The significance of PCSK-9's level and polymorphism in premature coronary artery disease: Relation to risk and severity.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a circulating protein that plays an important role in lipid metabolism and is linked to inflammation, which has implications for atherosclerosis and its severe cardiac effects. We studied the potential association of the PCSK-9 gene single nucleotide polymorphism (SNP), Oxidized low-density lipoprotein receptor 1- (OLR-1), and caspase-3 serum levels with the risk and severity of premature coronary artery disease (PCAD). The potential contribution of PCSK-9 serum level to the severity of PCAD patients was also assessed. METHOD: This case-control study included 120 PCAD patients (age < 45), and 60 age matched healthy controls. Serum PCSK-9 and caspase-3 levels and clinical characteristics were recorded. SYNTAX score was calculated to estimate the severity of the coronary artery lesions. The SNP rs2483205 of the PCSK-9 gene and the rs11053646 of the OLR-1gene were genotyped in all participants. RESULTS: Serum PCSK-9 levels were higher in PCAD patients and were significantly different among the three SYNTAX score groups (SS ≤ 12, 12 < SS ≤ 21.5, and SS > 21.5). The diagnostic cutoff values of PCSK-9 and caspase-3 levels for PCAD were > 3.2 ng/mL for both, yielding an area under the curve (AUC) of 0.98 and 0.92, sensitivity of 85 %, 98 %, and specificity of 99.5 %, 93 % for PCSK-9 and caspase-3, respectively. The genotypes TT + CT vs. CC of PCSK-9's rs2483205 SNP presented a higher risk for PCAD and higher SYNTAX scores. Furthermore, the rs11053646 SNP of OLR-1 presented the CG genotype as more risky and having higher SYNTAX scores. CONCLUSION: Circulating PCSK9 and caspase-3 concentrations were higher in PCAD patients and were associated with CAD severity. The SNPs of PCSK-9 (rs2483205) and OLR-1 (rs11053646) were associated with PCAD and its severity.

Effect of aerobic exercise, slow deep breathing and mindfulness meditation on cortisol and glucose levels in women with type 2 diabetes mellitus: a randomized controlled trial.

Background: Aerobic exercise combined with breathing exercise can be an integral part of diabetes mellitus treatment. This single-center, randomized, parallel-group study investigated the effect of the combination of aerobic exercise with slow deep breathing and mindfulness meditation on the glucose and cortisol levels of women with type 2 diabetes mellitus (T2DM). Materials and Methods: Fifty-eight middle-aged women with T2DM (mean age: 45.67 ± 2.92 years) were randomly assigned to either the aerobic training group (AT: n = 29; mean age [46.1 ± 2.7 years]) or the aerobic exercise combined with slow deep breathing and mindfulness meditation (AT + DMM: n = 29; mean age [45.24 ± 3.14 years]). Aerobic exercise was performed at 60%-75% of the maximum heart rate. The women in each group were asked to perform the training three times weekly over a 6-week period. The duration of each session was 40 min for the AT group and 60 min for the AT + DMM group. The two groups were asked to perform aerobic exercise at 60%-75% of the maximum heart rate. Their fasting blood glucose (FBG) and serum cortisol levels were measured at the baseline and after the 6 weeks. Results: Compared with the AT group, the group undertaking 6 weeks of aerobic training combined with slow, deep breathing exercises and mindfulness meditation showed significantly lower levels of FBG (p = 0.001) and cortisol levels (p = 0.01) than the AT group. Conclusion: The addition of slow deep breathing and mindfulness meditation to aerobic exercise can better control the glucose and cortisol levels of women with T2DM and thereby improve their outcomes and decrease their cardiometabolic risk.

Would the Actigraph Always be Sufficient for Sleep Analysis in Exercise-Based Studies? A Case Report of Negative Response of Sleep to Exercise.

Introduction Sleep deprivation is common after coronary artery bypass grafting (CABG). It is mostly managed well by exercise. The number of reported post-CABG cases that respond negatively to exercise is scanty. The etiology is usually associated with the underlying sleep pathology, and how it responds to exercise. Cases with undiagnosed central sleep apnea post CABG have not been reported before. Case description A medically stable male patient, 63 years old, hypertensive, but not diabetic, had entered coronary artery bypass grafting (CABG) 8 weeks before attending the outpatient cardiac rehabilitation unit and was referred for a cardiac rehabilitation program at this time. He entered a study in the cardiac rehabilitation center utilizing either aerobic or combined aerobic and resistance training for 10 weeks to improve sleep architecture and functional capacity post-CABG. After randomization, he entered the group doing combined aerobic and resistance exercises. All of the patients in this group improved except him, his sleep quality worsened, but his functional capacity improved. After a complete analysis of sleep on polysomnography, it was revealed that the patient had central sleep apnea that was mostly worsened by resistance training. The patient was withdrawn from the study by the 8th week, and his sleep condition improved gradually. After then, he was asked to attend the cardiac rehabilitation center again to share in aerobic exercise, having evidence that central sleep apnea does not respond negatively to this form of training. After 12 months of follow-up, the patient still shows no signs of sleep deprivation. Conclusion Sleep deprivation is prevalent in post-CABG patients, but with different presentations and it can generally improve by exercise. Identification of the underlying cause of the sleeping difficulty is a cornerstone of targeted treatment.

Serum pentraxin 3 in systemic lupus erythematosus: A potential indicator of cutaneous disease activity.

BACKGROUND: Although skin manifestations are common in systemic lupus erythematosus (SLE), there is still a lack of a diagnostic marker for cutaneous involvement. Pentraxin3 (PTX3) has been studied in SLE patients; however, it has not been investigated in relation to cutaneous manifestations. OBJECTIVE: To assess the serum PTX3 level in SLE patients, and to investigate its relationship with disease activity as well as with variable skin manifestations. PATIENTS AND METHODS: Thirty-four patients with SLE (17 patients with skin manifestations and 17 without) and 30 healthy subjects were included in the study. Patients were evaluated clinically for systemic and skin manifestations of SLE. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) and Cutaneous Lupus Erythematosus Activity and Severity Index (CLASI) scores were calculated. Serum level of PTX3 was measured in patients and controls using ELISA. RESULTS: Higher serum PTX3 level was found in SLE patients compared to controls (p < 0.001). Patients with skin manifestations showed higher SLEDAI-2k scores and had higher PTX3 level compared to those without skin manifestations (p = 0.015 and p < 0.001, respectively). PTX3 showed higher levels in association with malar rash (p < 0.001), mucosal ulcers (p < 0.001), alopecia (p < 0.001), and purpuric eruption (p = 0.002). Moreover, PTX3 level positively correlated with CLASI scores (p < 0.001). CONCLUSION: Our results reinforce the important role of Pentraxin3 in SLE patients with skin manifestations, and it may be considered an interesting biomarker for the pattern and extent of cutaneous involvement in SLE.

The five keys for a successful implementation of a cardiac telerehabilitation: a step-by-step effective digitalization of rehabilitation health services in Egypt.

BACKGROUND: Telerehabilitation enables patients to communicate with physicians through the Internet and may be utilized to evaluate patients' conditions and offer treatment plans. This method became necessary as a result of the COVID-19 pandemic and its influence on face-to-face rehabilitation choices. Many rehabilitation professionals throughout the world have turned to the 'online' approach, relying on smartphone and smartwatch services such as WhatsApp, Facebook, and various mobile applications that comply with the ESC requirements. MAIN BODY: Throughout this editorial, we examine the function of cardiac telerehabilitation in light of the journalistic '5 W,' taking into consideration the rising interest in this topic during the 'COVID era.' CONCLUSIONS: Telerehabilitation is the future of rehabilitation, particularly in the COVID age. Additionally, telerehabilitation has proved to be successful in the cardiac profession when compared to face-to-face treatments, implying that this type of rehabilitation may continue after the world is COVID-free, and forecasting that it would be the preferable choice in the future.

From HIV to COVID-19, Molecular mechanisms of pathogens' trade-off and persistence in the community, potential targets for new drug development.

Background: On the staggering emergence of the Omicron variant, numerous questions arose about the evolution of virulence and transmissibility in microbes. Main body of the abstract: The trade-off hypothesis has long speculated the exchange of virulence for the sake of superior transmissibility in a wide array of pathogens. While this certainly applies to the case of the Omicron variant, along with influenza virus, various reports have been allocated for an array of pathogens such as human immunodeficiency virus (HIV), malaria, hepatitis B virus (HBV) and tuberculosis (TB). The latter abide to another form of trade-off, the invasion-persistence trade-off. In this study, we aim to explore the molecular mechanisms and mutations of different obligate intracellular pathogens that attenuated their more morbid characters, virulence in acute infections and invasion in chronic infections. Short conclusion: Recognizing the mutations that attenuate the most morbid characters of pathogens such as virulence or persistence can help in tailoring new therapies for such pathogens. Targeting macrophage tropism of HIV by carbohydrate-binding agents, or targeting the TMPRSS2 receptors to prevent pulmonary infiltrates of COVID-19 is an example of how important is to recognize such genetic mechanisms.

Copeptin, miRNA-208, and miRNA-499 as New Biomarkers for Early Detection of Acute Coronary Syndrome.

cTn and CK-MB are gold standard biomarkers for acute coronary syndrome (ACS) but are less sensitive in the first 3 h after onset of symptoms. A need thus exists for novel biomarkers for early detection of ACS. We evaluated circulating copeptin, miRNA-208, and miRNA-499 as possible biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI). Sixty-five patients with probable ACS that presented within 4 h of the onset of chest pain (23 UA and 42 NSTEMI) and 25 apparently healthy individuals were studied. Two sets of blood samples collected in the first 3 h and at 6 h after onset were analyzed for copeptin levels via ELISA and miRNA-208 and miRNA-499 expression via real-time PCR. Copeptin, miRNA-208, and miRNA-499 expression levels were significantly increased in UA and NSTEMI patients compared with controls (p < 0.001) and in NSTEMT compared with UA patients (p < 0.001). Levels were also significantly elevated in UA and NSTEMI patients with negative cardiac troponin in the first 3 h (p < 0.001). ROC curves displayed AUC for prediction of ACS of 0.96 for copeptin, 0.97 for miRNA-208, and 0.97 for miRNA-499. Their combination improved AUC to 0.98. Copeptin and miRNA-208 and miRNA-499 expression are promising biomarkers for UA and NSTEMI that present in the first 3 h of pain onset. A combination of these markers with cTn may increase the accuracy of diagnosis by avoiding the gray zone of cTn as a biomarker.

Enhancement of the Molecular and Serological Assessment of Hepatitis E Virus in Milk Samples.

Hepatitis E virus (HEV) infection is endemic in developing and developed countries. HEV was reported to be excreted in the milk of ruminants, raising the possibility of transmission of HEV infection through the ingestion of contaminated milk. Therefore, the detection of HEV markers in milk samples becomes pivotal. However, milk includes inhibitory components that affect HEV detection assays. Previously it was reported that dilution of milk matrix improves the performance of HEV molecular assay, however, the dilution of milk samples is not the best strategy especially when the contaminated milk sample has a low HEV load. Therefore, the objective of this study is to compare the effect of extraction procedures on the efficiency of HEV RNA detection in undiluted milk samples. In addition, we assessed the effect of the removal of milk components such as fats and casein on the performance of the molecular and serological assays of HEV. Phosphate buffered saline (PBS) and different milk matrices (such as whole milk, skim milk, and milk serum) were inoculated with different HEV inoculums and subjected to two different extraction procedures. Method A includes manual extraction using spin column-based extraction, while method B includes silica-based automated extraction. Method A was more sensitive than method B in the whole milk and skim milk matrices with a LoD95% of 300 IU/mL, and virus recovery yield of 47%. While the sensitivity and performance of method B were significantly improved using the milk serum matrix, with LoD95% of 96 IU/mL. Interestingly, retesting HEV positive milk samples using the high sensitivity assay based on method B extraction and milk serum matrix increased the HEV RNA detection rate to 2-fold. Additionally, the performance of HEV serological assays such as anti-HEV IgG and HEV Ag in the milk samples was improved after the removal of the fat globules from the milk matrix. In conclusion, HEV RNA assay is affected by the components of milk and the extraction procedure. Removal of inhibitory substances, such as fat and casein from the milk sample increased the performance of HEV molecular and serological assays which will be suitable for the low load HEV milk with no further dilutions.

Replication of Hepatitis E Virus (HEV) in Primary Human-Derived Monocytes and Macrophages In Vitro.

HEV is the most causative agent of acute viral hepatitis globally. HEV causes acute, chronic, and extrahepatic manifestations. Chronic HEV infection develops in immunocompromised patients such as organ transplant patients, HIV-infected patients, and leukemic patients. The source of chronic HEV infection is not known. Also, the source of extrahepatic manifestations associated with HEV infection is still unclear. Hepatotropic viruses such as HCV and HBV replicate in peripheral blood mononuclear cells (PBMCs) and these cells become a source of chronic reactivation of the infections in allograft organ transplant patients. Herein, we reported that PBMCs and bone marrow-derived macrophages (BMDMs), isolated from healthy donors (n = 3), are susceptible to HEV in vitro. Human monocytes (HMOs), human macrophages (HMACs), and human BMDMs were challenged with HEV-1 and HEV-3 viruses. HEV RNA was measured by qPCR, the marker of the intermediate replicative form (ds-RNA) was assessed by immunofluorescence, and HEV capsid protein was assessed by flow cytometry and ELISA. HEV infection was successfully established in primary HMOs, HMACs, and human BMDMs, but not in the corresponding cells of murine origin. Intermediate replicative form (ds RNA) was detected in HMOs and HMACs challenged with HEV. The HEV load was increased over time, and the HEV capsid protein was detected intracellularly in the HEV-infected cells and accumulated extracellularly over time, confirming that HEV completes the life cycle inside these cells. The HEV particles produced from the infected BMDMs were infectious to naive HMOs in vitro. The HEV viral load was comparable in HEV-1- and HEV-3-infected cells, but HEV-1 induced more inflammatory responses. In conclusion, HMOs, HMACs, and human BMDMs are permissive to HEV infection and these cells could be the source of chronic and recurrent infection, especially in immunocompromised patients. Replication of HEV in human BMDMs could be related to hematological disorders associated with extrahepatic manifestations.

Joint remodeling outcome of serum levels of Dickkopf-1 (DKK1), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type II collagen (CTXII) in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is the most widespread chronic inflammatory rheumatic disease over the world. It is characterized by chronic proliferation of synovium, cartilage destruction, and periarticular erosion/bone loss. We investigated the serum levels of the C-telopeptide of type II collagen (CTX-II), Dickkopf-1 (DKK1), and cartilage oligomeric matrix protein (COMP) in relationship to the disease activity. MATERIAL AND METHODS: Serum COMP, CTX-II, and DKK1 levels were measured in 63 RA patients and 50 person age and gender matched as a healthy controls by ELISA test. Disease activity score (DAS) were calculated. RESULTS: The mean level of and COMP and CTX-II were significantly higher in patients with RA than in healthy controls (5.71 ±7.04 vs. 2.70 ±1.31 ng/ml, and 0.45 ±0.27 vs. 0.23 ±0.16 ng/ml, respectively; p < 0.001). Also, DKK1 serum levels were significantly higher in patients with RA than in healthy controls (6970.68 ±7566.68 vs. 3276.96 ±1306.77 pg/m; p < 0.001). There was a positive significant correlation between DKK1 and swollen joint (r = 0.42, p < 0.001). There were no significant differences in the number of patients, gender, the duration of RA disease, DAS, and RF. Sensitivity was 58.7% and specificity was 85.7% at a cut-off point (> 3.6 ng/ml) for serum COMP in RA patients, while, sensitivity was 100% and specificity was 52.4% at a cut-off point (> 0.15 ng/ml) for serum CTX-II and sensitivity was 68.3% and specificity was 95.2 % at a cut-off point (> 4876 pg/ml) for serum DKK1. CONCLUSIONS: Measurement of some serological biomarkers such as CTX-II, COMP, and DKK1 that reflect bone and cartilage destruction in RA patients could be used to indicate disease activity and early joint affection.

Does vitamin D status correlate with insulin resistance in obese prediabetic patients? An Egyptian multicenter study.

BACKGROUND: The link between Vitamin-D deficiency and type 2 diabetes (T2D) is well-established. Since prediabetic obese populations have the greatest risk to develop to T2D, it was important in our study to examine serum 25(OH) D3 concentration among prediabetic obese patients and to evaluate the correlation between serum level of vitamin D and BMI, FBS, HOMA IR and HbA1c among prediabetes patients. METHODS: A multicenter case control study was carried out among 101 prediabetic persons & 50 controls, after obtaining consent from subjects and clearance from institutional ethics committee. Serum vitamin D level, Plasma levels of glycosylated hemoglobin (HbA1c) and fasting insulin levels were measured by ELISA in both groups enrolled in the study. RESULTS: The prevalence of vitamin-D deficiency/insufficiency was (73.3%) (n = 74) among 101 prediabetic obese individuals. Also, A significant inverse correlation was observed between vitamin D levels & body mass index(r = - 0.28, P = 0.004); fasting blood sugar (r = - 0.22, P = 0.002); HOMA insulin resistance (r = - 0.25 P = 0.01); HbA1C (r = - 0.2, P= 0.004). CONCLUSIONS: High prevalence of vitamin D deficiency exists among obese prediabetic individuals and there is significant inverse correlation between BMI, FBS, HOMA IR, HbA1c and vitamin D level.

Rifaximin versus metronidazole in management of acute episode of hepatic encephalopathy: An open labeled randomized clinical trial.

BACKGROUND AND STUDY AIMS: Many regimens are tried in managing overt hepatic encephalopathy (HE). We investigated the efficacy of rifaximin versus metronidazole in management of an acute episode of HE on top of cirrhosis. PATIENTS AND METHODS: An open label prospective controlled trial was conducted on patients with an acute episode of HE on top of cirrhosis who were randomly divided into metronidazole-group (M-group) and rifaximin-group (R-group) with 60 patients in each. The main outcome measure was the clinical improvement of HE, duration of hospital stay and the changes in the level of serum ammonia after 3 days of starting therapy. RESULTS: Both M-group and R-group were comparable as regards age and sex (mean age 51 ±â€¯11 years and 49 ±â€¯12; male/female ratio 45:15 and 50:10, respectively). Forty-six patients (76.7%) in M-group compared with forty-five (75%) in R-group showed clinical improvement (p = 0.412). Hospital stays were comparable between both group; 4.2 ±â€¯2.1 and 3.9 ±â€¯1.7 for M-group and R-group; respectively (p = 0.435). There was no significant difference of venous ammonia levels (Mean of delta 160.77 ±â€¯185.34 µg/dL and 207.95 ±â€¯218.43 µg/dL with p 0.664 and 0.974 in M-group and R-group, respectively). No adverse events were reported throughout the whole study. CONCLUSION: Rifaximin and metronidazole are equally effective in management of acute episode of overt HE, therefore, re-auditing of treatment protocols of HE are warranted especially in limited resource settings.

Physiological Responses and Gene Expression in Ultrasound-Guided Supraclavicular Brachial Plexus Block: a Comparative Study.

BACKGROUND/AIMS: Ultrasound-guided supraclavicular brachial plexus block (BPB) has come into wider use as a regional anesthetic during upper limb operations. This study assessed the neurological and hemodynamic changes and gene expression after co-administration of midazolam or neostigmine with bupivacaine during supraclavicular BPB. METHODS: The study involved 90 adults divided into three groups: control (bupivacaine), midazolam (bupivacaine plus midazolam), and neostigmine (bupivacaine plus neostigmine). Blood samples were taken and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA levels were measured by real-time PCR, and oxidative stress markers were identified. In addition to the hemodynamic variables, the onset and duration of sensory and motor blockades, duration of analgesia, pain scores, time of first request for an analgesic, and amounts of analgesics ingested were evaluated. RESULTS: Compared with the control and neostigmine groups, the midazolam group experienced longer sensory and motor blockades, prolonged analgesia, lower pain scores at 12 h and 24 h, and lower need for postoperative analgesics. Moreover, the midazolam group exhibited lower oxidative stress markers with a higher fold change in IL-6 and TNF-α mRNA levels. CONCLUSION: Midazolam co-administered with bupivacaine provided better analgesic quality than did neostigmine with bupivacaine. This might be due to its superior antioxidant and anti-inflammatory effects.

Visfatin Serum Levels in Obese Type 2 Diabetic Patients: Relation to Proinflammatory Cytokines and Insulin Resistance.

Visfatin, an adipocytokine with insulin-mimetic activity, has been previously reported to associate with obesity. Herein, we aimed to investigate the serum level of visfatin and association with proinflammatory markers and insulin resistance in obese type 2 diabetic patients. A case control study was carried out among 80 diabetics and 40 non-diabetic healthy controls, after obtaining Anthropometric measurements and blood pressure. Serum level of visfatin and C-reactive protein (CRP) were measured by Enzyme Immunoassay. Interleukin 6 (IL6), tumor necrosis factor α (TNF-) were measured by ELISA and the homeostasis model assessment for insulin resistance was calculated as a marker of insulin resistance. Compared to healthy controls, diabetic patients showed a significant high serum levels of visfatin (40.33±9.98 vs 19.03±8.22), (P= 0.001), IL6 (12.06±2.69 vs 6.02±3.03), (P < 0.0001), TNF- (13.53±2.54 vs 8.70±3.40), P < 0.0001) and CRP (7.77±1.61 vs 6.01±1.99), (P=0.003). Also there was a strong positive correlation between serum level of visfatin, IL6, TNF- and CRP and some anthropometric characteristics including (WC,BMI and insulin resistance). Furthermore, among 80 diabetic patients, serum level of visfatin was positively correlated with IL6 (r=0.47, P < 0.0001), TNF- (r=0.62, P < 0.0001), CRP (r=0.4, P=0.002) respectively. In conclusion, there is a strong positive correlation between visfatin serum level and the inflammatory markers IL6, TNF- and CRP in type 2 diabetic patients. There is also a positive correlation with insulin resistance and BMI which indicates association of visfatin with obesity and type 2 diabetes mellitus.

Circulating Endothelial Cells and Platelet Microparticles in Mitral Valve Disease With and Without Atrial Fibrillation.

Hypercoagulability in mitral valve disease (MVD), a cause of atrial fibrillation (AF) and stroke, is potentially due to endothelial damage/dysfunction (marked by circulating endothelial cells [CECs]), platelet activation (soluble P-selectin [sPsel], platelet microparticles [PMPs], and soluble CD40 [sCD40]), and oxidized low-density lipoprotein (oxLDL) cholesterol. We measured these variables in 24 patients with MVD as well as in 21 with MVD + AF and compared them with 20 healthy controls (HCs). The CECs and PMPs were measured by flow cytometry; sPsel, oxLDL, and CD40 by enzyme-linked immunosorbent assay. Compared with HCs, sPsel and PMPs were equally higher in MVD and MVD + AF; sCD40 and oxLDL were higher in MVD + AF than in HCs and MVD; and CECs were higher in MVD than in the HCs, with further increases in MVD + AF (all P < .001). We conclude that excess platelet activation is present in MVD regardless of AF, and that increased endothelial damage in MVD is greater when compounded by AF.