoring and post-processing of mass spectrometry data. Additionally, we provide an example on how to apply the pipeline's machine learning method to identify high-confidence spectra and pinpoint the most reliable identifications from large datasets.

RNA sequencing and gene co-expression network of in vitro matured oocytes and blastocysts of buffalo.

In reproductive technologies, uncovering the molecular aspects of oocyte and embryo competence under different conditions is crucial for refining protocols and enhancing efficiency. RNA-seq generates high-throughput data and provides transcriptomes that can undergo additional computational analyses. This study presented the transcriptomic profiles of in vitro matured oocytes and blastocysts produced in vitro from buffalo crossbred (Bubalus bubalis), coupled with gene co-expression and module preservation analysis. Cumulus Oophorus Complexes, obtained from slaughterhouse-derived ovaries, were subjected to in vitro maturation to yield metaphase II oocytes (616) or followed in vitro fertilization and culture to yield blastocysts for sequencing (526). Oocyte maturation (72%, ±3.34 sd) and embryo development (21.3%, ±4.18 sd) rates were obtained from three in vitro embryo production routines following standard protocols. Sequencing of 410 metaphase II oocytes and 70 hatched blastocysts (grade 1 and 2) identified a total of 13,976 genes, with 62% being ubiquitously expressed (8,649). Among them, the differentially expressed genes (4,153) and the strongly variable genes with the higher expression (fold-change above 11) were highlighted in oocytes (BMP15, UCHL1, WEE1, NLRPs, KPNA7, ZP2, and ZP4) and blastocysts (APOA1, KRT18, ANXA2, S100A14, SLC34A2, PRSS8 and ANXA2) as representative indicators of molecular quality. Additionally, genes exclusively found in oocytes (224) and blastocysts (2,200) with specific biological functions were identified. Gene co-expression network and module preservation analysis revealed strong preservation of functional modules related to exosome components, steroid metabolism, cell proliferation, and morphogenesis. However, cell cycle and amino acid transport modules exhibited weak preservation, which may reflect differences in embryo development kinetics and the activation of cell signaling pathways between buffalo and bovine. This comprehensive transcriptomic profile serves as a valuable resource for assessing the molecular quality of buffalo oocytes and embryos in future in vitro embryo production assays.

Random Apollonian networks with tailored clustering coefficient.

We introduce a family of complex networks that interpolates between the Apollonian network and its binary version, recently introduced in E. M. K. Souza et al. [Phys. Rev. E 107, 024305 (2023)2470-004510.1103/PhysRevE.107.024305], via random removal of nodes. The dilution process allows the clustering coefficient to vary from C=0.828 to C=0 while maintaining the behavior of average path length and other relevant quantities as in the deterministic Apollonian network. Robustness against the random deletion of nodes is also reported on spectral quantities such as the ground-state localization degree and its energy gap to the first excited state. The loss of the 2π/3 rotation symmetry as a treelike network emerges is investigated in the light of the hub wavefunction amplitude. Our findings expose the interplay between the small-world property and other distinctive traits exhibited by Apollonian networks, as well as their resilience against random attacks.

Effects of Different Weekly Set Volumes on Strength and Perceptual Responses in Athletes.

This study investigated the effects of different resistance training (RT) volumes quantified by weekly sets at high intensity (load and effort) on dynamic strength adaptations and psychophysiological responses in trained individuals. Twenty-four athletes were randomly allocated to three groups that performed three (3 S, n=8), six (6 S, n=8), and nine (9 S, n=8) weekly sets, respectively, three times a week on the barbell back squat and bench press during an 8-week period. While all groups showcased strength gains (p<0.05), post hoc comparisons revealed that 6 S and 9 S elicited greater strength adaptations than 3 S in barbell back squat (p=0.027 and p=0.004, respectively) and bench press (p=0.001 and p=0.044, respectively). There were no differences between 6 S and 9 S conditions for back squat (p=0.999) and bench press (p=0.378). Although a time effect was observed for Session-RPE (p=0.014) and Total Quality Recovery scale (p=0.020), psychophysiological responses were similar among groups. Our findings suggest that performing six and nine weekly sets at high intensities led to greater strength gains compared to three weekly sets in strength-trained individuals, despite similar psychophysiological responses.

Enfermagem de práticas avançadas no atendimento pré-hospitalar: desafios e estratégias de implementação / Advanced practice nursing in pre-hospital care: challenges and implementation strategies / Enfermería de práctica avanzada en la atención prehospitalaria: desafíos y estrategias de implementación

Objetivo: Mapear e analisar os potenciais desafios e estratégias na implementação da Enfermagem de Práticas Avançadas, no modelo de atendimento pré-hospitalar móvel brasileiro, a partir da experiência de outros países. Métodos: Revisão narrativa, a partir da análise da literatura sobre o tema, realizada em duas etapas: Revisão de documentos de entidades internacionais e busca de artigos nas bases nas bases Pubmed, LILACS, Scielo e no Google Scholar. Ao final, foi realizada a análise de cada desafio elencado e suas respectivas estratégias, quando aplicados ao modelo pré-hospitalar móvel brasileiro. Resultados: Os principais desafios analisados foram: compreensão do papel dos enfermeiros de práticas avançadas; a definição do escopo de práticas e das políticas de formação e qualificação; a regulamentação da atuação; a redução da resistência médica; os custos de implementação e a definição de mecanismos de remuneração. As estratégias de enfrentamento incluem: a sensibilização do público, definição do conjunto de prerrogativas e dos mecanismos de credenciamento e formação, associados a constituição de currículos potentes. Conclusão: Foram mapeados e analisados desafios e estratégias, que permitiram antecipar o cenário de aplicação da proposta da Enfermagem de Práticas Avançadas no modelo pré-hospitalar brasileiro, viabilizando proposição de ações fundamentais para a implementação e o sucesso da estratégia no país. (AU)

Objective: To map and analyze the potential challenges and strategies in the implementation of Advanced Practice Nursing in the Brazilian mobile pre-hospital care model, based on the experience of other countries. Methods: Narrative review, based on the literature on the subject, carried out in two stages: Review of documents from international organizations and search for articles in the databases Pubmed, LILACS, Scielo and Google Scholar. At the end, the analysis of each challenge listed and their respective strategies was carried out, when applied to the Brazilian mobile prehospital model. Results: The main challenges analyzed were: understanding the role of advanced practice nurses; definition of the scope of training and qualification practices and policies; the regulation of performance; the reduction of medical resistance; implementation costs and definition of remuneration mechanisms. Coping strategies include: raising public awareness, defining the set of prerogatives and mechanisms for accreditation and training, associated with building powerful curricula. Conclusion: Challenges and strategies were mapped and analyzed, which made it possible to anticipate the scenario of application of the Advanced Practice Nursing proposal in the brazilian prehospital model, enabling the proposition of fundamental actions for the implementation and success of the strategy in the country. (AU)

Objetivos: Objetivos: Mapear y analizar los potenciales desafíos y estrategias en la implementación de la Enfermería de Práctica Avanzada en el modelo de atención prehospitalaria móvil brasileña, a partir de la experiencia de otros países. Métodos: Revisión narrativa, basada en la literatura sobre el tema, realizada en dos etapas: Revisión de documentos de organismos internacionales y búsqueda de artículos en las bases de datos Pubmed, LILACS, Scielo y Google Scholar. Al final, se realizó el análisis de cada desafío listado y sus respectivas estrategias, cuando se aplicó al modelo prehospitalario móvil brasileño. Resultados: Los principales desafíos analizados fueron: comprender el papel de las enfermeras de práctica avanzada; definición del alcance de las prácticas y políticas de formación y cualificación; la regulación del desempeño; la reducción de la resistencia médica; costos de implementación y definición de mecanismos de retribución. Las estrategias de afrontamiento incluyen: sensibilizar al público, definir el conjunto de prerrogativas y mecanismos de acreditación y formación, asociados con la construcción de planes de estudio potentes. Conclusión: Se mapearon y analizaron desafíos y estrategias que permitieron anticipar el escenario de aplicación de la propuesta de Enfermería de Práctica Avanzada en el modelo prehospitalario brasileño, posibilitando la proposición de acciones fundamentales para la implementación y éxito de la estrategia en el país. (AU)

The influence of long-range transported Saharan dust on the inflammatory potency of ambient PM2.5 and PM10.

Although desert dust promotes morbidity and mortality, it is exempt from regulations. Its health effects have been related to its inflammatory properties, which can vary between source regions. It remains unclear which constituents cause this variability. Moreover, whether long-range transported desert dust potentiates the hazardousness of local particulate matter (PM) is still unresolved. We aimed to assess the influence of long-range transported desert dust on the inflammatory potency of PM2.5 and PM10 collected in Cape Verde and to examine associated constituents. During a reference period and two Saharan dust events, 63 PM2.5 and PM10 samples were collected at four sampling stations. The content of water-soluble ions, elements, and organic and elemental carbon was measured in all samples and endotoxins in PM10 samples. The PM-induced release of inflammatory cytokines from differentiated THP-1 macrophages was evaluated. The association of interleukin (IL)-1ß release with PM composition was assessed using principal component (PC) regressions. PM2.5 from both dust events and PM10 from one event caused higher IL-1ß release than PM from the reference period. PC regressions indicated an inverse relation of IL-1ß release with sea spray ions in both size fractions and organic and elemental carbon in PM2.5. The PC with the higher regression coefficient suggested that iron and manganese may contribute to PM2.5-induced IL-1ß release. Only during the reference period, endotoxin content strongly differed between sampling stations and correlated with inflammatory potency. Our results demonstrate that long-range transported desert dust amplifies the hazardousness of local air pollution and suggest that, in PM2.5, iron and manganese may be important. Our data indicate that endotoxins are contained in local and long-range transported PM10 but only explain the variability in inflammatory potency of local PM10. The increasing inflammatory potency of respirable and inhalable PM from desert dust events warrants regulatory measures and risk mitigation strategies.

An Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism.

Upstream open reading frames (uORFs) are cis-acting elements that can dynamically regulate the translation of downstream ORFs by suppressing downstream translation under basal conditions and, in some cases, increasing downstream translation under stress conditions. Computational and empirical methods have identified uORFs in the 5'-UTRs of approximately half of all mouse and human transcripts, making uORFs one of the largest regulatory elements known. Because the prevailing dogma was that eukaryotic mRNAs produce a single functional protein, the peptides and small proteins, or microproteins, encoded by uORFs were rarely studied. We hypothesized that a uORF in the SLC35A4 mRNA is producing a functional microprotein (SLC35A4-MP) because of its conserved amino acid sequence. Through a series of biochemical and cellular experiments, we find that the 103-amino acid SLC35A4-MP is a single-pass transmembrane inner mitochondrial membrane (IMM) microprotein. The IMM contains the protein machinery crucial for cellular respiration and ATP generation, and loss of function studies with SLC35A4-MP significantly diminish maximal cellular respiration, indicating a vital role for this microprotein in cellular metabolism. The findings add SLC35A4-MP to the growing list of functional microproteins and, more generally, indicate that uORFs that encode conserved microproteins are an untapped reservoir of functional microproteins.

Use of platelet-rich plasma on in vitro maturation during bovine embryo production.

One of the crucial aspects to be considered for successful in vitro production (IVP) of embryos is the composition of the various media used throughout the stages of this reproductive biotechnology. The cell culture media employed should fulfill the metabolic requirements of both gametes during oocyte maturation and sperm development, as well as the embryo during its initial cell divisions. Most IVP protocols incorporate blood serum into the media composition as a source of hormones, proteins, growth factors, and nutrients. Numerous studies have suggested Platelet-Rich Plasma (PRP) as a substitute for fetal sera in cell culture, particularly for stem cells. Therefore, the objective of this study is to assess the potential use of PRP as a replacement for fetal bovine serum (FBS) during oocyte maturation for in vitro production of bovine embryos. During in vitro maturation (IVM), cumulus-oocyte complexes (COCs) were allocated into the following experimental groups: Group G1 (IVM medium with 5% PRP); Group G2 (MIV medium with 5% PRP and 5% SFB); Group G3 (MIV medium with 5% SFB); and Group G4 (MIV medium without either PRP or SFB). Subsequently, the cumulus-oocyte complexes were fertilized with semen from a single bull, and the resulting zygotes were cultured for seven days. Cleavage and blastocyst formation rates were assessed on days 2 and 7 of embryonic development, respectively. The quality of matured COCs was also evaluated by analyzing the gene expression of HSP70, an important protein associated with cellular stress. The results demonstrated that there were no significant differences among the experimental groups in terms of embryo production rates, both in the initial cleavage stages and blastocyst formation (except for the G4 group, which exhibited a lower blastocyst formation rate on D7, as expected). This indicates that PRP could be a cost-effective alternative to SFB in the IVP of embryos.