Quality of life in postmenopausal women with osteoporosis and osteopenia: associations with bone microarchitecture and nutritional status.

PURPOSE: Primary aim of the study was to investigate the status of different health-related quality of life (HRQoL) domains in postmenopausal women with osteoporosis and osteopenia, and to explore possible associations with bone microarchitecture and nutritional status. METHODS: This was a single-center cross-sectional study that included 232 postmenopausal women, from which they were divided into three groups-osteoporosis (OP, N = 63), osteopenia (OPIA, N = 123), and control group (N = 46). Detailed medical history data and anthropometric measurements were taken from all women. Bone structure parameters were taken with DXA device, with additional analysis of bone microarchitecture status with Trabecular Bone Score (TBS). Nutritional status was assessed with Mini Nutritional Assessment (MNA) questionnaire, and HRQoL with Medical Outcomes Study Short Form-36 (SF-36) questionnaire. RESULTS: Nutrition evaluation analysis have shown that patients in OP group had significantly lower values of MNA score compared to the OPIA group and control group (P = 0.005). Furthermore, a significant positive correlation was found between all of the SF-36 domains and MNA scores, while significant positive correlation was found between TBS values and Physical functioning (P < 0.001), Bodily pain (P = 0.027), Social functioning (P = 0.029), and Vitality domains (P = 0.041) in total investigated population. Further analyses were performed only in OP and OPIA groups, and TBS score showed significant positive correlation with Physical functioning (r = 0.248, P < 0.001) and Bodily pain domains as well (r = 0.180, P = 0.014), while MNA score positively correlated with each of the SF-36 domains. Multiple regression models have shown that MNA score retained significant association with each SF-36 domains, and TBS value with Physical functioning (P = 0.003), Social functioning (P = 0.012), and Vitality domains (P = 0.014). CONCLUSION: This study highlights the associations that TBS has with some domains of HRQoL in postmenopausal women with osteoporosis and osteopenia. Moreover, nutritional status could play a role in the complex interplay between TBS and HRQoL.

The Role of the Gap Junction Protein Connexin in Adrenal Gland Tumorigenesis.

Gap junctions (GJs) are important in the regulation of cell growth, morphology, differentiation and migration. However, recently, more attention has been paid to their role in the pathogenesis of different diseases as well as tumorigenesis, invasion and metastases. The expression pattern and possible role of connexins (Cxs), as major GJ proteins, under both physiological and pathological conditions in the adrenal gland, were evaluated in this review. The databases Web of Science, PubMed and Scopus were searched. Studies were evaluated if they provided data regarding the connexin expression pattern in the adrenal gland, despite current knowledge of this topic not being widely investigated. Connexin expression in the adrenal gland differs according to different parts of the gland and depends on ACTH release. Cx43 is the most studied connexin expressed in the adrenal gland cortex. In addition, Cx26, Cx32 and Cx50 were also investigated in the human adrenal gland. Cx50 as the most widespread connexin, along with Cx26, Cx29, Cx32, Cx36 and Cx43, has been expressed in the adrenal medulla with distinct cellular distribution. Considerable effort has recently been directed toward connexins as therapeutically targeted molecules. At present, there exist several viable strategies in the development of potential connexin-based therapeutics. The differential and hormone-dependent distribution of gap junctions within adrenal glands, the relatively large gap junction within this gland and the increase in the gap junction size and number following hormonal treatment would indicate that gap junctions play a pivotal role in cell functioning in the adrenal gland.

Metabolic Crossroads: Unveiling the Complex Interactions between Obstructive Sleep Apnoea and Metabolic Syndrome.

Obstructive sleep apnoea (OSA) and components of metabolic syndrome (MetS) are inextricably connected. Considering the increasing burden of MetS and OSA, in the present review, we aimed to collate and summarise the potential pathophysiological mechanisms linking these pathologies. In short, obesity appears to promote OSA development via multiple pathways, some of which are not directly related to mass but rather to metabolic complications of obesity. Simultaneously, OSA promotes weight gain through central mechanisms. On the other hand, diabetes mellitus contributes to OSA pathophysiology mainly through effects on peripheral nerves and carotid body desensitization, while intermittent hypoxia and sleep fragmentation are the principal culprits in OSA-mediated diabetes. Apart from a bidirectional pathophysiological relationship, obesity and diabetes mellitus together additively increase cardiovascular risk in OSA patients. Additionally, the emergence of new drugs targeting obesity and unequivocal results of the available studies underscore the need for further exploration of the mechanisms linking MetS and OSA, all with the aim of improving outcomes in these patients.

Differences in Plasma Cannabidiol Concentrations in Women and Men: A Randomized, Placebo-Controlled, Crossover Study.

The potential therapeutic benefits of cannabidiol (CBD) require further study. Here, we report a triple-blind (participant, investigator, and outcome assessor) placebo-controlled crossover study in which 62 hypertensive volunteers were randomly assigned to receive the recently developed DehydraTECH2.0 CBD formulation or a placebo. This is the first study to have been conducted using the DehydraTECH2.0 CBD formulation over a 12-week study duration. The new formulation's long-term effects on CBD concentrations in plasma and urine, as well as its metabolites 7-hydroxy-CBD and 7-carboxy-CBD, were analyzed. The results of the plasma concentration ratio for CBD/7-OH-CBD in the third timepoint (after 5 weeks of use) were significantly higher than in the second timepoint (after 2.5 weeks of use; p = 0.043). In the same timepoints in the urine, a significantly higher concentration of 7-COOH-CBD was observed p < 0.001. Differences in CBD concentration were found between men and women. Plasma levels of CBD were still detectable 50 days after the last consumption of the CBD preparations. Significantly higher plasma CBD concentrations occurred in females compared to males, which was potentially related to greater adipose tissue. More research is needed to optimize CBD doses to consider the differential therapeutic benefits in men and women.

Emerging Therapies for the Treatment of Atherosclerotic Cardiovascular Disease: From Bench to Bedside.

Primarily a consequence of sedentary lifestyle, atherosclerosis has already reached pandemic proportions, and with every year the burden of it is only increasing. As low-density lipoprotein cholesterol (LDL-C) represents a crucial factor in atherosclerosis formation and progression, stringent lipid-lowering therapy could conceivably be the key to preventing the unfavorable outcomes that arise as a consequence of atherosclerosis. The use of statins in lipid-lowering is often burdened by adverse events or is insufficient to prevent cardiovascular events as a monotherapy. Therefore, in the present review, the authors aimed to discuss the underlying mechanisms of dyslipidemia and associated atherosclerotic cardiovascular disease (ASCVD) and preclinical and clinical trials of novel therapeutic approaches to its treatment, some of which are still in the early stages of development. Apart from novel therapies, a novel change in perspective is needed. Specifically, the critical objective in the future management of ASCVD is to embrace emerging evidence in the field of atherosclerosis, because clinicians are often burden by common practice and personal experience, both of which have so far been shown to be futile in the setting of atherosclerosis.

Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence.

PURPOSE: We aimed to summarize current evidence regarding the impact of a high-dose statin loading before percutaneous coronary intervention (PCI) on short-term outcomes in patients presenting with the acute coronary syndrome (ACS). METHODS: This meta-analysis was based on a search of the MEDLINE, Cochrane Central Register of Controlled Trials, Ovid Journals, and SCOPUS for randomized controlled trials that compared high-dose atorvastatin or rosuvastatin with no or low-dose statin administered before planned PCI in statin-naive patients with ACS. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and all-cause mortality at 30 days. Prespecified subanalyses were performed with respect to statin and ACS type. RESULTS: A total of eleven trials enrolling 6291 patients were included, of which 75.4% received PCI. High-dose statin loading was associated with an overall 43% relative risk (RR) reduction in MACCE at 30 days (RR 0.57, 95% CI 0.41-0.77) in whole ACS population. This effect was primarily driven by the 39% reduction in the occurrence of MI (RR 0.61, 95% CI 0.46-0.80). No significant effect on all-cause mortality reduction was observed (RR 0.92, 95% CI 0.67-1.26). In the setting of ST-elevation myocardial infarction (STEMI), atorvastatin loading was associated with a 33% reduction in MACCE (RR 0.67, 95% CI 0.48-0.94), while in non-ST-elevation myocardial infarction ACS (NSTE-ACS), rosuvastatin loading was associated with 52% reduction in MACCE at 30 days (RR 0.48, 95% CI 0.34-0.66). The level of evidence as qualified with GRADE was low to high, depending on the outcome. CONCLUSION: A high-dose loading of statins before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days. Atorvastatin reduces MACCE in STEMI while rosuvastatin reduces MACCE in NSTE-ACS at 30 days.

Orthorexia nervosa and its association with narcissism in fitness center users.

PURPOSE: Orthorexia nervosa (ON) is an eating behavior where patients obsessively try to reach health through "purity" of food. Narcissism is a personality trait characterized with the self-belief of grandiosity, importance and need of appreciation. Both of these conditions are connected through self-image in way of reaching perfection through health and body image, whereas one of the ways for reaching it is exercising. This cross-sectional study aimed to investigate ON and its possible association with narcissism in fitness center users. METHODS: The study included 1017 fitness center users and three questionnaires were used for the assessment: general information, ORTO-R and Narcissistic personality inventory-13 (NPI-13). RESULTS: There was a significant negative correlation (r = - 0.467, p < 0.001) between the ORTO-R score and the NPI-13 score. Comparison of the ORTO-R score between different durations of using a fitness center showed statistically significant differences (H = 134.72, p < 0.001). The subjects who are using the fitness center for less than 1 year have the highest ORTO-R score, while those who are using it 1-3 years have the lowest ORTO-R score. Moreover, multiple linear regression showed that ORTO-R score retained significant association with NPI-13 (ß ± SE, - 0.416 ± 0.026, p < 0.001) and the duration of using a fitness center (0.576 ± 0.068, p < 0.001) after model adjustment for age and BMI. CONCLUSION: These results are implying that fitness center users could possibly be vulnerable of developing ON and that there is a strong association between ON and narcissism in this population. However, future larger-scale longitudinal studies are needed to address these findings. LEVEL OF EVIDENCE: Level V, cross-sectional survey-based study.

Effects of Wine Components in Inflammatory Bowel Diseases.

With the rising prevalence of Inflammatory bowel disease (IBD) worldwide, and the rising cost of treatment with novel biological drugs, there is an increasing interest in various diets and natural foods as a potential way to control/modulate IBD. As recent data indicates that diet can modify the metabolic responses essential for the resolution of inflammation, and as wine compounds have been shown to provide substantial anti-inflammatory effect, in this review we aimed to discuss the current evidence concerning the impact of biological compounds present in wine on IBD. A number of preclinical studies brought forth strong evidence on the mechanisms by which molecules in wine, such as resveratrol or piceatannol, provide their anti-inflammatory, anti-oxidative, anti-tumor, and microbiota-modulation effects. However, concerning the effects of alcohol, it is still unclear how the amount of ethanol ingested within the framework of moderate wine consumption (1-2 glasses a day) affects patients with IBD, as human studies regarding the effects of wine on patients with IBD are scarce. Nevertheless, available evidence justifies the conductance of large-scale RCT trials on human subjects that will finally elucidate whether wine can offer real benefits to the IBD population.

Circulating Levels of Dephosphorylated-Uncarboxylated Matrix Gla Protein in Patients with Acute Coronary Syndrome.

Vascular calcification contributes to the pathogenesis of coronary artery disease while matrix Gla protein (MGP) was recently identified as a potent inhibitor of vascular calcification. MGP fractions, such as dephosphorylated-uncarboxylated MGP (dp-ucMGP), lack post-translational modifications and are less efficient in vascular calcification inhibition. We sought to compare dp-ucMGP levels between patients with acute coronary syndrome (ACS), stratified by ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) status. Physical examination and clinical data, along with plasma dp-ucMGP levels, were obtained from 90 consecutive ACS patients. We observed that levels of dp-ucMGP were significantly higher in patients with NSTEMI compared to STEMI patients (1063.4 ± 518.6 vs. 742.7 ± 166.6 pmol/L, p < 0.001). NSTEMI status and positive family history of cardiovascular diseases were only independent predictors of the highest tertile of dp-ucMGP levels. Among those with NSTEMI, patients at a high risk of in-hospital mortality (adjudicated by GRACE score) had significantly higher levels of dp-ucMGP compared to non-high-risk patients (1417.8 ± 956.8 vs. 984.6 ± 335.0 pmol/L, p = 0.030). Altogether, our findings suggest that higher dp-ucMGP levels likely reflect higher calcification burden in ACS patients and might aid in the identification of NSTEMI patients at increased risk of in-hospital mortality. Furthermore, observed dp-ucMGP levels might reflect differences in atherosclerotic plaque pathobiology between patients with STEMI and NSTEMI.

Discontinuation of therapy in inflammatory bowel disease: Current views.

The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease (IBD). The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission. In patients with achieved long-term remission, the question of de-escalation or discontinuation of therapy arises, considering the possible side effects and economic burden of long-term therapy. For each of the drugs used in IBD (5-aminosalycaltes, immunomodulators, biological drugs, small molecules) there is a risk of relapse. Furthermore, studies show that more than 50% of patients who discontinue therapy will relapse. Based on the findings of large studies and meta-analysis, relapse of disease can be expected in about half of the patients after therapy withdrawal, in case of monotherapy with aminosalicylates, immunomodulators or biological therapy. However, longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor. It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking. Before making a decision on discontinuation of therapy, it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse. Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse. Several other predictive factors have also been identified, such as: High Crohn's disease activity index or Harvey Bradshaw index, younger age (< 40 years), longer disease duration (> 40 years), smoking, young age of disease onset, steroid use 6-12 months before cessation. An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs. The decision to discontinue therapy must be based on individual approach, taking into account the severity, extension, and duration of the disease, the possibility of side adverse effects, the risk of relapse, and patient's preferences.

Applying an explainable machine learning model might reduce the number of negative appendectomies in pediatric patients with a high probability of acute appendicitis.

The diagnosis of acute appendicitis and concurrent surgery referral is primarily based on clinical presentation, laboratory and radiological imaging. However, utilizing such an approach results in as much as 10-15% of negative appendectomies. Hence, in the present study, we aimed to develop a machine learning (ML) model designed to reduce the number of negative appendectomies in pediatric patients with a high clinical probability of acute appendicitis. The model was developed and validated on a registry of 551 pediatric patients with suspected acute appendicitis that underwent surgical treatment. Clinical, anthropometric, and laboratory features were included for model training and analysis. Three machine learning algorithms were tested (random forest, eXtreme Gradient Boosting, logistic regression) and model explainability was obtained. Random forest model provided the best predictions achieving mean specificity and sensitivity of 0.17 ± 0.01 and 0.997 ± 0.001 for detection of acute appendicitis, respectively. Furthermore, the model outperformed the appendicitis inflammatory response (AIR) score across most sensitivity-specificity combinations. Finally, the random forest model again provided the best predictions for discrimination between complicated appendicitis, and either uncomplicated acute appendicitis or no appendicitis at all, with a joint mean sensitivity of 0.994 ± 0.002 and specificity of 0.129 ± 0.009. In conclusion, the developed ML model might save as much as 17% of patients with a high clinical probability of acute appendicitis from unnecessary surgery, while missing the needed surgery in only 0.3% of cases. Additionally, it showed better diagnostic accuracy than the AIR score, as well as good accuracy in predicting complicated acute appendicitis over uncomplicated and negative cases bundled together. This may be useful in centers that advocate for the conservative treatment of uncomplicated appendicitis. Nevertheless, external validation is needed to support these findings.

The Predictors of Early Treatment Effectiveness of Intravitreal Bevacizumab Application in Patients with Diabetic Macular Edema.

The aim of this study was to establish whether multiple blood parameters might predict an early treatment response to intravitreal bevacizumab injections in patients with diabetic macular edema (DME). Seventy-eight patients with non-proliferative diabetic retinopathy (NPDR) and DME were included. The treatment response was evaluated with central macular thickness decrease and best corrected visual acuity increase one month after the last bevacizumab injection. Parameters of interest were the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), vitamin D, and apolipoprotein B to A-I ratio (ApoB/ApoA-I). The NLR (2.03 ± 0.70 vs. 2.80 ± 1.08; p < 0.001), MLR (0.23 ± 0.06 vs. 0.28 ± 0.10; p = 0.011), PLR (107.4 ± 37.3 vs. 135.8 ± 58.0; p = 0.013), and SII (445.3 ± 166.3 vs. 675.3 ± 334.0; p < 0.001) were significantly different between responder and non-responder groups. Receiver operator characteristics analysis showed the NLR (AUC 0.778; 95% CI 0.669-0.864), PLR (AUC 0.628; 95% CI 0.511-0.735), MLR (AUC 0.653; 95% CI 0.536-0.757), and SII (AUC 0.709; 95% CI 0.595-0.806) could be predictors of response to bevacizumab in patients with DME and NPDR. Patients with severe NPDR had a significantly higher ApoB/ApoA-I ratio (0.70 (0.57-0.87) vs. 0.61 (0.49-0.72), p = 0.049) and lower vitamin D (52.45 (43.10-70.60) ng/mL vs. 40.05 (25.95-55.30) ng/mL, p = 0.025). Alterations in the NLR, PLR, MLR, and SII seem to provide prognostic information regarding the response to bevacizumab in patients with DME, whilst vitamin D deficiency and the ApoB/ApoA-I ratio could contribute to better staging.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease.

BACKGROUND: Population of patients with inflammatory bowel disease (IBD) is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia, and many others. AIM: To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases. An additional aim was to determine possible associations between GDF-15 and multiple clinical, anthropometric and laboratory parameters in patients with IBD. METHODS: This cross-sectional study included 90 adult patients diagnosed with IBD, encompassing both Crohn's disease (CD) and ulcerative colitis (UC), and 67 healthy age- and sex-matched controls. All patients underwent an extensive workup, including colonoscopy with subsequent histopathological analysis. Disease activity was assessed by two independent gastroenterology consultants specialized in IBD, employing well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined following an overnight fasting, using electrochemiluminescence immunoassay. RESULTS: In patients with IBD, serum GDF-15 concentrations were significantly higher in comparison to the healthy controls [800 (512-1154) pg/mL vs 412 (407-424) pg/mL, P < 0.001], whereas no difference in GDF-15 was found between patients with CD and UC [807 (554-1451) pg/mL vs 790 (509-956) pg/mL, P = 0.324]. Moreover, multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age, sex, and C-reactive protein levels (P = 0.016 and P = 0.049, respectively). Finally, an association between GDF-15 and indices of anemia was established. Specifically, negative correlations were found between GDF-15 and serum iron levels (r = -0.248, P = 0.021), as well as GDF-15 and hemoglobin (r = -0.351, P = 0.021). Accordingly, in comparison to IBD patients with normal hemoglobin levels, GDF-15 serum levels were higher in patients with anemia (1256 (502-2100) pg/mL vs 444 (412-795) pg/mL, P < 0.001). CONCLUSION: For the first time, we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls, and the results imply that GDF-15 might be involved in IBD pathophysiology. Yet, it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Tackling the Antimicrobial Resistance "Pandemic" with Machine Learning Tools: A Summary of Available Evidence.

Antimicrobial resistance is recognised as one of the top threats healthcare is bound to face in the future. There have been various attempts to preserve the efficacy of existing antimicrobials, develop new and efficient antimicrobials, manage infections with multi-drug resistant strains, and improve patient outcomes, resulting in a growing mass of routinely available data, including electronic health records and microbiological information that can be employed to develop individualised antimicrobial stewardship. Machine learning methods have been developed to predict antimicrobial resistance from whole-genome sequencing data, forecast medication susceptibility, recognise epidemic patterns for surveillance purposes, or propose new antibacterial treatments and accelerate scientific discovery. Unfortunately, there is an evident gap between the number of machine learning applications in science and the effective implementation of these systems. This narrative review highlights some of the outstanding opportunities that machine learning offers when applied in research related to antimicrobial resistance. In the future, machine learning tools may prove to be superbugs' kryptonite. This review aims to provide an overview of available publications to aid researchers that are looking to expand their work with new approaches and to acquaint them with the current application of machine learning techniques in this field.

Mediterranean Diet Adherence, Physical Activity, and Advanced Glycation End Products in Complex PTSD: A Comprehensive Examination of Lifestyle and Cardiovascular Risk in War Veterans.

As accumulated evidence suggests that individuals with post-traumatic stress disorder (PTSD) encounter earlier and more frequent occurrences of cardiovascular diseases, the aim of this study was to ascertain the differences in lifestyle and cardiovascular risk between PTSD and complex PTSD patients. We enrolled 137 male war veterans with PTSD (89 had complex PTSD). The diagnosis was established based on 11th revision of International Classification of Diseases (ICD-11), and cardiovascular risk was estimated by the measurement of advanced glycation end products. Adherence to Mediterranean diet (MD) was lower in the complex PTSD group (2.2% vs. 12.5%, p = 0.015). Accordingly, patients with complex PTSD had lower healthy lifestyle scores in comparison to PTSD counterparts (50.6 ± 9.7 vs. 59.6 ± 10.1, p < 0.001), and a positive association was noted between MD adherence and a healthy lifestyle (r = 0.183, p = 0.022). On the other hand, differences were not noted in terms of physical activity (p = 0.424), fat % (p = 0.571) or cardiovascular risk (p = 0.573). Although complex PTSD patients exhibit worse adherence to MD and lower healthy lifestyle scores, these differences do not seem to impact physical activity, body composition, or estimated cardiovascular risk. More research is needed to clarify if this lack of association accurately reflects the state of the PTSD population or results from insufficient statistical power.

Chronic Effects of Oral Cannabidiol Delivery on 24-h Ambulatory Blood Pressure in Patients with Hypertension (HYPER-H21-4): A Randomized, Placebo-Controlled, and Crossover Study.

Background: Recent data indicate that cannabidiol (CBD), a nonintoxicating constituent of cannabis, is involved in several aspects of cardiovascular regulation, including blood pressure (BP). However, the impact of chronic CBD administration on 24-h BP and vascular health has not been previously examined in patients with hypertension. The primary aim of this randomized, triple-blind, placebo-controlled, and crossover study was to examine the influence of chronic CBD on 24-h ambulatory BP and arterial stiffness in hypertensive patients. Methods: Seventy patients with mild or moderate primary hypertension, who were untreated or receiving standard of care therapy, were randomly assigned to receive either 5 weeks of oral CBD or placebo-matched controls. Following a >2-week washout period, patients were crossed over to alternate therapy. The primary outcome of the study was dynamic in 24-h ambulatory BP and was assessed using two-way repeated measure analysis of variance. Results: Administration of CBD reduced average 24 h mean, systolic, and diastolic BP after 2.5 weeks (-3.22±0.90 mmHg [95% confidence interval -1.01 to -5.44 mmHg], -4.76±1.24 mmHg [-1.72 to -7.80 mmHg], and -2.25±0.80 mmHg [-0.30 to -6.01 mmHg], respectively (all p<0.05); however, these values largely remained stable following the uptitration of CBD dosing. There were no changes in liver enzymes or serious adverse events (AEs). There was no significant difference in pulse wave velocity (group×factor interaction: F=1.50, p=0.226) at different time points, regardless of the intervention arm. Conclusions: In conclusion, chronic administration of CBD reduces ambulatory BP in those with untreated and treated hypertension. In addition, lack of serious AEs implies safety and tolerability of the above-noted CBD formulation. ClinicalTrials.gov ID: NCT05346562, Registered April 6th 2022.

Trial of a Novel Oral Cannabinoid Formulation in Patients with Hypertension: A Double-Blind, Placebo-Controlled Pharmacogenetic Study.

Cannabidiol (CBD) is a non-psychoactive cannabinoid, and available evidence suggests potential efficacy in the treatment of many disorders. DehydraTECH™2.0 CBD is a patented capsule formulation that improves the bioabsorption of CBD. We sought to compare the effects of CBD and DehydraTECH™2.0 CBD based on polymorphisms in CYP P450 genes and investigate the effects of a single CBD dose on blood pressure. In a randomized and double-blinded order, 12 females and 12 males with reported hypertension were given either placebo capsules or DehydraTECH™2.0 CBD (300 mg of CBD, each). Blood pressure and heart rate were measured during 3 h, and blood and urine samples were collected. In the first 20 min following the dose, there was a greater reduction in diastolic blood pressure (p = 0.025) and mean arterial pressure MAP (p = 0.056) with DehydraTECH™2.0 CBD, which was probably due to its greater CBD bioavailability. In the CYP2C9*2*3 enzyme, subjects with the poor metabolizer (PM) phenotype had higher plasma CBD concentrations. Both CYP2C19*2 (p = 0.037) and CYP2C19*17 (p = 0.022) were negatively associated with urinary CBD levels (beta = -0.489 for CYP2C19*2 and beta = -0.494 for CYP2C19*17). Further research is required to establish the impact of CYP P450 enzymes and the identification of metabolizer phenotype for the optimization of CBD formulations.

Oromaxillofacial Surgery: Both a Treatment and a Possible Cause of Obstructive Sleep Apnea-A Narrative Review.

Obstructive sleep apnea (OSA) is a chronic, sleep-related breathing disorder. It is characterized by a nocturnal periodic decrease or complete stop in airflow due to partial or total collapse of the oropharyngeal tract. Surgical treatment of OSA is constantly evolving and improving, especially with the implementation of new technologies, and this is needed because of the very heterogeneous reasons for OSA due to the multiple sites of potential airway obstruction. Moreover, all of these surgical methods have advantages and disadvantages; hence, patients should be approached individually, and surgical therapies should be chosen carefully. Furthermore, while it is well-established that oromaxillofacial surgery (OMFS) provides various surgical modalities for treating OSA both in adults and children, a new aspect is emerging regarding the possibility that some of the surgeries from the OMFS domain are also causing OSA. The latest studies are suggesting that surgical treatment in the head and neck region for causes other than OSA could possibly have a major impact on the emergence of newly developed OSA, and this issue is still very scarcely mentioned in the literature. Both oncology, traumatology, and orthognathic surgeries could be potential risk factors for developing OSA. This is an important subject, and this review will focus on both the possibilities of OMFS treatments for OSA and on the OMFS treatments for other causes that could possibly be triggering OSA.

Role of Echocardiography in Diabetic Cardiomyopathy: From Mechanisms to Clinical Practice.

It has been well established that diabetes mellitus (DM) is considered as a core risk factor for the development of cardiovascular diseases. However, what is less appreciated is the fact that DM may affect cardiac function irrespective of cardiac pathologies to which it contributes, such as coronary artery disease and hypertension. Although echocardiography provides accurate and reproducible diagnostic and prognostic data in patients with DM, its use in these patients is still underappreciated, resulting in progression of DM-related heart failure in many patients. Hence, in the present review, we aimed to discuss the role of echocardiography in the contemporary management of diabetic cardiomyopathy (DCM), as well as the role of emerging echocardiographic techniques, which may contribute to earlier diagnosis and more appropriate management of this complication of DM. In order to improve outcomes, focus must be placed on early diagnosis of this condition using a combination of echocardiography and emerging biomarkers, but perhaps the more important thing is to change perspective when it comes to the clinical importance of DCM.

Serum Catestatin Concentrations Are Increased in Patients with Atrial Fibrillation.

The autonomic nervous system is crucial in initiating and maintaining atrial fibrillation (AF). Catestatin is a multipurpose peptide that regulates cardiovascular systems and reduces harmful, excessive activity of the sympathetic nervous system by blocking the release of catecholamines. We aimed to determine whether serum catestatin concentrations are associated with AF severity, duration indices, and various clinical and laboratory indicators in these individuals to better define the clinical value of catestatin in patients with AF. The present single center study enrolled 73 participants with AF and 72 healthy age-matched controls. Serum catestatin concentrations were markedly higher in AF patients than controls (14.11 (10.21-26.02) ng/mL vs. 10.93 (5.70-20.01) ng/mL, p = 0.013). Furthermore, patients with a more severe form of AF had significantly higher serum catestatin (17.56 (12.80-40.35) vs. 10.98 (8.38-20.91) ng/mL, p = 0.001). Patients with higher CHA2DS2-VASc scores (17.58 (11.89-37.87) vs. 13.02 (8.47-22.75) ng/mL, p = 0.034) and higher NT-proBNP levels (17.58 (IQR 13.91-34.62) vs. 13.23 (IQR 9.04-22.61), p = 0.036) had significantly higher serum catestatin concentrations. Finally, AF duration correlated negatively with serum catestatin levels (r = -0.348, p = 0.003). The results of the present study implicate the promising role of catestatin in the intricate pathophysiology of AF, which should be explored in future research.