Biomineralization of Polyelectrolyte-Functionalized Electrospun Fibers: Optimization and In Vitro Validation for Bone Applications.

In recent years, polyelectrolytes have been successfully used as an alternative to non-collagenous proteins to promote interfibrillar biomineralization, to reproduce the spatial intercalation of mineral phases among collagen fibrils, and to design bioinspired scaffolds for hard tissue regeneration. Herein, hybrid nanofibers were fabricated via electrospinning, by using a mixture of Poly ɛ-caprolactone (PCL) and cationic cellulose derivatives, i.e., cellulose-bearing imidazolium tosylate (CIMD). The obtained fibers were self-assembled with Sodium Alginate (SA) by polyelectrolyte interactions with CIMD onto the fiber surface and, then, treated with simulated body fluid (SBF) to promote the precipitation of calcium phosphate (CaP) deposits. FTIR analysis confirmed the presence of SA and CaP, while SEM equipped with EDX analysis mapped the calcium phosphate constituent elements, estimating an average Ca/P ratio of about 1.33-falling in the range of biological apatites. Moreover, in vitro studies have confirmed the good response of mesenchymal cells (hMSCs) on biomineralized samples, since day 3, with a significant improvement in the presence of SA, due to the interaction of SA with CaP deposits. More interestingly, after a decay of metabolic activity on day 7, a relevant increase in cell proliferation can be recognized, in agreement with the beginning of the differentiation phase, confirmed by ALP results. Antibacterial tests performed by using different bacteria populations confirmed that nanofibers with an SA-CIMD complex show an optimal inhibitory response against S. mutans, S. aureus, and E. coli, with no significant decay due to the effect of CaP, in comparison with non-biomineralized controls. All these data suggest a promising use of these biomineralized fibers as bioinspired membranes with efficient antimicrobial and osteoconductive cues suitable to support bone healing/regeneration.

Multi-Modality Imaging in Vasculitis.

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.

How Artificial Intelligence Can Enhance the Diagnosis of Cardiac Amyloidosis: A Review of Recent Advances and Challenges.

Cardiac amyloidosis (CA) is an underdiagnosed form of infiltrative cardiomyopathy caused by abnormal amyloid fibrils deposited extracellularly in the myocardium and cardiac structures. There can be high variability in its clinical manifestations, and diagnosing CA requires expertise and often thorough evaluation; as such, the diagnosis of CA can be challenging and is often delayed. The application of artificial intelligence (AI) to different diagnostic modalities is rapidly expanding and transforming cardiovascular medicine. Advanced AI methods such as deep-learning convolutional neural networks (CNNs) may enhance the diagnostic process for CA by identifying patients at higher risk and potentially expediting the diagnosis of CA. In this review, we summarize the current state of AI applications to different diagnostic modalities used for the evaluation of CA, including their diagnostic and prognostic potential, and current challenges and limitations.

Taxonomic implications of normal and abnormal stomatal complexes in Indigofera L. (Indigofereae, Faboideae, Fabaceae).

This study is the first to report the foliar and stem epidermal micro-morphology of 13 taxa of Indigofera L. (Fabaceae) using light (LM) and scanning electron microscopy (SEM). The micro-morphological characteristics studied here are related to the epidermal cell shape, size, frequency, anticlinal wall pattern, and stomatal complex types, size, position, frequency, and index. The study revealed 19 major normal stomatal types with eight subtypes and seven major abnormal stomatal types with 13 subtypes. The stomatal index was lower on the abaxial leaf surface than on the adaxial surface. Notably, the adaxial surface of I. hochstetteri had the highest stomatal index (27.46%), while the abaxial surface of I. oblongifolia had the lowest (9.95%). The adaxial surface of I. hochstetteri also displayed the highest average stomatal frequency (38.67), while the adaxial surface of I. spinosa had the lowest average frequency (9.37). SEM analysis revealed that most leaves had slightly sunken to sunken stomata, while stem stomata were positioned at the same level as epidermal cells in most taxa. Indigofera's foliar and stem epidermal anatomy recommends their application as baseline data coupled with other taxonomic data for the delimitation and differentiation of closely related taxa in the genus. The study provides a comprehensive description, illustrations, images, and micrographs of the stomatal types, as well as a taxonomic key for distinguishing the studied taxa of Indigofera.

Intravenous Iron for Acute and Chronic Heart Failure with Reduced Ejection Fraction (HFrEF) Patients with Iron Deficiency: An Updated Systematic Review and Meta-Analysis.

Patients with heart failure (HF) and iron deficiency are at increased risk of adverse clinical outcomes. We searched databases for randomized controlled trials that compared IV iron to placebo, in patients with HF with reduced ejection fraction (HFrEF). A total of 7813 participants, all having HFrEF with 3998 receiving IV iron therapy, and 3815 control recipients were included. There was a significant improvement in Kansas City Cardiomyopathy Questionnaire favouring IV iron with MD 7.39, 95% CI [3.55, 11.22], p=0.0002. Subgroup analysis, based on acute and chronic HF, has displayed a sustained statistical significance. Additionally, a significant increase in the left ventricular ejection fraction % was observed, with MD 3.76, 95% CI [2.32, 5.21], p<0.00001. A significant improvement in 6-minute walk test was noted, with MD 34.87, 95% CI [20.02, 49.72], p<0.00001. Furthermore, IV iron showed significant improvement in NYHA class, peak VO2, serum ferritin, and haemoglobin levels. Finally, despite the lack of difference in terms of all-cause hospitalisation and HF-related death, IV iron was associated with a significant reduction in HF-related, any cardiovascular reason hospitalisations, and all-cause death; which supports the need for implementation of IV iron as a standard of care in patients with HF and iron deficiency.

Chemical angioplasty vs. balloon plus chemical angioplasty for delayed cerebral ischemia: a pilot study of PbtO2 outcomes.

BACKGROUND: Delayed cerebral ischaemia (DCI) is a major cause of morbidity and mortality after aneurysmal subarachnoid haemorrhage (aSAH). Chemical angioplasty (CA) and transluminal balloon angioplasty (TBA) are used to treat patients with refractory vasospasm causing DCI. Multi-modal monitoring including brain tissue oxygenation (PbtO2) is routinely used at this centre for early detection and management of DCI following aSAH. In this single-centre pilot study, we are comparing these two treatment modalities and their effects on PbtO2. METHODS: Retrospective case series of patients with DCI who had PbtO2 monitoring as part of their multimodality monitoring and underwent either CA or TBA combined with CA. PbtO2 values were recorded from intra-parenchymal Raumedic NEUROVENT-PTO® probes. Data were continuously collected and downloaded as second-by-second data. Comparisons were made between pre-angioplasty PbtO2 and post-angioplasty PbtO2 median values (4 h before angioplasty, 4 h after and 12 h after). RESULTS: There were immediate significant improvements in PbtO2 at the start of intervention in both groups. PbtO2 then increased by 13 mmHg in the CA group and 15 mmHg in the TBA plus CA group in the first 4 h post-intervention. This improvement in PbtO2 was sustained for the TBA plus CA group but not the CA group. CONCLUSION: Combined balloon plus chemical angioplasty results in more sustained improvement in brain tissue oxygenation compared with chemical angioplasty alone. Our findings suggest that PbtO2 is a useful tool for monitoring the response to angioplasty in vasospasm.

Ambulatory intracranial pressure in humans: ICP increases during movement between body positions.

Introduction: Positional changes in intracranial pressure (ICP) have been described in humans when measured over minutes or hours in a static posture, with ICP higher when lying supine than when sitting or standing upright. However, humans are often ambulant with frequent changes in position self-generated by active movement. Research question: We explored how ICP changes during movement between body positions. Material and methods: Sixty-two patients undergoing clinical ICP monitoring were recruited. Patients were relatively well, ambulatory and of mixed age, body habitus and pathology. We instructed patients to move back and forth between sitting and standing or lying and sitting positions at 20 s intervals after an initial 60s at rest. We simultaneously measured body position kinematics from inertial measurement units and ICP from an intraparenchymal probe at 100 Hz. Results: ICP increased transiently during movements beyond the level expected by body position alone. The amplitude of the increase varied between participants but was on average ∼5 mmHg during sit-to-stand, stand-to-sit and sit-to-lie movements and 10.8 mmHg [95%CI: 9.3,12.4] during lie-to-sit movements. The amplitude increased slightly with age, was greater in males, and increased with median 24-h ICP. For lie-to-sit and sit-to-lie movements, higher BMI was associated with greater mid-movement increase (ß = 0.99 [0.78,1.20]; ß = 0.49 [0.34,0.64], respectively). Discussion and conclusion: ICP increases during movement between body positions. The amplitude of the increase in ICP varies with type of movement, age, sex, and BMI. This could be a marker of disturbed ICP dynamics and may be particularly relevant for patients with CSF-diverting shunts in situ.

Carboxymethyl Chitosan-Coated Cyanidin-3-O-Glucoside-Beared Nanonutriosomes Suppress Palmitic Acid-Induced Hepatocytes Injury.

Cyanidin-3-O-glucoside (C3G) is classified as an anthocyanin (ACN) and is recognized for its remarkable antioxidant properties. Yet, the inadequate physicochemical stability of C3G restricts its potential for various biological applications. Thus, in this study, carboxymethyl chitosan (CMC)-coated nanonutriosomes (NS) were synthesized as a novel carrier for encapsulating C3G (CMC-C3G-NS) to improve C3G stability. CMC-C3G-NS exhibited a diameter of less than 200 nm along with an encouraging encapsulation efficiency exceeding 90%. Notably, the formulated CMC-C3G-NS possessed better stability under various pH, ionic, and oxygen conditions, improved controlled release properties, and higher hepatocellular uptake than uncoated particles (C3G-NS), indicating a longer retention time of C3G in a physiological environment. Of utmost significance, CMC-C3G-NS demonstrated superior alleviating effects against palmitic acid (PA)-induced oxidative hepatic damage compared to C3G-NS. Our study provided promising nanocarriers with the potential to deliver hydrophilic ACNs and controlled release properties for PA-induced hepatotoxicity alleviation.

Assessment of bone gain and neurosensory affection with the sandwich osteotomy technique for vertically deficient posterior mandible using a full digital workflow versus conventional protocol: A randomized split mouth study.

BACKGROUND: Using the sandwich osteotomy technique in the posterior mandible is delicate. This study aimed to assess the safety and the amount of bone gain using a full digital workflow versus the conventional procedure. PATIENTS AND METHODS: This split mouth study included 10 patients with bilateral vertically deficient posterior mandible. One side received conventional sandwich interpositional bone grafting (control group), while the other side received the same protocol using two patient-specific guides. The first guide (cutting guide) was used to place the osteotomies safely and accurately according to the predetermined dimensions and locations, and the second guide was used to fix the mobilized bony segment, leaving the desired gap to be filled with a particulate xenogenic bone graft. RESULTS: Full neurosensory recovery was documented at 2 months postoperative for all patients and bilaterally. After 4 months, there was a statistically significant difference in vertical bone gain between both groups (p = 0.001), measuring an average of 3.76 ± 0.72 mm in the study group and 2.69 ± 0.37 mm in the control group. No statistically significant difference was found between the planned vertical augmentation (3.85 ± 0.58 mm) and the obtained vertical bone gain (3.76 ± 0.72 mm) in the study group (p = 0.765) proving the accuracy of the guided procedure. CONCLUSION: Computer-guided sandwich interpositional grafting is predictable regarding the execution of the osteotomies and the accuracy of fixation of the transport segment.

Efficacy of selenium on patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

INTRODUCTION: Postoperative complications pose significant challenges in cardiac surgery and with the evolution of selenium as a potential anti-inflammatory agent, some studies reported its inefficiency. Thus, we conducted our meta-analysis to evaluate the impact of selenium supplementation on cardiac surgery patients. METHODS: Different databases such as PubMed, Embase, and Cochrane Library from inception till January 2024 were searched identifying a total of seven randomized-controlled trials involving selenium supplementation after cardiac surgery. Risk ratio (RR) and Mean difference (MD) were calculated with a 95% confidence interval (CI). RESULTS: The selenium intervention significantly raised the incidence of Acute Kidney injury (RR 0.76; 95% CI: 0.59, 0.98; P = 0.04) while significantly reducing the duration of hospital stay (MD -1.33; 95% CI: -2.51, -0.16; P = 0.03) and postoperative CRP levels (SMD -0.18; 95% CI: -0.34, -0.02; P = 0.03). The effect of selenium intervention on days spent in ICU (MD -0.01; 95% CI: -0.28, 0.25; P = 0.92), mortality (RR 1.07; 95% CI: 0.84, 1.37; P = 0.57) and incidence of hospital acquired infections (RR 0.98; 95% CI: 0.76, 1.26; P = 0.88) is insignificant. CONCLUSION: Selenium supplementation did not significantly reduce major postoperative complications in cardiac surgery patients. However, its ability to modulate inflammation, as reflected in decreased C-reactive protein levels, highlights its potential role in managing the inflammatory response. Future investigations should focus on optimized selenium supplementation strategies in conjunction with other antioxidants to enhance its benefits.

Modern Internet Search Analytics: Is There a Difference in What Patients are Searching Regarding the Operative and Nonoperative Management of Scoliosis?

STUDY DESIGN: Observational Study. OBJECTIVES: This study aimed to investigate the most searched types of questions and online resources implicated in the operative and nonoperative management of scoliosis. METHODS: Six terms related to operative and nonoperative scoliosis treatment were searched on Google's People Also Ask section on October 12, 2023. The Rothwell classification was used to sort questions into fact, policy, or value categories, and associated websites were classified by type. Fischer's exact tests compared question type and websites encountered between operative and nonoperative questions. Statistical significance was set at the .05 level. RESULTS: The most common questions concerning operative and nonoperative management were fact (53.4%) and value (35.5%) questions, respectively. The most common subcategory pertaining to operative and nonoperative questions were specific activities/restrictions (21.7%) and evaluation of treatment (33.3%), respectively. Questions on indications/management (13.2% vs 31.2%, P < .001) and evaluation of treatment (10.1% vs 33.3%, P < .001) were associated with nonoperative scoliosis management. Medical practice websites were the most common website to which questions concerning operative (31.9%) and nonoperative (51.4%) management were directed to. Operative questions were more likely to be directed to academic websites (21.7% vs 10.0%, P = .037) and less likely to be directed to medical practice websites (31.9% vs 51.4%, P = .007) than nonoperative questions. CONCLUSIONS: During scoliosis consultations, spine surgeons should emphasize the postoperative recovery process and efficacy of conservative treatment modalities for the operative and nonoperative management of scoliosis, respectively. Future research should assess the impact of website encounters on patients' decision-making.

Age is Associated with Level of First-Time Anterior Cervical Discectomy and Fusion: An Ordinal Analysis of Factors Influencing Timing of Cervical Degeneration.

BACKGROUND: Symptomatic cervical spondylosis is often treated with anterior cervical decompression and fusion (ACDF). However, few factors can predict which cervical level will degenerate and require intervention. This analysis evaluates pre-procedural factors associated with level of first-time single-level ACDF. METHODS: We performed a retrospective analysis of patients who underwent single-level ACDF without prior history of spine surgery. Mann Whitney U-tests and Spearman rank-order correlation were performed for analyses of associations between variables of interest and ACDF level. Adjusted odds-ratios were calculated by proportional-odds logistic regression, with age, sex, body mass index (BMI), current tobacco use, history of neck trauma, preoperative radicular symptoms, and preoperative myelopathic symptoms as covariates. RESULTS: 141 patients met inclusion criteria, and age demonstrated a negative correlation with ACDF level, such that younger patients tended to have ACDF performed at inferior subaxial levels (p=0.0006, rho = -0.31, moderately strong relationship). Patients with pre-operative radicular symptoms and myelopathic symptoms were more likely to have ACDF performed at inferior (p=0.0001) and superior (p<0.0001) levels, respectively. Patient sex, BMI, current tobacco use, and history of neck trauma were not predictive of ACDF level. When adjusting for the above variables in a proportional-odds ordinal logistic regression model, a one year increase in age conferred a 4% increase in the odds of requiring an ACDF at a given superior level compared to the adjacent inferior level. CONCLUSIONS: Age is correlated with level of first-time single level ACDF. Individual subaxial levels may have unique biomechanical properties that influence degeneration.

Magnitude of Bone Disease in Transfusion-Dependent and Non-Transfusion-Dependent ß-Thalassemia Patients.

Introduction ß-Thalassemia is a common inherited disease in the northern part of Iraq. A considerable number of transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) ß-thalassemia patients suffer bone problems. The objective of this study was to evaluate the degree of bone disease in the TDT and NTDT patients using a dual-energy X-ray absorptiometry (DEXA) scan. Patients and methods In this study, 53 TDT and 20 NTDT patients aged ≥10 years were enrolled. Their bone status was assessed using the DEXA scan at the lumbar spine (L1-L4) and femoral neck. The effect of physical, biochemical, and hormonal characteristics on the bone mineral density (BMD) parameters was evaluated. The value of the BMD Z-score was the measure to decide on the magnitude of bone disease. Results and discussion The mean age of the enrolled patients was 24.1 years. The BMD Z-score values were significantly lower among the TDT patients at the lumbar spine and femoral neck (BMD Z-score: -2.05 and -1.51 versus -2.29 and -0.71; p=0.044 and 0.009, respectively). The proportion of osteoporosis at the lumbar spine was significantly higher in the TDT group than in the NTDT group (69.8% versus 40%; p <0.001). The BMD Z-score correlated significantly with patient BMI and parathyroid hormone (PTH) level in both the TDT and NTDT groups. No correlation was found with age, hemoglobin (Hb), and serum levels of calcium, vitamin D, ferritin, phosphorus, and alkaline phosphatase (ALP). Conclusions Impaired bone density was encountered at high proportions in our thalassemia patients. TDT patients suffered more severe bone disease than NTDT patients.

To repair or to replace in mitral valve infective endocarditis? an updated meta-analysis.

BACKGROUND: Valve infective endocarditis (IE) is a potentially life-threatening condition that affects patients' livelihoods. Current surgical options in mitral valve IE include mitral valve repair (MVr) or replacement (MVR). While each procedure boasts its merits, doubt remains as to which type of surgery is superior. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane literature databases for studies comparing MVR and MVr in mitral valve IE. Any randomized controlled trial (RCT) or observational studies that compare MVR vs. MVr in mitral valve IE were eligible. Our dichotomous outcomes were extracted in the form of event and total, and risk and hazard ratio (RR)(HR) with 95% confidence interval (CI) and were pooled and calculated using RevMan 5.0. RESULTS: Our study included 23 studies with a total population of 11,802 patients. Compared to MVR, MVr had statistically significant lower risks of both early mortality with RR [0.44; 95% CI, 0.38-0.51; p < 0.001] and long-term follow-up mortality with HR [0.70; 95% CI, 0.58-0.85; p = 0.0004]. Moreover, MVr was associated with a statistically significant lower risk of IE recurrence with RR [0.43; 95% CI, 0.32-0.58; p < 0.001]; however, no statistically significant differences between both groups in terms of re-operations with RR [0.83; 95% CI, 0.41-1.67; p = 0.60]. CONCLUSION: Our results suggest that MVr was superior in terms of in-hospital mortality, long-term survival, and risk of recurrence without significance in valve reoperation. Therefore, MVr is appropriate as a primary treatment choice and should be considered whenever possible in most IE patients.

Light microscopical and parasitological analyses revealed the beneficial effects of silver nanoparticles and various myrrh extracts against Trichinella spiralis infection in mice.

Trichinella spiralis infection is a food-borne zoonotic disease caused by nematodes that dwell in the tissues, presenting a significant public health concern. This study aimed to evaluate the effectiveness of different treatments including silver nanoparticles (AgNPs), myrrh biosynthesized AgNPs "AgNPs synthesized using plant-based green technologies", myrrh extract, and myrrh essential oil, as alternative treatments against T. spiralis infection. Parasitological, histopathological, and cytotoxicity assessments were conducted to investigate the effects of various concentrations of these treatments in reducing the populations of adult worms and larvae during both the intestinal and muscular phases of T. spiralis-infected mice. The results showed that the highest antihelminthic efficacy against the intestinal phase of T. spiralis was achieved by myrrh extract (86.66%), followed closely by AgNPs (84.96%) and myrrh AgNPs (82.51%) at higher concentrations (800 mg/kg for myrrh extract, 40 µg/mL for AgNPs, and 40 µg/mL for myrrh AgNPs). While the group treated with myrrh essential oil showed the lowest percentage of adult reduction (78.14%). However, all treatments demonstrated comparable effects in reducing the larvae population in the muscle phase. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. Additionally, a comprehensive assessment of the cytotoxicity of AgNPs indicated low toxicity levels. This study supports that AgNPs synthesized using plant-based green technologies hold therapeutic potential for the treatment of T. spiralis infection. These findings present a promising avenue for the development of novel antiparasitic drugs that are both effective and safe. RESEARCH HIGHLIGHTS: Myrrh extract has the highest antihelminthic efficacy against the intestinal phase of T. spiralis. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. During intestinal phase of T. spiralis, varying levels of nanoparticle precipitation were detected in the liver, brain, lung, and intestine. During the muscular phase, the highest amount of AgNPs precipitation was detected in the liver, followed by the brain, and lung.

Lower limb coronal malalignment correction by percutaneous osteotomy and schanz screws fixation.

Pediatric knee deformities are common, and the classic treatment is corrective osteotomy. The aim of this study to assess the safety and efficacy of percutaneous low-energy osteotomy and casting with shanz screws fixation in treatment of Genu varum in children equal or younger than 7 years. This is a prospective nonrandomized case series study was conducted. A total of 38 patients (total of 60 limbs: 36 varus and 24 valgus) were treated by percutaneous low-energy osteotomy and casting with shanz screws fixation and observed over 2-5 years. Clinical and radiological outcomes were evaluated at the end of follow-up period by standing scanogram which enabled tibiofemoral angles and the mechanical axis to be measured and the rate of complications. There was a statistically significant improvement of the radiographic parameters in the form of tibiofemoral angle and MAD. Clinically, all the cases were completely corrected just one patient (two limbs) complicated by over-correction but statically non-significant and. pin tract infection in shanz screws fixation was noticed in one Patient. Percutaneous low-energy osteotomy and casting with shanz screws fixation is a simple, safe, and effective method in dealing with 7 years and younger children with pathological knee deformities. Level of evidence: Therapeutic level IV.

Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. It follows an autosomal dominant inheritance pattern in most cases, with incomplete penetrance and heterogeneity. It is familial in 60% of cases and most of these are caused by pathogenic variants in the core sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1). Genetic testing using targeted disease-specific panels that utilize next-generation sequencing (NGS) and include sarcomeric genes with the strongest evidence of association and syndrome-associated genes is highly recommended for every HCM patient to confirm the diagnosis, identify the molecular etiology, and guide screening and management. The yield of genetic testing for a disease-causing variant is 30% in sporadic cases and up to 60% in familial cases and in younger patients with typical asymmetrical septal hypertrophy. Genetic testing remains challenging in the interpretation of results and classification of variants. Therefore, in 2015 the American College of Medical Genetics and Genomics (ACMG) established guidelines to classify and interpret the variants with an emphasis on the necessity of periodic reassessment of variant classification as genetic knowledge rapidly expands. The current guidelines recommend focused cascade genetic testing regardless of age in phenotype-negative first-degree relatives if a variant with decisive evidence of pathogenicity has been identified in the proband. Genetic test results in family members guide longitudinal clinical surveillance. At present, there is emerging evidence for genetic test application in risk stratification and management but its implementation into clinical practice needs further study. Promising fields such as gene therapy and implementation of artificial intelligence in the diagnosis of HCM are emerging and paving the way for more effective screening and management, but many challenges and obstacles need to be overcome before establishing the practical implications of these new methods.

A comparative analysis of univariate versus multivariate eco-friendly spectrophotometric manipulations for resolving severely overlapped spectra of vonoprazan and amoxicillin new combination.

Vonoprazan and amoxicillin are pharmacological combinations that demonstrate synergistic effects in treating Helicobacter pylori (H. pylori), a global public health concern associated with peptic ulcer disease and gastric cancer. Four spectrophotometric methods were developed, including two univariate techniques (Fourier self-deconvolution and ratio difference) and two multivariate chemometric approaches (partial least squares and principal component regression). These methods provide innovative solutions for effectively resolving and accurately quantifying the overlapping spectra of vonoprazan and amoxicillin. The concentration ranges covered were 3-60 µg ml-1 for vonoprazan and 5-140 µg ml-1 for amoxicillin. To assess the environmental sustainability of the methodologies, various measures such as the Green Analytical Procedure Index (GAPI), National Environmental Method Index (NEMI), Analytical GREEnness Calculator, and Analytical Eco-scale, as well as RGB12 and hexagon toll were implemented. The validation of the developed techniques was carried out in compliance with ICH standards. The present study is highly significant because it is the first time that the mixture has been determined using the current approaches. The comparative analysis demonstrated no significant difference in terms of accuracy and precision compared to reference HPLC method (p = 0.05). The established spectrophotometric methods offer a straightforward, rapid, and cost-effective alternative to complex analytical techniques for determining the vonoprazan and amoxicillin mixture. They show potential for routine analysis in research laboratories and pharmaceutical industries.

Anticancer evaluations of iodoquinazoline substituted with allyl and/or benzyl as dual inhibitors of EGFRWT and EGFRT790M: design, synthesis, ADMET and molecular docking.

Fifteen new iodoquinazoline derivatives, 5a,b to 18, are reported in this study and their anticancer evaluation as dual inhibitors of EGFRWT and EGFRT790M. The new derivatives were designed according to the target of structural requirements of receptors. Cytotoxicity of our compounds was evaluated against MCF-7, A549, HCT116 and HepG2 cell lines using MTT assay. Compounds 18, 17 and 14b showed the highest anticancer effects with IC50 = 5.25, 6.46, 5.68 and 5.24 µM, 5.55, 6.85, 5.40 and 5.11 µM and 5.86, 7.03, 6.15 and 5.77 µM against HepG2, MCF-7, HCT116 and A549 cell lines, respectively. The eight highly effective compounds 10, 13, 14a, 14b, 15, 16, 17 and 18 were inspected against VERO normal cell lines to evaluate their cytotoxicity. Our conclusion was that compounds 10, 13, 14a, 14b, 15, 16, 17 and 18 possessed low toxicity against VERO normal cells with IC50 increasing from 43.44 to 52.11 µM. All compounds were additionally assessed for their EGFRWT and EGFRT790M inhibitory activities. Additionally, their ability to bind with EGFRWT and EGFR receptors was confirmed by molecular docking. Compound 17 exhibited the same inhibitory activity as erlotinib. Compounds 10, 13, 14b, 16 and 18 excellently inhibited VEGFR-2 activity with IC50 ranging from 0.17 to 0.50 µM. Moreover, compounds 18, 17, 14b and 16 remarkably inhibited EGFRT790M activity with IC50 = 0.25, 0.30, 0.36 and 0.40 µM respectively. As planned, compounds 18, 17 and 14b showed excellent dual EGFRWT/EGFRT790M inhibitory activities. Finally, our compounds 18, 17 and 14b displayed good in silico ADMET calculated profiles.

The Efficacy of Trigger Site Surgery in the Elimination of Chronic Migraine Headache: An Update in the Rate of Success and Failure.

Migraine headache (MH) is a prevalent neurovascular disorder that affects approximately 15% of the global population. They are more common in women and typically affect young and middle-aged individuals. Chronic MH is characterized by headaches occurring on ≥15 days per month for over three months. While only 5% of MHs are refractory, about 20%-50% do not respond to pharmacologic treatments. As a result, surgical interventions have emerged as an alternative method to eliminate MH since 2000 AD. These surgical treatments primarily target the peripheral mechanisms of MH, focusing on common trigger sites. Migraine surgery involves neurolysis of sensory branches of trigeminal and occipital nerves that supply the face and back of the head. Numerous clinical studies conducted between 2000 and 2021 have extensively described surgical interventions and their prognostic outcomes. After surgery, up to 80% of patients reported complete elimination of headaches, while 20%-35% experienced no relief. The failure to achieve complete elimination of MH can be attributed to various factors. The most common reason for a partial clinical response is the failure to identify all trigger sites or inadequate surgery on the trigger sites. In this review, we aim to provide an overview of current surgical interventions for MH at different trigger sites, including recent updates, success and failure rates, and potential causes of failure.