Endocarditis Infecciosa Mural Apical del Ventrículo Izquierdo: Presentación de caso clínico y revisión bibliográfica / Infectious Apical Mural Endocarditis of the Left Ventricle: Clinical case presentation and bibliographic review

RESUMEN La endocarditis mural es una forma infrecuente de infección intracardiaca que afecta al endocardio no valvular que pue- de presentarse con complicaciones similares a la endocarditis infecciosa valvular. Se recomienda la ecocardiografía para confirmar el diagnóstico cuando exista un alto índice de sospecha. Con respecto al tratamiento, existe evidencia limitada acerca de las estrategias terapéuticas en la endocarditis mural, sin embargo en la mayoría de casos reportados se recomienda iniciar antibioticoterapia dirigida asociado a una intervención quirúrgica precoz. A continuación, se presenta un caso clínico de un paciente masculino de 74 años con fenómenos embólicos sistémicos, en quien se documenta por ecocardiograma transesofágico una endocarditis mural en ápex del ventrículo izquierdo asociado a una bacteriemia por Staphylococcus aureus. Este caso pone de manifiesto la importancia de una valoración ecocardiográfica detallada de las válvulas y cámaras cardíacas ante la sospecha de una endocarditis infecciosa.

ABSTRACT Mural endocarditis is an uncommon form of intracardiac infection affecting the non valvular endocardium that can present with complications similar to valvular infective endocarditis. Echocardiography is recommended to confirm the diagnosis when there is a high index of suspicion. Regarding treatment, there is limited evidence about therapeutic strategies in mural endocarditis, however in most reported cases it is recommended to initiate targeted antibiotic therapy associated with early surgical intervention. The following is a clinical case of a 74-year-old male patient with systemic embolic phenomena, in whom a transesophageal echocardiogram documented mural endocarditis in the apex of the left ventricle associated with Staphylococcus aureus bacteremia. This case highlights the importance of a detailed echocardiographic assessment of the cardiac valves and chambers when infective endocarditis is suspected.

Synthesis of Novel Heterocyclic Ferrocenyl Chalcones and Their Biological Evaluation.

Breast cancer is currently the most commonly diagnosed cancer, with 287,850 new cases estimated for 2022 as reported by the American Cancer Society. Therefore, finding an effective treatment for this disease is imperative. Chalcones are α,ß-unsaturated systems found in nature. These compounds have shown a wide array of biological activities, making them popular synthetic targets. Chalcones consist of two aromatic substituents connected by an enone bridge; this arrangement allows for a large number of derivatives. Given the biological relevance of these compounds, novel ferrocene-heterocycle-containing chalcones were synthesized and characterized based on a hybrid drug design approach. These heterocycles included thiophene, pyrimidine, thiazolyl, and indole groups. Fourteen novel heterocyclic ferrocenyl chalcones were synthesized and characterized. Herein, we also report their cytotoxicity against triple-negative breast cancer cell lines MDA-MB-231 and 4T1 and the noncancer lung cell line MRC-5. System 3 ferrocenyl chalcones displayed superior anticancer properties compared to their system 1 analogues. System 3 chalcones bearing five-membered heterocyclic substituents (thiophene, pyrazole, pyrrole, and pyrimidine) were the most active toward the MDA-MB-231 cancer cell line with IC50 values from 6.59 to 12.51 µM. Cytotoxicity of the evaluated compounds in the 4T1 cell line exhibited IC50 values from 13.23 to 213.7 µM. System 3 pyrazole chalcone had consistent toxicity toward both cell lines (IC50 ∼ 13 µM) as well as promising selectivity relative to the noncancer MRC-5 control. Antioxidant activity was also evaluated, where, contrary to anticancer capabilities, system 1 ferrocenyl chalcones were superior to their system 3 analogues. Antioxidant activity comparable to that of ascorbic acid was observed for thiophene-bearing ferrocenyl chalcone with EC50 = 31 µM.

Similar outcomes after newly implemented rats approach compared to standard vats for anatomical lung resection. A propensity-score matched analysis.

INTRODUCTION: Outcomes after the introduction of surgical innovations can be impaired by learning periods. The aim of this study is to compare the short-term outcomes of a recently implemented RATS approach to a standard VATS program for anatomical lung resections. METHODS: Retrospective review of consecutive patients undergoing pulmonary anatomical resection through a minimally invasive approach since RATS approach was applied in our department (June 01, 2018, to November 30, 2019). Propensity score matching was performed according to patients' age, gender, ppoFEV1, cardiac comorbidity, type of malignancy, and type of resection. Outcome evaluation includes: overall morbidity, significant complications (cardiac arrhythmia, pneumonia, prolonged air leak, and reoperation), 30-day mortality, and length of hospital stay. Data were compared by two-sided chi-square or Fisher's exact test for categorical and Mann-Whitney U test for continuous variables. RESULTS: A total of 273 patients (206 VATS, 67 RATS) were included in the study. After propensity score matching, data of 132 patients were analyzed. The thirty-days mortality was nil. Overall morbidity (RATS: 22.4%, VATS: 29.2%; p=0.369), major complications (RATS: 9% vs VATS: 9.2%; p=0.956) and the rates of specific major complications (cardiac arrhythmia RATS: 4.5%, VATS: 4.6%, p=1; pneumonia RATS:0%, VATS:4.6%, p=0.117; prolonged air leak RATS: 7.5%; VATS: 4.6%, p=0.718) and reoperation (RATS: 3%, VATS: 1.5%, p=1) were comparable between both groups. The median length of stay was 3 days in both groups (p=0.101). CONCLUSIONS: A RATS program for anatomical lung resection can be implemented safely by experienced VATS surgeons without increasing morbidity rates.

"Obesity paradox" has not an impact on minimally invasive anatomical lung resection.

INTRODUCTION: The paradoxical benefit of obesity, the 'obesity paradox', has been analyzed in lung surgical populations with contradictory results. Our goal was assessing the relationship of body mass index (BMI) to acute outcomes after minimally invasive major pulmonary resections. METHODS: Retrospective review of consecutive patients who underwent pulmonary anatomical resection through a minimally invasive approach for the period 2014-2019. Patients were grouped as underweight, normal, overweight and obese type I, II and III. Adjusted odds ratios regarding postoperative complications (overall, respiratory, cardiovascular and surgical morbidity) were produced with their exact 95% confidence intervals. All tests were considered statistically significant at p<0.05. RESULTS: Among 722 patients included in the study, 37.7% had a normal BMI and 61.8% were overweight or obese patients. When compared with that of normal BMI patients, adjusted pulmonary complications were significantly higher in obese type I patients (2.6% vs 10.6%, OR: 4.53 [95%CI: 1.86-12.11]) and obese type II-III (2.6% vs 10%, OR: 6.09 [95%CI: 1.38-26.89]). No significant differences were found regarding overall, cardiovascular or surgical complications among groups. CONCLUSIONS: Obesity has not favourable effects on early outcomes in patients undergoing minimally invasive anatomical lung resections, since the risk of respiratory complications in patients with BMI≥30kg/m2 and BMI≥35kg/m2 is 4.5 and 6 times higher than that of patients with normal BMI.

Exploring Titanium(IV) Complexes as Potential Antimicrobial Compounds.

Due to the rapid mutation of pathogenic microorganisms, drug-resistant superbugs have evolved. Antimicrobial-resistant germs may share their resistance genes with other germs, making them untreatable. The search for more combative antibiotic compounds has led researchers to explore metal-based strategies centered on perturbing the bioavailability of essential metals in microbes and examining the therapeutic potential of metal complexes. Given the limited knowledge on the application of titanium(IV), in this work, eight Ti(IV) complexes and some of their corresponding ligands were screened by the Community for Open Antimicrobial Drug Discovery for antimicrobial activity. The compounds were selected for evaluation because of their low cytotoxic/antiproliferative behavior against a human non-cancer cell line. At pH 7.4, these compounds vary in terms of their solution stability and ligand exchange lability; therefore, an assessment of their solution behavior provides some insight regarding the importance of the identity of the metal compound to the antimicrobial therapeutic potential. Only one compound, Ti(deferasirox)2, exhibited promising inhibitory activity against the Gram-positive bacteria methicillin-resistant Staphylococcus aureus and minimal toxicity against human cells. The ability of this compound to undergo transmetalation with labile Fe(III) sources and, as a consequence, inhibit Fe bioavailability and ribonucleotide reductase is evaluated as a possible mechanism for its antibiotic effect.

The robotic surgery learning curve of a surgeon experienced in video-assisted thoracoscopic surgery compared with his own video-assisted thoracoscopic surgery learning curve for anatomical lung resections.

OBJECTIVES: Robotic surgery, although it shares some technical features with video-assisted thoracoscopic surgery (VATS), offers some advantages, such as ergonomic design and a 3-dimensional view. Thus, the learning curve for robotic lung resection could be expected to be shorter than that of VATS for surgeons who are proficient in VATS. The goal of this study was to analyse the robotic learning curve of a VATS experienced surgeon and to compare it to his own VATS learning curve for anatomical lung resections. METHODS: We conducted a retrospective observational study based on the prospectively recorded data of the first 150 anatomical lung resections performed with VATS (75 cases) and with the robotic (75 cases) approach by the same surgeon in our centre. Learning curves were analysed using the cumulative sum method to assess the trends for total operating time and surgical failure (intraoperative complications, conversion, technical postoperative complications and reintervention) across case sequences. Subsequently, using adequate statistical tests, we compared the postoperative outcomes in both groups. RESULTS: The median operating time was similar for both approaches (P = 0.401). Surgical failure rate was higher for the robotic cases (21.3% vs 12%; P = 0.125). Based on cumulative sum analyses, operating time decreased starting with case 34 in the VATS group and with case 32 in the robotic cohort. Surgical failure tended to decline starting with case 28 in the VATS group and with case 32 in the robotic group. Perioperative results were similar in both groups. CONCLUSIONS: When we compared robotic and VATS learning curves for anatomical lung resection, we did not find any differences. Postoperative outcomes were also similar with both approaches.

Clinic Staff Perspectives on Barriers and Facilitators to Integrating Transgender Healthcare into Family Planning Clinics.

Purpose: Although some research exists about transgender and nonbinary people's reproductive health needs, little research has explored the expansion of transgender health care in a family planning clinic context. This study investigates the expansion of transition-related care in family planning clinics in the United States from the perspective of clinic staff members. Methods: Between 2018 and 2019, 25 in-depth interviews with family planning clinic staff across the United States explored themes in incorporation and continuation of transgender care. Qualitative data were also collected at several national reproductive health professional conferences in sessions focused on transgender health care. Content analysis on the type of care available at clinics from public websites was analyzed using descriptive statistics. Results: Family planning clinics became invested in offering transition related care through existing patient requests and community requests, including from staff members themselves. Clinics faced administrative and scheduling challenges in adding care. They reported that medical protocol components were easiest to learn. Analysis of clinic websites indicates that ∼10% of nationally networked clinics offer transgender care compared to 21% of independent member clinics of the Abortion Care Network. Conclusions: Family planning clinics should consider adding transgender care based on patient or community demand as an extension of existing expertise in providing patient-centered care. Clinics should be aware that tool kits and protocols already exist to support integrating transition related care in family planning clinics.

Efecto del Programa de Rehabilitación Cardiaca del Hospital San Vicente Paúl sobre parámetros bioquímicos, antropométricos y funcionales en pacientes con cardiopatía isquémica del 1º de enero del 2014 al 31 de diciembre del 2015 / Effect of the Cardiac Rehabilitation Program of the Hospital San Vicente Paúl on biochemical, anthropometric and functional parameters in patients with ischemic heart disease from January 1, 2014 to December 31, 2015

Resumen Introducción y objetivos: Los programas de rehabilitación cardiaca (RHC) son considerados como los más eficaces entre las intervenciones de prevención secundaria. El cual su función es mejorar la sobrevida como así también, la calidad de vida de estos enfermos. El objetivo fundamental de este trabajo es analizar el impacto de un Programa de Rehabilitación Cardiaca en pacientes portadores de cardiopatía isquémica con respecto a parámetros bioquímicos, antropométricos y funcionales. Pacientes y métodos: Fue un estudio observacional retrospectivo, unicéntrico, con seguimiento de 3 años. Se incluyo un total de 228 pacientes. Con criterios de inclusión: >18 años, con EAC y al menos una comorbilidad de riesgo cardiovascular que completaran el PRC. Se excluyó enfermedad valvular sin cardiopatía isquémica preexistente, infarto agudo al miocardio reciente, ángor inestable, obstrucción del tracto de salida del ventrículo izquierdo, y los que no cumplieron el PRC. Resultados: De los 228 pacientes que se incluyeron el PRC del HSVP el 70,7% eran hombres y el 29,3% eran mujeres con diagnóstico de cardiopatía isquémica. El promedio de edad era de 60.2 +- 11.4 años en total entre hombres y mujeres. El peso de los pacientes masculinos previo al ingreso del PRC fue de 77,7 kg +-13,2 kg, y las mujeres 69,7 kg +- 13,1 kg. Al final del fue de 75,5 kg +-13,1 kg y el de las mujeres era de 68,3 +- 13,1 kg. En la caminata de 6 minutos el promedio de mujeres al inicio fue de 390,0 mts y el de los hombres de 386,6, y la segunda vez posterior a la rehabilitación en hombres fue de 595,8 +- 107,2 y el de las mujeres fue de 549+-102,4. Los niveles de PCR de los hombres al inicio del programa fue de 1,2 +-2,4 mg/dL y el de las mujeres fue de 1,5 +- 1,9 mg/dL al finalizar los hombres tuvieron un promedio de 1,8+-3,0 Conclusiones: Los PRC dependen de la participación de profesionales de la salud que trabajen en equipo para alcanzar resultados finales, los cuales están basados no solo en el ejercicio sino también en el cambio de estilo de vida del paciente, por lo tanto, necesita de servicios asociados como fisioterapia, nutrición, psicología.

Abstract Effect of the Cardiac Rehabilitation Program of the Hospital San Vicente Paúl on biochemical, anthropometric and functional parameters in patients with ischemic heart disease from January 1, 2014 to December 31, 2015 Introduction and objectives: Cardiac Rehabilitation Programs, are considered the most effective programs among secondary prevention interventions. The function is to improve survival as well as the quality of life of these patients. The main objective of this work is to analyze the impact of Cardiac Rehabilitation Program in patients with ischemic heart disease with the respect biochemical, anthropometric and functional parameters. Patients and method: A observational, retrospective single-center, study with a 3-year-follow up. A total of 228 patients were included, witch 70.7% were men with an average of 60.2+-11.4 years. The inclusion criteria were: > 18 years with CAD and at least one cardiovascular risk comorbidity and completed the Cardiac Rehabilitation Program. Valvular disease without pre-existing ischemic heart disease, recent acute myocardial infarction, unstable angina, left ventricular outflow tract obstruction, and those who did not went to the Program. Results: The 228 patients who were included in the HSVP CRP, 70.7% were men and 29.3% were women with a diagnosis of ischemic heart disease. The average age was 60.2 + - 11.4 years in total between men and women. The weight of male patients prior to admission to the CRP was 77.7 kg + -13.2 kg, and women 69.7 kg + -13.1 kg. At the end of the program, the weight of the men was 75.5 kg + -13.1 kg and that of the women was 68.3 + - 13.1 kg. The total waist circumference at the start of the program was 100.1 ± 11.4 cm. In women the average was 98.4 + - 12.7cm, that of men was 101.1 + - 10.8 cm. At the end of the program, the total average of men and women was 96.7 + - 11.0, the average of women at the end of the program was 96.2 + - 12.6 cm and of men was 96. 9 + - 10. In the 6-minute walk, the average of women at the beginning was 390.0 meters and that of men was 386.6, and the second time after rehabilitation in men was 595.8 + - 107.2 and the of women it was 549 + -102.4. In men, the previous total cholesterol was 154.8 + -39.7 mg / dL and that of women was 162.0 + -40.2 mg / dL and at the end of the program the value of men was 161 .6 + -46.0 mg / dL and 170.8 + -41.8 mg / dL for women. The CRP levels of the men at the beginning of the program was 1.2 + -2.4 mg / dL and that of the women was 1.5 + - 1.9 mg / dL at the end of the program, the men had an average of 1.8 + -3.0. Conclusion: The Cardiac Rehabilitation Program depends on the partipation of health professionals care who work as a team to achieve final results, witch are based not only on exercise but also on the change in the patient's lifestyle, therefore, they need associated services such as physiotherapy, nutrition, psychology.

Raw data of silver extraction from sodium-silver jarosite using three different lixiviants in alkaline medium.

This article presents the raw data of silver concentration ([Ag]) obtained as a function of time (t) from silver leaching experiments, which were conducted using a synthetic sodium-silver jarosite and different complexing agents: thiosulfate, thiocyanate, and cyanide. Leaching experiments were performed under different conditions of temperature, pH and lixiviant concentration. The data refer to the article "Silver leaching from jarosite-type compounds using cyanide and non-cyanide lixiviants: a kinetic approach" (Islas et al., 2021), in which they were used to determine the leaching kinetics of jarosite-type compounds. The datasets were obtained experimentally from batch experiments. Concentration of silver, [Ag], was determined in each experiment as a function of time by atomic absorption spectroscopy. The information presented in this article can be useful for engineering students interested in mineral processing; particularly, for the calculation of kinetic parameters of silver leaching process. The data could also help in the formulation, implementation, or optimization of strategies for extraction of valuable metals from residues generated by the hydrometallurgical industry.

Iron Chelator Transmetalative Approach to Inhibit Human Ribonucleotide Reductase.

Efforts directed at curtailing the bioavailability of intracellular iron could lead to the development of broad-spectrum anticancer drugs given the metal's role in cancer proliferation and metastasis. Human ribonucleotide reductase (RNR), the key enzyme responsible for synthesizing the building blocks of DNA replication and repair, depends on Fe binding at its R2 subunit to activate the catalytic R1 subunit. This work explores an intracellular iron chelator transmetalative approach to inhibit RNR using the titanium(IV) chemical transferrin mimetic (cTfm) compounds Ti(HBED) and Ti(Deferasirox)2. Whole-cell EPR studies reveal that the compounds can effectively attenuate RNR activity though seemingly causing different changes to the labile iron pool that may account for differences in their potency against cells. Studies of Ti(IV) interactions with the adenosine nucleotide family at pH 7.4 reveal strong metal binding and extensive phosphate hydrolysis, which suggest the capacity of the metal to disturb the nucleotide substrate pool of the RNR enzyme. By decreasing intracellular Fe bioavailability and altering the nucleotide substrate pool, the Ti cTfm compounds could inhibit the activity of the R1 and R2 subunits of RNR. The compounds arrest the cell cycle in the S phase, indicating suppressed DNA replication, and induce apoptotic cell death. Cotreatment cell viability studies with cisplatin and Ti(Deferasirox)2 reveal a promising synergism between the compounds that is likely owed to their distinct but complementary effect on DNA replication.

Similar outcomes after newly implemented rats approach compared to standard vats for anatomical lung resection. A propensity-score matched analysis.

INTRODUCTION: Outcomes after the introduction of surgical innovations can be impaired by learning periods. The aim of this study is to compare the short-term outcomes of a recently implemented RATS approach to a standard VATS program for anatomical lung resections. METHODS: Retrospective review of consecutive patients undergoing pulmonary anatomical resection through a minimally invasive approach since RATS approach was applied in our department (June 01, 2018, to November 30, 2019). Propensity score matching was performed according to patients' age, gender, ppoFEV1, cardiac comorbidity, type of malignancy, and type of resection. Outcome evaluation includes: overall morbidity, significant complications (cardiac arrhythmia, pneumonia, prolonged air leak, and reoperation), 30-day mortality, and length of hospital stay. Data were compared by two-sided chi-square or Fisher's exact test for categorical and Mann-Whitney U test for continuous variables. RESULTS: A total of 273 patients (206 VATS, 67 RATS) were included in the study. After propensity score matching, data of 132 patients were analyzed. The thirty-days mortality was nil. Overall morbidity (RATS: 22.4%, VATS: 29.2%; p=0.369), major complications (RATS: 9% vs VATS: 9.2%; p=0.956) and the rates of specific major complications (cardiac arrhythmia RATS: 4.5%, VATS: 4.6%, p=1; pneumonia RATS:0%, VATS:4.6%, p=0.117; prolonged air leak RATS: 7.5%; VATS: 4.6%, p=0.718) and reoperation (RATS: 3%, VATS: 1.5%, p=1) were comparable between both groups. The median length of stay was 3 days in both groups (p=0.101). CONCLUSIONS: A RATS program for anatomical lung resection can be implemented safely by experienced VATS surgeons without increasing morbidity rates.

"Obesity paradox" has not an impact on minimally invasive anatomical lung resection.

INTRODUCTION: The paradoxical benefit of obesity, the 'obesity paradox', has been analyzed in lung surgical populations with contradictory results. Our goal was assessing the relationship of body mass index (BMI) to acute outcomes after minimally invasive major pulmonary resections. METHODS: Retrospective review of consecutive patients who underwent pulmonary anatomical resection through a minimally invasive approach for the period 2014-2019. Patients were grouped as underweight, normal, overweight and obese type I, II and III. Adjusted odds ratios regarding postoperative complications (overall, respiratory, cardiovascular and surgical morbidity) were produced with their exact 95% confidence intervals. All tests were considered statistically significant at p<0.05. RESULTS: Among 722 patients included in the study, 37.7% had a normal BMI and 61.8% were overweight or obese patients. When compared with that of normal BMI patients, adjusted pulmonary complications were significantly higher in obese type I patients (2.6% vs 10.6%, OR: 4.53 [95%CI: 1.86-12.11]) and obese type II-III (2.6% vs 10%, OR: 6.09 [95%CI: 1.38-26.89]). No significant differences were found regarding overall, cardiovascular or surgical complications among groups. CONCLUSIONS: Obesity has not favourable effects on early outcomes in patients undergoing minimally invasive anatomical lung resections, since the risk of respiratory complications in patients with BMI≥30kg/m2 and BMI≥35kg/m2 is 4.5 and 6 times higher than that of patients with normal BMI.

Design of Potential Pharmaceutical-Based Metal Complexes Derived from Cromolyn a Mast Cell Stabilizer.

A series of pharmaceutical metal complexes (pMCs) were produced and characterized using the mast cell stabilizer, cromolyn, and bioactive metal ions (Zn+2, Mg+2, and Ca+2). Three novel pMCs, Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca, were formed through reactions under controlled temperature and pH conditions. Additional characterization for these materials was performed employing a number of solid-state characterization techniques, such as thermogravimetric analysis (TGA), powder and single-crystal X-ray diffraction (PXRD and SCXRD), and scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS). TGA demonstrated that these metal complexes showed an enhanced thermal stability due to the strong coordination with the ligand, cromolyn. PXRD data indicates a high degree of crystallinity as well as a unique packing arrangement for each pMCs. SEM analysis showed materials with well-defined morphologies, while EDS presented elemental evidence for the unique composition of each pMCs. The crystal structure for these materials was elucidated through SCXRD, and a variety of binding modes and packing motifs were found within each respective metal complex. Only two-dimensional (2D) structures were achieved under the conditions studied. These binding modalities might affect the activity and delivery of cromolyn sodium (CS). The stability of the metal complexes was assessed in phosphate-buffered saline (PBS, pH = 7.40) and fasted-state simulated gastric fluids (FaSSGF, pH = 1.60). Dissolution studies show high stability and slow degradation for the metal complexes, while a higher dissolution was observed for the drug compound in PBS. Neither CS nor the pMCs dissolved significantly in FaSSGF at 37 °C.

Using X-ray Diffraction Techniques for Biomimetic Drug Development, Formulation, and Polymorphic Characterization.

Drug development is a decades-long, multibillion dollar investment that often limits itself. To decrease the time to drug approval, efforts are focused on drug targets and drug formulation for optimal biocompatibility and efficacy. X-ray structural characterization approaches have catalyzed the drug discovery and design process. Single crystal X-ray diffraction (SCXRD) reveals important structural details and molecular interactions for the manifestation of a disease or for therapeutic effect. Powder X-ray diffraction (PXRD) has provided a method to determine the different phases, purity, and stability of biological drug compounds that possess crystallinity. Recently, synchrotron sources have enabled wider access to the study of noncrystalline or amorphous solids. One valuable technique employed to determine atomic arrangements and local atom ordering of amorphous materials is the pair distribution function (PDF). PDF has been used in the study of amorphous solid dispersions (ASDs). ASDs are made up of an active pharmaceutical ingredient (API) within a drug dispersed at the molecular level in an amorphous polymeric carrier. This information is vital for appropriate formulation of a drug for stability, administration, and efficacy purposes. Natural or biomimetic products are often used as the API or the formulation agent. This review profiles the deep insights that X-ray structural techniques and associated analytical methods can offer in the development of a drug.

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity.

Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

Comprehensive assessment of left ventricular myocardial function by two-dimensional speckle-tracking echocardiography.

BACKGROUND: Left ventricular ejection fraction (LVEF) results from the combined action of longitudinal and circumferential contraction, radial thickening, and basal and apical rotation. The study of these parameters together may lead to an accurate assessment of the cardiac function. METHODS: Ninety healthy volunteers, categorized by gender and age (≤ 55 and >  55 years), were evaluated using two-dimensional speckle tracking echocardiography. Transversal views of the left ventricle (LV) were obtained to calculate circumferential strain and left ventricular twist, while three apical views were obtained to determine longitudinal strain (LS) and mitral annular plane systolic excursion (MAPSE). We established the integral myocardial function of the LV according to: 1. The Combined Deformation Parameter (CDP), which includes Deformation Product (DP) - Twist x LS (° x %) - and Deformation Index (DefI) -Twist / LS (° / %)-; and 2. the Torsion Index (TorI): Twist / MAPSE (° / cm). RESULTS: The mean age of our patients was 50.3 ± 11.1 years. CDP did not vary with gender or age. The average DP was - 432 ± 172 ° x %, and the average DefI was - 0.96 ± 0.36 ° / %. DP provides information about myocardial function (normal, pseudonormal, depressed), and the DefI quotient indicates which component (s) is/are affected in cases of abnormality. TorI was higher in volunteers over 55 years (16.5 ± 15.2 vs 13.1 ± 5.0 °/cm, p = 0.003), but did not vary with gender. CONCLUSIONS: The proposed parameters integrate values of twisting and longitudinal shortening. They allow a complete physiological assessment of cardiac systolic function, and could be used for the early detection and characterization of its alteration.

Myocardial Contraction during the Diastolic Isovolumetric Period: Analysis of Longitudinal Strain by Means of Speckle Tracking Echocardiography.

BACKGROUND: According to the ventricular myocardial band model, the diastolic isovolumetric period is a contraction phenomenon. Our objective was to employ speckle-tracking echocardiography (STE) to analyze myocardial deformation of the left ventricle (LV) and to confirm if it supports the myocardial band model. METHODS: This was a prospective observational study in which 90 healthy volunteers were recruited. We evaluated different types of postsystolic shortening (PSS) from an LV longitudinal strain study. Duration of latest deformation (LD) was calculated as the time from the start of the QRS complex of the ECG to the latest longitudinal deformation peak in the 18 segments of the LV. RESULTS: The mean age of our subjects was 50.3 ± 11.1 years. PSS was observed in 48.4% of the 1620 LV segments studied (19.8%, 13.5%, and 15.1% in the basal, medial, and apical regions, respectively). PSS was more frequent in the basal, medial septal, and apical anteroseptal segments (>50%). LD peaked in the interventricular septum and in the basal segments of the LV. CONCLUSIONS: The pattern of PSS and LD revealed by STE suggests there is contraction in the postsystolic phase of the cardiac cycle. The anatomical location of the segments in which this contraction is most frequently observed corresponds to the main path of the ascending component of the myocardial band. This contraction can be attributed to the protodiastolic untwisting of the LV.