Ferric carboxymaltose-induced hypophosphatemia - a case series.

Hypophosphatemia may cause serious complications. Depending on its severity and duration, signs and symptoms range from fatigue to life-threatening events, like severe rhabdomyolysis and mental status changes. Long-term consequences include osteomalacia. Hypophosphatemia may be secondary to the use of parental iron, mostly associated with ferric carboxymaltose (FCM), with an incidence of around 45% to 70%. We describe three cases of hypophosphatemia in patients with chronic iron deficiency anemia, requiring repeated FCM infusions. The patients' presentation to the Rheumatology department included musculoskeletal symptoms of severe hypophosphatemia and long-term hypophosphatemic osteomalacia, with fractures. We aim to raise awareness for ferric carboxymaltose-induced hypophosphatemia, an entity increasingly described in the literature that can be responsible for severe disability or potentially life-threatening adverse events.

Validating alternative oxidase (AOX) gene family as efficient marker consortium for multiple-resilience in Xylella fastidiosa-infected Vitis holobionts.

KEY MESSAGE: AOX gene family in motion marks in-born efficiency of respiration adjustment; can serve for primer screening, genotype ranking, in vitro-plant discrimination and a SMART perspective for multiple-resilient plant holobiont selection. The bacteria Xylella fastidiosa (Xf) is a climate-dependent, global threat to many crops of high socio-economic value, including grapevine. Currently designed breeding strategies for Xf-tolerant or -resistant genotypes insufficiently address the danger of biodiversity loss by focusing on selected threats, neglecting future environmental conditions. Thus, breeding strategies should be validated across diverse populations and acknowledge temperature changes and drought by minimizing the metabolic-physiologic effects of multiple stress-induced oxygen shortages. This research hypothesizes that multiple-resilient plant holobionts achieve lifelong adaptive robustness through early molecular and metabolic responses in primary stress target cells, which facilitate efficient respiration adjustment and cell cycle down-regulation. To validate this concept open-access transcriptome data were analyzed of xylem tissues of Xf-tolerant and -resistant Vitis holobionts from diverse trials and genetic origins from early hours to longer periods after Xf-inoculation. The results indicated repetitive involvement of alternative oxidase (AOX) transcription in episodes of down-regulated transcripts of cytochrome c oxidase (COX) at various critical time points before disease symptoms emerged. The relation between transcript levels of COX and AOX ('relCOX/AOX') was found promising for plant discrimination and primer screening. Furthermore, transcript levels of xylem-harbored bacterial consortia indicated common regulation with Xf and revealed stress-induced early down-regulation and later enhancement. LPS priming promoted the earlier increase in bacterial transcripts after Xf-inoculation. This proof-of-principle study highlights a SMART perspective for AOX-assisted plant selection towards multiple-resilience that includes Xf-tolerance. It aims to support timely future plant diagnostics and in-field substitution, sustainable agro-management, which protects population diversity and strengthens both conventional breeding and high-tech, molecular breeding research. Furthermore, the results suggested early up-regulation of bacterial microbiota consortia in vascular-enriched tissues as a novel additional trait for future studies on Xf-tolerance.

Chemical and biological prospection of marine sponges belonging to the class Demospongiae: a review.

Marine sponges belonging to the class Demospongiae have been shown to be promising sources of bioactive compounds, investigated from the perspective of potential medical applications. This review aimed to collect studies on biological activities of clinical importance and the chemical composition of sponge species from that class, highlighting the structure/activity relationship. To carry out this work, collections were carried out in the Science Direct, Pubmed, Scielo and Google Scholar databases, using the following descriptors: antimicrobial marine sponges, antioxidant marine sponges and marine sponges biological activity. The inclusion criteria were considered: (1) publications from the year 2022 onwards; (2) written in English or Portuguesen and (3) with information on biological assays of extracts, fractions or isolated compounds. The following were excluded: (1) duplicate works; (2) works whose content was not within the scope of the study and (3) studies that did not evaluate biological activities. Results demonstrate that 274 compounds were isolated from different metabolic classes, being evaluated in several biological assays. From the analysis of the data, it is concluded that the compounds studied demonstrate promise for the development of medicines for the control of microorganisms and the treatment of tumors, acting through different mechanisms of action.

Chemical Profile, Antioxidant and Antimicrobial Activity of Marine Sponge Species Combined with Multivariate Statistical Analyses: Desmapsamma anchorata, Dysidea etheria and Echinodictyum dendroides.

Marine sponges are sources of bioactive compounds, sparking pharmacological interest. This study aimed to evaluate the chemical profile, antioxidant, and antibacterial activities of the species Desmapsamma anchorata, Dysidea etheria, and Echinodictyum dendroides. The chemical profile was characterized by the identification and quantification of polyphenols. Antioxidant activity was assessed using different methods. Antibacterial and modulatory activities were evaluated through microdilution against pathogenic strains. The polyphenols were found in low abundance in the extracts. In the antioxidant assays, the EACDa and EMDa extracts exhibited better inhibitory results. In the antibacterial evaluation, extracts presented MIC ≥ 1024 µg mL-1. The modulation of the extracts in combination with antibiotics showed significant effects against the multiresistant bacterium Pseudomonas aeruginosa. This study contributes to the deepening of chemical and biological knowledge of sponge species, indicating that their extracts can act as good modulators of bacterial resistance to aminoglycoside antibiotics, warranting further investigation into their mechanisms of action.

Challenges of Renal Function Assessment in Breast Cancer Patients Treated With Abemaciclib: A Case Report.

Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor used for hormone-receptor-positive and human epidermal growth factor receptor 2 (HER-2)-negative breast cancer, can lead to elevated serum creatinine without implications on the true renal function. Although clinical trials have shown no increase in other kidney function biomarkers, this may still represent a challenge in cancer patients. We report a case of a 74-year-old female who presented with creatinine and cystatin-C elevation during treatment with abemaciclib without an equivalent decrease in measured glomerular filtration rate (GFR) with renal scintigraphy. The confirmation of adequate kidney function allowed for the maintenance of treatments that would otherwise be limited by renal impairment. Healthcare providers should be aware of abemaciclib's effect on serum creatinine but should not eliminate the possibility of actual kidney injury. Alternative biomarkers for GFR assessment are recommended, although the usefulness of cystatin-C in patients receiving abemaciclib should be investigated in greater depth.

Sole Stenting Versus Stent-Assisted Coiling For Treating Dissecting Posterior Circulation Aneurysms: A Systematic Review And Meta-Analysis.

BACKGROUND: Among the reconstructive methods for treating dissecting posterior circulation aneurysms (DPCAs), there are stent-assisted coiling (SAC), and sole stenting (SS) therapy. Despite SAC being widely employed when compared to SS, no study systematically analyzed the difference in their outcomes. METHODS: The authors conducted a meta-analysis of studies employing both therapies to compare their outcomes. A search was performed in January 2024, including only studies with consecutive patients submitted to SS or SAC. The studies had to have at least one of the following outcomes: complete aneurysm occlusion, complications, mortality, aneurysm recurrence, retreatment, and good clinical outcome. Odds Ratio (OR) with 95% confidence interval (CI) were utilized for statistics. RESULTS: In a pooled analysis of 17 studies, comparing 173 SS and 377 SAC procedures for DPCAs, no significant differences were found in related mortality (OR 1.44; 95% CI 0.49-4.27); total mortality (OR 1.33; 95% CI 0.53-3.37); retreatment (OR 0.45; 95% CI 0.16-1.26); recurrence (OR 1.00; 95% CI 0.43-2.33); postoperative complete aneurysmal occlusion (OR 0.79; 95% CI 0.09-6.77); follow-up complete aneurysmal occlusion (OR 1.57; 95% CI 0.62-3.94); intraoperative complications (OR 1.04; 95% CI 0.29-3.73); postoperative complications (OR 1.22; 95% CI 0.61-2.45); hemorrhagic complications (OR 2.16; 95% CI 0.77-6.06); ischemic complications (OR 1.68; 95% CI 0.68-4.15). Good clinical outcomes significantly favored SAC (OR 0.45; 95% CI 0.23-0.86). CONCLUSION: The findings suggest there is no substantial basis for favoring SAC over SS across all cases. Instead, an individualized approach should be considered, according to the patient's characteristics, surgeon skills, and the available material.

Current management of inherited retinal degenerations in Portugal (IRD-PT survey).

Inherited retinal dystrophies/degenerations (IRDs) are the leading cause of visual impairment and incurable familial blindness in the Western world. Given the clinical and genetic heterogeneity, establishing a molecular diagnosis is especially relevant. The aim of this study was to perform the first nationwide survey to understand the prevalence and current management of IRDs in Portugal. A response was obtained from 26 healthcare providers (HCP) (76.5% response rate). Only 4 respondents reported not managing IRD patients. Most HCPs (68.1%) reported managing up to 100 patients, while three currently manage between 501 and 1000 patients. Based on the Portuguese population, an estimated IRD prevalence of 0.031%, i.e., about 1 in 3000 individuals, was calculated. In most HCPs (86.3%), most patients are adults, and non-syndromic retinitis pigmentosa is the most frequent diagnosis. Only 4 HCPs currently use the national, web-based IRD registry (IRD-PT). However, all but one respondent expressed interest in participating in such a registry. Genetic testing is available in 54.5%, with 58.3% HCPs reporting solved rates between 61-80%, but 4 to 9 months to get a genetic test result in 83.4% of cases. Based on this survey, the prevalence of biallelic RPE65-associated disease in Portugal is 0.00031%, i.e., approximately 1:300,000 individuals. Data from this study provide vital background information on national differences in the diagnosis and management of IRD patients. Nationwide implementation of the IRD-PT registry should be encouraged and supported to provide population-based reference data and to identify patients eligible for current and future therapies.

Are vitamin D intake and serum levels in the mid-trimester of pregnancy associated with preeclampsia? Results from a Brazilian multicentre cohort.

OBJECTIVE: To explore the association between serum levels and food intake of Vitamin D (VD) among healthy women in mid-pregnancy and preeclampsia. STUDY DESIGN: In a Brazilian multicentre cohort of healthy nulliparous pregnant women from five maternity centres we developed a nested case-control analysis comparing cases with and without preeclampsia. Women were enrolled and followed during prenatal care, including only singleton pregnancies, without any fetal malformations or previous chronic maternal disease. We matched 87 cases of preeclampsia to eligible controls randomly selected in a 1:1 ratio, by age and region. MAIN OUTCOME MEASURES: Blood samples from these were collected, and a 24-hour recall of food intake was obtained in mid-pregnancy, between 19 and 21 weeks. VD serum levels (25-hydroxyvitamin D) were measured by liquid chromatography-tandem mass spectrometry and were categorized as deficient, insufficient, and sufficient. The dietary intake of VD was estimated with the 24-hour diet recall applied at the same time and from supplementation. Maternal characteristics and VD levels were compared between cases and controls with OR and respective 95 %CI. Multivariate analysis using the Path method was used to assess relationships among VD, PE, BMI, skin colour/ethnicity, and diet. RESULTS: The maternal characteristics of both groups were similar, except for the higher occurrence of obesity among women with preeclampsia (OR 3.47, 95 %CI 1.48-8.65). Dietary intake of VD was similar in both groups, and most of the women in both groups consumed insufficient VD (82.2 vs 79.3 % in the groups with and without PE). CONCLUSIONS: Levels and dietary intake of VD were not associated with PE in this Brazilian sample of healthy pregnant women; however, BMI and skin colour/ethnicity were associated with PE.

Genipa americana L.: A Review on Traditional Uses, Phytochemistry and Biological Activities.

Genipa americana L. (Rubiaceae), genip tree, has therapeutic and nutritional potential. This revision aimed to gather information on botanical characteristics, popular uses, phytochemical, and pharmacological aspects of the tree. The methodology adopted integrated literature published between 2000 and 2024, as well as consultations with the World International Intellectual Property Organization (WIPO); resulting in 39 articles and 11 patents to promote this research. The species, which is native and not endemic to Brazil, is most prevalent in the Amazon biome as it is suitable for reconstructing degraded areas, as well as having various traditional applications. Iridoids are the main secondary metabolites present in the species, especially ginipin, geniposide acid, and geniposide, which are the most prevalent in the fruit. The patents registered with the WIPO indicate its use as a colorant, insecticide, anti-inflammatory, and antioxidant potential, in evidence of its antimicrobial and antioxidant activities. Further studies are needed on the mechanisms of the chemical components' action and on ethnopharmacology.

Punicalagin increases follicular activation, development and activity of superoxide dismutase 1, catalase, and glutathione peroxidase 1 in cultured bovine ovarian tissues.

Context The overproduction of reactive oxygen species (ROS) during in vitro culture of ovarian tissues impairs follicular development and survival. Aims To evaluate the effects of punicalagin on the development and survival of primordial follicles, stromal cell and collagen fibres, as well as on the levels of mRNA for nuclear factor erythroid 2-related factor 2 (NRF2 ), superoxide dismutase 1 (SOD1 ), catalase (CAT ), glutathione peroxidase 1 (GPX1 ) and perirredoxin 6 (PRDX6 ), and activity of antioxidant enzymes in cultured bovine ovarian tissues. Methods Bovine ovarian cortical tissues were cultured for 6days in α-MEM+ alone or with 1.0, 10.0, or 100.0µM punicalagin at 38.5°C with 5% CO2 . Follicle morphology and growth, stromal cell density, and collagen fibres were evaluated by classical histology, while the expression of mRNA was evaluated by real-time PCR. The activity of enzymes was analysed by the Bradford method. Key results Punicalagin improved follicle survival and development, reduced mRNA expression for SOD1 and CAT , but did not influence stromal cells or collagen fibres. Punicalagin (10.0µM) increased the levels of thiol and activity of SOD1, CAT , and GPX1 enzymes. Conclusions Punicalagin (10.0µM) promotes follicle survival and development and activates SOD1, CAT , and GPX1 enzymes in bovine ovarian tissues. Implications Punicalagin improves follicle development and survival in cultured ovarian tissues.

Kidney transplantation in multiple myeloma in 2023: A short review.

Patients with multiple myeloma (MM) frequently present with kidney involvement, of which a non-negligible proportion will progress to end-stage kidney disease. Kidney transplantation (KT) is the preferred kidney replacement therapy for selected patients; however, there are still many uncertainties regarding its application in MM patients. The risk of hematological relapse and subsequent graft loss or patient death often leads nephrologists to deem these patients unfit for KT. As such, data on KT in MM patients are heterogeneous and originate from individual case reports and small case series. Although MM is still an incurable disease, the addition of newer drugs and autologous hematopoietic stem cell transplant (HSCT) in the standard of care has been increasing patients' overall survival in recent decades. Risk stratification using cytogenetic studies and minimal residual disease detection are helpful in assessing the risk of relapse in patients who attain a complete response after HSCT. The greatest challenges remain the correct identification of patients who will most probably benefit from KT from a survival perspective and the determination of how long relapse-free survival should be before the transplant is performed.

Cytotoxic and Anti-HSV-1 Effects of Caulerpin Derivatives.

Marine organisms represent a potential source of secondary metabolites with various therapeutic properties. However, the pharmaceutical industry still needs to explore the algological resource. The species Caulerpa lamouroux Forssk presents confirmed biological activities associated with its major compound caulerpin, such as antinociceptive, spasmolytic, antiviral, antimicrobial, insecticidal, and cytotoxic. Considering that caulerpin is still limited, such as low solubility or chemical instability, it was subjected to a structural modifications test to establish which molecular regions could accept structural modification and to elucidate the cytotoxic bioactive structure in Vero cells (African green monkey kidney cells, Cercopithecus aethiops; ATCC, Manassas, VA, USA) and antiviral to Herpes simplex virus type 1. Substitution reactions in the N-indolic position with mono- and di-substituted alkyl, benzyl, allyl, propargyl, and ethyl acetate groups were performed, in addition to conversion to their acidic derivatives. The obtained analogs were submitted to cytotoxicity and antiviral activity screening against Herpes simplex virus type 1 by the tetrazolium microculture method. From the semi-synthesis, 14 analogs were obtained, and 12 are new. The cytotoxicity assay showed that caulerpin acid and N-ethyl-substituted acid presented cytotoxic concentrations referring to 50% of the maximum effect of 1035.0 µM and 1004.0 µM, respectively, values significantly higher than caulerpin. The antiviral screening of the analogs revealed that the N-substituted acids with methyl and ethyl groups inhibited Herpes simplex virus type 1-induced cytotoxicity by levels similar to the positive control acyclovir.

Genomic Landscape of Osteosarcoma of Bone in an Older-Aged Patient Population and Analysis of Possible Etiologies Based on Molecular Signature.

Background: Osteosarcoma (OS), the most common primary malignant bone tumor, occurs mostly in the pediatric and adolescent (P/A) population where it has been subject to intense study whereas OS arising in the older-aged adult population has undergone less scrutiny. Materials and Methods: In this study, we assess the molecular aberrations detected in eight older adult patients (>59 years of age) with OS of bone by whole-exome sequencing (WES) on formalin-fixed, paraffin-embedded tissue and quantified the contributions of endogenous and exogenous mutational processes to tumor mutational burden and to tumorigenesis through computational analysis. Results: We identified 86 clinically significant somatic mutations. TP53 mutations occurred in OSs of three patients and one patient harbored a pathogenic germline mutation of TP53. Loss-of-heterozygosity of DNA-damage repair genes occurred in all six tumors evaluated. Computational analysis of single nucleotide variants within each tumor detected eight distinct mutagenic processes of which age-associated mutational processes, thiopurine chemotherapy, and defective homologous DNA recombination repair contributed the most to both tumor mutation burden and tumor pathogenesis. Conclusion: The genomic landscape of our older OS patients deciphered by WES is extremely diverse with only 15% of mutated somatic genes uncovered in our study previously described in P/A-enriched OS studies. Endogenous age-related mutagenic processes, defective DNA homologous recombination repair, and exogenous effects of chemotherapy are mainly responsible for pathogenic mutations in OS occurring in our cohort.

Birds optimize fruit size consumed near their geographic range limits.

Animals can adjust their diet to maximize energy or nutritional intake. For example, birds often target fruits that match their beak size because those fruits can be consumed more efficiently. We hypothesized that pressure to optimize diet-measured as matching between fruit and beak size-increases under stressful environments, such as those that determine species' range edges. Using fruit-consumption and trait information for 97 frugivorous bird and 831 plant species across six continents, we demonstrate that birds feed more frequently on closely size-matched fruits near their geographic range limits. This pattern was particularly strong for highly frugivorous birds, whereas opportunistic frugivores showed no such tendency. These findings highlight how frugivore interactions might respond to stressful conditions and reveal that trait matching may not predict resource use consistently.

Increased expression of miR-320b in blood plasma of patients in response to SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recent research has demonstrated how epigenetic mechanisms regulate the host-virus interactions in COVID-19. It has also shown that microRNAs (miRNAs) are one of the three fundamental mechanisms of the epigenetic regulation of gene expression and play an important role in viral infections. A pilot study published by our research group identified, through next-generation sequencing (NGS), that miR-4433b-5p, miR-320b, and miR-16-2-3p are differentially expressed between patients with COVID-19 and controls. Thus, the objectives of this study were to validate the expression of these miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR) and to perform in silico analyses. Patients with COVID-19 (n = 90) and healthy volunteers (n = 40) were recruited. MiRNAs were extracted from plasma samples and validated using qRT-PCR. In addition, in silico analyses were performed using mirPath v.3 software. MiR-320b was the only miRNA upregulated in the case group com-pared to the control group. The in silico analyses indicated the role of miR-320b in the regulation of the KITLG gene and consequently in the inflammatory process. This study confirmed that miR-320b can distinguish patients with COVID-19 from control participants; however, further research is needed to determine whether this miRNA can be used as a target or a biomarker.

Is Stroke risk analysis (SRA) a reliable method for predicting atrial fibrillation? A systematic review.

INTRODUCTION: Atrial fibrillation is responsible for a considerable number of cases of cardioembolism, accounting for 17% to 30% of the etiologies of all strokes. The software known as Stroke Risk Analysis (SRA) detects patients at high risk of paroxysmal atrial fibrillation by analyzing a continuous electrocardiogram recorded over different periods of time. OBJECTIVES: This article aims to carry out a systematic review investigating the effectiveness of the SRA method in predicting the risk of stroke patients having paroxysmal atrial fibrillation as the cause of the event. METHODS: The methods correspond to the format of the International Prospective Register of Systematic Reviews Protocol, according to CRD Identification Code: CRD42021253974. A systematic search was carried out in BMJB, PubMed/MEDLINE, Science Direct and LILACS. Six cohort studies met the inclusion criteria, representing a total of 2,088 participants with stroke, and compared the detection of patients with paroxysmal atrial fibrillation on the continuous recording electrocardiogram with a time variation of 1 to 48h with the use of SRA. RESULTS: Studies have shown that SRA has a high negative predictive value (between 96 and 99.1%) and can contribute to the selection of patients at high risk of paroxysmal atrial fibrillation to be referred for implantable cardiac monitoring to continue the investigation. CONCLUSIONS: A sequential combination of SRA with implantable cardiac monitoring is a promising strategy for detecting undiagnosed paroxysmal atrial fibrillation. Thus, the SRA can act as a cost-effective pre-selection tool to identify patients at higher risk of having paroxysmal atrial fibrillation as a possible cause of stroke and who may benefit from implantable cardiac monitoring. However, the lack of randomized studies is a limitation that must be considered.

O armário: Fruiting phenology data for 4,462 plant taxa in Portugal (1926-2013).

Species phenology - the timing of key life events - is being altered by ongoing climate changes with yet underappreciated consequences for ecosystem stability. While flowering is generally occurring earlier, we know much less about other key processes such as the time of fruit ripening, largely due to the lack of comprehensive long-term datasets. Here we provide information on the exact date and site where seeds of 4,462 taxa were collected for the Index Seminum (seed exchange catalogue) of the Botanic Garden of the University of Coimbra, between 1926 and 2013. Seeds were collected from spontaneous and cultivated individuals across Portugal, including both native and introduced taxa. The database consists of 127,747 curated records with information on the species, or infraspecific taxa (including authority), and the day and site where seeds were collected. All records are georeferenced and provided with a confidence interval for the collection site. Taxonomy was first curated manually by in-house botanists and then harmonized according to the GBIF backbone taxonomy.