The Influence of Non-Dipping Pattern of Blood Pressure in Gestational Hypertension on Early Onset of Hypertension Later in Life-Single Center Experience in Very-High-Risk Southeast and Central European Country.

Gestational hypertension (GH) and preeclampsia (PE) are associated with the onset of hypertension. This study aimed to investigate whether the blood pressure (BP) pattern in GH is associated with the prevalence of hypertension later in life. In this prospective cohort study pregnant women screened for GH underwent medical history, laboratory analysis, ambulatory blood pressure monitoring (AMBP), and transthoracic echocardiography (with left ventricular global longitudinal strain (LVGLS)) assessment. Overall, 138 GH (67 non-dippers and 71 dippers), 55 preeclamptic, and 72 normotensive pregnant controls were included. Women were followed in the postpartum period, first after 6 weeks and later on, for the occurrence of hypertension. The median follow-up was 8.97 years (8.23; 9.03). Non-dippers and PE compared with normotensives and dippers had a higher prevalence of hypertension onset (p < 0.01), as well as significantly reduced absolute values of LVGLS during pregnancy, after delivery, and at the time of onset of hypertension during follow-up (p < 0.01). Night-time diastolic BP, LVGLS, age, and left ventricular ejection fraction were the strongest predictors of postpartum onset of hypertension. The non-dipping BP pattern in GH was significantly associated with the onset of hypertension later in life, as well as with decreased systolic function.

Iron Photoredox Catalysis-Past, Present, and Future.

Photoredox catalysis of organic reactions driven by iron has attracted substantial attention throughout recent years, due to potential environmental and economic benefits. In this Perspective, three major strategies were identified that have been employed to date to achieve reactivities comparable to the successful noble metal photoredox catalysis: (1) Direct replacement of a noble metal center by iron in archetypal polypyridyl complexes, resulting in a metal-centered photofunctional state. (2) In situ generation of photoactive complexes by substrate coordination where the reactions are driven via intramolecular electron transfer involving charge-transfer states, for example, through visible-light-induced homolysis. (3) Improving the excited-state lifetimes and redox potentials of the charge-transfer states of iron complexes through new ligand design. We seek to give an overview and evaluation of recent developments in this rapidly growing field and, at the same time, provide an outlook on the future of iron-based photoredox catalysis.

High-Efficiency Photoinduced Charge Separation in Fe(III)carbene Thin Films.

Symmetry-breaking charge separation in molecular materials has attracted increasing attention for optoelectronics based on single-material active layers. To this end, Fe(III) complexes with particularly electron-donating N-heterocyclic carbene ligands offer interesting properties with a 2LMCT excited state capable of oxidizing or reducing the complex in its ground state. In this Communication, we show that the corresponding symmetry-breaking charge separation occurs in amorphous films of pristine [Fe(III)L2]PF6 (L = [phenyl(tris(3-methylimidazol-2-ylidene))borate]-). Excitation of the solid material with visible light leads to ultrafast electron transfer quenching of the 2LMCT excited state, generating Fe(II) and Fe(IV) products with high efficiency. Sub-picosecond charge separation followed by recombination in about 1 ns could be monitored by transient absorption spectroscopy. Photoconductivity measurements of films deposited on microelectrode arrays demonstrated that photogenerated charge carriers can be collected at external contacts.

Photophysical Integrity of the Iron(III) Scorpionate Framework in Iron(III)-NHC Complexes with Long-Lived 2LMCT Excited States.

Fe(III) complexes with N-heterocyclic carbene (NHC) ligands belong to the rare examples of Earth-abundant transition metal complexes with long-lived luminescent charge-transfer excited states that enable applications as photosensitizers for charge separation reactions. We report three new hexa-NHC complexes of this class: [Fe(brphtmeimb)2]PF6 (brphtmeimb = [(4-bromophenyl)tris(3-methylimidazol-2-ylidene)borate]-, [Fe(meophtmeimb)2]PF6 (meophtmeimb = [(4-methoxyphenyl)tris(3-methylimidazol-2-ylidene)borate]-, and [Fe(coohphtmeimb)2]PF6 (coohphtmeimb = [(4-carboxyphenyl)tris(3-methylimidazol-2-ylidene)borate]-. These were derived from the parent complex [Fe(phtmeimb)2]PF6 (phtmeimb = [phenyltris(3-methylimidazol-2-ylidene)borate]- by modification with electron-withdrawing and electron-donating substituents, respectively, at the 4-phenyl position of the ligand framework. All three Fe(III) hexa-NHC complexes were characterized by NMR spectroscopy, high-resolution mass spectroscopy, elemental analysis, single crystal X-ray diffraction analysis, electrochemistry, Mößbauer spectroscopy, electronic spectroscopy, magnetic susceptibility measurements, and quantum chemical calculations. Their ligand-to-metal charge-transfer (2LMCT) excited states feature nanosecond lifetimes (1.6-1.7 ns) and sizable emission quantum yields (1.7-1.9%) through spin-allowed transition to the doublet ground state (2GS), completely in line with the parent complex [Fe(phtmeimb)2]PF6 (2.0 ns and 2.1%). The integrity of the favorable excited state characteristics upon substitution of the ligand framework demonstrates the robustness of the scorpionate motif that tolerates modifications in the 4-phenyl position for applications such as the attachment in molecular or hybrid assemblies.

The effect of continuous positive airway pressure treatment on hypertensive disorder in pregnant women with obstructive sleep apnea.

PURPOSE: Our study aimed to determine the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on the incidence and severity of hypertensive syndrome in pregnancy. METHODS: The study included women with high-risk pregnancies and the Epworth Sleepiness Scale score ≥ of 10. Polygraphic testing was done between 18 and 20 weeks. Participants were divided into three groups: pregnant women with OSA starting treatment with CPAP for 4 weeks between 24 and 28 gestational weeks, women with OSA treated conservatively, and women without OSA as the control group. Participants were followed up regularly for 4 weeks until the delivery and 1 week after for the occurrence of hypertensive syndrome and other maternal complications. RESULTS: Among the 110 women enrolled in the study, the prevalence of hypertensive syndrome in 41 pregnant women with OSA treated conservatively was 39%, 50 women with OSA treated with CPAP 26%, and 19 women in the control group 21%, p = 0.1. The group treated with CPAP when compared with the conservatively treated group had a significantly lower incidence of severe forms of hypertensive syndrome (8% vs. 24%, p = 0.02.), and after 1 month of treatment had higher night oxygen saturation (92%, vs. 87%, p = 0.003) and lower Epworth Sleepiness Scale score (respectively, 4.2 ± 2.3 vs. 9.4 ± 4.1, p < 0001). The respiratory event index was significantly associated with hypertension severity (patients with preeclampsia 9.5 ± 4.9 vs. without hypertension 6.9 ± 4.5, p = 0.04). CONCLUSION: CPAP therapy significantly reduced the incidence of severe forms of hypertensive syndrome in pregnant women with OSA.

Impact of the COVID-19 Pandemic on Cardiology Emergency Department Visits.

In 2020, decreased emergency department (ED) visits and hospitalization rates during the COVID-19 outbreak were reported. There is no data about cardiovascular emergencies and mortality for the whole COVID-19 year.This study aimed to compare the rates of cardiology ED visits, hospital admissions, and intrahospital mortality between the pre-COVID-19 and COVID-19 years in a single high-volume center.The retrospective observational cross-sectional study analyzed data on the number of ED visits, hospital admissions by different cardiovascular diagnoses, and outcomes.A total of 11744 patients visited the cardiology ED in the pre-COVID-19 year compared with 9145 in the COVID-19 year, indicating an overall decrease of 22.1% (P = 0.02) (IR 78.76 versus 61.33; incidence rate ratios (IRR) 1.28, P = 0.00), with an observed decrease of 25.5% in the number of hospitalizations (33.1% versus 31.6%, P = 0.02). A marked decrease in hospitalizations for cardiovascular emergencies was observed for hypertensive heart disease (-72.8%, P < 0.0001), acute coronary syndrome (-17.8%, P < 0.0001), myocardial and pericardial diseases and endocarditis (-61.2%, P = 0.00), and valvular heart disease (-70.8%, P < 0.0001). In the COVID-19 year, patients had increased need for mechanical ventilatory support (7% versus 6.3%, P = 0.03) with no overall difference in intrahospital mortality (IR 2.71 versus 2.78, IRR 0.98, 95% CI 0.82-1.16, P = 0.39).Decreased ED visits and hospitalizations not just in outbreaks but through the whole COVID-19 year highlight the risk of continuous delay of needed care for emergency life-threatening cardiovascular diseases. Urgent comprehensive strategies that will address patient- and system-related factors to decrease morbidity and mortality and prevent collateral damage of the pandemic are needed.

Left Atrial Strain as a Predictor of Left Ventricular Diastolic Dysfunction in Patients with Arterial Hypertension.

Background and Objectives: There is emerging evidence of the usefulness of left atrial strain (LAS) in the assessment of diastolic dysfunction (DD). In this study we assess the sensitivity and specificity of LAS, to determine cut-off values and their association to DD with increased left atrial pressure (LAP) in patients with well-treated arterial hypertension. Materials and Methods: We performed a cross-sectional study on 180 subjects with well-treated arterial hypertension. All patients underwent transthoracic echocardiography. Patients were divided into two groups: a group without increased LAP and/or DD and a group with increased LAP DD. Results: In multivariate logistic regression, LAS proved to be the strongest statistically significant predictor of DD with increased LAP (OR 0.834, p < 0.0005), with AUC 0.885 and a set cut-off value of 24.27% with high sensitivity of 78.9% and specificity of 84.6%. The set cut-off for LAS > 24.27% was significantly highly prevalent in the group of DD with increased LAP 78.9% when compared to the group without increased LAP 15.4%, p < 0.0001. Conclusion: The findings of this study suggest that LAS could be a useful and highly sensitive and specific marker in the evaluation of DD. There is the potential for using LAS in everyday practice as a standard parameter in diastolic function assessment.

Gender Related Differences in the Clinical Presentation of Hypertrophic Cardiomyopathy-An Analysis from the SILICOFCM Database.

Background and Objectives: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease that affects approximately 1 in 500 people. Due to an incomplete disease penetrance associated with numerous factors, HCM is not manifested in all carriers of genetic mutation. Although about two-thirds of patients are male, it seems that female gender is associated with more severe disease phenotype and worse prognosis. The objective of this study was to evaluate the gender related differences in HCM presentation. Materials and Methods: This study was conducted as a part of the international multidisciplinary SILICOFCM project. Clinical information, laboratory analyses, electrocardiography, echocardiography, and genetic testing data were collected for 362 HCM patients from four clinical centers (Florence, Newcastle, Novi Sad, and Regensburg). There were 33% female patients, and 67% male patients. Results: Female patients were older than males (64.5 vs. 53.5 years, p < 0.0005). The male predominance was present across all age groups until the age of 70, when gender distribution became comparable. Females had higher number of symptomatic individuals then males (69% vs. 52%, p = 0.003), most frequently complaining of dyspnea (50% vs. 30%), followed by chest pain (30% vs. 17%), fatigue (26% vs. 13%), palpitations (22% vs. 13%), and syncope (13% vs. 8%). The most common rhythm disorder was atrial fibrillation which was present in a similar number of females and males (19% vs. 13%, p = 0.218). Levels of N-terminal pro-brain natriuretic peptide were comparable between the genders (571 vs. 794 ng/L, p = 0.244). Echocardiography showed similar thickness of interventricular septum (18 vs. 16 mm, p = 0.121) and posterolateral wall (13 vs. 12 mm, p = 0.656), however, females had a lower number of systolic anterior motion (8% vs. 16%, p = 0.020) and other mitral valve abnormalities. Conclusions: Female patients are underrepresented but seem to have a more pronounced clinical presentation of HCM. Therefore, establishing gender specific diagnostic criteria for HCM should be considered.

Optimal outcome factors in maternity and newborn care for inpatient (hospital maternity ward-HMW) and outpatient deliveries (outhospital maternity clinics -OMC).

BACKGROUND AND OBJECTIVES: The aim of the study was to use the United States Optimality Index (OI-US) to assess the feasibility of its application in making decisions for more optimal methods of delivery and for more optimal postpartum and neonatal outcomes. Numerous worldwide associations support the option of women giving birth at maternity outpatient clinics and also at home. What ought to be met is the assessments of requirements and what could be characterized as the birth potential constitute the basis for making the right decision regarding childbirth. MATERIALS AND METHODS: The study is based on a prospective follow-up of pregnant women and new mothers (100 participants) who were monitored and gave birth at the hospital maternity ward (HMW) and pregnant women and new mothers (100 participants) who were monitored and gave birth at the outhospital maternity clinics (OMC). Selected patients were classified according to the criteria of low and medium-risk and each of the parameters of the OI and the total OI were compared. RESULTS: The results of this study confirm the benefits of intrapartum and neonatal outcome, when delivery was carried out in an outpatient setting. The median OI of intrapartum components was significantly higher in the outpatient setting compared to the hospital maternity ward (97 range from 24 to 100 vs 91 range from 3 to 100). The median OI of neonatal components was significantly higher in the outpatient compared to the inpatient delivery. (99 range from 97 to 100 vs 96 range from 74 to 100). Certain components from the intrapartum and neonatal period highly contribute to the significantly better total OI in the outpatient conditions in relation to hospital conditions. CONCLUSION: Outpatient care and delivery provide multiple benefits for both the mother and the newborn.

EFFECT OF DIPPING PATTERN OF GESTATIONAL HYPERTENSION ON MATERNAL SYMPTOMS AND PHYSICAL FINDINGS, BIRTH WEIGHT AND PRETERM DELIVERY.

The study aimed to determine if the non-dipping pattern of blood pressure (BP) influences preterm delivery in gestational hypertension (GH), but also maternal clinical findings and birth weight. Sixty women with GH, i.e. 30 women with a dipping BP profile (control group) and 30 non-dippers (study group), were included in the study. Echocardiography was performed in all subjects, as well as ambulatory blood pressure monitoring (ABPM) during third trimester. ABPM was repeated 6-8 weeks after delivery. Thirteen women with preterm delivery were classified as non-dippers and only four as dippers (p=0.01). The average and peak systolic and diastolic night-time BP had negative linear correlation with birth weight (p<0.0005). Total vascular resistance (p<0.0005) and mass index (p=0.014) were significantly higher as compared with women with term delivery, while ejection fraction (EF) (p=0.007) and circumferential systolic velocity (p=0.042) were significantly reduced in the preterm delivery group. Multivariate binary logistic regression identified the average night-time systolic BP, left ventricular mass index and EF as independent predictors of preterm delivery. Study results suggested a relationship of the non-dipping BP pattern in GH with preterm delivery, birth weight, and maternal clinical findings.

Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and ß-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations. METHODS: As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography. RESULTS: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079). CONCLUSIONS: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

HPV TYPING AS A SCREENING PROGRAM FOR PREVENTION AND EARLY DETECTION OF CERVICAL CANCER IN DIFFERENT MONTENEGRO REGIONS.

The objective of our research was to compare the results of human papillomavirus (HPV) typing and occurrence of the most important risk factors for cervical cancer obtained in the towns of northern, central and southern regions of Montenegro, in subjects between 30 and 35 years of age, in accordance with the new screening program introduced by the Ministry of Health of Montenegro in 2018. The study included 400 patients aged 30-35 years from Rozaje, Berane, Budva and Podgorica, 100 from each town, who underwent HPV typing in accordance with the latest screening program for early detection and prevention of cervical cancer, approved by the Ministry of Health of Montenegro in 2018. The material was obtained and sampled at the Health Clinics in Rozaje, Berane, Podgorica and Budva. Specially designed brushes were used to take swabs from the cervices, which were then sampled in separate collection tubes that contained a liquid transport medium. The samples were then sent for further analysis to the Institute of Public Health of Montenegro where HPV typing was performed using the real-time polymerase chain reaction method. The results were encrypted and obtained electronically. The data obtained from the questionnaires each subject filled out in accordance with this program were analyzed and the subjects willingly agreed to partake in the screening program. Nearly one-quarter of subjects had a positive HPV finding. The group of HPV positive women included significantly more women from Podgorica (χ2-test=26.455, p<0.001), women with very good living conditions (χ2-test=12.264, p<0.001), women who smoked cigarettes (χ2-test=5.074, p=0.024), women who had the first sexual intercourse between the ages of 17 and 20 (χ2-test=5.874, p=0.015), and women who did not have permanent partners (χ2-test=6.061, p=0.014). Among the observed socio-demographic characteristics and sexual behaviors of our subjects that proved to be non-significant variables in their HPV statuses we excluded the length of smoking habit (χ2-test=0.638, p=0.424) and protected sexual intercourse (χ2-test=2.628, p=0.105). By implementing the screening program and HPV typing, we came to a conclusion that the problem of cervical cancer could be solved or at least mitigated by raising awareness of the causes and incidence of cervical cancer, as well as by being well informed on its curability, predictability and protection during intercourse, which would contribute to positive changes.

Endotracheal stent increased survival length in patients with invasive thymic adenocarcinoma.

We reported the first case of inoperative thymic adenocarcinoma successfully palliative treated by the double-stent procedure. In a patient who expressed stridor, computed tomography was done and necrotic mediastinal mass, which protrudes into a trachea, was demonstrated. Fiberoptic bronchoscopy showed tracheal infiltration and 70% stenosis; therefore, surgical resection was inapplicable. Recanalization with repeated argon plasma coagulation and debridement of necrotic mass was performed, followed by placement of the endotracheal stent, radiotherapy, and chemotherapy. After 1 year, the patient developed gastric aspiration and tracheoesophageal fistula; therefore, the esophageal stent was placed. The outcome was lethal, but the placement of endotracheal stent significantly increased a length of survival for the patient with invasive thymic adenocarcinoma.

Subacute invasive pulmonary aspergillosis as a rare cause of pneumothorax in immunocompetent patient: brief report.

Subacute invasive pulmonary aspergillosis (IPA) represents a form of chronic pulmonary aspergillosis which affects immunocompetent individuals or mildly immunocompromised persons with underlying pulmonary disease. Pneumothorax can be a rare complication of subacute IPA due to a leakage of air from an air-filled lung cavitation into the pleural space. Herein, we report rare and unusual case of pneumothorax in a patient with pulmonary cavity infection. A 40-year-old woman was admitted to thoracic surgery due to complete pneumothorax of the left lung. She was active smoker with untreated chronic obstructive pulmonary disease (COPD). After thoracic drainage multiple cavity forms in the both lungs were noticed. Galactomannan antigen was positive in bronchoalveolar lavage as well as culture of Aspergillus fumigatus. Antifungal treatment by voriconazole was started and continued during 6 months with a favorable outcome. This case highlights that subacute IPA is a diagnose that should be considered in patients with end-stage COPD, low body mass index, or patient who developed pneumothorax. The results of our case show that voriconazole is a safe and effective treatment as primary or salvage therapy in subacute forms of IPA, irrespective of the immunological status of the patients.

Scoring Systems in Assessing Survival of Critically Ill ICU Patients.

BACKGROUND: The aim of this study was to determine which of the most commonly used scoring systems for evaluation of critically ill patients in the ICU is the best and simplest to use in our hospital. MATERIAL AND METHODS: This prospective study included 60 critically ill patients. After admittance to the ICU, APACHE II, SAPS II, and MPM II0 were calculated. During further treatment in the ICU, SOFA and MPM II were calculated at 24 h, 48 h, and 72 h and 7 days after admittance using laboratory and radiological measures. RESULTS: In comparison with survivors, non-survivors were older (p<0.01) and spent significantly more days on mechanical ventilation (p<0.01). ARDS was significantly more common in patients who survived compared to those who did not (chi-square=7.02, p<0.01), which is not the case with sepsis (chi-square=0.388, p=0.53). AUROC SAPS II was 0.690, and is only slightly higher than the other 2 AUROC incipient scoring systems, MPM II and APACHE II (0.654 and 0.623). The APACHE II has the highest specificity (81.8%) and MPM II the highest sensitivity (85.2%). MPM II(7day) AUROC (1.0) shows the best discrimination between patients who survived and those who did not. MPM II(48) (0.836), SOFA(72) (0.821) and MPM II(72) (0.817) also had good discrimination scores. CONCLUSIONS: APACHE II and SAPS II measured on admission to the ICU were significant predictors of complications. MPM II(7day) has the best discriminatory power, followed by SOFA(7day) and MPM II(48). MPM II(7day) has the best calibration followed by SOFA(7day) and APACHE II.

Predictors for hospital readmission after cardiac surgery.

BACKGROUND AND AIM OF THE STUDY: Unplanned hospital readmissions are responsible for increased health care costs and have direct influence on patient quality of life. The aim of the study was to determine the predictors for hospital readmission after open-heart surgery. METHODS: Prospective study analyzed all patients who underwent cardiac surgery in the year 2012. Follow-up period was one year from the date of operation. Patients were divided in two groups based on their readmission status. RESULTS: In the study period of one year, 1268 patients who underwent cardiac surgery were included. A total of 121 patients (9.54%) were readmitted within one year after the operation. The main reasons for readmission were congestive heart failure (17.3%), sternal dehiscence (14.9%), rhythm and conduction disturbances (14.9%), wound infection (11.6%), recurrent angina pectoris (11.6%), and pericardial effusion (10.7%). Independent predictors for hospital readmission were previous stroke (p = 0.002), chronic heart failure (p < 0.0005), and postoperative pericardial effusion (p = 0.006). CONCLUSIONS: Our study determined risk factors and predictors for hospital readmission after cardiac surgery. This may help to reduce readmission rates.

Influence of spinal and general anesthesia on the metabolic, hormonal, and hemodynamic response in elective surgical patients.

BACKGROUND: The aim of the study was to determine the significance of spinal anesthesia in the suppression of the metabolic, hormonal, and hemodynamic response to surgical stress in elective surgical patients compared to general anesthesia. MATERIAL AND METHODS: The study was clinical, prospective, and controlled and it involved 2 groups of patients (the spinal and the general anesthesia group) who underwent the same surgery. We monitored the metabolic and hormonal response to perioperative stress based on serum cortisol level and glycemia. We also examined how the different techniques of anesthesia affect these hemodynamic parameters: systolic arterial pressure (AP), diastolic AP, heart rate (HR), and arterial oxygen saturation (SpO2). These parameters were measured before induction on anesthesia (T1), 30 min after the surgical incisions (T2), 1 h postoperatively (T3) and 24 h after surgery (T4). RESULTS: Serum cortisol levels were significantly higher in the general anesthesia group compared to the spinal anesthesia group (p<0.01). Glycemia was significantly higher in the general anesthesia group (p<0.05). There was a statistically significant, positive correlation between serum cortisol levels and glycemia at all times observed (p<0.01). Systolic and diastolic AP did not differ significantly between the groups (p=0.191, p=0.101). The HR was significantly higher in the general anesthesia group (p<0.01). SpO2 values did not differ significantly between the groups (p=0.081). CONCLUSIONS: Based on metabolic, hormonal, and hemodynamic responses, spinal anesthesia proved more effective than general anesthesia in suppressing stress response in elective surgical patients.

Integration of 3D-QSAR, molecular docking, and machine learning techniques for rational design of nicotinamide-based SIRT2 inhibitors.

Selective inhibitors of sirtuin-2 (SIRT2) are increasingly recognized as potential therapeutics for cancer and neurodegenerative diseases. Derivatives of 5-((3-amidobenzyl)oxy)nicotinamides have been identified as some of the most potent and selective SIRT2 inhibitors reported to date (​Ai et al., 2016​; ​Ai et al., 2023​, ​Baroni et al., 2007​). In this study, a 3D-QSAR (3D-Quantitative Structure-Activity Relationship) model was developed using a dataset of 86 nicotinamide-based SIRT2 inhibitors from the literature, along with GRIND-derived pharmacophore models for selected inhibitors. External validation parameters emphasized the reliability of the 3D-QSAR model in predicting SIRT2 inhibition within the defined applicability domain. The interpretation of the 3D-QSAR model facilitated the generation of GRIND-derived pharmacophore models, which in turn enabled the design of novel SIRT2 inhibitors. Furthermore, based on molecular docking results for the SIRT1-3 isoforms, two classification models were developed: a SIRT1/2 model using the Naive Bayes algorithm and a SIRT2/3 model using the k-nearest neighbors algorithm, to predict the selectivity of inhibitors for SIRT1/2 and SIRT2/3. External validation parameters of the selectivity models confirmed their predictive power. Ultimately, the integration of 3D-QSAR, selectivity models and prediction of ADMET properties facilitated the identification of the most promising selective SIRT2 inhibitors for further development.

Aminomethylations of electron-deficient compounds-bringing iron photoredox catalysis into play.

The α-functionalisation of N-containing compounds is an area of broad interest in synthetic chemistry due to their presence in biologically active substances among others. Visible light-induced generation of nucleophilic α-aminoalkyl radicals as reactive intermediates that can be trapped by electron-deficient alkenes presents an attractive and mild approach to achieve said functionalisation. In this work, [Fe(iii)(phtmeimb)2]PF6 (phtmeimb = phenyl(tris(3-methylimidazol-2-ylidene))borate), an N-heterocyclic carbene (NHC) complex based on Earth-abundant iron, was used as photoredox catalyst to efficiently drive the formation of α-aminoalkyl radicals from a range of different α-trimethylsilylamines and their subsequent addition to a number of electron-deficient alkenes under green light irradiation. Mechanistic investigations elucidated the different reaction steps of the complete photocatalytic cycle. In terms of yields and substrate scope, we show that [Fe(iii)(phtmeimb)2]PF6 can compete with noble metal photoredox catalysts, for instance outcompeting archetypal [Ru(bpy)3]Cl2 under comparable reaction conditions, illustrating that iron photocatalysts can efficiently facilitate photoredox reactions of synthetic value.

Cardiac biomarkers alterations in rapid weight loss and high-intensity training in judo athletes: a crossover pilot study.

BACKGROUND: Studies evaluating alterations in cardiac biomarkers in rapid sport-associated weight loss (RWL) and high-intensity sport-specific training (HISST) are lacking. This pilot study aimed to examine the effects of RWL and HISST on heart rate, blood pressure, cardiac biomarkers, and left ventricular systolic function. Nine elite male judokas participated in the presented survey. METHODS: The athletes underwent a baseline assessment and two testing protocols, the first phase with RWL where they had to lose 5% of their body weight simultaneously with HISST, and the second phase after 7 days, in which only HISST was performed. Participants underwent electrocardiogram, biomarker, and transthoracic echocardiogram evaluation after each phase. RESULTS: In the first phase (RWL and HISST) athletes, heart rate increased significantly, 58.11 (7.78) versus 79 (9.25), P=0.001; as well as cardiac biomarkers: lactate dehydrogenase isoenzyme 175.33 (31.22) vs. 238.56 (56), P=0.003; aspartate aminotransferase 16.56 (4.61) vs. 29 (9.96), P=0.027; creatine kinase isoenzyme-MB 13 (11.5;24) vs. 29.11 (10.05), P=0.004; and high sensitivity cardiac troponin 10 (0) vs. 14.49 (6.4), P=0.045. In the second phase, only HISST was associated with a significant increase in the alanine aminotransferase isoenzyme, 37.78 (11.22) vs. 26 (8.03), P=0.024, together with creatine kinase 472 (185;654) vs. 166.88 (56.57), P=0.01, compared to the initial measurement. CONCLUSIONS: RWL combined with HISST produced significant alterations in cardiac biomarkers without impairment of left ventricular systolic function.