A Comparison of In Vitro Studies between Cobalt(III) and Copper(II) Complexes with Thiosemicarbazone Ligands to Treat Triple Negative Breast Cancer.

Metal complexes have gained significant attention as potential anti-cancer agents. The anti-cancer activity of [Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH 1 (where phen = 1,10-phenanthroline and MeATSC = 9-anthraldehyde-N(4)-methylthiosemicarbazone) and [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 2 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide) was investigated by analyzing DNA cleavage activity. The cytotoxic effect was analyzed using CCK-8 viability assay. The activities of caspase 3/7, 9, and 1, reactive oxygen species (ROS) production, cell cycle arrest, and mitochondrial function were further analyzed to study the cell death mechanisms. Complex 2 induced a significant increase in nicked DNA. The IC50 values of complex 1 were 17.59 µM and 61.26 µM in cancer and non-cancer cells, respectively. The IC50 values of complex 2 were 5.63 and 12.19 µM for cancer and non-cancer cells, respectively. Complex 1 induced an increase in ROS levels, mitochondrial dysfunction, and activated caspases 3/7, 9, and 1, which indicated the induction of intrinsic apoptotic pathway and pyroptosis. Complex 2 induced cell cycle arrest in the S phase, ROS generation, and caspase 3/7 activation. Thus, complex 1 induced cell death in the breast cancer cell line via activation of oxidative stress which induced apoptosis and pyroptosis while complex 2 induced cell cycle arrest through the induction of DNA cleavage.

Indonesian Study: Triiodothyronine for Infants Less than 5 Months Undergoing Cardiopulmonary Bypass.

This study evaluates the efficacy and safety of oral triiodothyronine on time to extubation for infants less than 5 months undergoing heart surgery in Indonesia, and primarily relates to patients in emerging programs with high malnutrition and mortality. In this randomized, double-blind, placebo-controlled trial, oral triiodothyronine (T3, Tetronine®) 1 µg/kg-body weight/dose or placebo (saccharum lactis) was administered via nasogastric tube every 6 h for 60 h to treatment group. A total of 120 patients were randomized into T3 (61 patients) and placebo (59 patients) groups. The majority of the patients had moderate to severe malnutrition (55.83%) with a high post-operative mortality rate of 23.3%. The T3 group showed significantly higher serum FT3 levels from 1 until 48 h post cross-clamp removal (p < 0.0001), lower incidence of low cardiac output syndrome at both 6 h (28 [45.9%] vs. 39 [66.1%] patients, p = 0.03, OR 2.3, 95% CI: 1.10-4.81) and 12 h after cross-clamp removal (25 [41.7%] vs. 36 [63.2%], p = 0.02, OR 2.40, 95% CI: 1.14-5.05). Although not statistically significant, the treatment group had shorter median (IQR) intubation time (2.59 [1.25-5.24] vs. 3.77 [1.28-6.64] days, p = 0.16, HR 1.36, 95% CI: 0.88-2.09)] and lower mortality (10 [16.4%] vs. 18 [30.5%], p = 0.07]. Patients with Aristotle score < 10.0 (low risk) receiving T3 had faster extubation than placebo patients (p = 0.021, HR of 1.90, 95% CI: 1.10-3.28) and were significantly less likely to require CPR or experience infection (p = 0.027, OR 8.56, 95% CI:0.99-73.9 and p = 0.022, OR 4.09 95% CI: 1.16-14.4, respectively). Oral T3 supplementation reduced overall incidence of low cardiac output syndrome and significantly reduced the time to extubation in low-risk patients. Therefore, prophylactic oral T3 administration may be beneficial in these patients.Trial Registration: ClinicalTrials.gov NCT02222532.

Targeting backdoor androgen synthesis through AKR1C3 inhibition: A presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer.

BACKGROUND: Localized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP). METHODS: This was an open label, single-site, Phase II neoadjuvant trial in men with high to very-high-risk PC, as defined by NCCN criteria. Patients received 12 weeks of apalutamide (Apa), abiraterone acetate plus prednisone (AAP), degarelix, and Indo followed by RP. Primary objective was to determine the pathologic complete response (pCR) rate. Secondary objectives included minimal residual disease (MRD) rate, defined as residual cancer burden (RCB) ≤ 0.25cm3 (tumor volume multiplied by tumor cellularity) and elucidation of molecular features of resistance. RESULTS: Twenty patients were evaluable for the primary endpoint. Baseline median prostate-specific antigen (PSA) was 10.1 ng/ml, 4 (20%) patients had Gleason grade group (GG) 4 disease and 16 had GG 5 disease. At RP, 1 (5%) patient had pCR and 6 (30%) had MRD. Therapy was well tolerated. Over a median follow-up of 23.8 months, 1 of 7 (14%) men with pathologic response and 6 of 13 (46%) men without pathologic response had a PSA relapse. There was no association between prostate hormone levels or HSD3B1 genotype with pathologic response. CONCLUSIONS: In men with high-risk PC, pCR rates remained low even with combinatorial AR-directed therapy, although rates of MRD were higher. Ongoing follow-up is needed to validate clinical outcomes of men who achieve MRD.

Sustaining a legacy in STEM the Prof. Tara Prasad Dasgupta way: The role of a mentor in our lives.

A mentoring relationship is a close, individualized relationship that develops over time between a graduate student and his/her adviser, and that includes both caring and guidance. Although there is a connection between mentors and advisers, not all mentors are advisers and not all advisers are mentors, but in this case, one adviser was a mentor to all. In his eloquent style, an inspirational mentor of underrepresented individuals in Jamaica by the name of Prof. Tara Prasad Dasgupta, AKA Prof., paved the way for many us who studied in the Department of Chemistry, The University of the West Indies, Mona Campus, Jamaica from 1974 until his passing on Monday, April 2020 due to the complications of the COVID-19. Based on his effective mentoring style and the fact that there is low percentage of underrepresented individuals who pursue Ph.D. degrees in the STEM subjects around the world, more so here in the U.S.A., Europe, and in the U.K., hence there is a need to write about a story on sustaining a legacy in STEM the Prof. Tara Prasad Dasgupta way, viz., the role of a mentor in our lives. As such, his style is documented here, along with testimonies from his former graduate students, including myself.

Copper-tolfenamic acid: evaluation of stability and anti-cancer activity.

The non-steroidal anti-inflammatory drug, Tolfenamic acid (TA) acts as an anti-cancer agent in several adult and pediatric cancer models. Copper (Cu) is an important element with multiple biological functions and has gained interest in medical applications. Recently, [Cu(TA)2(bpy)] (Cu-TA) has been synthesized in order to enhance therapeutic activity. In this study, we synthesized Cu-TA using an established method, characterized it by UV visible spectroscopy and Fourier-transform infrared spectroscopy (FTIR), and tested its anti-cancer activity using twelve cell lines representing various cancers, such as Ewing sarcoma, glioblastoma, medulloblastoma, neuroblastoma, pancreatic and prostate. The anti-proliferative activity of Cu-TA was determined at 48 h post-treatment and compared with the parental compound, TA. The IC50 values were calculated using GraphPad Prism software. The biological stability of Cu-TA was evaluated using twelve-month-old powder and six-month-old stock solution. Cardiomyocytes (H9C2) were used to test the cytotoxicity in non-malignant cells. Cu-TA showed higher anti-proliferative activity, and the IC50 values were 30 to 80% lower when compared with TA. H9C2 cells were non-responsive to Cu-TA, suggesting that it is selective towards malignant cells. Comparison of the twelve-month-old powder and six-month-old stock solution using the Panc1 cell line showed similar IC50 values (<5% variation), confirming the stability of Cu-TA either in powder or solution form. These findings demonstrate the potential of Cu-TA as an effective anti-cancer agent. Further studies to delineate the detailed mechanism of action of Cu-TA for specific cancer model are underway.

Towards lead compounds as anti-cancer agents via new phaeosphaeride A derivatives.

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor studies were carried out on the U937, HCT-116, PC3, MCF-7, A549, К562, NCI-H929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 (IC50 = 0.59 ±â€¯0.27 µM) was observed to be 11 times more active than PPA (IC50 = 6.5 ±â€¯0.30 µM) towards the NCI-H929 cell line, with a therapeutic index of 18. Compound 6 was determined to be over half and 16 times more active than etoposide towards the NCI-H929 (IC50 = 0.9 ±â€¯0.05 µM) and A549 (IC50 = 100 ±â€¯7.0 µM) cell lines, respectively.

Oral Triiodothyronine Supplementation Decreases Low Cardiac Output Syndrome After Pediatric Cardiac Surgery.

The oral triiodothyronine for infants and children undergoing cardiopulmonary bypass (OTICC) trial showed that Triiodothyronine (T3) supplementation improved hemodynamic and clinical outcome parameters. We tested the validity of low cardiac output syndrome (LCOS), derived using clinical parameters and laboratory data, by comparing the LCOS diagnosis with objective parameters commonly measured in a cardiac intensive care unit (CCU) setting. OTICC, a randomized, placebo-controlled trial included children younger than 3 years with an Aristotle score between 6 and 9. We used the existing trial data set to compare the LCOS diagnosis with echocardiographic hemodynamic parameters. Additionally, we determined if LCOS, prospectively assigned during a clinical trial, served as an early predictor of clinical outcomes. All LCOS subjects at 6 and 12 h after cross-clamp release later showed significantly lower pulse pressure, stroke volume and cardiac output, and higher systemic vascular resistance. These LCOS patients also had significantly longer time to extubation (TTE) and higher mortality rate. LCOS incidence was significantly lower in the T3 treatment group [n = 86 vs. 66, respectively, p < 0.001; OR (95% CI) 0.43 (0.36-0.52)] particularly at 6 h. Also, LCOS patients in the placebo group had significantly lower FT3 serum levels over time. These analyses confirm that early clinically defined LCOS successfully predicts cardiac dysfunction determined later by objective hemodynamic echocardiographic parameters. Furthermore, early LCOS significantly impacts TTE and mortality. Finally, the data support prior clinical trial data, showing that oral T3 supplementation decreases early LCOS in concordance with reducing TTE.

Two Community Clusters of Legionnaires' Disease Directly Linked to a Biologic Wastewater Treatment Plant, the Netherlands.

A biologic wastewater treatment plant was identified as a common source for 2 consecutive Legionnaires' disease clusters in the Netherlands in 2016 and 2017. Sequence typing and transmission modeling indicated direct and long-distance transmission of Legionella, indicating this source type should also be investigated in sporadic Legionnaires' disease cases.

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors.

BACKGROUND/AIMS: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated. METHODS: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression (by Western blot and qPCR), apoptotic cells and cell cycle phase distribution (by flow cytometry) were evaluated. A pilot study was performed using athymic nude mice [treated with vehicle/Cu-TA (25 or 50 mg/kg) 3 times/week for 4 weeks. RESULTS: The IC50 value for Cu-TA was about half than TA.Both agents repressed the protein expression of Sp1/Sp3/survivin, Cu-TA was more effective than TA. Especially effect on survivin inhibition was 5.2 (MIA PaCa-2) or 6.4 (Panc1) fold higher and mRNA expression of only survivin was decreased. Apoptotic cells increased with Cu-TA treatment in both cell lines, while Panc1 showed both effect on apoptosis and cell cycle (G2/M) arrest. Cu-TA decreased the tumor growth in mouse xenografts (25 mg/kg: 48%; 50 mg/kg: 68%). Additionally, there was no change observed in mice body weights, indicating no overt toxicity was occurring. CONCLUSION: These results show that Cu-TA can serve as an effective survivin inhibitor for inhibiting PaCa cell growth.

Polynuclear ruthenium organometallic complexes containing a 1,3,5-triazine ligand: synthesis, DNA interaction, and biological activity.

It is now well established that ruthenium complexes are attractive alternatives to platinum-based anticancer agents. Most of the ruthenium compounds currently under investigation contain a single metal center. The synthesis of multinuclear analogues may provide access to novel complexes with enhanced biological activity. In this work, we have synthesized a set of three trinuclear complexes containing organometallic ruthenium fragments-(arene)RuCl-coordinated to a 2,4,6-tris(di-2-pyridylamino)-1,3,5-triazine core [(Arene = benzene (2), p-cymene (1), or hexamethylbenzene (3)]. The interaction of the complexes with DNA was extensively studied using a variety of biophysical probes as well as by molecular docking. The complexes bind strongly to DNA with apparent binding constants ranging from 2.20 to 4.79 × 104 M-1. The binding constants from electronic absorption titrations were an order of magnitude greater. The mode of binding to the nucleic acid was not definitively determined, but the evidence pointed to some kind of non-specific electrostatic interaction. None of the complexes displayed any significant antimicrobial activity against the organisms that were studied and exhibited anticancer activity only at high (> 100 µM) concentration.

Coordination of different ligands to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes.

Trace elements such as copper and cobalt have been associated with virus-host interactions. However, studies to show the effect of conjugation of copper(II) or cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food additives or mosquito repellent such as 2-acetylethiazole or citral, respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections have not been explored. In this study, we show that four compounds comprising of thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a copper(II) complex with acetylethTSC as a ligand (compound 2), a thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III) complex with a citral-thiosemicarbazone ligand (compound 4) increased DENV2 and ZIKV replication in both mosquito C6/36 cells and human keratinocytes (HaCaT cells). Treatment of both cell lines with compounds 2 or 4 showed increased dengue viral titers at all three tested doses. Enhanced dengue viral plaque formation was also noted at the tested dose of 100µM, suggesting higher production of infectious viral particles. Treatment with the compounds 2 or 4 enhanced ZIKV and DENV2 RNA levels in HeLa cell line and primary cultures of mouse bone marrow derived dendritic cells. Also, pre- or post treatments with conjugated compounds 2 or 4 showed higher loads of ZIKV or DENV2 envelope (E) protein in HaCaT cells. No changes in loads of E-protein were found in ZIKV-infected C6/36 cells, when compounds were treated after infection. In addition, we tested bis(1,10-phenanthroline)copper(II) chloride ([Cu(phen)2]Cl2, (compound 5) and tris(1,10-phenanthroline)cobalt(III) chloride ([Co(phen)3]Cl3, (compound 6) that also showed enhanced DENV2 loads. Also, we found that copper(II) chloride dehydrate (CuCl2·2H2O) or cobalt(II) chloride hexahydrate (CoCl2·6H2O) alone had no effects as "free" cations. Taken together, these findings suggest that use of Cu(II) or Co(III) conjugation to organic compounds, in insect repellents and/or food additives could enhance DENV2/ZIKV loads in human cells and perhaps induce pathogenesis in infected individuals or individuals pre-exposed to such conjugated complexes. IMPORTANCE: Mosquito-borne diseases are of great concern to the mankind. Use of chemicals/repellents against mosquito bites and transmission of microbes has been the topic of interest for many years. Here, we show that thiosemicarbazone ligand(s) derived from 2-acetylethiazole or citral or 1,10-phenanthroline upon conjugation with copper(II) or cobalt(III) metal centers enhances dengue virus (serotype 2; DENV2) and/or Zika virus (ZIKV) infections in mosquito, mouse and human cells. Enhanced ZIKV/DENV2 capsid mRNA or envelope protein loads were evident in mosquito cells and human keratinocytes, when treated with compounds before/after infections. Also, treatment with copper(II) or cobalt(III) conjugated compounds increased viral titers and number of plaque formations. These studies suggest that conjugation of compounds in repellents/essential oils/natural products/food additives with copper(II) or cobalt(III) metal centers may not be safe, especially in tropical and subtropical places, where several dengue infection cases and deaths are reported annually or in places with increased ZIKV caused microcephaly.

Kinetics and mechanism of the oxidation of a cobaloxime by sodium hypochlorite in aqueous solution: Is it an outer-sphere mechanism?

The kinetics and mechanism of the oxidation of [Co(dmgBF2)2(OH2)2] (where dmgBF2 = difluoroboryldimethylglyoximato) by sodium hypochlorite (NaOCl) were investigated by stopped-flow spectrophotometry at 450 nm over the temperature range of 10 °C ≤ θ ≤ 25 °C, pH range of 5.0 ≤ pH ≤ 7.8, and at an ionic strength of 0.60 M (NaCl). The pKa1 value for [Co(dmgBF2)2(H2O)2] was calculated as 5.27 ± 0.14 at I = 0.60 (NaCl). The redox process was dependent on pH and oxidant concentration in a complex manner, that is, kobs = ((k2[H+] + k1Ka)/([H+] + Ka))[OCl-]T, where at 25.3 °C, k1 was calculated as 3.54 × 104 M-1 s-1, and k2 as 2.51 × 104 M-1 cm-1. At a constant pH value, while varying the concentration of sodium hypochlorite two rate constants were calculated, viz., k'1 = 7.56 s-1 (which corresponded to a reaction pathway independent of the NaOCl concentration) and k'2 = 2.26 × 104 M-1 s-1, which was dependent on the concentration of NaOCl. From the variation in pH, [Formula: see text], and [Formula: see text] were calculated as 58 ± 16 kJ mol-1, 46 ± 1 kJ mol-1, 34 ± 55 J mol-1 K-1, and -6 ± 4 Jmol-1 K-1, respectively. The self-exchange rate constant, k11, for sodium hypochlorite (as ClO-) was calculated to be 1.2 × 103 M-1 s-1, where an outer-sphere electron transfer mechanism was assumed. A green product, [Co(dmgBF2)2(OH2)(OH)]·1.75NaOCl, which can react with DMSO, was isolated from the reaction at pH 8.04 with a yield of 13%.

Combined genetic and bioactivity-based prioritization leads to the isolation of an endophyte-derived antimycobacterial compound.

AIM: To initiate a genetic and bioactivity-based screening programme of culturable endophytes to identify micro-organisms capable of producing bioactive polyketides and peptides. METHODS AND RESULTS: Fungal endophytes were isolated from flowers, leaves and roots of Rhoeo spathacea, revealing a community consisting of Colletotrichum sp., Fusarium sp., Guignardia sp., Phomopsis sp., Phoma sp. and Microdochium sp. Genetic screening showed that all isolates had polyketide synthase (PKS) genes and most had nonribosomal peptide synthetase (NRPS) genes. Ethyl acetate extracts of the fungal isolates exhibited antiproliferative activity against at least one of the seven bacterial and mycobacterial test strains. Nuclear Magnetic Resonance -guided fractionation of the crude extract from a Fusarium sp. strain which exhibited strong antiproliferative activity against Mycobacterium tuberculosis resulted in the isolation of the polyketide javanicin. This compound was active against Myco. tuberculosis (MIC = 25 µg ml(-1)) and Mycobacterium phlei (MIC = 50 µg ml(-1)). CONCLUSIONS: The medicinal plant R. spathacea hosts a variety of fungal endophytes capable of producing antibacterial and antimycobacterial compounds. There is a positive correlation between the presence of PKS and/or NRPS encoding genes in endophytes and the bioactivity of their respective organic extracts. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the fungal endophytic diversity of R. spathacea, and the isolation of an antimycobacterial compound from the plant which has been traditionally used for the treatment of tuberculosis symptoms.

A novel copper(II) complex identified as a potent drug against colorectal and breast cancer cells and as a poison inhibitor for human topoisomerase IIα.

A novel complex, [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIα, which may account for the observed anti-cancer effects.

Synthesis of natural phaeosphaeride A derivatives and an in vitro evaluation of their anti-cancer potential.

Derivatives of phaeosphaeride A (PPA) were synthesised and characterised; then anti-cancer studies were carried out on the A549 cancer cell line. It was found that the acetyl derivative (compound 3) displayed comparable in vitro cytotoxicity to that of PPA (EC50=49±7 µM and EC50=46±5 µM, respectively), while chloroacetyl derivative 6 (EC50=33±7 µM) was found to have better efficacy towards the A549 cancer cell line.

Sotorasib Is a Pan-RASG12C Inhibitor Capable of Driving Clinical Response in NRASG12C Cancers.

KRASG12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRASG12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRASG12C tumors. Because amino acid sequences of the three main RAS isoforms-KRAS, NRAS, and HRAS-are highly similar, we hypothesized that some KRASG12C inhibitors might also target NRASG12C and/or HRASG12C, which are less common but critical oncogenic driver mutations in some tumors. Although some inhibitors, like adagrasib, were highly selective for KRASG12C, others also potently inhibited NRASG12C and/or HRASG12C. Notably, sotorasib was five-fold more potent against NRASG12C compared with KRASG12C or HRASG12C. Structural and reciprocal mutagenesis studies suggested that differences in isoform-specific binding are mediated by a single amino acid: Histidine-95 in KRAS (Leucine-95 in NRAS). A patient with NRASG12C colorectal cancer treated with sotorasib and the anti-EGFR antibody panitumumab achieved a marked tumor response, demonstrating that sotorasib can be clinically effective in NRASG12C-mutated tumors. SIGNIFICANCE: These studies demonstrate that certain KRASG12C inhibitors effectively target all RASG12C mutations and that sotorasib specifically is a potent NRASG12C inhibitor capable of driving clinical responses. These findings have important implications for the treatment of patients with NRASG12C or HRASG12C cancers and could guide design of NRAS or HRAS inhibitors. See related commentary by Seale and Misale, p. 698. This article is featured in Selected Articles from This Issue, p. 695.

Cardiac Abnormalities in Hispanic/Latina Women With Prior De Novo Hypertensive Disorders of Pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with long-term maternal risks for cardiovascular disease for reasons that remain incompletely understood. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a multi-center community-based cohort of Hispanic/Latino adults recruited 2008 to 2011, was used to evaluate the associations of history of de novo HDP (gestational hypertension, preeclampsia, eclampsia) with echocardiographic measures of cardiac structure and function in Hispanic/Latina women with ≥1 prior pregnancy and the proportion of association mediated by current hypertension (>140/90 mm Hg or antihypertensive therapy). RESULTS.: The study cohort included 5168 Hispanic/Latina women with an average age (SD) of 58.7 (9.7) years at time of echocardiogram. Prior de novo HDP was reported by 724 (14%) of the women studied and was associated with lower left ventricle (LV) ejection fraction -0.66 (95% confidence interval [CI], -1.21 to -0.11), higher LV relative wall thickness 0.09 (95% CI, 0-0.18), and 1.39 (95% CI, 1.02-1.89) higher risk of abnormal LV geometry after adjusting for blood pressure and other confounders. The proportion of the association mediated by current hypertension between HDP and LV ejection fraction was 0.09 (95% CI, 0.03-0.45), LV relative wall thickness was 0.28 (95% CI, 0.16-0.51), abnormal LV geometry was 0.14 (95% CI, 0.12-0.48), concentric left ventricular hypertrophy was 0.31 (95% CI, 0.19-0.86), and abnormal LV diastolic dysfunction was 0.58 (95% CI, 0.26-0.79). CONCLUSIONS.: In a large cohort of Hispanic/Latina women those with history of de novo HDP had detectable and measurable subclinical alterations in cardiac structure and both systolic and diastolic dysfunction that were only partially mediated by current hypertension.

Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions.

In the present Special Issue on "Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions", an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties [...].

Uncovering an Easily Overlooked Cause of Dyspnea: Partial Anomalous Pulmonary Venous Connection of the Right Pulmonary Vein to the Superior Vena Cava Leading to Right Heart Enlargement.

This case report describes a rare variant of partial anomalous pulmonary venous connections (PAPVCs) in a patient who presented with an insidious progression of dyspnea on exertion as an adult, leading to the diagnosis of PAPVC. The patient had an anomalous right upper pulmonary vein connecting to an anomalous pulmonary-azygos trunk that connected to the cranial superior vena cava (SVC), producing a large left-to-right extracardiac shunt. The diagnosis of PAPVC was made after evaluating for causes of right heart chamber enlargement. This case highlights the importance of considering PAPVC as a potential cause of unclear etiology for exertional dyspnea, right-sided chamber enlargements, and intact atrial septum. The onset and severity of symptoms in patients with PAPVC depend on various factors, including the number of pulmonary veins, site of connection, pulmonary vascular resistance, atrial compliance, and the presence of other congenital heart defects. Therefore, clinicians should maintain a high level of suspicion for PAPVC in patients with these types of symptoms.

Synthesis, characterization, and preliminary in vitro studies of vanadium(IV) complexes with a Schiff base and thiosemicarbazones as mixed-ligands.

[VO(Sal-L-tryp)(H2O)] 1 (where sal-L-tryp = N-salicylidene-L-tryptophanate) was used as a precursor to produce the novel complexes, [VO(Sal-L-tryp)(MeATSC)].1.5C2H5OH 2 (where MeATSC = 9-Anthraldehyde-N(4)-methylthiosemicarbazone), [VO(Sal-L-tryp)(N-Ethhymethohcarbthio)].H2O 3 (where N-Ethhymethohcarbthio = (E)-N-ethyl-2-(4-hydroxy-3-methoxybenzylidene)hydrazinecarbothioamide), and [VO(Sal-L-tryp)(acetylethTSC)].C2H5OH 4 (where acetylethTSC = (E)-N-ethyl-2-(1-(thiazol-2-yl)ethylidene)hydrazinecarbothioamide), by reaction with the respective thiosemicarbazone. The chemical and structural properties of these ligands and complexes were characterised by elemental analysis, ESI MS, FT-IR, UV-visible, ESR, 1H and 13C NMR spectroscopy, and X-ray crystallography. DMSO and DMSO-d6 solutions of compounds 1-4 were oxidised in air to produce vanadium(V) species which were verified by ESI MS and 51V NMR spectroscopy. Anti-cancer properties of compounds 2-4 were examined with three colon cancer cell lines, HTC-116, Caco-2, and HT-29, and also with non-cancerous colonic myofibroblasts, CCD18-Co. Compounds 2-3 exhibited less inhibitory effects in the CCD-18Co cells, indicating a possible cytotoxic selectivity towards colon cancer cells. In general, those compounds which exhibited anti-proliferative activity on cancer cells, but did not affect non-cancerous cells, may have a potential in chemotherapy.