In Situ Nanoencapsulation of Curcumin in Soy Protein Isolate Amyloid-like Aggregates for Enhanced Wound Healing.

The importance of amyloid nanofibrils made from food proteins is rising in diverse fields, such as biomedicine and food science. These protein nanofibrils (PNFs) serve as versatile and sustainable building blocks for biomaterials, characterized by their high ß-sheet content and an ordered hydrogen bond network. These properties offer both stability and flexibility, along with an extreme aspect ratio and reactive functional groups. Plant-derived amyloid nanofibrils, such as soy protein isolate (SPI) PNFs, are increasingly favored due to their affordability and sustainability compared with animal proteins. This study aimed to explore the formation and application of SPI amyloid-like aggregates (SPIA) and their nanoencapsulation of curcumin (Cur) for biomedical purposes, particularly in wound healing. Under specific conditions of low pH and high temperature, SPIA formed, exhibited an amyloid nature, and successfully encapsulated Cur, thereby enhancing its stability and availability. Spectroscopic and microscopic analyses confirmed structural changes in SPIA upon the incorporation of Cur and the fabrication of SPIA@Cur. The obtained results indicate that in the presence of Cur, SPIA forms faster, attributed to accelerated SPI denaturation, an increased nucleation rate, and enhanced self-assembly facilitated by Cur's hydrophobic interactions and π-π stacking with SPI peptides. In vitro studies demonstrated the biocompatibility, biodegradability, and antioxidant properties of SPIA@Cur along with controlled release behavior. In vivo experiments in male Wistar rats revealed that both SPIA and SPIA@Cur significantly accelerate wound closure compared with untreated wounds, with SPIA@Cur showing slightly better efficacy. The histological analysis supported enhanced wound healing, indicating the potential of SPIA@Cur for biomedical applications.

Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases.

Currently, one of the most significant and rapidly growing unmet medical challenges is the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). This challenge encompasses the imperative development of efficacious therapeutic agents and overcoming the intricacies of the blood-brain barrier for successful drug delivery. Here we focus on the delivery aspect with particular emphasis on cell-penetrating peptides (CPPs), widely used in basic and translational research as they enhance drug delivery to challenging targets such as tissue and cellular compartments and thus increase therapeutic efficacy. The combination of CPPs with nanomaterials such as nanoparticles (NPs) improves the performance, accuracy, and stability of drug delivery and enables higher drug loads. Our review presents and discusses research that utilizes CPPs, either alone or in conjugation with NPs, to mitigate the pathogenic effects of neurodegenerative diseases with particular reference to AD and PD.

Exploring the significance of potassium homeostasis in copper ion binding to human αB-Crystallin.

αB-Crystallin (αB-Cry) is a small heat shock protein known for its protective role, with an adaptable structure that responds to environmental changes through oligomeric dynamics. Cu(II) ions are crucial for cellular processes but excessive amounts are linked to diseases like cataracts and neurodegeneration. This study investigated how optimal and detrimental Cu(II) concentrations affect αB-Cry oligomers and their chaperone activity, within the potassium-regulated ionic-strength environment. Techniques including isothermal titration calorimetry, differential scanning calorimetry, fluorescence spectroscopy, inductively coupled plasma atomic emission spectroscopy, cyclic voltammetry, dynamic light scattering, circular dichroism, and MTT assay were employed and complemented by computational methods. Results showed that potassium ions affected αB-Cry's structure, promoting Cu(II) binding at multiple sites and scavenging ability, and inhibiting ion redox reactions. Low concentrations of Cu(II), through modifications of oligomeric interfaces, induce regulation of surface charge and hydrophobicity, resulting in an increase in chaperone activity. Subunit dynamics were regulated, maintaining stable interfaces, thereby inhibiting further aggregation and allowing the functional reversion to oligomers after stress. High Cu(II) disrupted charge/hydrophobicity balance, sewing sizable oligomers together through subunit-subunit interactions, suppressing oligomer dissociation, and reducing chaperone efficiency. This study offers insights into how Cu(II) and potassium ions influence αB-Cry, advancing our understanding of Cu(II)-related diseases.

Improving the Prediction of 1-Year Right Ventricular Failure After Left Ventricular Assist Device Implantation.

Previous predictive models for postimplant right heart failure (RHF) following left ventricular assist device (LVAD) implantation have demonstrated limited performance on validation datasets and are susceptible to overfitting. Thus, the objective of this study was to develop an improved predictive model with reduced overfitting and improved accuracy in predicting RHF in LVAD recipients. The study involved 11,967 patients who underwent continuous-flow LVAD implantation between 2008 and 2016, with an RHF incidence of 9% at 1 year. Using an eXtreme Gradient Boosting (XGBoost) algorithm, the training data were used to predict RHF at 1 year postimplantation, resulting in promising area under the curve (AUC)-receiver operating characteristic (ROC) of 0.8 and AUC-precision recall curve (PRC) of 0.24. The calibration plot showed that the predicted risk closely corresponded with the actual observed risk. However, the model based on data collected 48 hours before LVAD implantation exhibited high sensitivity but low precision, making it an excellent screening tool but not a diagnostic tool.

Clinical Characteristics and Outcomes of COVID-19 Patients in Mazandaran Province, Iran.

Background: The problem issue of coronaviruses is one of the most serious problems in the world. The present study aimed to investigate and describe the clinical characteristics, risk factors of fatality rate, and length of hospital stay in patients with COVID-19 in Mazandaran province. Materials and Methods: In this epidemiological study, data from COVID-19 patients admitted to hospitals in Mazandaran province from July 22 to August 21, 2020, were reported. Multivariate logistic regression methods and the Cox proportional hazards model were used to determine the risk factors of fatality. Results: Out of the 6759 hospitalized patients, 3111(46.03%) patients had comorbidity; 19.77% of them had diabetes, 19.97% had hypertension, and 15.28% had heart failure. Cox regression model on COVID-19 patient data showed that risk factors for fatality including having age over 60 years (HR: 1.93; P< 0.001), intubation (HR: 4.22; P<0.001), SpO2≤ 93% (HR: 2.57; P=0.006), comorbidities of cancer (HR: 1.87; P=0.006), chronic blood diseases (HR: 1.83; P=0.049), heart failure (HR: 1.63; P<0.001), and chronic kidney disease (HR: 1.98; P<0.001). Conclusion: Paying much attention to risk factors for fatality can help identify patients with a poor prognosis in the early stages. More assessments should also be performed to examine the underlying mechanisms of these risk factors. Highlighting death-relate d risk factors is crucial to increase preparedness through appropriate medical care and prevention regulations.

Timelines of adverse event journeys of LVAD patients.

OBJECTIVE: The INTERMACS Events data set contains an expansive collection of temporal evidence of the course of adverse events (AEs) of >15 000 patients that have received a left ventricular assist device (LVAD). The chronology of AEs may contain insightful information of the "AE journeys" of LVAD patients. The purpose of this study is to investigate the timelines of AEs within the INTERMACS database. METHODS: Descriptive statistics were applied to 86 912 recorded AEs of 15 820 patients with a continuous flow-LVAD between 2008 to 2016, extracted from INTERMACS registry. The characteristics of the timelines of AE journeys were investigated by posing six descriptive research questions. RESULTS: The analysis revealed several time-related characteristics and patterns of the AE journey after LVAD including the most common time of occurrences of AEs after surgery, duration of AEs journeys, the time of first and last AEs, and the time gaps between AEs. CONCLUSION: The INTERMACS Event dataset is a valuable resource for research about the timeline of AE journeys of patients who received an LVAD. It is necessary for future studies to first explore and consider the time-related characteristics of the data set such as diversity and sparsity to effectively choose an appropriate scope of time and time granularity and to acknowledge potential challenges.

The structural and functional consequences of melatonin and serotonin on human αB-crystallin and their dual role in the eye lens transparency.

Crystallins are the major soluble lens proteins, and α-crystallin, the most important protective protein of the eye lens, has two subunits (αA and αB) with chaperone activity. αB-crystallin (αB-Cry) with a relatively wide tissue distribution has an innate ability to interact effectively with the misfolded proteins, preventing their aggregation. Melatonin and serotonin have also been identified in relatively high concentrations in the lenticular tissues. This study investigated the effect of these naturally occurring compounds and medications on the structure, oligomerization, aggregation, and chaperone-like activity of human αB-Cry. Various spectroscopic methods, dynamic light scattering (DLS), differential scanning calorimetry (DSC), and molecular docking have been used for this purpose. Based on our results, melatonin indicates an inhibitory effect on the aggregation of human αB-Cry without altering its chaperone-like activity. However, serotonin decreases αB-Cry oligomeric size distribution by creating hydrogen bonds, decreases its chaperone-like activity, and at high concentrations increases protein aggregation.

In search of similarity in adverse events journeys of patients with left ventricular assist devices.

OBJECTIVE: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Event data set contains an expansive collection of longitudinal evidence of the course of adverse events (AEs) of >15,000 patients who have received a left ventricular assist device (LVAD). Buried in the huge Event data set is knowledge that can provide a deeper understanding of the patterns of the "AE journey" of patients with LVAD. Thus, the goal of this study was to examine the Event data set from a comprehensive perspective to identify unique relationships and patterns of AEs, alert potential challenges, and suggest future research directions. METHODS: A sequential pattern mining algorithm called SPADE (ie, Sequential PAttern Discovery using Equivalence classes) was applied to 86,912 recorded AEs of 15,820 patients with a continuous-flow LVAD between 2008 and 2016, extracted from the publicly accessible INTERMACS registry. The patterns of AE journey were investigated by posing 5 descriptive research questions about most common types of AE, concomitant AEs, AE sequences, AE subsequences, and interesting relations between AEs. RESULTS: The analysis revealed several characteristics of patterns of the AE journey of patients who received an LVAD that accounts for the types and temporal ordering of successive AEs, combinations of AEs, and their timing after surgery. CONCLUSIONS: The high diversity and sparsity of the types and timing of AE occurrences make the AE journeys of patients dissimilar from each other, impeding the discovery of highly-patterned AE journeys among the patients. This study suggests 2 salient directions for future studies to tackle this issue using cluster analysis to cluster patients into more similar groups and translate these results into a practical clinical tool to forecast the next AE based on the history of previous AEs.

Modulation of Nrf2/HO-1 by Natural Compounds in Lung Cancer.

Oxidative stresses (OSs) are considered a pivotal factor in creating various pathophysiological conditions. Cells have been able to move forward by modulating numerous signaling pathways to moderate the defects of these stresses during their evolution. The company of Kelch-like ECH-associated protein 1 (Keap1) as a molecular sensing element of the oxidative and electrophilic stress and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) as a master transcriptional regulator of the antioxidant response makes a master cytoprotective antioxidant pathway known as the Keap1/Nrf2 pathway. This pathway is considered a dual-edged sword with beneficial features for both normal and cancer cells by regulating the gene expression of the array of endogenous antioxidant enzymes. Heme oxygenase-1 (HO-1), a critical enzyme in toxic heme removal, is one of the clear state indicators for the duality of this pathway. Therefore, Nrf2/HO-1 axis targeting is known as a novel strategy for cancer treatment. In this review, the molecular mechanism of action of natural antioxidants on lung cancer cells has been investigated by relying on the Nrf2/HO-1 axis.

Neuroprotective Effect of Propolis Polyphenol-Based Nanosheets in Cellular and Animal Models of Rotenone-Induced Parkinson's Disease.

Considering the central role of oxidative stress in the onset and progress of Parkinson's diseases (PD), search for compounds with antioxidant properties has attracted a growing body of attention. Here, we compare the neuroprotective effect of bulk and nano forms of the polyphenolic fraction of propolis (PFP) against rotenone-induced cellular and animal models of PD. Mass spectrometric analysis of PFP confirmed the presence of multiple polyphenols including kaempferol, naringenin, coumaric acid, vanillic acid, and ferulic acid. In vitro cellular experiments indicate the improved efficiency of the nano form, compared to the bulk form, of PFP in attenuating rotenone-induced cytotoxicity characterized by a decrease in cell viability, release of lactate dehydrogenase, increased ROS generation, depolarization of the mitochondrial membrane, decreased antioxidant enzyme activity, and apoptosis induction. In vivo experiments revealed that while no significant neuroprotection was observed relating to the bulk form, PFP nanosheets were very effective in protecting animals, as evidenced by the improved behavioral and neurochemical parameters, including decreased lipid peroxidation, increased GSH content, and antioxidant enzyme activity enhancement. We suggest that improved neuroprotective effects of PFP nanosheets may be attributed to their increased water solubility and enrichment with oxygen-containing functional groups (such as OH and COOH), leading to increased antioxidant activity of these compounds.

Limitations of receiver operating characteristic curve on imbalanced data: Assist device mortality risk scores.

OBJECTIVE: In the left ventricular assist device domain, the receiver operating characteristic is a commonly applied metric of performance of classifiers. However, the receiver operating characteristic can provide a distorted view of classifiers' ability to predict short-term mortality due to the overwhelmingly greater proportion of patients who survive, that is, imbalanced data. This study illustrates the ambiguity of the receiver operating characteristic in evaluating 2 classifiers of 90-day left ventricular assist device mortality and introduces the precision recall curve as a supplemental metric that is more representative of left ventricular assist device classifiers in predicting the minority class. METHODS: This study compared the receiver operating characteristic and precision recall curve for 2 classifiers for 90-day left ventricular assist device mortality, HeartMate Risk Score and Random Forest for 800 patients (test group) recorded in the Interagency Registry for Mechanically Assisted Circulatory Support who received a continuous-flow left ventricular assist device between 2006 and 2016 (mean age, 59 years; 146 female vs 654 male patients), in whom 90-day mortality rate is only 8%. RESULTS: The receiver operating characteristic indicates similar performance of Random Forest and HeartMate Risk Score classifiers with respect to area under the curve of 0.77 and Random Forest 0.63, respectively. This is in contrast to their precision recall curve with area under the curve of 0.43 versus 0.16 for Random Forest and HeartMate Risk Score, respectively. The precision recall curve for HeartMate Risk Score showed the precision rapidly decreased to only 10% with slightly increasing sensitivity. CONCLUSIONS: The receiver operating characteristic can portray an overly optimistic performance of a classifier or risk score when applied to imbalanced data. The precision recall curve provides better insight about the performance of a classifier by focusing on the minority class.

The anti-platelet drug ticlopidine inhibits FapC fibrillation and biofilm production: Highlighting its antibiotic activity.

Multidrug resistance of bacteria and persistent infections related to biofilms, as well as the low availability of new antibacterial drugs, make it urgent to develop new antibiotics. Here, we evaluate the antibacterial and anti-biofilm properties of ticlopidine (TP), an anti-platelet aggregation drug, TP showed antibacterial activity against both gram-positive (MRSA) and gram-negative (E. coli, and P. aeruginosa) bacteria over a long treatment period. TP significantly reduced the survival of gram-negative bacteria in human blood though impact on gram-positives was more limited. TP may cause death in MRSA by inhibiting staphyloxanthin pigment synthesis, leading to oxidative stress, while scanning electron microscopy imaging indicate a loss of membrane integrity, damage, and consequent death due to lysis in gram-negative bacteria. TP showed good anti-biofilm activity against P. aeruginosa and MRSA, and a stronger biofilm degradation activity on P. aeruginosa compared to MRSA. Measuring fluorescence of the amyloid-reporter Thioflavin T (ThT) in biofilm implicated inhibition of amyloid formation as part of TP activity. This was confirmed by assays on the purified protein in P. aeruginosa, FapC, whose fibrillation kinetics was inhibited by TP. TP prolonged the lag phase of aggregation and reduced the subsequent growth rate and prolonging the lag phase to very long times provides ample opportunity to exert TP's antibacterial effect. We conclude that TP shows activity as an antibiotic against both gram-positive and gram-negative bacteria thanks to a broad range of activities, targeting bacterial metabolic processes, cellular structures and the biofilm matrix.

Amyloid management by chaperones: The mystery underlying protein oligomers' dual functions.

Protein oligomerization has two notable aspects: it is crucial for the performing cellular and molecular processes accurately, and it produces amyloid fibril precursors. Although a clear explanation for amyloidosis as a whole is lacking, most studies have emphasized the importance of protein misfolding followed by formation of cytotoxic oligomer structures, which are responsible for disorders as diverse as neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and metabolic disorders, such as type 2 diabetes. Constant surveillance by oligomeric protein structures known as molecular chaperones enables cells to overcome the challenge of misfolded proteins and their harmful assemblies. These molecular chaperones encounter proteins in cells, and benefit cell survival as long as they perform correctly. Thus, this review highlights the roles of structural aspects of chaperone protein oligomers in determining cell fate-either succumbing to amyloid oligomers or survival-as well as experimental approaches used to investigate these entities.

Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials.

Background: Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed. Methods: We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days. Results: Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04-1.66]; p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15-1.45]; p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65-2.84]; p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60-1.09]; p-value = 0.16). Conclusion: Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19. Clinical Trial Registration: www.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

Bivalent metal ions induce formation of α-synuclein fibril polymorphs with different cytotoxicities.

α-Synuclein (α-Syn) aggregates are key components of intracellular inclusion bodies characteristic of Parkinson's disease (PD) and other synucleinopathies. Metal ions have been considered as the important etiological factors in PD since their interactions with α-Syn alter the kinetics of fibrillation. In the present study, we have systematically explored the effects of Zn2+, Cu2+, Ca2+, and Mg2+ cations on α-Syn fibril formation. Specifically, we determined fibrillation kinetics, size, morphology, and secondary structure of the fibrils and their cytotoxic activity. While all cations accelerate fibrillation, we observed distinct effects of the different ions. For example, Zn2+ induced fibrillation by lower tlag and higher kapp and formation of shorter fibrils, while Ca2+ ions lead to formation of longer fibrils, as evidenced by dynamic light scattering and atomic force microscopy studies. Additionally, the morphology of formed fibrils was different. Circular dichroism and attenuated total reflection-Fourier transform infrared spectroscopies revealed higher contents of ß-sheets in fibrils. Interestingly, cell viability studies indicated nontoxicity of α-Syn fibrils formed in the presence of Zn2+ ions, while the fibrils formed in the presence of Cu2+, Ca2+, and Mg2+ were cytotoxic. Our results revealed that α-Syn fibrils formed in the presence of different divalent cations have distinct structural and cytotoxic features.

Inhibiting mTTR Aggregation/Fibrillation by a Chaperone-like Hydrophobic Amino Acid-Conjugated SPION.

Transthyretin (TTR) aggregation via misfolding of a mutant or wild-type protein leads to systemic or partial amyloidosis (ATTR). Here, we utilized variable biophysical assays to characterize two distinct aggregation pathways for mTTR (a synthesized monomer TTR incapable of association into a tetramer) at pH 4.3 and also pH 7.4 with agitation, referred to as mTTR aggregation and fibrillation, respectively. The findings suggest that early-stage conformational changes termed monomer activation here determine the aggregation pathway, resulting in developing either amorphous aggregates or well-organized fibrils. Less packed partially unfolded monomers consisting of more non-regular secondary structures that were rapidly produced via a mildly acidic condition form amorphous aggregates. Meanwhile, more hydrophobic and packed monomers consisting of rearranged ß sheets and increased helical content developed well-organized fibrils. Conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with leucine and glutamine (L-SPIONs and G-SPIONs in order) via a trimethoxysilane linker provided the chance to study the effect of hydrophobic/hydrophilic surfaces on mTTR aggregation. The results indicated a powerful inhibitory effect of hydrophobic L-SPIONs on both mTTR aggregation and fibrillation. Monomer depletion was introduced as the governing mechanism for inhibiting mTTR aggregation, while a chaperone-like property of L-SPIONs by maintaining an mTTR native structure and adsorbing oligomers suppressed the progression of further fibril formation.

Seroepidemiology of HBV, HCV, HIV, HTLV, and CMV in Pregnant Women Referring to Sari Birth Cohort.

Background: Congenital infections are among the most important conditions threatening human fetal health, the majority of which are caused by viral agents. Screening pregnant women for viral infections is essential because such infections can cause serious consequences for both the mother and the infant. So, this study aimed to serologically investigate sexually transmitted viral infections in pregnant women and also find the association between the prevalence of viral infections and epidemiological parameters in pregnant women of Sari, Iran. Materials and Methods: This descriptive, observational study was performed in pregnant women referring to Sari Birth Cohort Center between 2018 and 2020. A total of 1092 blood samples were investigated for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), and cytomegalovirus (CMV) serological markers by enzyme-linked immunosorbent assay (ELISA). Results: The prevalence of HBsAg positivity, HCV, HIV, and HTLV was 0.2%, 0.09%, 0.09%, and 0.2%, respectively. The percentage of participants with CMV-IgM and -IgG antibody titers above normal was 0.2% and 91.8%, respectively. Pregnant women whose educational level was bachelor's degree or lower, those who did not use a male condom before pregnancy, or those with a family history of infectious disease were found to be more likely to have HBV, HCV, HIV, HTLV, and CMV infections. Conclusion: Family history, maternal age, pregnancy stage, and not using a male condom are among the risk factors for sexually transmitted viral infections in pregnant women in Sari.

Epidemiological data of national Kawasaki disease registry in Iran, 2007-2019.

Introduction: Kawasaki disease(KD) is a vasculitis of childhood that tends to influence the coronary arteries. There is no national data about the prevalence of KD in Iran. This study aimed to perform a national registry in Iran for 13 years. Methods: In this retrospective study, the data for KD extracted from medical records of <19 year-old patients admitted to tertiary hospitals in Iran between 2007 and 2019 were recorded in the national KD registry system. Age, admission date, gender, location, and presence of KD criteria, laboratory and echocardiography findings, and treatment modalities were evaluated. Complete KD was considered if ≥4 clinical criteria of the KD existed and otherwise, incomplete KD was considered. Results: Data from 1,682 KD patients including 999(59.39%) boys and 683(40.61%) girls and male/female ratio of 1.46 were evaluated. The mean age was 3.08 ± 2.49 years and 1465(87%) were living in urban regions. The yearly incidence of the disease was between 2.62 to 3.03 from 2015 to 2019. The highest age-specific incidence was observed in children <1-year-old. Incomplete and resistant KD included 1,321(78.54%) and 9(0.54%) patients, respectively. Abnormal echocardiography was detected in 619(36.80%) patients. Leukocytosis, with dominancy of neutrophils, anemia, thrombocytosis and increased ESR and CRP were the most noticeable laboratory findings. No death due to KD disease was reported. Conclusion: Based on this study, most of the KD cases are presented with atypical presentation in Iran. So, increasing awareness of primary healthcare workers by educating and updating their data is very important in timely diagnosis and management of the disease.

Structural and functional studies of D109A human αB-crystallin contributing to the development of cataract and cardiomyopathy diseases.

αB-crystallin (heat shock protein ß5/HSPB5) is a member of the family of small heat shock proteins that is expressed in various organs of the human body including eye lenses and muscles. Therefore, mutations in the gene of this protein (CRYAB) might have many pathological consequences. A new mutation has recently been discovered in the α-crystallin domain of this chaperone protein which replaces aspartate 109 with alanine (D109A). This mutation can cause myofibrillar myopathy (MFM), cataracts, and cardiomyopathy. In the current study, several spectroscopic and microscopic analyses, as well as gel electrophoresis assessment were applied to elucidate the pathogenic contribution of human αB-crystallin bearing D109A mutation in development of eye lens cataract and myopathies. The protein oligomerization, chaperone-like activity and chemical/thermal stabilities of the mutant and wild-type protein were also investigated in the comparative assessments. Our results suggested that the D109A mutation has a significant impact on the important features of human αB-crystallin, including its structure, size of the protein oligomers, tendency to form amyloid fibrils, stability, and chaperone-like activity. Given the importance of aspartate 109 in maintaining the proper structure of the α-crystallin domain, its role in the dimerization and chaperone-like activity, as well as preserving protein stability through the formation of salt bridges; mutation at this important site might have critical consequences and can explain the genesis of myopathy and cataract disorders. Also, the formation of large light-scattering aggregates and disruption of the chaperone-like activity by D109A mutation might be considered as important contributing factors in development of the eye lens opacity.

Machine Learning Approaches to Analyzing Adverse Events Following Durable LVAD Implantation.

BACKGROUND: This study employed machine learning approaches to analyze sequences of adverse events (AEs) after left ventricular assist device (LVAD) implantation. METHODS: Data on patients implanted with the HeartWare HVAD durable LVAD were extracted from the ENDURANCE and ENDURANCE Supplemental clinical trials, with follow-up through 5 years. Major AEs included device malfunction, major bleeding, major infection, neurological dysfunction, renal dysfunction, respiratory dysfunction, and right heart failure (RHF). Time interval and transition probability analyses were performed. We created a Sankey diagram to visualize transitions between AEs. Hierarchical clustering was applied to dissimilarity matrices based on the longest common subsequence to identify clusters of patients with similar AE profiles. RESULTS: A total of 568 patients underwent HVAD implantation with 3590 AEs. Bleeding and RHF comprised the highest proportion of early AEs after surgery whereas infection and bleeding accounted for most AEs occurring after 3 months. The highest transition probabilities were observed with infection to infection (0.34), bleeding to bleeding (0.31), RHF to bleeding (0.31), RHF to infection (0.28), and bleeding to infection (0.26). Five distinct clusters of patients were generated, each with different patterns of time intervals between AEs, transition rates between AEs, and clinical outcomes. CONCLUSIONS: Machine learning approaches allow for improved visualization and understanding of AE burden after LVAD implantation. Distinct patterns and relationships provide insights that may be important for quality improvement efforts.