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This study investigates the non-native interactions between the photosensitizer protoporphyrin IX (PPIX) and human serum albumin (HSA). Non-covalent binding between small molecules and proteins, is crucial for various applications in biomedicine, food processing, energy conversion, and sensing. The research focuses on the role of a series of organic solvents in facilitating the binding of water-insoluble PPIX to the protein. By using dialysis and centrifugation for sample preparation and combining experimental and computational methods for characterization, the study found that non-protic solvents such as THF and DMSO are more effective in forming the PPIX:HSA complex compared to protic solvents. Additionally, the temporary presence of these organic solvents during incubation does not cause significant and irreversible changes in the protein structure. Instead, THF and DMSO temporarily loosen the protein, increasing the distance between two tyrosine residues (Y138 and Y161) that are believed to coordinate the porphyrin at its binding site. This finding underscores the importance of selecting appropriate solvents to enhance the binding efficiency of small ligands to proteins., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lorenzo Brancaleon reports financial support was provided by the National Institutes of Health. Abdullah Albalawi reports financial support was provided by Saudi Arabian Cultural Mission. Erick Y. Morales Orrante reports financial support was provided by CIMA-Louis Stokes Alliance for Minority Participation (LSAMP) Program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Obesity is one of the non-communicable chronic diseases with the highest increase in recent decades in Latin America, affecting children, adolescents, and especially young adults. Forty percent of adults have a body mass index greater than 25 kg/m2. Numerous studies have demonstrated a relationship between obesity and cardiovascular diseases such as hypertension, coronary artery disease, heart failure, cardiac arrhythmias, diabetes, sleep apnea, and oncological diseases, among others. Weight loss in individuals with overweight and obesity has been shown to reduce the risk of developing comorbidities or improve their progression. Healthcare professionals must initiate patient care by considering their values and treatment goals, facilitating reflection, and fostering responsibility to promote long-term improvements. The initial approach, communication, and physician's attitude during the evaluation of a patient with obesity are significant determinants for successful treatment and patient health. The objective of this document is to compile the available information on the disease and present practical and summarized clinical management recommendations based on scientific evidence.

We investigated the interaction of a series of metal-protoporphyrins (PPIXs) with bovine β- lactoglobulin (BLG) using a combination of optical spectroscopy and computational simulations. Unlike other studies, the simulations were not merely used to rationalize the experimental data but were employed to refine the experimental data itself. The study was carried out at two pH values, 5 and 9, where BLG is known to have different conformation dictated by the so-called Tanford transition which occurs near pH 7.5. The transition is postulated to regulate access to the interior binding cavity of the protein, thus the pH variation was used as a parameter to investigate whether PPIXs access the central cavity of BLG. The results of our study show that indeed binding increases significantly at alkaline pH, however, the increased affinity is not due to the accessibility of the central cavity. Instead, binding appears to be determined by the tendency of PPIXs to form large inhomogeneous aggregates at acidic pH which hinders interactions with proteins. The binding site determined through a combination of experimental and computational methods is located at the interface between two BLG monomers where the long α-helix segment of the protein face each other. This region is rich in positively charged Lys residues that interact with the propionic acid chains of the protoporphyrins. Establishing the modality of binding between protoporphyrins and BLG would have important consequences for the use of BLG:PPIX complexes in applications such as artificial photoreceptors, artificial metallo-enzymes, delivery of photosensitizers for phototherapy and even solar energy conversion., Competing Interests: Declaration of Competing Interest Lorenzo Brancaleon reports financial support was provided by National Institutes of Health. Lorenzo Brancaleon reports financial support was provided by Army Research Office., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The COVID-19 quarantine in Mexico has meant that household members spend more time inside the home, increasing the demand for direct and indirect care by minors, the elderly, chronically ill and disabled. This forced a reconfiguration of the provision of these services by household members. The aim of the document is twofold: first, to describe socioeconomic and demographic aspects of Mexican households around care activities during the quarantine and second, to estimate the determinants of the provision of care in the quarantine. The information was obtained from the Survey of Care and COVID-19 in Mexican Homes during Quarantine (SCCMHQ). The propensity score-matching technique is used as a quasi-experimental procedure to estimate the causal effects of a treatment variable (presence of minors, elderly, chronically ill, disability, or domestic service in the home) in Mexican households. The Probit model shows that age and economic dependency are determinants of caregiving for treatment groups with minors, disability and chronic disease. In addition, sex, home income, and current employment situation are significant for treatment groups with a disability, paid domestic work, and minors, respectively. A positive "net" effect of the treatment variables in the probability of care provision was also observed. Particularly, the existence of minors at home was highly effective to promote direct and indirect care. The confinement solution is characterized by a balance between genders, except in the case of households with disabilities. This shows that a cultural and functional change is possible in the distribution of care responsibilities, which can be consolidated through public policies., Competing Interests: Conflict of interestNo potential conflict of interest was reported by the authors., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)

Neuroendocrine tumors (NETs) comprise a heterogenous group of rare malignancies, which are increasing in incidence worldwide. To further understand the epidemiology of NETs in the Republic of Panama, the present study used two study groups, which included patients from several hospitals and clinics throughout the country, who were referred to the three largest national reference centers: The Complejo Hospitalario Metropolitano, Hospital Santo Tomas and Instituto Oncologico Nacional. These two groups comprised a retrospective cohort, which included cases reported between 2016 and 2017, and a second cohort, which was retrospective, but data were continuously collected from patients diagnosed with NETs between 2018 and 2019. Data from 157 patients with NETs reported that 83% of patients were in the 40-80 years old age group. The majority of cases (46%) presented as grade G1 tumors, while 29% were G3. Computerized tomography scans with contrast, and analysis of the Ki-67 biomarker and immunohistology markers (chromogranin A and synaptophysin) was performed in the majority of the cases. The results revealed that the most frequent anatomical sites for the primary tumor were the colorectum (17.2%), pancreas (12.7%) and stomach (12.1%), and the most frequent organ with metastasis was the liver, accounting for 34% of all cases. In conclusion, the present study is the first comprehensive study of NET in Panama to the best of our knowledge, which provides evidence of the demographic characteristics of the population, clinical features and overall survival for the affected population in this Central American country., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Cukier et al.)

Recently, pharmaceutical and personal care products (PPCPs) have received considerable attention because of their increasing use. Analysis of PPCPs presents a significant analytical challenge, with high-performance liquid chromatography (HPLC) in reversed-phase mode, as the most widely used analytical technique. To facilitate the optimization of the procedures that are applied in the early stages of sample preparation, a simple and fast HPLC method is proposed in this work for the separation of some PPCPs with a wide range of hydrophilicity. Two columns were evaluated (Atlantis dC18 and Discovery HS F5); as for mobile phases: a formate buffer (40 mmol L-1, pH 4) and methanol were tested in a gradient mode. The fluorinated column allowed better separation in a shorter time and better resolution for all analytes (Rs > 1). The proposed method delivered good performance for the tracing of PPCPs and is a suitable alternative to traditional C18-based HPLC methods.

The use of chitosan to harvest microalgae is a strategic step that seeks to reach an economically competitive price to recover lipids, proteins, and pigments. The aim of the present work was to design low-molecular-weight chitosan from shrimp shells and its physicochemical characterization, to be used for the harvesting of wild microalgae consortia. The chitosan was obtained by chemical deacetylation of shrimp shells, and physicochemical characterization was made using the instrumental methods DSC, TGA, X-ray, FTIR, and SEM. The harvesting of wild microalgae consortia was performed by the jar test method. The obtained chitosan had a low molecular weight (169 KDa), a deacetylation degree of 83 %, a decomposition temperature (T D ) of 280 °C, and a crystallinity of 38.2 %. The microalgae genera found in the consortium were Scenedesmus sp., Chlorella sp., Schroderia sp., and Chlamydomonas sp. The microalgae removal efficiency of the chitosan was 99.2 % with 20 mg L -1 ., Competing Interests: The authors report no declarations of interest., (© 2020 The Authors. Published by Elsevier B.V.)

Objective: Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements (ALKr) in Latin America., Methods: A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion. ALKr detection was performed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to assess method variability. Demographic and clinicopathologic characteristics were analyzed., Results: Among the 5,130 patients screened, 8.4% (n = 433) had nonevaluable FISH tests. Evaluable FISH analyses revealed positive ALKr in 6.8% (320/4,697) of the study population, which included patients from 9 countries. ALKr distribution for each country was: Mexico 7.6% (79/1,034), Colombia 4.1% (10/242), Argentina 6.0% (153/2,534), Costa Rica 9.5% (13/137), Panama 4.4% (5/114), Uruguay 5.4% (2/37), Chile 8.6% (16/185), Venezuela 8.9% (13/146), and Peru 10.8% (29/268). RT-PCR showed high positive (83.6%) and negative (99.7%) predictive values when compared to the gold standard FISH. In contrast, IHC only showed a high negative predictive value (94.6%)., Conclusions: Although there is a clear country and continental variability in terms of ALKr frequency, this difference is not significant and the overall incidence of ALKr in Latin America does not differ from the rest of the world., (© 2018 S. Karger AG, Basel.)

Objectives: Contrasting other EGFR mutations (EGFRm) in lung adenocarcinomas, insertions in exon 20 (exon20ins) are generally associated with resistance to targeted therapy, limiting therapeutic options and impoverishing the prognosis compared to other EGFRm. We sought to extensively characterize exon20ins from a large cohort of lung adenocarcinomas in Hispanic patients., Materials and Methods: This was a region-wide, observational longitudinal cohort study to evaluate characteristics and outcomes of patients with exon20ins in lung adenocarcinoma, based on a secondary analysis of electronic records from the Geno1.2-CLICaP Platform and extended genotype testing. Patients from six Latin-American countries were included (Argentina, Colombia, Costa Rica, Ecuador, Panama, and Mexico). Data obtained included the molecular spectrum (extended genotyping for mutations in BRAF, NRAS, PIK3CA, Her2 and MEK1, as well as for EGFR amplification, ALK and PD-L1 protein expression), clinic-pathologic characteristics, prevalence and outcomes to therapeutic approach., Results and Conclusions: 4.005 patients diagnosed with stage III/IV lung adenocarcinoma from 2011 to 2016 were initially screened. Among these, 88 patients had a confirmed exon20 in. and were included; median age was 66-years, 62.5% were females, 64% were never smokers and 39% presented with brain metastases. The H773insH variant was the most frequent, making up 21.6% of cases. A common EGFRm was concomitantly found in 36.4% (del19/L858R), and 8% (G719X/L861Q/S768I) of cases. Five cases had additional mutations in PI3K, KRAS and MEK1, 26% had EGFR amplification and 81.7% had PD-L1 expression 1-50%. Overall response rate to first-line therapy was 28% and overall survival was 16.4 months. Prognosis was positively influenced by the concomitant presence of common EGFRm and response to first-line. Our results suggest that patients with EGFR exon20ins have similar clinical characteristics to those with common EGFRm but a poorer prognosis. Last, the mean PD-L1 expression in this population seems higher than for patients with common EGFRm., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This study describes the real-world characteristics, treatment sequencing, and outcomes among Hispanic patients with locally advanced/metastatic ALK-positive non-small-cell lung cancer (NSCLC) treated with crizotinib., Methods: A retrospective patient review was conducted for several centers in Latin America. Clinicians identified ALK-positive NSCLC patients who received crizotinib and reported their clinical characteristics, treatments, and survival. Overall survival and progression-free survival (PFS) were described. A Random Forest Tree (RFT) model was constructed to predict brain progression., Results: A total of 73 patients were included; median age at diagnosis was 58 years, 60.3% were female, and 93.2% had adenocarcinoma. Eighty-nine percent of patients were never smokers/former smokers, 71.1% had ≥2 sites of metastasis, and 20.5% had brain metastases at diagnosis. The median PFS on first-line crizotinib was 7.07 months (95% CI 3.77-12.37) and the overall response rate was 52%. Of those who discontinued crizotinib, 55.9% progressed in the central nervous system (CNS). The RFT model reached a sensitivity of 100% and a specificity of 88% for prediction of CNS progression., Conclusions: The overall response rate and the PFS observed in Hispanic patients with ALK-positive NSCLC treated with first-line crizotinib were similar to those in previous reports. An RFT model is helpful in predicting CNS progression and can help clinicians tailor treatments in a resource-limited practice., (© 2018 S. Karger AG, Basel.)

Dual purpose systems that treat wastewater and produce lipid rich microalgae biomass have been indicated as an option with great potential for production of biodiesel at a competitive cost. The aim of the present work was to develop a dual purpose system for the treatment of the anaerobic effluents from pig waste utilizing Neochloris oleoabundans and to evaluate its growth, lipid content and lipid profile of the harvested biomass and the removal of nutrients from the media. Cultures of N. oleoabundans were established in 4 L flat plate photobioreactors using diluted effluents from two different types of anaerobic filters, one packed with ceramic material (D1) and another one packed with volcanic gravel (D2). Maximum biomass concentration in D1 was 0.63 g L(-1) which was significantly higher than the one found in D2 (0.55 g L(-1)). Cultures were very efficient at nutrient removal: 98% for NNH4(+) and 98% for PO4(3-). Regarding total lipid content, diluted eflluents from D2 promoted a biomass containing 27.4% (dry weight) and D1 a biomass containing 22.4% (dry weight). Maximum lipid productivity was also higher in D2 compared to D1 (6.27±0.62 mg L(-1) d(-1) vs. 5.12±0.12 mg L(-1) d(-1)). Concerning the FAMEs profile in diluted effluents, the most abundant one was C18:1, followed by C18:2 and C16:0. The profile in D2 contained less C18:3 (linolenic acid) than the one in D1 (4.37% vs. 5.55%). In conclusion, this is the first report demonstrating that cultures of N. oleoabundans treating anaerobic effluents from pig waste are very efficient at nutrient removal and a biomass rich in lipids can be recovered. The maximum total lipid content and the most convenient FAMEs profile were obtained using effluents from a digester packed with volcanic gravel., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Malignant gliomas, such as glioblastoma multiforme (GBM), present some of the greatest challenges in the management of cancer patients worldwide. Even with aggressive surgical resections and recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal and quality of life is poor. Although new molecular pathways crucial to the biology and invasive ability of GBM are coming to light, translation of basic science achievements into clinical practice is slow. Optimal management requires a multidisciplinary approach and knowledge of potential complications arising from both disease and treatment. To help illustrate "where we are going" with GBM, we here include a detailed depiction of the molecular alterations underlying this fatal disease, as well as intensive research over the past two decades that has led to considerable advances in the understanding of basic GBM biology, pathogenesis and therapeutic approaches.

Designing molecular targeted therapy with high specificity based on novel tumor biomarkers is a high priority in lung cancer research. Several molecular aberrations have been already identified in non-small cell lung cancer (NSCLC), with subsequent development of drugs targeted to these aberrations. A more recent actionable target is MET, a multifaceted receptor tyrosine kinase which frequently interacts with other key oncogenic tyrosine kinases including epidermal growth factor receptor (EGFR) and ERBB3 leading to resistance to anti-EGFR therapies. However a phase III trial enrolling only patients with MET-positive tumors was stopped in early March due to futility since there was no evidence that the addition of onartuzumab to erlotinib has any positive effect. From the results of the MET lung phase III trial, we provide new pieces of information that can contribute to further preclinical validation and also be part of the armamentarium for clinical translational research.

Copper (Cu) and cholesterol (Cho) are both associated with neurodegenerative illnesses in humans and animals models. We studied the effect in Wistar rats of oral supplementation with trace amounts of Cu (3 ppm) and/or Cho (2%) in drinking water for 2 months. Increased amounts of nonceruloplasmin-bound Cu were observed in plasma and brain hippocampus together with a higher concentration of ceruloplasmin in plasma, cortex, and hippocampus. Cu, Cho, and the combined treatment Cu + Cho were able to induce a higher Cho/phospholipid ratio in mitochondrial membranes with a simultaneous decrease in glutathione content. The concentration of cardiolipin decreased and that of peroxidation products, conjugated dienes and lipoperoxides, increased. Treatments including Cho produced rigidization in both the outer and inner mitochondrial membranes with a simultaneous increase in permeability. No significant increase in Cyt C leakage to the cytosol was observed except in the case of cortex from rats treated with Cu and Cho nor were there any significant changes in caspase-3 activity and the Bax/Bcl2 ratio. However, the A β (1-42)/(1-40) ratio was higher in cortex and hippocampus. These findings suggest an incipient neurodegenerative process induced by Cu or Cho that might be potentiated by the association of the two supplements.

Age is one of the main factors involved in the development of neurological illnesses, in particular, Alzheimer, and it is widely held that the rapid aging of the world population is accompanied by a rise in the prevalence and incidence of Alzheimer disease. However, evidence from recent decades indicates that Cu and Cho overload are emerging causative factors in neurodegeneration, a hypothesis that has been partially investigated in experimental models. The link between these two variables and the onset of Alzheimer disease has opened up interesting new possibilities requiring more in-depth analysis. The aim of the present study was therefore to investigate the effect of the association of Cu + Cho (CuCho) as a possible synergistic factor in the development of an Alzheimer-like pathology in Wistar rats. We measured total- and nonceruloplasmin-bound Cu and Cho (free and sterified) contents in plasma and brain zones (cortex and hippocampus), markers of oxidative stress damage, inflammation, and programmed cell death (caspase-3 and calpain isoforms). The ratio beta-amyloid (1-42)/(1-40) was determined in plasma and brain as neurodegenerative biomarker. An evaluation of visuospatial memory (Barnes maze test) was also performed. The results demonstrate the establishment of a prooxidative and proinflammatory environment after CuCho treatment, hallmarked by increased TBARS, protein carbonyls, and nitrite plus nitrate levels in plasma and brain zones (cortex and hippocampus) with a consequent increase in the activity of calpains and no significant changes in caspase-3. A simultaneous increase in the plasma A β 1-42/A β 1-40 ratio was found. Furthermore, a slight but noticeable change in visuospatial memory was observed in rats treated with CuCho. We conclude that our model could reflect an initial stage of neurodegeneration in which Cu and Cho interact with one another to exacerbate neurological damage.

In order to establish the spectrum of β-thalassemia (β-thal) mutations in the Venezuelan population for the first time, 127 unrelated subjects either with a suspicion of β-thal trait or with a clinically recognized β-thal syndrome of different degrees of severity, were studied. DNA from these subjects was analyzed by a polymerase chain reaction (PCR)-based reverse dot-blot method or amplification refractory mutation system (ARMS). Prototype β-globin gene sequencing of relevant DNA was performed to confirm the mutations. Fifteen different mutations were identified accounting for 92.0% of the mutant alleles explored, revealing a significant genetic heterogeneity at the β-globin gene locus in this population. The most frequent mutations were codon 39 (C >T) 34.1%, IVS-I-1 (G >A) 11.1%, IVS-I-6 (T > C) 6.6%, IVS-I-110 (G >A) 6.6%, IVS-II-849 (A >G) 6.6%, -88 (C >T) 6.0%, -29 (A >G) 5.2%, followed by the less common IVS-I-5 (G >A) 3.7%, the 1,393 bp deletion 3.0%, IVS-II-1 (G >A) 3.0%, -86 (C >G) 2.2%, IVS-II-1 (G >T) 1.5%, codons 41/42 (-TCTT) 1.5%, IVS-II-745 (C >G) 0.7% and deletional δβ-thal 0.7%. Overall, these data demonstrate that the major sources of β-thal alleles in Venezuela, as expected, are of Mediterranean and African origins. This is the first large study defining the molecular spectrum of β-thal in the highly admixed population of Venezuela and lays the foundation for genetic counseling as well as implementing comprehensive clinical care programs. Diversity of haplotypes associated with some of the β-thal mutations can be explained by in situ recombination events in Venezuela.

Background: Several previous studies reported that the Venezuelan Warao Indians presented unusual genetic characteristics., Aim: The present study checked previous reports of a high frequency of hereditary persistence of fetal hemoglobin (HPFH) and examined other hematological traits., Subjects and Methods: Standard hematology, electrophoresis on cellulose acetate, fetal hemoglobin alkali denaturation, gamma-globin chain, DNA amplification and sequencing, and denaturing gradient gel electrophoresis determinations were performed in 269 individuals living in two localities of the Orinoco River Delta., Results: Two beta(s) genes, in apparently non-related individuals, were found. HPFH, detected in this same population of Warao Indians 25 years ago, was present in heterozygous form in five individuals from a large kindred, with hemoglobin F levels ranging from 3.7% to 8%, and with a pancellular distribution. The HPFH mutation was of the deletional type. beta-globin gene haplotypes were determined by direct counting (through family studies) in 150 chromosomes; 26% of the 150 examined cluster presented haplotype 2, 22% haplotype 6, and 13% a new, Warao haplotype. Haplotype 3, of probable African origin, was also found with a frequency of 5%., Conclusions: The presence of the HPFH mutation was confirmed, and the new beta-globin gene haplotype together with the presence of other rare variants indicates that the Warao are very distinctive in relation to other Native Americans. Evidence was also found of a slight admixture from Africa-derived subjects (Layrisse et al. 1988).

The propositus is a two year old child with a severe hemolytic anemia and increased level of Hb F. The Hbs A, A2 and F were eluted and quantitated by cation exchange high-performance liquid chromatography (HPLC-CE). DNA was isolated from peripheral blood leukocytes by a salting-out extraction procedure. The beta globin gone was amplified and the presence of the beta thalassemia mutation was determined by PCR followed of Reverse Dot Blot. Her hematological parameters were as follows: Hb: 7.0 g/dL, Hct: 24.8%, VCM: 87.4 fl, CHCM: 27.8 fl. The haemoglobin study showed an 97% increase of Hb F and Hb A2 normal. The molecular study suggested the presence of beta(IVSII-829) mutation in trans to deltabeta Thalassemia. The propositus inherited her mother's deltabeta-thalassemia gene mutation and her father's beta(IVSH-829) mutation. This is the first time the diagnosis has been performed in a Venezuelan family at-risk of compound heterozygotes for beta-thalassemia and delta beta-thalassemia.

The hemoglobinopathies are a very heterogeneous group of congenital hemolytic anemias, which includes hemoglobin (Hb) variants, thalassemia and hereditary persistence of fetal hemoglobin (HPFH). The aim of this study was to determine the frequency of hemoglobinopathies using the High Performance Liquid Chromatography (HPLC-CE) technique with the beta-thalassemia Short Program of Variant* Bio Rad. Four thousand blood samples from anemic patients from the Laboratorio de Investigación de Hemoglobinas Anormales, Hospital Universitario de Caracas were studied. Twenty six percent of the anemia patients had hemoglobinopathies. The Hb S was the most frequent variant found, followed by the Hb C and Hb D. Also we observed the association of beta thalassemia with Hb S and Hb C. The quantification of the Hb A by HPLC-CE allowed us to classify the double heterozygote Hb S-Beta Thalassemia in Hb S-beta+ Tal Type 1, Hb S-beta+ Tal Type 2, Hb S-beta(0) Thalassemia. The double heterozygote patients with Hb C-Beta thalassemia were also classified. The HPLC-CE is a rapid, reproducible and precise technique. The reliability of HbA2 measurement by HPLC for the detection of beta thalassaemia without any false positive or false negative results is of great advantage. HPLC may be an appropriate method for rapid screening in population surveys for beta thalassemia and hemoglobin variants carriers. Due to the high incidence of cases, in our country this is very important for their clinical management and the genetic and anthropological impact of an early and precise diagnosis.