The oxygen initial dip in the brain of anesthetized and awake mice.

An ongoing controversy in brain metabolism is whether increases in neural activity cause a local and rapid decrease in oxygen concentration (i.e., the "initial dip") preceding functional hyperemia. This initial dip has been suggested to cause a transient increase in vascular deoxyhemoglobin with several imaging techniques and stimulation paradigms, but not consistently. Here, we investigate contributors to this initial dip in a distinct neuronal network, an olfactory bulb (OB) glomerulus most sensitive to a specific odorant (ethyl tiglate [ET]) and a site of strong activation and energy consumption upon ET stimulation. Combining two-photon fluorescence and phosphorescence lifetime microscopy, and calcium, blood flow, and pO2 measurements, we characterized this initial dip in pO2 in mice chronically implanted with a glass cranial window, during both awake and anesthetized conditions. In anesthetized mice, a transient dip in vascular pO2 was detected in this glomerulus when functional hyperemia was slightly delayed, but its amplitude was minute (0.3 SD of resting baseline). This vascular pO2 dip was not observed in other glomeruli responding nonspecifically to ET, and it was poorly influenced by resting pO2. In awake mice, the dip in pO2 was absent in capillaries as well as, surprisingly, in the neuropil. These high-resolution pO2 measurements demonstrate that in awake mice recovered from brain surgery, neurovascular coupling was too fast and efficient to reveal an initial dip in pO2.

Novel diarylated tacrine derivatives: Synthesis, characterization, anticancer, antiepileptic, antibacterial, and antifungal activities.

In this study, our goal was to synthesize novel aryl tacrine derivatives and assess their potential as anticancer, antibacterial agents, and enzyme inhibitors. We adopted a two-step approach, initiating with the synthesis of dibromotacrine derivatives 3 and 4 through the Friedlander reaction. These intermediates underwent further transformation into diarylated tacrine derivatives 3a-e and 4a-e using a Suzuki-Miyaura cross-coupling reaction. Thorough characterization of these novel diarylated tacrines was achieved using various spectroscopic techniques. Our findings highlighted the potent anticancer effects of these innovative compounds across a range of cancer cell lines, including lung, gynecologic, bone, colon, and breast cancers, while demonstrating low cytotoxicity against normal cells. Notably, these compounds surpassed the control drug, 5-Fluorouracil, in terms of antiproliferative activity in numerous cancer cell lines. Moreover, our investigation included an analysis of the inhibitory properties of these novel compounds against various microorganisms and cytosolic carbonic anhydrase enzymes. The results suggest their potential for further exploration as cancer-specific, enzyme inhibitory, and antibacterial therapeutic agents. Notably, four compounds, namely, 5,7-bis(4-(methylthio)phenyl)tacrine (3d), 5,7-bis(4-(trifluoromethoxy)phenyl)tacrine (3e), 2,4-bis(4-(trifluoromethoxy)phenyl)-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-amine (4e), and 6,8-dibromotacrine (3), emerged as the most promising candidates for preclinical studies.

A metagenomic survey of bacterial communities from kurut: The fermented cow milk in Kyrgyzstan.

Kurut is a traditional dry dairy product mostly consumed in Central Asia. In this study, the distribution of the dominant bacteria present in kurut samples (n=84) originated from seven (Chuy, Issyk-Kul, Talas, Naryn, Jalal-Abad, Osh, and Batken) regions in Kyrgyzstan were analyzed with Illumina iSeq100 platform. The dominant phylum detected was Firmicutes followed by Proteobacteria, Actinobacteria, Cyanobacteria/Chloroplast, and Tenericutes. The most abundant family detected was Lactobacillaceae followed by Streptococcaceae, Enterococcaceae, Chloroplast, and Leuconostocaceae. At the genus level, Lactobacillus was the predominant one in samples and Streptococcus, Enterococcus, Lactococcus, and Streptophyta followed this. Further comprehensive characterization analyses in kurut samples may have potential applications both in industrial starter culture developments and also future therapeutic approaches based on potential strains with probiotic properties.

Comparison of Anthropometric and Cephalometric Measurements Obtained by Stereophotogrammetry and 3D Computed Tomography of the Nose Before Septorhinoplasty.

INTRODUCTION: Computed tomography (CT) is normally used in evaluation of patients with esthetic and functional nasal deformities. Stereophotogrammetry (SPG) is a measurement device that is an alternative to CT and does not harm human health. In this single-center retrospective study, we aimed to evaluate measurements obtained with CT and SPG. METHODS: The measurements of 18 patients who applied to our clinic between January 2022 and August 2022 and planned for septorhinoplasty were performed on both 3D images obtained with paranasal sinus CT and SPG device (SLR type Vectra H1 system). Measurements included that dorsocolumellar length, columella-filtral length, nasal tip projection ratio (dorsocolumellar length/columella-filtral length), columella-labial angle, nasofrontal angle, tip deviation direction, tip deviation angle, tip deviation distance and dorsal nasal hump. RESULTS: Most of patients were male (61.1%). Mean age was 24.5 years. Only columella-labial angle measurements showed a low level of significant difference (p < 0.05). However, there was no significance difference in other measurements (p > 0.05). A significant strong correlation was observed between all Vectra and CT measurements (p = 0.000). CONCLUSION: SPG device can be applied quickly in polyclinic without giving radiation to patient. Measurements can be taken automatically using a software. Its use in postoperative period does not carry any risk. Disadvantage of SPG is lack of information about internal nasal passage. However, there is a strong correlation between measurements obtained from both measurement devices. Therefore, SPG can be considered as an alternative to CT imaging in operation planning. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Phytochemical analysis and biological evaluation of Ferulago setifolia K. Koch.

BACKGROUND: Ferulago setifolia K. Koch (Apiaceae) has been the subject of this study, aiming to comprehensively determine its phenolic fingerprint and evaluate its various biological activities. The liquid chromatography-tandem mass spectrometry analysis of the 70% methanol extract of F. setifolia (FS) revealed the presence of 23 phytochemicals, among which chlorogenic acid, quinic acid, kaempferol-3-O-glucoside, and quercetin-3-O-glucoside were identified as the major phenolics in the extract. RESULTS: The biological screening included examinations of antioxidant, antibacterial, antiproliferative, and cytotoxic activities. The FS extract displayed moderate 2,2-diphenyl-1-picrylhydrazyl radical scavenging and ferric-reducing capacity, indicating moderate antioxidant activity. Furthermore, FS exhibited significant antiproliferative effects on cancer cells while showing low cytotoxicity on normal cells. The antibacterial activity findings revealed that FS demonstrated potent activity against Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus, and Escherichia coli. CONCLUSION: The findings of this study suggest that the methanolic extract of FS holds promise as a potential source of biologically active compounds. It can be utilized for the development of pharmaceutical formulations, thanks to its significant antiproliferative and antibacterial activities. Additionally, FS can serve as a valuable source of chlorogenic acid for industrial applications. © 2023 Society of Chemical Industry.

Liquid chromatography-tandem mass spectrometry profile and antioxidant, antimicrobial, antiproliferative, and enzyme activities of Thymus pectinatus and Thymus convolutus: in vitro and in silico approach.

BACKGROUND: The objective of this study is to investigate the antiproliferative, antioxidant, antimicrobial, and enzyme activity capacities and phytochemical compositions of Thymus pectinatus (TP), Thymus convolutus (TC), which are endemic to Türkiye. Quantitative analysis of phenolic compounds in the extracts was conducted using liquid chromatography-tandem mass spectrometry, targeting 53 phenolic compounds. RESULTS: Rosmarinic acid, quinic acid, and cynaroside were identified as the major compounds, exhibiting quantitative variation in both extracts. The extracts had a high total phenolic content, with 113.57 ± 0.58 mg gallic acid equivalents (GAE)/g extract for TP and 130.52 ± 1.05 mg GAE/g extract for TC. Furthermore, although both extracts exhibited high total flavonoid content; the TP extract (75.12 ± 1.65 mg quercitin equivalents (QE)/g extract) displayed a higher flavonoid content than the TC extract (30.24 ± 0.74 mg QE/g extract) did. The extracts had a promising antiproliferative effect on C6, HeLa, and HT29 cancer cell lines with a less cytotoxic effect (10.5-14.2%) against normal cells. Both extracts exhibited very potent inhibitory activity against the xanthine oxidase enzyme, with half-maximal inhibitory concentration values of respectively 2.07 ± 0.03 µg mL-1 and 2.76 ± 0.06 µg mL-1 and moderate activity against tyrosinase and α-glucosidase. Docking simulations proved that rosmarinic acid and cynaroside, the major components of the extracts, were the most potent inhibitors of xanthine oxidase. According to antimicrobial activity results, the TC extract exhibited moderate activity against Staphylococcus aureus, and the TP extract had strong activity against both Enterococcus faecium and S. aureus. CONCLUSION: These findings emphasize the beneficial effects of the two endemic Thymus species on human health and suggest their potential use as plant-derived bioactive agents. © 2024 Society of Chemical Industry.

Ferruginoside†D: A Novel Phenylethanoid from Verbascum leiocarpum.

A novel phenylethanoid, ferruginoside D, together with fourteen known compounds were isolated from the Verbascum leiocarpum for the first time. Chemical structures of isolated compounds were determined by spectroscopic analysis including HR-ESI-MS and NMR spectra. The antioxidant, α-glucosidase inhibitory properties, and antiproliferative activities against multiple cell lines (A172, C6, HeLa, A2780, SW620, HT29, Beas2B, RPE, and HSF) of the isolated compounds were evaluated in vitro. According to the results, iridoids, flavonoids (luteolin and apigenin), and phenylethanoids (poliumoside and isoverbascoside) with strong antiproliferative potential were also found to have cytostatic effects. Furthermore, the investigation revealed that compounds luteolin, poliumoside, verbascoside, isoverbascoside, ferruginoside C, ferruginoside D, and ursolic acid show potent alpha-glucosidase inhibitory activity, while compounds luteolin, verbascoside, and isoverbascoside exhibit substantial antioxidant activity. The new compound (ferruginoside D) was found moderately active against cancer cell lines, with strong alpha-glucosidase inhibitory activity, and moderate antioxidant properties.

Iliski, a software for robust calculation of transfer functions.

Understanding the relationships between biological processes is paramount to unravel pathophysiological mechanisms. These relationships can be modeled with Transfer Functions (TFs), with no need of a priori hypotheses as to the shape of the transfer function. Here we present Iliski, a software dedicated to TFs computation between two signals. It includes different pre-treatment routines and TF computation processes: deconvolution, deterministic and non-deterministic optimization algorithms that are adapted to disparate datasets. We apply Iliski to data on neurovascular coupling, an ensemble of cellular mechanisms that link neuronal activity to local changes of blood flow, highlighting the software benefits and caveats in the computation and evaluation of TFs. We also propose a workflow that will help users to choose the best computation according to the dataset. Iliski is available under the open-source license CC BY 4.0 on GitHub (https://github.com/alike-aydin/Iliski) and can be used on the most common operating systems, either within the MATLAB environment, or as a standalone application.

Novel amino acid Schiff base Zn(II) complexes as new therapeutic approaches in diabetes and Alzheimer's disease: Synthesis, characterization, biological evaluation, and molecular docking studies.

Schiff bases are compounds that have gained importance in the paint industry due to their colorful nature and in the field of chemistry and biochemistry due to their biological activities. Various biological applications of Schiff bases, such as antitumor, antifungal, antibacterial, antioxidant, antituberculosis, and anthelmintic, have been widely studied. Within the scope of the study, 5-bromo-2-hydroxybenzaldehyde and amino acid methyl esters (isoleucine, phenylalanine, and methionine) and amino acid Schiff bases were synthesized first. The synthesis of the new Zn(II) complexes of these Schiff bases was carried out by the reaction of synthesized Schiff bases and Zn(OAc)2 ·2H2 O. The structures of the synthesized complexes were elucidated using elemental analysis, Fourier transform infrared, nuclear magnetic resonance, UV-visible, and thermal analysis spectroscopy techniques. These synthesized salts were found to be effective inhibitor compounds for the α-glycosidase, and acetylcholinesterase enzyme with Ki values in the range of 30.50 ± 3.82-38.17 ± 6.26 µM for α-glycosidase, 3.68 ± 0.54-10.27 ± 1.68 µM for butyrylcholinesterase, and 6.26 ± 0.83-15.73 ± 4.73 µM for acetylcholinesterase, respectively.

Predictivity of the comorbidity indices for geriatric syndromes.

BACKGROUND: The aging population and increasing chronic diseases make a tremendous burden on the health care system. The study evaluated the relationship between comorbidity indices and common geriatric syndromes. METHODS: A total of 366 patients who were hospitalized in a university geriatric inpatient service were included in the study. Sociodemographic characteristics, laboratory findings, and comprehensive geriatric assessment(CGA) parameters were recorded. Malnutrition, urinary incontinence, frailty, polypharmacy, falls, orthostatic hypotension, depression, and cognitive performance were evaluated. Comorbidities were ranked using the Charlson Comorbidity Index(CCI), Elixhauser Comorbidity Index(ECM), Geriatric Index of Comorbidity(GIC), and Medicine Comorbidity Index(MCI). Because, the CCI is a valid and reliable tool used in different clinical settings and diseases, patients with CCI score higher than four was accepted as multimorbid. Additionally, the relationship between geriatric syndromes and comorbidity indices was assessed with regression analysis. RESULTS: Patients' mean age was 76.2 ± 7.25 years(67.8% female). The age and sex of multimorbid patients according to the CCI were not different compared to others. The multimorbid group had a higher rate of dementia and polypharmacy among geriatric syndromes. All four indices were associated with frailty and polypharmacy(p < 0.05). CCI and ECM scores were related to dementia, polypharmacy, and frailty. Moreover, CCI was also associated with separately slow walking speed and low muscle strength. On the other hand, unlike CCI, ECM was associated with malnutrition. CONCLUSIONS: In the study comparing the four comorbidity indices, it is revealed that none of the indices is sufficient to use alone in geriatric practice. New indices should be developed considering the complexity of the geriatric cases and the limitations of the existing indices.

Successful treatment with therapeutic plasmapheresis of a pediatric patient with Guillain-Barré syndrome associated with neurobrucellosis.

Brucellosis is a multisystemic disease that can present with multiple signs and symptoms. Rarely, brucellosis can manifest as neurobrucellosis, with central or peripheral nervous system involvement. Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease that progresses rapidly, causing ascending muscle weakness, and is accompanied by areflexia/hyporeflexia. Regarding GBS etiology, it is thought to be an autoimmune disease, triggered by a previous bacterial or viral infection. There are a few Brucella-associated GBS case reports in the literature and in our opinion, only one of them is a pediatric patient. Herein we reported a case of GBS associated with neurobrucellosis, who was successfully treated with therapeutic plasmapheresis (TP) due to poor response to IVIG treatment.

Complete Left-Atrial Lesion Set versus Pulmonary Vein Isolation Only in Patients with Paroxysmal AF Undergoing CABG or AVR.

Background and Objectives: In patients with paroxysmal atrial fibrillation (AF) undergoing CABG or aortic valve surgery, many surgeons are not willing to open the left atrium to perform a complete left-sided Cox-Maze lesion set. Pulmonary vein isolation (PVI) is often favored in those patients. We investigated the outcome of patients with isolated pulmonary vein isolation compared to those receiving an extended left atrial (LA) lesion set. Materials and Methods: Between 2003 and 2016, 817 patients received concomitant surgical AF ablation in our institution. A total of 268 patients with paroxysmal AF were treated by surgical ablation concomitant to AVR or CABG. Of those, 86 patients underwent a complete left-sided lesion set, while 182 patients were treated with an isolated pulmonary vein isolation. The primary endpoint was freedom from atrial fibrillation at 12 months' follow-up. Results: There were no statistically significant differences regarding baseline characteristics. No major ablation-related complications were observed in any of the groups. In the PVI group, three patients (1.6%) had an intraoperative stroke, while two (2.3%) patients experienced a stroke in the LA ablation group (p = 0.98). In-hospital mortality was 3.4% in the PVI group, and 2.8% in the extended LA group (p = 0.33). Freedom from AF at 12 months' follow-up was 76% in the extended LA ablation group and 70% in the PVI group, showing no statistically significant difference (p = 0.32). Conclusion: Surgical AF ablation concomitant to CABG or AVR in patients with paroxysmal AF is safe and effective. There was no statistically significant difference between the compared lesion sets in terms of freedom from AF, survival or stroke rate after 12 months.

Synthesis, biological evaluation (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic) and molecular docking study of hydroxy methoxy benzoin/benzil analogous.

In this work, due to the biological activity evaluation, a series of hydroxy methoxy benzoins (1-8), benzils (10-16) and methoxy benzoin/benzil-O-ß-d-glucosides (17-28) were synthesized. Antioxidant (FRAP, CUPRAC, DPPH), antimicrobial (16 microorganisms, and two yeast), enzyme inhibition (α-amylase, α-glucosidase, AChE, BChE, and tyrosinase) of all synthesized benzoin/benzil analogs were investigated. Benzoins (1-8) showed the most effective antioxidant properties compared to all three methods. Compound 28 against α-amylase, compound 9 against α-glucosidase, compound 11 against AChE, compound 2 against BChE, and compound 13 against tyrosinase showed the best activities with the better or similar IC50 values as used standards. Hydroxy methoxy benzoin compounds (1-8) among all four groups were seen as the most effective against the tested microorganism. Molecular docking analysis showed that all tested compounds 1-28 (0.01-2.22 µM) had the best binding affinity against AChE enzyme. Cytotoxic effects of the many of compounds (1-16, 21, and 24) also investigated and it was found that they caused different effects in different cells. The LDH tests of compounds 1a + b, 4, 7, 8, 9, 11, 12, 21, and 24, seemed to be effective compared to the positive control cisplatin. The cytotoxicity of compounds 6 (9.24%) for MCF7 cancer cells, 8 (5.16%) and 4 (8.26%) for HT29 cancer cells, 24 (9.84%) for Hep3B cells and 8 (8.52%), 7 (5.70%), 4 (6.94) and 9 (7.22%) for C6 cells were at normal values. And also cytotoxic activity of four compounds (5, 9, 21, and 24) among the all synthetic groups, were evaluated to the HeLa and RPE. Compound 5 showed anticancer activity on HeLa and RPE cancer cells as much as or better than cisplatin which was used as standard.

The Relationship between the Most Common Subtypes of Dementia and Orthostatic Hypotension in Older Adults.

BACKGROUND: It is crucial to evaluate the causes of morbidity and mortality in elderly patients with dementia, such as orthostatic hypotension (OH), which may affect their daily life activities, reduce the quality of life, and increase the caregiver burden. OBJECTIVE: We aimed to investigate the relationship between OH and the most common subtypes of dementia in detail. METHODS: A total of 268 older adults with dementia diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and behavioral variant frontotemporal dementia (bvFTD), and 539 older adults without dementia were included in this prospective study. Comprehensive geriatric assessment including comorbidity, medication evaluation, and the head-up tilt test was also performed. RESULTS: Of the participants, 13.8, 8.3, 6.4, and 4.8% had AD, DLB, bvFTD, and VaD, respectively. After adjusting for age, gender, the presence of comorbidities, and usage of OH-induced drugs; AD, DLB, and VaD were associated with OH (odds ratio [OR]: 2.23 confidence interval [CI] 95% 1.31-3.80; p = 0.003; OR: 3.68 CI 95% 1.98-6.83; p < 0.001, and OR: 3.56 CI 95% 1.46-8.69; p = 0.005, respectively). Furthermore, VaD was independently related to diastolic OH (OR: 4.19 CI 95% 1.66-10.57; p = 0.002), whereas AD and DLB were not. CONCLUSIONS: This study shows that elderly patients with DLB, AD, and VaD often have OH, a disabling autonomic dysfunction feature. Moreover, diastolic OH may play a role in the development of VaD. Therefore, considering potential complications of OH, it is essential to evaluate OH in the follow-up and management of those patients.

Novel 2-amino-4-aryl-6-pyridopyrimidines and N-alkyl derivatives: Synthesis, characterization and investigation of anticancer, antibacterial activities and DNA/BSA binding affinities.

A series of new 2-amino-4-aryl-6-pyridopyrimidines, and their N-alkyl bromide derivatives were designed and synthesized by employing methyl substituted azachalcones. These novel compounds were evaluated and compared to the well-known chemotherapeutics in terms of their anti-cancer and anti-microbial functions, and their DNA/protein binding affinities. In order for the cell proliferation, cytotoxicity and microdilution features to be observed, various cancer cell lines (Hep3B, A549, HeLa, C6, HT29, MCF7) were treated with 2-amino-4-aryl-6-pyridopyrimidines (1-9) and their N-alkyl bromide derivatives (2a-c, 3a-c,5a-c,6a-c, 8a-c, 9a-c). Studies on the cells revealed that both pyrimidines and their alkyl derivatives (i) have a high anti-proliferative and anti-microbial activities, (ii) cause cell rounding, cytoplasmic blebs, and anomalous globular structure, and (iii) strongly bound to DNA/BSA macromolecules. Especially the length of the alkyl chain of the N-alkyl bromides has an increasing effect on the antiproliferative, antibacterial and cytotoxic functions, also DNA/protein binding affinity. Those results indicate the novel compounds to be promising antiproliferative agents, and their anti-cancer potential makes them candidates to be used for cancer therapy.

Validation of population-based cutoffs for low muscle mass and strength in a population of Turkish elderly adults.

BACKGROUND: Despite differences between the studies regarding methods for estimating low muscle mass, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends use of two standard deviations (SDs) below the reference sex-specific means of healthy young adults. AIMS: The aim of this study was to determine the cutoff points of skeletal muscle mass index (SMI) and handgrip strength (HS) in Turkish population and to compare the power of different cutoff points to predict comprehensive geriatric assessment (CGA) parameters. METHODS: Two hundred and eight young healthy volunteers (104 women, 104 men) were included in the study to define SMI, HS cutoff values. 1150 older adults (784 women, 366 men) underwent CGA, including physical performance, activities of daily living (ADL), HS and frailty. Body composition was obtained from every participant by bioimpedance analysis (BIA). CGA parameters of sarcopenic patients according to EWGSOP and new Turkish cutoff points were compared. RESULTS: SMI cutoff points were defined 5.70 kg/m2 for women, 8.33 kg/m2 for men. HS thresholds were calculated as 14 kg for women, 28 kg for men using measurements of healthy young adult reference. Considering the new threshold values, the prevalence of sarcopenia was 10% (7% women, 17% men). When new sarcopenia criteria were applied and covariates were adjusted, sarcopenia was found to be more closely related to ADL impairment, balance, frailty in men, and balance, slow walking speed, ADL impairment, frailty in women (p < 0.05). DISCUSSION: Muscle mass and strength may vary between populations because of ethnicity and other related discrepancies. The evaluation of sarcopenia according to the present guidelines may cause overdiagnosis in some populations. CONCLUSION: Cutoff points specific to populations should be determined.

Assessment of factors that increase risk of falling in older women by four different clinical methods.

BACKGROUND: Women aged 65 years and over are at increased risk of falling. Falls in this age group increase the risk of morbidity and mortality. AIMS: The aim of the present study was to find the most common factors that increase the risk of falling in older women, by using four different assessment methods. METHODS: 682 women, who attended a geriatric outpatient clinic and underwent comprehensive geriatric assessment, were included in the study. History of falling last year, the Timed Up and Go (TUG) test, Performance-Oriented Mobility Assessment (POMA), and 4-m walking speed test were carried out on all patients. RESULTS: The mean age (SD) of patients were 74.4 (8.5) years. 31.5% of women had a history of falling in the last year. 11%, 36.5%, and 33.3% of patients had a falling risk according to POMA, TUG and 4-m walking speed test, respectively. We identified the following risk factors that increase the risk of falling, according to these four methods: urinary incontinence, dizziness and imbalance, using a walking stick, frailty, dynapenia, higher Charlson Comorbidity Index and Geriatric Depression Scale score, and lower basic and instrumental activities of daily living scores (p < 0.05). We found a significant correlation between all the assessment methods (p < 0.001). CONCLUSION: There is a strong relationship between fall risk and dizziness, using a walking stick, dynapenia, high number of comorbidities, low functionality, and some geriatric syndromes such as depression, frailty, and urinary incontinence in older women. Therefore, older women should routinely be screened for these risk factors.

Surgical revision after percutaneous mitral valve repair by edge-to-edge device in high-risk patients.

BACKGROUND: Patients scheduled for surgery after unsuccessful MitraClip® intervention present increasingly with multiple comorbidities, and they are often referred to the heart team to suggest the most appropriate intervention. The publication of successful results of initial patient cohorts treated with the MitraClip device has resulted in recruitment of more seriously ill patients, who otherwise would have been denied catheter-based/surgical treatment. There has been increasingly reports on conventional surgery after failed mitral valve repair with the MitraClip device. However, data on such procedures remain scarce and mostly focused on individual case studies. The inevitable increase in use of MitraClip, however, will raise the number of patients in need of surgery post MitraClip, making it imperative for surgeons to understand challenges and outcome data related with surgery in this patient cohort. We present our long-term institutional experience with surgery after MitraClip intervention in highest risk patients. METHODS: Eighteen patients underwent surgery of the mitral valve at our Institution between January 2015 and June 2020. These patients developed recurrent mitral regurgitation grade more than 2° at various intervals after MitraClip. Mitral valve repair was performed where possible and gross examination Valve/MitraClip were intra-operatively documented. Implanted MitraClip devices were analyzed histopathologically to evaluate the healing process and rule out inflammation. Regular patient follow-up was performed. RESULTS: Mean patient age was 74 (±9 years) and MitraClip implantation was performed at various tertiary institutions. Sixteen out of eighteen (16/18) patients received mitral valve replacement, whereas the remaining two patients received mitral valve repair and extracorporal membrane oxygenation, respectively. Four patients died of sepsis and intractable multi organ failure in-hospital. The remaining patients were discharged alive out of hospital to different rehabilitation centers. Follow-up was complete in all patients. CONCLUSIONS: Surgery is demanding when patients require surgery for persistent or recurrent mitral regurgitation after MitraClip therapy and can be successfully implemented as a possible therapy option for selective cases as an interdisciplinary approach despite calculated high perioperative mortality risk. These patients should not be denied surgery outright.

Synthesis, Antiproliferative and Cytotoxic Activities, DNA Binding Features and Molecular Docking Study of Novel Enamine Derivatives.

Novel enamine derivatives were synthesized from the reaction of lactone and chalcones and their antiproliferative and cytotoxic activities against six cancer cell lines (e. g., HeLa, HT29, A549, MCF7, PC3 and Hep3B) and one normal cell lines (e. g., FL) were investigated along with their mode of interactions with CT-DNA. Most of the enamine derivatives with IC50 values of 86-168 µM demonstrated much stronger antiproliferative activity than the starting molecules against the cancer cells. While, among the enamine derivatives, four compounds displayed higher cytotoxic potency than the control drugs (5-fluorouracil and cisplatin) against the Hep3B cell lines, these compounds did not exhibit any significant toxicity against normal cells, FL. The UV/VIS spectral data suggest that eight compounds cause hypochromism with a slight bathochromic shift (∼6 nm), indicating that they bind to the DNA by way of an intercalative or minor groove binding mode. The binding constants of the compounds are in the range of 0.1×103 M-1 -2.3×104 M-1 . The antiproliferative activity of studied enamine derivatives could possibly be due to their DNA binding as well as their cytotoxic properties. In addition to these assays, the chalcones and enamine derivatives were investigated by molecular docking to calculate the synergistic effect of antiproliferative activities against six human cancer cell lines.

Quinoline-based promising anticancer and antibacterial agents, and some metabolic enzyme inhibitors.

A series of substituted quinolines was screened for their antiproliferative, cytotoxic, antibacterial activities, DNA/protein binding affinity, and anticholinergic properties by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation, lactate dehydrogenase cytotoxicity, and microdilution assays, the Wolfe-Shimmer equality method, the Ellman method, and the esterase assay, respectively. The results of the cytotoxic and anticancer activities of the compounds displayed that 6-bromotetrahydroquinoline (2), 6,8-dibromotetrahydroquinoline (3), 8-bromo-6-cyanoquinoline (10), 5-bromo-6,8-dimethoxyquinoline (12), the novel N-nitrated 6,8-dimethoxyquinoline (13), and 5,7-dibromo-8-hydroxyquinoline (17) showed a significant antiproliferative potency against the A549, HeLa, HT29, Hep3B, and MCF7 cancer cell lines (IC50 = 2-50 µg/ml) and low cytotoxicity (∼7-35%) as the controls, 5-fluorouracil and cisplatin. The compound-DNA linkages are hyperchromic or hypochromic, causing variations in their spectra. This situation shows that they can be bound to DNA with the groove-binding mode, with Kb value in the range of 2.0 × 103 -2.2 × 105 M-1 . Studies on human Gram(+) and Gram(-) pathogenic bacteria showed that the substituted quinolines exhibited selective antimicrobial activities with MIC values of 62.50-250 µg/ml. All tested quinoline derivatives were found to be effective inhibitors of acetylcholinesterase (AChE) and the human carbonic anhydrase I and II isoforms (hCA I and II), with Ki values of 46.04-956.82 nM for hCA I, 54.95-976.93 nM for hCA II, and 5.51-155.22 nM for AChE. As a result, the preliminary data showed that substituted quinolines displayed effective pharmacological features. Molecular docking studies were performed to investigate the binding modes and interaction energies for compounds 2-17 with AChE (PDB ID: 4EY6), hCA I (PDB ID: 1BMZ), and hCA II (PDB ID: 2ABE).