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Mohamed Jahromi,1 Torki Al-Otaibi,2 Nashwa Othman,3 Osama Gheith,2 Tarek Mahmoud,2 Prasad Nair,2 Medhat A Halim,2 Narayanam Nampoory1,21Clinical Research, Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait; 2Nephrology Department, Hamid Al-Essa Organ Transplant Center, Kuwait City, Kuwait; 3Education, Clinical Services Division, Dasman Diabetes Institute, Kuwait City, KuwaitIntroduction and aim: New onset diabetes after transplantation (NODAT) is a serious metabolic complication following kidney transplantation. Although beta-cell dysfunction is considered the main contributing factor in the development of this complication, its exact etiology is yet to be identified. We aimed to investigate NODAT among kidney transplant cohort in Kuwait with special stress on correlation between its risk factors and interferon gamma genotyping.Materials and methods: We surveyed 309 kidney transplant recipients from Hamed Al Essa Transplantation Centre, Kuwait. The participants were categorized into cohorts according to the development of NODAT diagnosed based on the American Diabetes Association guidelines. Statistical analyses were performed using SPSS software. We genotyped interferon gamma as the leading immunosignature for T lymphocyte.Results: No relationship between ethnicity and the development of NODAT was identified. However, there was a significant difference in age between cohorts. Younger patients demonstrated a lower rate of NODAT while, NODAT reached its maximum in 40–60-year age group. IFNG TT genotype was significantly associated with NODAT (p=0.005), while IFNG AA was considerably higher in the non-NODAT group.Conclusion: Beside the conventional contributing factors of NODAT, our results might represent a suitable platform for a larger cytokine and chemokine spectrum genotyping.Keywords: ethnicity, NODAT, transplantation, immunosuppression

Abstract Background CHA2DS2-VASc score-related differences have been reported in atrial fibrotic remodeling and prognosis of atrial fibrillation (AF) patients after ablation. There are currently no data on the efficacy of low voltage zone (LVZ)-guided ablation in persistent AF patients according to CHA2DS2-VASc score. We assessed in a cohort of persistent AF patients the extent of LVZ, the regional distribution of LA voltage and the outcome of LA voltage-guided substrate ablation in addition to PVI according to CHA2DS2-VASc score. Methods 138 consecutive persistent AF patients undergoing a first voltage-guided catheter ablation were enrolled. 58 patients with CHAD2DS2-VASc score ≥ 3 and 80 patients with CHAD2DS2-VASc score ≤ 2 were included. LA voltage maps were obtained using 3D-electroanatomical mapping system in sinus rhythm. LVZ was defined as

BackgroundObesity is a risk factor for atrial fibrillation (AF). Data regarding left atrial (LA) remodeling in obese patients are scarce. Whether obesity favors AF recurrence after catheter ablation (CA) is still controversial. We assessed the distribution of epicardial atrial fat on computed tomography (CT), LA bipolar voltage, low-voltage zone (LVZ) extent, and the outcome of voltage-guided ablation of persistent AF in obese and non-obese patients.MethodsA total of 139 patients with persistent AF undergoing a first voltage-guided ablation were enrolled and divided into two groups: 74 were non-obese and 65 were obese. Epicardial adipose tissue (EAT) was assessed on a CT scanner. LA endocardial voltage maps were obtained using a 3D mapping system in sinus rhythm. LVZ was defined as a bipolar peak-to-peak voltage amplitude

Abstract Background The atrioventricular reentrant tachycardia (AVRT) is the most common tachycardia associated with accessory pathways (APs). Although sporadic Wolff-Parkinson-White (WPW) syndrome has been well-described, AP occurrence in identical twins with WPW syndrome remains rarely reported. Case presentation We report a case of 14-year-old monozygotic twin brothers referred for an electrophysiology (EP) study. Twin A presented with recurrent symptomatic narrow complex tachycardia after exercise, noted for 3 years. His 12-lead surface electrocardiogram (ECG) did not show ventricular pre-excitation. However, an orthodromic AVRT utilizing a concealed right posteroseptal AP was found and successfully ablated. AVRT did not recur 12 months after the procedure. Twin B was asymptomatic. During his medical examination for firefighter volunteerism, his 12-lead ECG showed a spontaneous ventricular pre-excitation. EP study revealed a short anterograde right midseptal AP, which was then successfully eliminated by catheter ablation. His 12-lead ECG showed no ventricular pre-excitation recurrence 12 months after the procedure. Conclusions These identical twin brothers had a right-side AP in almost the same place but showed completely different phenotypes. This case clearly illustrates the difficulty in understanding genetic contribution in the origin of atrioventricular APs. Environmental exposure could play a role in their clinical presentations and AP electrophysiological properties.

BackgroundGender-related differences have been reported in atrial fibrotic remodeling and prognosis of atrial fibrillation (AF) patients after ablation. We assessed in persistent AF the regional distribution of left atrial (LA) bipolar voltage and the extent of low-voltage zones (LVZ) according to gender as well as the results of a voltage-guided substrate ablation.MethodsConsecutive patients who underwent a voltage-guided AF ablation were enrolled. LA endocardial voltage maps were obtained using a 3D electro-anatomical mapping system in sinus rhythm. LVZ was defined as

Background Anogenital warts (AGW) have an important impact on quality of life since they cause discomfort and shame. AGW cannot be effectively treated with a single technique. Objective To compare effectiveness and safety of intralesional vitamin D3 injection and cryotherapy in the treatment of AGW. Patients and methods A randomized comparative clinical study included patients with AGW attending to dermatology, Venerology and andrology clinics, Suez Canal University hospitals, Ismailia, Egypt. 36 patients were divided randomly into 2 groups, group A, included 18 patients who were treated with cryotherapy alone and group B that included 18 patients who were treated with cryotherapy then 0.25–1 ml of intralesional vitamin D3 injection in the same session. Results Complete response was obtained in 55.6% versus 94.4% of patients and clinical recurrence occurred in 27.9% versus 5.6% of patients in group A and B respectively (P

Abstract Background We identified two families with Paget's disease of bone (PDB) linked to the p.Pro392Leu mutation within the SQSTM1 gene displaying a possible digenism. This study aimed at identifying this second genetic variant cosegregating with the p.Pro392Leu mutation and at characterizing its impact on the clinical and cellular phenotypes of PDB. Methods Whole exome sequencing was performed in one patient per family and two healthy controls. We compared clinical characteristics of PDB in 14 relatives from the two families. The osteoclastic phenotype was compared in in vitro differentiated osteoclasts from 31 participants carrying the DOCK6 and/or SQSTM1 variants. Tridimensional models of SQSTM1 and DOCK6 proteins were generated to evaluate the impact of these variants on their stability and flexibility. Statistical analyses were performed with Graphpad prism. Results Whole-exome sequencing allowed us to identify the p.Val45Ile missense variant in the DOCK6 gene in patients. In both families, the mean age at PDB diagnosis was delayed in pagetic patients carrier of the p.Val45Ile variant alone compared to those carrying the p.Pro392Leu mutation alone (67 vs. 44 years, P = 0.03). Although both p.Val45Ile and p.Pro392Leu variants gave rise to a pagetic phenotype of osteoclast versus healthy controls, the p.Val45Ile variant was found to attenuate the severity of the osteoclastic phenotype of PDB caused by the p.Pro392Leu mutation when both variants were present. The DOCK6 mRNA expression was higher in carriers of the p.Val45Ile variant than in pagetic patients without any mutations and healthy controls. Structural bioinformatics analyses suggested that the p.Pro392Leu mutation might rigidify the UBA domain and thus decrease its possible intramolecular interaction with a novel domain, the serum response factor–transcription factor (SRF-TF)-like domain, whereas the p.Val45Ile variant may decrease SRF-TF-like activity. Conclusion The p.Val45Ile variant may attenuate the severity of the clinical phenotype of PDB in patient carriers of both variants. In vitro, the rare variant of the DOCK6 may have a modifier effect on the p.Pro392Leu mutation, possibly via its effect on the SRF-TF-like.

Disability is a problem with the body-function or body-structure, activity limitations, such as individual's difficulty in carrying out actions in life situations. One example of physical disability is a foot disability or an injury on foot that prevents people’s ability in doing activities, where disabled people will find it hard to move from one place to another. Not only needing assistive devices, disabled people who use wheelchairs also need special facilities to do their activities. One of the activities is to shop. In Indonesia there are still no facilities that make disabled people with wheelchairs to shop at supermarkets in ease. Therefore, an innovation is indeed needed to make an integrated, automated, and special trolleys so it can facilitate and increase awareness of the importance of special facilities for disabled people in Indonesia. The EFD (Ergonomic Function Deployment) method is used to design the trolley according to the respondent's wishes. EFD is a development of QFD by adding a new relationship between consumer needs and the ergonomic aspects of the product. The product attributes that is used are derived from the ergonomics aspect which is known as ENASE (Effective, Comfortable, Safe, Healthy and Efficient). The prioritized variables of product design are trolleys for disabled people that run automatically, have an additional trolley basket (opening an additional trolley), have a soft back and seat, and have a strong locking system so that it makes it easier for users with a weight of 0.06048. The priority of consumer needs (Customer Needs) from the results of the HOE design are 3,4,7,8,9.10,11,14,5,6,12,13,16,18,19,1,15,2, and 17 and the Priority of Technical Requirements from the results of the HOE design are C, A, B, E and D

Abstract Background Manipulative parasites are thought to liberate molecules in their external environment, acting as manipulation factors with biological functions implicated in their host’s physiological and behavioural alterations. These manipulation factors are part of a complex mixture called the secretome. While the secretomes of various parasites have been described, there is very little data for a putative manipulative parasite. It is necessary to study the molecular interaction between a manipulative parasite and its host to better understand how such alterations evolve. Methods Here, we used proteomics to characterize the secretome of a model cestode with a complex life cycle based on trophic transmission. We studied Schistocephalus solidus during the life stage in which behavioural changes take place in its obligatory intermediate fish host, the threespine stickleback (Gasterosteus aculeatus). We produced a novel genome sequence and assembly of S. solidus to improve protein coding gene prediction and annotation for this parasite. We then described the whole worm’s proteome and its secretome during fish host infection using LC–MS/MS. Results A total of 2290 proteins were detected in the proteome of S. solidus, and 30 additional proteins were detected specifically in the secretome. We found that the secretome contains proteases, proteins with neural and immune functions, as well as proteins involved in cell communication. We detected receptor-type tyrosine-protein phosphatases, which were reported in other parasitic systems to be manipulation factors. We also detected 12 S. solidus-specific proteins in the secretome that may play important roles in host–parasite interactions. Conclusions Our results suggest that S. solidus liberates molecules with putative host manipulation functions in the host and that many of them are species-specific. Graphical abstract

Background: Unfractionated heparin (UFH) is used as an anticoagulant during the atrial fibrillation (AF) ablation procedure to prevent the occurrence of thromboembolic events. Guidelines recommend an activated clotting time (ACT) greater than 300 s (s) based on studies of patients treated with vitamin K antagonist (VKA) for their AF. However, direct oral anticoagulants (DOACs) have supplanted VKAs in AF and are now used as first-line therapy. It is recommended not to interrupt them during the procedure, which could interfere with the ACT measures. Objective: To assess the real-life relationship between ACT, DOAC concentrations, and UFH anti-Xa activity in patients treated by uninterrupted DOAC therapy. Methods: We conducted a single-center retrospective study. We analyzed consecutive patients with AF who underwent catheter ablation under DOAC therapy. Results: In total, 40 patients were included, including 15 (37.5%), 20 (50.0%), and 5 (12.5%) on rivaroxaban, apixaban, and dabigatran, respectively. Baseline ACT was significantly lower in the apixaban group. ACT was linearly correlated with the residual concentration of apixaban and dabigatran but not with rivaroxaban. After UFH injection, ACT was linearly correlated with the anti-Xa activity, regardless of DOAC. Patients in the apixaban group received a higher total dose of UFH during the procedure to achieve a target ACT > 300 s, which resulted in significantly higher anti-Xa activity during the procedure. Conclusion: Our results raise the question of optimal management of intra-procedural heparin therapy and highlight the limitations of the ACT test, particularly in patients on apixaban.

The aim of this study is to determine the mediating role of the institute reputation between institute social responsibility and student loyalty. The present study uses a multi-stage sampling technique, which first creates four clusters; including Karachi, Quetta, Peshawar, and Lahore, and picks one cluster; namely Lahore, randomly for the purpose of the study. Second, proportionate sampling technique is used to calculate the proportionate values of every individual educational institute. Finally, systematic sampling is used to compute the sampling interval kth number of individual univer-sities. Data are collected from the provincial capital city of Punjab province (Lahore) and a total of 511 questionnaires are distributed among postgraduate students under business education discipline of private HEIs, 206 questionnaires are excluded from the sample due to some missing and misleading values, and final analysis is run by using SmartPLS 3.2.8 on 345 questionnaires. Findings elucidate that institutes social responsibility did not have any direct relationship with student loyalty. However, institute social responsibility has indirect relationship with student loyalty thru the mediating variable of institute reputation. Institute reputation also has a significant and positive influence on student loyalty.

Penerimaan Pengguna terhadap suatu sistem berbasis teknologi informasi dan komunikasi penting untuk dilakukan karena menjadi indikator bahwa sistem tersebut akan diterima dan digunakan oleh pengguna untuk mendukung penyelesaian atau pencapaian target pekerjaan. Pengukuran penerimaan Pengguna terhadap sistem informasi elektronik ibu hamil (SIMBUMIL) yang dilakukan pada penelitian ini, bertujuan untuk mengetahui penerimaan dan pendapat para Bidan sebagai Pengguna terhadap SIMBUMIL, berkaitan dengan aspek kemudahan, kegunaan, dan keinginan untuk menggunakan SIMBUMIL sebagai alat yang dapat mendukung pekerjaan. Penerimaan Pengguna SIMBUMIL dapat diketahui dengan mengukur penerimaan Pengguna terhadap SIMBUMIL. Metode yang digunakan untuk mengukur penerimaan Pengguna dilakukan dalam tiga tahap, yaitu tahap pelatihan, tahap survey, dan tahap analisis. Model pengukuran terhadap kemudahan, kegunaan, dan keinginan untuk menggunakan SIMBUMIL menggunakan Technology Acceptance Model (TAM). Aspek kemudahan diukur dengan menggunakan pertanyaan yang mewakili Variabel Perceived Ease of Use (PEU). Pengukuran kegunaan SIMBUMIL bagi Pengguna dilakukan dengan menggunakan Variabel Perceived Of Usefullness (POU). Penerimaan Pengguna terhadap SIMBUMIL diketahui melalui pertanyaan untuk variabel use of SIMBUMIL. Hasil yang diperoleh dari pengukuran ini adalah Pengguna dapat menjelaskan kemudahan dan manfaat yang akan mereka dapatkan jika menggunakan SIMBUMIL, selain itu Pengguna juga dapat menentukan hal-hal yang harus dilakukan ketika menggunakan SIMBUMIL dalam pekerjaan seperti pemeriksaan yang lebih teliti karena hasil pemeriksaan akan digunakan oleh Pengguna lain.

CLEC12A is a myeloid inhibitory receptor that negatively regulates inflammation in mouse models of autoimmune and autoinflammatory arthritis. Reduced CLEC12A expression enhances myeloid cell activation and inflammation in CLEC12A knock-out mice with collagen antibody-induced or gout-like arthritis. Similarly to other C-type lectin receptors, CLEC12A harbours a stalk domain between its ligand binding and transmembrane domains. While it is presumed that the cysteines in the stalk domain have multimerisation properties, their role in CLEC12A expression and/or signaling remain unknown. We thus used site-directed mutagenesis to determine whether the stalk domain cysteines play a role in CLEC12A expression, internalisation, oligomerisation, and/or signaling. Mutation of C118 blocks CLEC12A transport through the secretory pathway diminishing its cell-surface expression. In contrast, mutating C130 does not affect CLEC12A cell-surface expression but increases its oligomerisation, inducing ligand-independent phosphorylation of the receptor. Moreover, we provide evidence that CLEC12A dimerisation is regulated in a redox-dependent manner. We also show that antibody-induced CLEC12A cross-linking induces flotillin oligomerisation in insoluble membrane domains in which CLEC12A signals. Taken together, these data indicate that the stalk cysteines in CLEC12A differentially modulate this inhibitory receptor’s expression, oligomerisation and signaling, suggestive of the regulation of CLEC12A in a redox-dependent manner during inflammation.

Background and Objectives : The rate of mother-to-child transmission of human immunodeficiency virus (HIV) type 1 has been reported to be high in Saudi Arabia. We report the rate of such transmission among a cohort of HIV-infected women enrolled in an HIV program at a tertiary care facility in Riyadh. Methods : All HIV-infected women who became pregnant and delivered during their follow-up between January 1994 and June 2006 were included in this study. HIV viral load and CD4+ T-lymphocyte count near-term, the mode of delivery, and the HIV status of the newborn at 18 months were recorded. All women were counseled and managed according to the three-step PACTG 076 protocol. Results : Of 68 HIV-infected women in the cohort, 31 had 40 pregnancies; one aborted at 13 weeks gestation. The mode of delivery was elective cesarean delivery in 28 pregnancies (70%) at 36 weeks gestation, and 11 (27.5%) had normal spontaneous vaginal delivery. The median CD4+ T-lymphocyte count near-term was 536 cells per cubic millimeter and the median viral load for 25 pregnancies was 1646 copies/mL, with only nine pregnancies (22.5%) having viral loads of more than 1000 copies/mL. Fourteen pregnancies (35%) had undetectable HIV prior to delivery. All patients were taking antiretroviral therapy during pregnancy and delivery. All 39 newborns tested negative for HIV infection at the age of 18 months; none of the newborns was breastfed. Conclusions : Contrary to previous local experience, diagnosis, management, and antiretroviral therapy almost eliminated mother-to-child transmission of HIV-1 in our patient population.

Small heat shock proteins (sHSPs) are oligomeric stress proteins characterized by an α-crystallin domain (ACD) surrounded by a N-terminal arm and C-terminal extension. Publications on sHSPs have reported that they exist in prokaryotes and eukaryotes but, to our knowledge, not in viruses. Here we show that sHSPs are present in some cyanophages that infect the marine unicellular cyanobacteria, Synechococcus and Prochlorococcus. These phage sHSPs contain a conserved ACD flanked by a relatively conserved N-terminal arm and a short C-terminal extension with or without the conserved C-terminal anchoring module (CAM) L-X-I/V, suggested to be implicated in the oligomerization. In addition, cyanophage sHSPs have the signature pattern, P-P-[YF]-N-[ILV]-[IV]-x(9)-[EQ], in the predicted β2 and β3 strands of the ACD. Phylogenetically, cyanophage sHSPs form a monophyletic clade closer to bacterial class A sHSPs than to cyanobacterial sHSPs. Furthermore, three sHSPs from their cellular host, Synechococcus, are phylogenetically close to plants sHSPs. Implications of evolutionary relationships between the sHSPs of cyanophages, bacterial class A, cyanobacteria, and plants are discussed.

Methane (CH₄) and nitrous oxide (N₂O) are critical biogenic greenhouse gases (GHGs) with global warming potentials substantially greater than that of carbon dioxide (CO₂). The exchange of these gases in tropical forests, particularly via foliar processes, remains poorly understood. We quantified foliar CH₄ and N₂O fluxes among tropical tree species and examined their potential association with the leaf economics spectrum (LES) traits. Sampling within Lawachara National Park, Bangladesh, we used in-situ measurements of foliar CH₄ and N₂O fluxes employing off-axis integrated cavity output spectroscopy (CH₄, CO₂ and H₂O) and optical feedback-cavity enhanced absorption spectroscopy (N₂O) analyzers. Leaves were measured under dark, low, and high (0, 100, and 1000 μmol·m -2 ·s -1 ) light conditions. Surveyed tree species exhibited both net foliar uptake and efflux of CH₄, with a mean flux not different from zero, suggesting negligible net foliar emissions at the stand level. Plant families showed differences in CH₄, but not N₂O fluxes. Consistent efflux was observed for N₂O, with a mean of 0.562 ± 0.060 pmol·m -2 ·s -1 . Pioneer species exhibited a higher mean N₂O flux (0.81 ± 0.17 pmol·m -2 ·s -1 ) compared to late-successional species (0.37 ± 0.05 pmol·m -2 ·s -1 ). Pioneer species also showed a trend toward a higher mean CH₄ flux (0.24 ± 0.21 nmol·m -2 ·s -1 ) compared to mid-successional (-0.01 ± 0.26 nmol·m -2 ·s -1 ) and late-successional species (-0.05 ± 0.28 nmol·m -2 ·s -1 ). Moreover, among all leaf traits within the leaf economic spectrum, a significant positive relationship was observed between leaf N₂O flux and total leaf nitrogen. Our results suggest that pioneer tree species significantly contribute to net CH₄ and N₂O emissions, potentially counteracting the carbon sequestration benefits in regenerating tropical forests. These findings indicate that accurate GHG budgeting should include direct measurements of foliar CH₄ and N₂O fluxes. Moreover, the results suggest that forest conservation and management strategies that prioritize late successional species will better mitigate GHG emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The neurocutaneous flap was developed based on the understanding that every superficial cutaneous nerve includes vessels, also known as vasa nervorum or paraneural vessels, which run around and inside the nerves and deliver blood to the skin above. A cutaneous perforator connected to paraneural vessels that vascularize the skin and nerves is referred to as a neurocutaneous perforator. The lateral antebrachial cutaneous nerve (LACN), the most dependable blood supply from the primary underlying veins of the neurocutaneous flap, is the subject of this study., Methods: We reviewed the results of 30 flap coverage procedures in 10 children. The applied flap was based distally along the radial aspect of the hand and wrist. The pivot point of the flap was located dorsally. This study considered patients with posttraumatic tissue loss, vital structure exposure, or hand contractures with an LACN flap. There was a case-by-case assessment., Results: Thirteen male patients were included; their ages ranged from 6 to 65 years. Demographic data, preoperative cause of trauma, and postoperative complications were collected. Statistically significant improvements were observed after flap healing., Conclusions: The LACN flap is a more versatile flap with less morbidity than other alternative flaps for coverage of soft tissue defect restoration around the hand, wrist, and distal forearm., Competing Interests: Conflicts of interest and sources of funding: nine declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Mushroom farming using agri-waste as substrates can offer a sustainable solution to the food security challenges of inadequate and imbalanced diets. Developing strategies to exploit the potential of the mushroom industry fully is yet to be explored in Bangladesh. We, thus, conducted this study to investigate the challenges and opportunities associated with mushroom farming, as well as the characteristics of farms and employees engaged in this industry. A directional stepwise multiple regression analysis showed self-motivation, spawn cost, farm size, and training are the key influencing factors driving profitability. Farm surveys identified SWOT factors with 24 sub-factors cross-validated with expert consultations. The sub-factors were categorized as beneficial (strength and opportunities) and cost (weakness and threats) to formulate the SWOT strategies using the Grey-TOPSIS method. Results indicate a favorable scenario exists for the industry in Bangladesh, with significant opportunities (group weight 0.53) and minimal threats (group weight 0.09). We proposed 12 strategic alternatives for the sustainable growth of this industry. This top-ranking strategy is not only to secure funding (relative closeness, C +  = 0.87) but also to provide more accessible loan options envisioning a strategic expansion of business operations in Bangladesh. The evaluation highlighted the significance of collaboration with other mushroom farmers to maximize the gain in marketing that will substantially expand the local demand ( C +  = 0.697). Besides, product diversification is also underscored as an important strategy for the growth of the industry. These prioritized SWOT strategies lay the groundwork for policy development, aiding decision-makers in steering the mushroom industry towards sustainable growth for developing countries like Bangladesh. Promoting such an eco-friendly industry will generate ample opportunities for women's employment and appreciable profit while contributing to environmental improvement through recycling agri-waste., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The ORF3a is a large accessory protein in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which plays an important role in virulence and viral replication; especially in inflammasome activation and apoptosis. However,, the existing cryo-EM structure of SARS-CoV-2 ORF3a is incomplete, . making it challenging to understand its structural and functional features. The aim of this study is to investigate the dynamic behaviors of the full-sequence homology model of ORF3a and compare it with the cryo-EM structure using microsecond molecular dynamics simulations. The previous studies indicated that the unresolved residues of the cryo-EM structure are not only involved in the pathogenesis of the SARS-CoV-2 but also exhibit a significant antigenicity. The dynamics scenario of homology model revealed higher RMSD, Rg, and SASA values with stable pattern when compared to the cryo-EM structure. Moreover, the RMSF analysis demonstrated higher fluctuations at specific positions (1-43, 97-110, 172-180, 219-243) in the model structure, whereas the cryo-EM structure displayed lower overall drift (except 1-43) in comparison to the model structure.Secondary structural features indicated that a significant unfolding in the transmembrane domains and β-strand at positions 166 to 172, affecting the stability and compactness of the cryo-EM structure , whereas the model exhibited noticeable unfolding in transmembrane domains and small-coiled regions in the N-terminal. , The results from molecular docking and steered molecular dynamics investigations showed the model structure had a greater number of non-bonding interactions, leading to enhanced stability when compared to the cryo-EM structure. Consequently, higher forces were necessary for unbinding of the baricitinib and ruxolitinib inhibitors from the model structure.. Our findings can help better understanding of the significance of unresolved residues at the molecular level. Additionally, this information can guide researchers for experimental endeavors aimed at completing the full-sequence structure of the ORF3a.Communicated by Ramaswamy H. Sarma.

HIV-1 integrase (IN), a major protein in the HIV life cycle responsible for integrating viral cDNA into the host DNA, represents a promising drug target. Small peptides have emerged as antiviral therapeutics for HIV because of their facile synthesis, highly selective nature, and fewer side effects. However, selecting the best candidates from a vast pool of peptides is a daunting task. In this study, multistep virtual screening was employed to identify potential peptides from a list of 280 HIV inhibitory peptides. Initially, 80 peptides were selected based on their minimum inhibitory concentrations (MIC). Then, molecular docking was performed to evaluate their binding scores compared to HIP000 and HIP00N which are experimentally validated HIV-1 integrase binding peptides that were used as a positive and negative control, respectively. The top-scoring docked complexes, namely, IN-HIP1113, IN-HIP1140, IN-HIP1142, IN-HIP678, IN-HIP776, and IN-HIP777, were subjected to initial 500 ns molecular dynamics (MD) simulations. Subsequently, HIP776, HIP777, and HIP1142 were selected for an in-depth mechanistic study of peptide interactions, with multiple simulations conducted for each complex spanning one microsecond. Independent simulations of the peptides, along with comparisons to the bound state, were performed to elucidate the conformational dynamics of the peptides. These peptides exhibit strong interactions with specific residues, as revealed by snapshot interaction analysis. Notably, LYS159, LYS156, VAL150, and GLU69 residues are prominently involved in these interactions. Additionally, residue-based binding free energy (BFE) calculations highlight the significance of HIS67, GLN148, GLN146, and SER147 residues within the binding pocket. Furthermore, the structure-activity relationship (SAR) analysis demonstrated that aromatic amino acids and the overall volume of peptides are the two major contributors to the docking scores. The best peptides will be validated experimentally by incorporating SAR properties, aiming to develop them as therapeutic agents and structural models for future peptide-based HIV-1 drug design, addressing the urgent need for effective HIV treatments., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The L84S mutation has been observed frequently in the ORF8 protein of SARS-CoV-2, which is an accessory protein involved in various important functions such as virus propagation, pathogenesis, and evading the immune response. However, the specific effects of this mutation on the dimeric structure of ORF8 and its impacts on interactions with host components and immune responses are not well understood. In this study, we performed one microsecond molecular dynamics (MD) simulation and analyzed the dimeric behavior of the L84S and L84A mutants in comparison to the native protein. The MD simulations revealed that both mutations caused changes in the conformation of the ORF8 dimer, influenced protein folding mechanisms, and affected the overall structural stability. In particular, the 73 YIDI 76 motif has found to be significantly affected by the L84S mutation, leading to structural flexibility in the region connecting the C-terminal β4 and β5 strands. This flexibility might be responsible for virus immune modulation.  The free energy landscape (FEL) and principle component analysis (PCA) have also supported our investigation. Overall, the L84S and L84A mutations affect the ORF8 dimeric interfaces by reducing the frequency of protein-protein interacting residues (Arg52, Lys53, Arg98, Ile104, Arg115, Val117, Asp119, Phe120, and Ile121) in the ORF8 dimer.  Our findings provide detail insights for further research in designing structure-based therapeutics against the SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

The net effect of forest disturbances, such as fires and harvesting, on soil greenhouse gas fluxes is determined by their impacts on both biological and physical factors, as well as the temporal dynamics of these effects post-disturbance. Although harvesting and fire may have distinct effects on soil carbon (C) dynamics, the temporal patterns in soil CO 2 and CH 4 fluxes and the potential differences between types of disturbances, remain poorly characterized in boreal forests. In this study, we measured soil CO 2 and CH 4 fluxes using a off-axis integrated cavity output spectroscopy system in snow-free seasons over two years in post-harvest and post-fire chronosequence sites within a mixedwood boreal forest in northwestern Ontario, Canada. Soil CO 2 efflux showed a post-disturbance peak, with differing dynamics depending on the disturbance type: post-harvest stands exhibited a nearly tenfold increase (from ∼1 to ∼11 μmol CO 2 . m -2. s -1 ) from 1 to 9-10 years post-disturbance, followed by a steep decline; post-fire stands showed a more gradual increase, peaking at ∼6-7.2 μmol CO 2 . m -2. s -1 after ∼12-15 years. The youngest post-harvest stands were net sources of CH 4 ,whereas post-fire stands were never net CH 4 sources. In both disturbance types, the strength of the CH 4 sink increased with stand age, approaching ∼2.4 nmol . m -2. s -1 by 15 years post-disturbance. Volumetric water content, bulk density, litter depth, and pH were significant predictors of CO 2 fluxes; for CH 4 fluxes, litter depth, pH, and the interaction of VWC and soil temperature were significant predictors in both disturbance types, with EC also showing a relationship in post-harvest stands. Our findings indicate that while soil CH 4 oxidation rapidly recovers following disturbance, both post-harvest and post-fire stands show a multi-decade release of soil CO 2 that is too large to be offset by C gains over this period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: According to Bangladesh Demographic and Health Survey (2022), neonatal mortality, comprising 67% of under-5 deaths in Bangladesh, is significantly attributed to prematurity and low birth weight (LBW), accounting for 32% of neonatal deaths. Respiratory distress syndrome (RDS) is a prevalent concern among preterm and LBW infants, leading to substantial mortality. The World Health Organization (WHO) recommends bubble continuous positive airway pressure (bCPAP) therapy, but the affordability and accessibility of conventional bCPAP devices for a large number of patients become major hurdles in Bangladesh due to high costs and resource intensiveness. The Vayu bCPAP, a simple and portable alternative, offers a constant flow of oxygen-enriched, filtered, humidified, and pressurized air. Our study, conducted in five health facilities, explores the useability, acceptability, and perceived treatment outcome of Vayu bCPAP in the local context of Bangladesh., Methods: A qualitative approach was employed in special care newborn units (SCANUs) of selected facilities from January to March 2023. Purposive sampling identified nine key informants, 40 in-depth interviews with service providers, and 10 focus group discussions. Data collection and analysis utilized a thematic framework approach led by trained anthropologists and medical officers., Results: Service providers acknowledged Vayu bCPAP as a lightweight, easily movable, and cost-effective device requiring minimal training. Despite challenges such as consumable shortages and maintenance issues, providers perceived the device as user-friendly, operable with oxygen cylinders, and beneficial during referral transportation. Treatment outcomes indicated effective RDS management, reduced hospital stays, and decreased referrals. Though challenges existed, healthcare providers and facility managers expressed enthusiasm for Vayu bCPAP due to its potential to simplify advanced neonatal care delivery., Conclusions: The Vayu bCPAP device demonstrated useability, acceptability, and favorable treatment outcomes in the care of neonates with RDS. However, sustained quality service necessitates continuous monitoring, mentoring and retention of knowledge and skills. Despite challenges, the enthusiasm among healthcare providers underscores the potential of Vayu bCPAP to save lives and simplify neonatal care delivery. Development of Standard Operating procedure on Vayu bCPAP is required for systematic implementation. Further research is needed to determine how the utilization of Vayu bCPAP devices enhances accessibility to efficient bCPAP therapy for neonates experiencing RDS., Competing Interests: CB and SW were employed by Save the Children Federation, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Banik, Halim, Md. Abdullah, Oishee, Boyce, Dey, Mannan, Moni, Shabuj, Jahan, Chowdhury, Afroze, Wall and Shahidullah.)

This study aims to analyze the impact of trade openness and Sustainable Development Goals, Financial Development, and Technology on the economic growth of Brazil, Russia, India, China and Colombia, Indonesia, Vietnam, Egypt, Turkey, South Africa countries. The present analysis employs a balanced panel data set from 1996 to 2022. This study also uses various tests, such as the Johansen-Fisher cointegration and Granger causality test. The study's findings suggest that economic growth, trade openness, Sustainable Development Goals, financial development, inflation, technology, labor forces, and financial openness have a long-term relationship among them. In the long run, a positive relationship exists between economic growth, trade openness, and the sustainable development goals index in (BRIC) and (CIVETS) countries. Based on the heterogeneous panel non-causality tests, the findings demonstrate that trade openness and Sustainable Development Goals are a unidirectional causality between trade openness, Sustainable Development Goals, and economic growth., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Md. Abdul Halim reports a relationship with Mawlana Bhashani Science and Technology University that includes: employment and non-financial support. Md. Abdul Halim has patent No with royalties paid to No. Nothing else that may be perceived to have influenced the submitted work. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in viral replication and transcription and received great attention as a vital target for drug/peptide development. Therapeutic agents such as small-molecule drugs or peptides that interact with the Cys-His present in the catalytic site of Mpro are an efficient way to inhibit the protease. Although several emergency-approved vaccines showed good efficacy and drastically dropped the infection rate, evolving variants are still infecting and killing millions of people globally. While a small-molecule drug (Paxlovid) received emergency approval, small-molecule drugs have low target specificity and higher toxicity. Besides small-molecule drugs, peptide therapeutics are thus gaining increasing popularity as they are easy to synthesize and highly selective and have limited side effects. In this study, we investigated the therapeutic value of 67 peptides targeting Mpro using molecular docking. Subsequently, molecular dynamics (MD) simulations were implemented on eight protein-peptide complexes to obtain molecular-level information on the interaction between these peptides and the Mpro active site, which revealed that temporin L, indolicidin, and lymphocytic choriomeningitis virus (LCMV) GP1 are the best candidates in terms of stability, interaction, and structural compactness. These peptides were synthesized using the solid-phase peptide synthesis protocol, purified by reversed-phase high-performance liquid chromatography (RP-HPLC), and authenticated by mass spectrometry (MS). The in vitro fluorometric Mpro activity assay was used to validate the computational results, where temporin L and indolicidin were observed to be very active against SARS-CoV-2 Mpro with IC 50 values of 38.80 and 87.23 μM, respectively. A liquid chromatography-MS (LC-MS) assay was developed, and the IC 50 value of temporin L was measured at 23.8 μM. The solution-state nuclear magnetic resonance (NMR) structure of temporin L was determined in the absence of sodium dodecyl sulfate (SDS) micelles and was compared to previous temporin structures. This combined investigation provides critical insights and assists us to further develop peptide inhibitors of SARS-CoV-2 Mpro through structural guided investigation., (© 2023 European Peptide Society and John Wiley & Sons, Ltd.)

Addressing the acute pesticide poisoning and toxicity to humans, is a global challenge of top priority. Serum albumin is the most abundant plasma protein, capable of binding with herbicide and pesticide residues. This study reports multifaceted approaches for in-depth and robust investigation of the molecular interactions of selected pesticides, including propanil (PPL), bromoxynil (BXL), metolachlor (MLR) and glyphosate (GPE) with bovine serum albumin (BSA) proteins using experimental (Raman and FTIR spectroscopy, native mass spectrometry and high field 1 H NMR), molecular dynamics (MD) simulation and principal component analysis (PCA). The binding of pesticides with BSA resulted in BSA amide I and amide II Raman spectral shifts. PCA of Raman spectra of serum-pesticide complexes showed the grouping of pesticides on the score plot based on the similarities and differences in pesticides' chemical structures. Native mass spectrometry results revealed strong adduct formation of the pesticides with the protein. The observed changes in chemical shifts, peak broadening or peak disappearance of characteristic proton signals of the pesticides, indicated altered chemical environments due to binding BSA-pesticides interactions. The results of MD simulation conducted for over 500 ns revealed strong pesticides interaction with LEU197, LEU218, LEU237, TRP213, SER286 and ILE289 residues to the site I of BSA. Free energy landscapes provided insights into the conformational changes in BSA on the binding of pesticides. Overall, the experimental and computational results are in consonant and indicate the binding of pesticides into the site I and site II (sub-domain IIA) of the BSA via hydrogen bonding, non-covalent and hydrophobic interactions.Communicated by Ramaswamy H. Sarma.

Background: Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown., Aim: The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC., Methods: Immunohistochemistry was performed on tissue sections as follows: CAC ( n = 59); sporadic CRC (sCRC) ( n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) ( n = 22); paracancerous IBD (pIBD) ( n = 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases., Results: Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS ( P < 0.01) and IL-1β ( P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa ( P < 0.001), whereas IL-1β was higher ( P < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases., Conclusion: Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by Upsala Medical Society.)

Objectives: Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes., Materials and Methods: We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury., Results: Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%)., Conclusions: We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.

Objectives: The benefits of reduction in low-density lipoprotein cholesterol by evolocumab by nearly 60% has not been evaluated among kidney transplant recipients to our knowledge. We assessed the efficacy and safety of evolocumab, a proprotein convertase subtilisin/kexin-9 inhibitor, in reducing lipids and cardiovascular events among kidney transplant recipients in a randomized controlled study., Materials and Methods: Between June 2017 and June 2019, we enrolled 197 kidney transplant recipients with high cardiovascular risk score (>20). Patients who received evolocumab (140 mg/2 weeks) comprised group 1 (n = 98), and patients maintained on statin therapy comprised group 2 (n = 99). We followed patients clinically and with necessary laboratory investigations over 24 months., Results: The 2 groups had comparable demographic characteristics (P > .05). Before enrollment in the study, smokers were significantly more prevalent in group 1, whereas posttransplant diabetes mellitus was more prevalent in group 2 (P = .033). Moreover, baseline serum creatinine was higher in group 1, whereas immunosuppression was equivalent in both groups (P > .05). We found no significant differences between the 2 groups concerning cardiovascular events, and both graft and patient outcomes were comparable (P > .05). The higher baseline cholesterol in group 1 (5.5 vs 4.7 mmol/L; P < .001) decreased significantly after 3 months and thereafter (P = .031) compared with levels in group 2 and baseline values (P < .001). We reported 2 cases of acute myocardial infarction and 1 atrial fibrillation in group 2., Conclusions: Proprotein convertase subtilisin/kexin-9 inhibitors, as an added therapy to statins, are safe and effective in treating hypercholesterolemia after kidney transplant. Evolocumab can minimize cardiovascular events after kidney transplant in patients with high events at baseline. Longer-term trials with larger number of patients are needed to confirm its beneficial effects on cardiovascular complications and patient and graft survival.

Objectives: Posttransplant anemia might be associated with cardiovascular morbidity and increased mortality. To our knowledge, the debate on anemia correction has neither been revisited nor decided definitively. We aimed to assess the effects of full correction of posttransplant anemia on the cardiovascular system and quality of life among renal transplant recipients with stable graft function who were using erythropoietin-stimulating agents., Materials and Methods: We enrolled 247 kidney recipients with stable graft function to be assessed for anemia. Eligible patients were randomized to achieve targeted hemoglobin of 11 to 12 g/dL (group 1, n = 183) or of 13 to 15 g/dL (group 2, n = 64) with the use of erythropoietin-stimulating agents. Patients underwent monthly clinical and laboratory evaluations of kidney graft function. Quality of life and echocardiography were assessed at study start and at 12 months., Results: The 2 groups were comparable regarding pretransplant characteristics. In group 2, we observed comparable posttransplant complications (P > .05) but better graft function at 6 months and better cardiac indexes at 1 year of the study (P < .05). At 12 months, quality of life had improved after full correction of posttransplant anemia in the renal transplant recipients who received erythropoietinstimulating agents., Conclusions: Full correction of posttransplant anemia in renal transplant recipients was associated with improved quality of life and cardiac indexes without an effect on cardiovascular comorbidity.

Objectives: COVID-19, which began in Wuhan, China, in December 2019, has caused a large global pandemic and poses a serious threat to public health. As of March 20, 2023, over 13 billion COVID-19 vaccine doses had been administered worldwide, with the United States accounting for almost 672 million of total administered vaccine doses. Some COVID-19 patients experience sudden and rapid deterioration with onset of fatal cytokine storm syndrome, which increased interest in the mechanisms, diagnosis, and therapy of cytokine storm syndrome. Although the prototypic concept of cytokine storm syndrome was first proposed 116 years ago, we have only begun to study and understand it over the past 30 years. Clinical data suggest that Th1, Th2, and Th3 and macrophage origin cytokines have effects on cytokine storm syndrome. We aimed to study the effects of cytokine gene polymorphisms in cytokine storm syndrome mechanisms and progression of COVID-19 among kidney transplant recipients., Materials and Methods: We screened 309 patients who had undergone kidney transplant at the Hamad Al Essa organ transplant center. From February 2020 through February 2022, 64 patients (20.7%) developed COVID-19 infection. Patient blood samples were screened for the key Th1, Th2, Th3, and macrophage cytokines gene polymorphisms., Results: We observed that only transforming growth factor-β C (+869) T codon 10, but not interferon-γ T (+874) A, interleukin 6 G (-174) C, and interleukin 4C (-490) T, was significantly associated with progression of COVID-19 and cytokine storm syndrome mechanisms (P < 0.001)., Conclusions: Our finding can be a profoundly important factor in the initiation of cytokine storm syndrome and progress of COVID-19.