Neck shrivel in European plum is caused by cuticular microcracks, resulting from rapid lateral expansion of the neck late in development.

MAIN CONCLUSION: Susceptibility to neck shrivel in European plum is due to cuticular microcracking resulting from high surface area growth rates in the neck region, late in development. Susceptibility to the commercially important fruit disorder 'neck shrivel' differs among European plum cultivars. Radial cuticular microcracking occurs in the neck regions of susceptible cultivars, but not in non-susceptible ones, so would seem to be causal. However, the reason for the microcracking is unknown. The objective was to identify potential relationships between fruit growth pattern and microcracking incidence in the neck (proximal) and stylar (distal) ends of selected shrivel-susceptible and non-susceptible cultivars. Growth analysis revealed two allometric categories: The first category, the 'narrow-neck' cultivars, showed hypoallometric growth in the neck region (i.e., slower growth than in the region of maximum diameter) during early development (stages I + II). Later (during stage III) the neck region was 'filled out' by hyperallometric growth (i.e., faster than in the region of maximum diameter). The second category, the 'broad-neck' cultivars, had more symmetrical, allometric growth (all regions grew equally fast) throughout development. The narrow-neck cultivars exhibited extensive radial cuticular microcracking in the neck region, but little microcracking in the stylar region. In contrast, the broad-neck cultivars exhibited little microcracking overall, with no difference between the neck and stylar regions. Across all cultivars, a positive relationship was obtained for the level of microcracking in the neck region and the difference in allometric growth ratios between stage III and stages I + II. There were no similar relationships for the stylar region. The results demonstrate that accelerated stage III neck growth in the narrow-neck plum cultivars is associated with more microcracking and thus with more shrivel.

CT-IGFBP-4 as a Predictive Novel Biomarker of Ischemic Cardiovascular Events and Mortality: A Systematic Review.

Methods: The electronic databases PubMed, medRxiv, ScienceDirect, and Google Scholar were searched for relevant literature from inception to the 10th of December, 2021. Thus, retrieved literature was screened by title and abstract, followed by full-text screening based on the eligibility criteria. The risk of bias was accessed using the quality in prognostic studies (QUIPSs) tool. The data on cardiovascular outcomes about CT-IGFBP-4 levels were studied and the results were synthesized. Results: Five studies with a total of 1,417 participants were included in our study. The studies reported a low risk of bias. The mean age of the participants was 66.14 and more than 65% were males. Elevated CT-IGFBP-4 levels were associated with poor cardiovascular outcomes and increased mortality in severely ill patients. In contrast, there were no significant findings in the case of stable patients. Sandwich ELISA using lithium-heparin plasma provided a better detection limit of 0.15 ng/ml, low cross-reactivity (<2%), and generated linear results between 12 and 500 ng/ml. Conclusion: CT-IGFBP-4 is an efficient biomarker for the prediction of MACE and mortality in patients with severe ischemic cardiovascular events.

Computational investigations on the dynamic binding effect of molecular tweezer CLR01 toward intrinsically disordered HIV-1 Nef.

Intrinsically disordered proteins (IDPs) are highly flexible molecules that undergo disorder to order transition through their interaction with other molecules. IDPs play a vital role in several biological processes ranging from molecular recognition to several human diseases through the protein-protein interaction. The dynamic flexibility of IDPs and their implications in several human diseases enable these molecules to serve as novel therapeutic targets. However, the challenging task is to develop novel drugs against IDPs because of their lack of stable structures and the nature of high conformational flexibility. In this study, we have calculated the dynamic binding effect of the supramolecular tweezer CLR01 against the intrinsically disordered HIV-1 Nef by employing molecular docking and dynamics simulation approaches. From docking results, we predicted the strong binding affinity of the tweezer with the target residues of Nef. The docking results were further validated from the molecular dynamics simulation studies confirming the conformational stability of Nef upon tweezer binding. These findings provide useful insights into the development of potent inhibitors for targeting Nef protein functions.

Del Nido Cardioplegia in Coronary Artery Bypass Grafting Surgery: A safe, efficacious and economic alternative to St. Thomas solution; an experience from a developing nation.

INTRODUCTION: del Nido cardioplegia is a newer solution getting popular worldwide, whereas in Nepal, St. Thomas cardioplegia solution is conventionally used. There is no national recommendation on cardioplegia solutions supported by evidences from Nepalese studies. This study aimed to evaluate and compare the efficacy of these solutions in Nepalese patients undergoing coronary artery bypass grafting. METHODS: Patients undergoing coronary revascularization, from May 2018 to December 2019, were randomized into St. Thomas and del Nido groups based on the cardioplegia administered, with 45 patients in each group. Preoperative, intraoperative, and postoperative parameters and cost of cardioplegia preparation in the two groups were compared. RESULTS: The cardiopulmonary bypass time (106.13 ± 24.65 minutes vs 107.62 ± 18.69 minutes, p = 0.02), aortic cross clamp time (66.22 ± 15.40 minutes vs 72.07 ± 12.23 minutes, p = 0.04), volume (1059.22 ± 100.30 ml vs 1526.67 ± 271.81 ml, p < 0.001) and number of cardioplegia doses (1.00 ± 0.00 vs 2.51 ± 0.66, p < 0.001) were significantly lower with del Nido cardioplegia. A lower CPK-MB at second post-operative (59.91 ± 31.62 vs 73.82 ± 37.25, p = 0.03) and a higher left ventricle ejection fraction at discharge (56.33 ± 8.94% vs 50.45 ± 8.55%, p < 0.001) was observed in del Nido group. There was one death in St. Thomas group. ICU and hospital stay were similar in both groups. St. Thomas solution was found to be costlier than del Nido solution (USD 5.40 ± 0.96 vs USD 3.50 ± 0.34, p < 0.001). CONCLUSION: The del Nido cardioplegia was found to be efficacious, safe and more economical alternative to St. Thomas solution.

Computational investigations of potential inhibitors of monkeypox virus envelope protein E8 through molecular docking and molecular dynamics simulations.

The World Health Organization (WHO) has declared the monkeypox outbreak a public health emergency, as there is no specific therapeutics for monkeypox virus (MPXV) disease. This study focused on docking various commercial drugs and plant-derived compounds against the E8 envelope protein crucial for MPXV attachment and pathogenesis. The target protein structure was modeled based on the vaccinia virus D8L protein. Notably, maraviroc and punicalagin emerged as potential ligands, with punicalagin exhibiting higher binding affinity (- 9.1 kcal/mol) than maraviroc (- 7.8 kcal/mol). Validation through 100 ns molecular dynamics (MD) simulations demonstrated increased stability of the E8-punicalagin complex, with lower RMSD, RMSF, and Rg compared to maraviroc. Enhanced hydrogen bonding, lower solvent accessibility, and compact motions also attributed to higher binding affinity and stability of the complex. MM-PBSA calculations revealed van der Waals, electrostatic, and non-polar solvation as principal stabilizing energies. The binding energy decomposition per residue favored stable interactions between punicalagin and the protein's active site residues (Arg20, Phe56, Glu228, Tyr232) compared to maraviroc. Overall study suggests that punicalagin can act as a potent inhibitor against MPXV. Further research and experimental investigations are warranted to validate its efficacy and safety.

Investigating the binding affinity of andrographolide against human SARS-CoV-2 spike receptor-binding domain through docking and molecular dynamics simulations.

SARS-CoV-2 is a positive-sense single-stranded RNA virus that causes a deadly coronavirus disease (COVID-19) in humans. The infection of SARS-CoV-2 in humans involves a viral surface spike glycoprotein containing the receptor-binding domain (RBD). The interactions of SARS-CoV-2 with the host angiotensin-converting enzyme 2 (ACE2) receptor are mediated by RBD. It binds to the host ACE2 and influences viral replication and disease pathogenesis. Therefore, targeting the RBD to prevent SARS-CoV-2 infections is of utmost importance. In this study, we used docking and molecular dynamics simulations to understand the binding effect of andrographolide on the SARS-CoV-2 spike protein. During docking, a strong binding affinity was observed between the ligand and the target receptor protein. MD results demonstrated higher conformational fluctuations in the ligand-free protein compared to the bound form. Several residues in the active sites make conformational rearrangements for the S protein to interact with the ligand. While RBD experiences conformational transition to gain more stability upon binding with the ligand. This binding is strengthened via several non-covalent interactions that make the complex structure more stable with higher binding affinity. Overall findings of the study may shed some valuable insights concerning the development of potential therapeutics in the strategies for COVID-19 prevention.

Draft Genome Sequence of Lactiplantibacillus plantarum DMR09, Isolated from Spontaneously Fermented Dahi.

The draft genome sequence of Lactiplantibacillus plantarum DMR09, which was isolated from spontaneously fermented homemade cow dahi, was analyzed. The genome profile of L. plantarum DMR09 revealed 3,315,630 bp and a GC content of 44.5%, with 3,036 protein-encoding genes, 72 rRNA genes, and 65 tRNA genes.

Knowledge, Attitudes, and Practices Concerning COVID-19 in Nepal.

BACKGROUND: Coronavirus disease-2019 (COVID-19) severely affects patients with chronic diseases. Adequate knowledge, attitudes, and practice related to COVID-19 is associated with decrease morbidity and mortality. Therefore, this aimed to assess knowledge, attitudes, and practice toward COVID-19 disease among chronic diseases patients visiting tertiary hospitals in Kathmandu. METHODS: A cross-sectional study was conducted among chronic disease patients who visited Tribhuvan University Teaching Hospital and Manmohan Cardiothoracic Vascular and Transplant Center, Kathmandu. Structured questionnaire was used to collect patients' socio-demographic data and perspectives on COVID-19. RESULTS: Four hundred chronic disease patients participated in the study, with 53.2% female and 46.8% male, and 56.8% of age ≥50 years. Overall, 55.5% of the participants had good knowledge, 56.2% had good practice, and 30.7% had positive attitude towards COVID-19. Younger patients, 18-34 years, were found to have higher odds of having good knowledge compared to other age groups (aOR: 2.5; 95% CI: 1.3-6.0). The patients with less than average family income and those unable to read and write had lower odds of having positive attitude towards COVID-19 (aOR: 0.6; 95% CI: 0.4-0.9 and aOR: 0.4; 95%CI: 0.2-0.9, respectively). A statistically significant correlation was found between the patients' knowledge and practice, knowledge and attitude, and attitude and practice (p <0.001). CONCLUSIONS: Nearly half of the chronic disease patients in Nepal had poor knowledge and practice whereas more than two-third had negative attitude towards COVID-19 disease. Older age of the patient was significantly associated with poor knowledge and practice.

Review of current status of cardiovascular and thoracic surgery in Nepal: An analysis from collection of institutional database.

OBJECTIVE: Data collected from various institutions around the country was analyzed to assess the current status of cardiovascular and thoracic surgery in the country. METHODS: We collected data from institutions performing cardiovascular and thoracic surgery from all over the country through direct correspondence for the year 2019. Individual institution data on the number of surgeries performed for cardiac, vascular, and thoracic surgery and its outcome in terms of mortality were compiled. The data were further evaluated depending on the type of procedures performed. RESULTS: Overall, a total of 2264 cardiac surgeries were performed in the country in the year 2019. The majority of the surgeries were for valvular heart surgery accounting for 34.3%, followed by congenital surgeries (32.8%) and surgeries for coronary artery disease (25.9%). A total of 649 thoracic surgeries were documented, which is probably marginally less than the actual numbers because we were unable to include an additional few institutions performing low-volume or isolated thoracic procedures in this report. A total of 852 vascular procedures were performed in the country, which is probably underreported. The mortality rates for complex congenital procedures were higher than those reported in the literature and that of adult procedures such as valvular heart disease and coronary artery disease similar to literature. CONCLUSION: We evaluated the recent status of cardiovascular and thoracic surgery in the country with respect to the type of procedures and the postoperative outcomes.

An unusual penetrating shrapnel in the heart.

Penetrating heart trauma is a surgical emergency and can be fatal. However, cardiac penetration occurring due to non-explosive shrapnel is a rare occurrence. We report a case of a 20-year-old man, who sustained a laceration in his left chest, while he was breaking a rock with a chisel and a hammer. He was diagnosed to have an intramyocardial foreign body in his left ventricle. He underwent left ventriculotomy, foreign body localization under fluoroscopic guidance and successful extraction of the shrapnel from the left ventricular cavity.

Cardiac Myxoma among Patients Undergoing Cardiac Surgery in a Tertiary Care Center: A Descriptive Cross-sectional Study.

INTRODUCTION: Heart neoplasms are rare tumors. Myxoma is the commonest primary benign tumor of the heart presenting with features of obstruction, arrhythmia, and embolism. Surgical excision of the tumor is the gold standard of treatment. The aim of the study is to find out the prevalence of cardiac myxoma among all cardiac surgeries operated during the study period. METHODS: A descriptive cross-sectional study was done among 3800 patients undergoing surgery for cardiac tumors in a tertiary care center after obtaining approval from the Institutional Review Committee (Reference number- 36/(6-11)E2/077/078). The data was collected retrospectively from August 2012 to August 2020 using convenience sampling method. Statistical analysis was performed using Microsoft Excel 2016. Point estimate at 95% Confidence Interval was calculated along with frequency, percentage, mean and standard deviation. RESULTS: There were 26 (0.68%) (0.42-0.94 at 95% Confidence Interval) myxoma among 3800 cardiac surgeries performed over eight years. The mean age of the patients was 54.76±14.31 (range 17-75) years. Twenty (76.92%) patients were females. The commonest presenting symptom was shortness of breath in 19 (73.07%) patients. En masse excision with the closure of the atrial septal defect was the principal surgical technique. The mean Intensive Care Unit stay and hospital stays were 2.92±1.29 and 6.26±2.61 days respectively. There was no perioperative mortality. CONCLUSIONS: Cardiac myxoma was the most common cardiac tumor encountered as in other studies.

Spectrum of coronary anomalies and their categorical approach: rare case series.

The incidence of coronary artery anomalies (CAAs) is 0.2-1.2% of the population. Its paradox of being a rare entity with presentation ranging from sudden cardiac death, congestive heart failure, myocardial infarction to being clinically silent, asserts a challenge to its treating physician. Among the various major categories of CAA, we describe four different types of these anomalies in our retrospective evaluation over 2 years. They include - coronary cameral fistula with coronary aneurysm, congenital atresia of left main, anomalous aortic origin of left anterior descending (LAD) and circumflex artery (LCx) with malignant LAD course, anomalous origin of left coronary artery from pulmonary artery (ALCAPA). Although the child with ALCAPA succumbed despite every possible and available timely efforts, other patients had good postoperative recovery and a brief hospital stay.

Risk Factors of Coronary Artery Disease: A Hospital-Based Study.

BACKGROUND: Coronary artery disease is among the leading cause of morbidity and mortality worldwide. There are limited scientific evidence on the risk factors for coronary artery disease specific to the Nepalese context. This study aimed to determine the association of various modifiable cardiovascular risk factors with coronary artery disease in Nepal. METHODS: It is a hospital-based case-control study conducted among 300 participants. Case group comprised of 150 newly diagnosed coronary artery disease patients attending Manmohan Cardiothoracic Vascular and Transplant Centre while the Age and sex matched non-cardiac patients (n=150) from the outpatient department of the Department of General Practice and Emergency Medicine of Tribhuvan University Teaching Hospital were recruited as controls. Adjusted odds ratios (AOR) were calculated using multivariable logistic regression. RESULTS: Of the 300 participants, 208 (69.3%) were males and 92 (30.7%) were females. The mean age was 59.8 years ± 11 years (standard deviation). In multivariable analysis, current smoking (AOR=3.05, 95% CI: 1.61-5.78), hypertension (AOR=1.82, 95% CI: 1.08-3.09), diabetes (AOR=3.78, 95% CI: 1.91-7.47), family history of coronary artery disease (AOR=2.92, 95% CI: 1.27-6.71), and low high density lipoprotein (AOR= 2.0, 95% CI: 1.17-3.42) were significantly associated with coronary artery disease. Current alcohol use (AOR=0.51, 95% CI: 0.29-0.89) was identified as a protective factor for coronary artery disease. CONCLUSIONS: Among the modifiable cardiovascular risk factors, smoking, hypertension, diabetes, and low level of high density lipoprotein were significantly associated with coronary artery disease, which should be considered while developing public health interventions for cardiovascular disease prevention in Nepal in future.

Atrial Septal Defect Closure Via Mini Thoracotomy and with Peripheral Cannulation.

BACKGROUND: Atrial septal defect is one of the most common congenital cardiac disorders requiring intervention. We compared a minimally invasive method for atrial septal defect closure that included total peripheral cannulation and an anterior mini-thoracotomy incision of 5 cm or less with a median sternotomy approach. METHODS: This was a retrospective cross-sectional study among patients with Atrial Septal Defect. The preoperative variables, intraoperative data, and postoperative outcomes of patients undergoing minimally invasive atrial septal defect closure with total peripheral cannulation and atrial septal defect closure via median sternotomy were collected and compared. RESULTS: Fifty-five patients underwent minimally invasive closure of the atrial septal defect with total peripheral cannulation and 55 patients that underwent surgery by median sternotomy were included for comparison. There were 61.81% (34) female and 38.18% (21) male in the mini-thoracotomy group while there were 52.72% (29) female and 47.27% (26) male in the median sternotomy group. The mean age at surgery was 23.4 and 28.6 years in mini-thoracotomy and median sternotomy groups of patients respectively. The most common symptom was exertional shortness of breath in both groups. The mean length of stay in the intensive care unit was 1.8 and 2.5 days in mini-thoracotomy and median sternotomy groups respectively, and the length of stay in the hospital was 4.5 days and 4.8 days in mini-thoracotomy and median sternotomy groups respectively. There was a significant association was found between the mini-thoracotomy and median sternotomy group in relation to mean size of the incision, average time for cardiopulmonary bypass, average cross-clamp time, and fluid drained on the first day after surgery. CONCLUSIONS: Atrial septal defect closure with a mini-invasive approach is safe and cost-effective with very few perioperative complications and good patient satisfaction.

Congenital giant aneurysm of the left atrial appendage in an infant.

Aneurysm of the left atrial appendage is a rare pathological condition. We describe the diagnostic work-up and surgical management of a child with giant congenital aneurysm of the left atrial appendage.

Exploring the conformational dynamics and flexibility of intrinsically disordered HIV-1 Nef protein using molecular dynamic network approaches.

Intrinsically disordered proteins represent a class of proteins that lack fixed and well-defined three-dimensional structures in solution. HIV-1 Nef is an intrinsically disordered peripheral membrane protein involved in the replication and pathogenesis of HIV-1 infection. Nef controls expression levels of cell surface CD4 molecules that are essential for adaptive immunity. Despite the lack of fixed and stable structures, Nef physically interacts with the host cellular proteins (AP-1/MHC-I) and modulates intracellular trafficking pathways. Therefore, it is essential to understand how this dynamic conformational flexibility affects Nef structures and function. In this study, we combined all-atom molecular dynamics (MD) simulations and dynamic network approaches to better understand the structure and dynamics of Nef in two different forms, the free unbound and the bound state. Using the MD simulation approach, we show that the intrinsically disordered Nef exhibit a large dynamic field with more atomic fluctuations and lesser thermodynamic stability in the unbound conditions. The conformations of Nef change over time, and this protein remains more compact, folded, and stable in the bound form. The dynamic network analysis revealed regions of the protein capable of modulating the conformational behavior of the disordered Nef. The average betweenness centrality (BC) unveiled residues that are critical for mediating protein-protein interactions. The average shortest path length (L) and the perturbation response scanning exposed residues that are likely to be important in steering protein conformational changes. Overall, the study demonstrates how all-atom MD simulations combined with the dynamic network approach can be used to gain further insights into the structure and dynamics-function relationship of intrinsically disordered HIV-1 Nef. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02698-8.

Dynamic conformational flexibility and molecular interactions of intrinsically disordered proteins.

Intrinsically disordered proteins (IDPs) are highly flexible and undergo disorder to order transition upon binding. They are highly abundant in human proteomes and play critical roles in cell signaling and regulatory processes. This review mainly focuses on the dynamics of disordered proteins including their conformational heterogeneity, protein-protein interactions, and the phase transition of biomolecular condensates that are central to various biological functions. Besides, the role of RNA-mediated chaperones in protein folding and stability of IDPs were also discussed. Finally, we explored the dynamic binding interface of IDPs as novel therapeutic targets and the effect of small molecules on their interactions.

Patent arterial duct and vascular ring in a premature infant.

We report a case of a 750 grams premature female who was scheduled for surgical ligation of a patent arterial duct. Intra-operative findings showed a patent arterial duct in association to a retro-esophageal aortic arch creating a complete vascular ring around the trachea, which was successfully divided. A vascular ring should be ruled-out in premature infants prior to ductal ligation at bidimensional echocardiography.

Right posterior-lateral minithoracotomy access for treating congenital heart disease.

A modified right posterior-lateral minithoracotomy with the aid of peripheral cardiopulmonary bypass is a surgical option that has been adopted in our institution in selected patients with simple congenital heart disease. We present our selection criteria, describe our technique, and analyze our results with this modified technique.