Tetrahydrocarbazole is the central core for several biologically active alkaloids, and regioselective synthesis of this core is a challenging task. Herein, we report an efficient strategy for the synthesis of this core involving palladium-catalyzed intramolecular arylation reaction with excellent regioselectivity (>99%) starting from N-phenyl-bromoalkene without having any relocation of double bonds via competitive palladium-catalyzed isomerization reaction. Broad functional group tolerance and exclusive regioselectivity have been observed for meta-substituted halide substrates. Furthermore, this reaction can be scalable on the gram scale.
Sickle cell disease (SCD) is characterized by hemolysis, vaso-occlusion, and ischemia. HIV-1 infection was previously shown to be suppressed in SCD PBMCs. Here, we report that HIV-1 suppression is attributed to the increased expression of iron, hypoxia, and interferon-induced innate antiviral factors. Inhibition of upregulated antiviral genes, HMOX-1, CDKN1A, and CH25H, increased HIV-1 replication in SCD PBMCs, suggesting their critical role in HIV-1 suppression. Levels of IFN-ß were elevated in SCD patients. Sickle cell hemoglobin (HbS) treatment of THP-1-derived and primary monocyte-derived macrophages induced production of IFN-ß, upregulated antiviral gene expression, and suppressed HIV-1 infection. Infection with mouse-adapted EcoHIV was suppressed in the SCD mice that also exhibited elevated levels of antiviral restriction factors. Our findings suggest that hemolysis and release of HbS leads to the induction of IFN-ß production, induction of cellular antiviral state by the expression of iron and IFN-driven factors, and suppression of HIV-1 infection.
Pectinolytic enzymes are among the important group of industrial enzymes that have wide applications in different food industries. In this study, pectinase-based silica nanocarriers were synthesized using co-precipitation and cross-linking techniques. The resulting silica nanoparticles were investigated using scanning electron microscopy (SEM), energy-dispersive electron microscopy (EDEX), and X-ray diffraction (XRD) for determination of its morphology, elemental composition, and crystalline pattern. Under the optimal immobilization conditions like 1.5 % glutaraldehyde, 3000 IU/mg pectinase concentration, 90 min immobilization time and 40 °C immobilization temperature, pectinase showed maximum immobilization yield. The immobilization of pectinase onto the silica nanocarriers led to enhanced catalytic characteristics, displaying higher enzymatic activity across various temperature and pH levels compared to soluble pectinase. Moreover, the immobilization substantially improved the temperature stability of pectinase, exhibiting 100 % of its initial activity even after 120 h of pre-incubation at 50 °C. Additionally, the silica nanocarrier pectinase retained 100 % of its original activity even after being reused 10 times in a single batch of reactions. These findings indicate that the immobilization of silica nanocarriers effectively enhances pectinase's industrial capabilities, making it economically feasible for industrial use and an efficient system for various biotechnological applications.
Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), often associated with atherosclerosis. However, SCAD has been increasingly recognized as a distinct entity, especially in young females without traditional cardiovascular risk factors. We present a case of a 56-year-old female with systemic lupus erythematosus (SLE) who developed multivessel SCAD involving the right coronary artery (RCA) and ramus. The patient's clinical presentation included typical chest pain, elevated troponins, and ST depressions on electrocardiography. Coronary angiography confirmed the presence of SCAD, classified as type 4 in the RCA and type 2 in the ramus. Prompt diagnosis and treatment resulted in a favorable prognosis. This case emphasizes the importance of considering SCAD in SLE patients presenting with ACS symptoms, particularly in younger women without evident cardiovascular risk factors. Early invasive coronary angiography is recommended for accurate diagnosis and timely management. SCAD can lead to significant complications and requires meticulous attention during angiographic procedures. Conservative management is often preferred, as most uncomplicated cases of SCAD heal spontaneously. Further research is needed to determine optimal treatment strategies and long-term outcomes for patients with SCAD, especially in the presence of underlying inflammatory conditions like SLE.
Applications of photochemistry are becoming very popular in modern-day life due to its operational simplicity, environmentally friendly and economically sustainable nature in comparison to thermochemistry. In particular photoinduced radical polymerisation (PRP) reactions are finding more biological applications and especially in the areas of dental restoration processes, tissue engineering and artificial bone generation. A type-II photoinitiator and co-initiator-promoted PRP turned out to be a cost-effective protocol, and herein we report the design and synthesis of a new efficient co-initiator for a PRP reaction via a barrierless sequential conjugate addition reaction. Experimental mechanistic observations have been further complemented by computational data. Time for newly synthesised 1,2-benzenedithiol (DTH) based co-initiator promoted polymerisation of urethane dimethacrylate (UDMA, 70 %) and triethylene glycol dimethacrylate (TEGDMA, 30 %) in presence of 450â nm LED (15â W) under the aerobic conditions is 38â seconds. Polymeric material has high glass transition temperature, improved mechanical strength (860 BHN) and longer in-depth polymerisation (3â cm).
In patients with sickle cell disease (SCD), chronic hemolysis and frequent blood transfusions cause iron overload and accumulation in the kidneys. The iron deposition is found in the renal cortex and correlates with the severity of hemolysis. In this study, we observed a significant accumulation of iron in the renal cortex of a mouse model of SCD, and assessed the expression of the proteins involved in maintaining renal iron homeostasis. Despite the intracellular iron accumulation, the levels of the transferrin receptor in the kidneys were increased, but the levels of the iron exporter ferroportin were not altered in SCD mice. Ferroportin is regulated by hepcidin, which binds to it and promotes its degradation. We found reduced serum hepcidin levels but increased renal hepcidin production in SCD mice. Furthermore, we observed significant macrophage infiltration and increased expression of intercellular adhesion molecule 1 in the endothelial cells of the kidneys in SCD mice. These observations correlated with elevated levels of proinflammatory cytokines IL-1ß and IL-6, which can potentially stimulate hepcidin expression. Taken together, our results demonstrate that in individuals with SCD, a renal inflammation state induces renal hepcidin production that blocks the upregulation of ferroportin levels, resulting in dysregulation of iron homeostasis in the kidney and iron deposition in the renal cortex.
Anemia, Sickle Cell , Hepcidins , Mice , Animals , Hepcidins/metabolism , Hemolysis , Endothelial Cells/metabolism , Iron/metabolism , Anemia, Sickle Cell/genetics
The Ebola virus (EBOV) transcriptional regulation involves host protein phosphatases PP1 and PP2A, which dephosphorylate the transcriptional cofactor of EBOV polymerase VP30. The 1E7-03 compound, which targets PP1, induces VP30 phosphorylation and inhibits EBOV infection. This study aimed to investigate the role of PP1 in EBOV replication. When EBOV-infected cells were continuously treated with 1E7-03, the NP E619K mutation was selected. This mutation moderately reduced EBOV minigenome transcription, which was restored by the treatment with 1E7-03. Formation of EBOV capsids, when NP was co-expressed with VP24 and VP35, was impaired with NPE 619K. Treatment with 1E7-03 restored capsid formation by NP E619K mutation, but inhibited capsids formed by WT NP. The dimerization of NP E619K, tested in a split NanoBiT assay, was significantly decreased (~ 15-fold) compared to WT NP. NP E619K bound more efficiently to PP1 (~ 3-fold) but not B56 subunit of PP2A or VP30. Cross-linking and co-immunoprecipitation experiments showed fewer monomers and dimers for NP E619K which were increased with 1E7-03 treatment. NP E619K showed increased co-localization with PP1α compared to WT NP. Mutations of potential PP1 binding sites and NP deletions disrupted its interaction with PP1. Collectively, our findings suggest that PP1 binding to the NP regulates NP dimerization and capsid formation, and that NP E619K mutation, which has the enhanced PP1 binding, disrupts these processes. Our results point to a new role for PP1 in EBOV replication in which NP binding to PP1 may facilitate viral transcription by delaying capsid formation and EBOV replication.
The inhalation, ingestion, and body absorption of noxious gases lead to severe tissue damage, ophthalmological issues, and neurodegenerative disorders; death may even occur when recognized too late. In particular, methanol gas present in traces can cause blindness, non-reversible organ failure, and even death. Even though ample materials are available for the detection of methanol in other alcoholic analogs at ppm level, their scope is very limited because of the use of either toxic or expensive raw materials or tedious fabrication procedures. In this paper, we report on a simple synthesis of fluorescent amphiphiles achieved using a starting material derived from renewable resources, this material being methyl ricinoleate in good yields. The newly synthesized bio-based amphiphiles were prone to form a gel in a broad range of solvents. The morphology of the gel and the molecular-level interaction involved in the self-assembly process were thoroughly investigated. Rheological studies were carried out to probe the stability, thermal processability, and thixotropic behavior. In order to evaluate the potential application of the self-assembled gel in the field of sensors, we performed sensor measurements. Interestingly, the twisted fibers derived from the molecular assembly could be able to display a stable and selective response towards methanol. We believe that the bottom-up assembled system holds great promise in the environmental, healthcare, medicine, and biological fields.
Transcription activation of latent human immunodeficiency virus-1 (HIV-1) occurs due to HIV-1 rebound, the interruption of combination antiretroviral therapy, or development of drug resistance. Thus, novel HIV-1 inhibitors, targeting HIV-1 transcription are needed. We previously developed an HIV-1 transcription inhibitor, 1E7-03, that binds to the noncatalytic RVxF-accommodating site of protein phosphatase 1 and inhibits HIV-1 replication in cultured cells and HIV-1-infected humanized mice by impeding protein phosphatase 1 interaction with HIV-1 Tat protein. However, host proteins and regulatory pathways targeted by 1E7-03 that contribute to its overall HIV-1 inhibitory activity remain to be identified. To address this issue, we performed label-free quantitative proteome and phosphoproteome analyses of noninfected and HIV-1-infected CEM T cells that were untreated or treated with 1E7-03. 1E7-03 significantly reprogramed the phosphorylation profile of proteins including PPARα/RXRα, TGF-ß, and PKR pathways. Phosphorylation of nucleophosmin (NPM1) at Ser-125 residue in PPARα/RXRα pathway was significantly reduced (>20-fold, p = 1.37 × 10-9), followed by the reduced phosphorylation of transforming growth factor-beta 2 at Ser-46 (TGF-ß2, >12-fold, p = 1.37 × 10-3). Downregulation of NPM1's Ser-125 phosphorylation was further confirmed using Western blot. Phosphorylation mimicking NPM1 S125D mutant activated Tat-induced HIV-1 transcription and exhibited enhanced NPM1-Tat interaction compared to NPM1 S125A mutant. Inhibition of Aurora A or Aurora B kinases that phosphorylate NPM1 on Ser-125 residue inhibited HIV-1, further supporting the role of NPM1 in HIV-1 infection. Taken together, 1E7-03 reprogrammed PPARα/RXRα and TGF-ß pathways that contribute to the inhibition of HIV-1 transcription. Our findings suggest that NPM1 phosphorylation is a plausible target for HIV-1 transcription inhibition.
HIV-1 , Nucleophosmin , Animals , Humans , Mice , Phosphorylation , Protein Phosphatase 1/metabolism , HIV-1/genetics , PPAR alpha/metabolism , Transforming Growth Factor beta/metabolism , Transcription, Genetic
Meckel's diverticulum (MD)1, the most common congenital anomaly of the gastrointestinal tract, occurs in 2% of the population with males being more symptomatic than females. In this case, a 32-year-old male presented with sudden onset colicky abdominal pain, bilious vomiting, and absolute constipation. Emergency laparotomy was done on his virgin abdomen, as a result MD and vitelline cyst along with a fibrous cord connecting the two were identified. Knotting of an ileal loop around this cord had resulted in intestinal obstruction. Meckel's diverticulectomy, along with cord resection, was carried out. The patient made smooth recovery and was discharged on the fifth postoperative day with no complications. The importance of this study is to highlight the case of symptomatic MD in an adult male as it can be a cause of intestinal obstruction and should always be considered in a patient presenting with symptoms of intestinal obstruction.
Cysts , Intestinal Obstruction , Meckel Diverticulum , Adult , Female , Male , Humans , Meckel Diverticulum/diagnosis , Meckel Diverticulum/diagnostic imaging , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Abdominal Pain/etiology , Laparotomy/adverse effects , Cysts/surgery
Introduction: Cocaine is a highly addictive substance that stimulates the sympathetic nervous system and cardiovascular system. A multitude of adverse cardiovascular events are associated with cocaine use including arrhythmia, congestive heart failure, coronary artery spasm and myocarditis. Case Report: We present a rare case of Takotsubo cardiomyopathy after recent use of cocaine in a female without any other identifiable risk factor. Discussion: Takotsubo cardiomyopathy (TCM) is a reversible cause of cardiomyopathy characterized by transient decrease in ejection fraction. Cocaine is a sympathomimetic that causes catecholamine surge and a variety of cardiovascular abnormalities. The association of cocaine use with Takotsubo cardiomyopathy is a rare occurrence, however the prognosis is generally good if diagnosis is made promptly. Conclusion: Physician vigilance is required to diagnose this rare cause of cardiomyopathy and reduce morbidity and mortality. LEARNING POINTS: This case highlights the need to investigate the use of cocaine in patients with cardiovascular disease because it may influence the disease diagnosis and management strategies.Left heart catheterization is imperative for diagnosis, and cessation of cocaine is the primary goal of post discharge therapy.This case shows that TCM should be suspected in a patient with a history of cocaine use.
Primary cardiac tumors are very rare and are often confused with other conditions due to clinical presentations or initial imaging. Here, we present a rare case of a 56-year-old male with right ventricular mass incidentally found on imaging. Appropriate testing should be conducted to rule out the possibility of a benign tumor. Asymptomatic patients with co-morbidities can be managed without surgery. More research is needed to devise guidelines for the management of these cases.
BACKGROUND: With the rapid development of the genomic sequence data for the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants Delta (B.1.617.2) and Omicron (B.1.1.529), it is vital to successfully identify mutations within the genome. OBJECTIVE: The main objective of the study is to investigate the full-length genome mutation analysis of 157 SARS-CoV-2 and its variant Delta and Omicron isolates. This study also provides possible effects at the structural level to understand the role of mutations and new insights into the evolution of COVID-19 and evaluates the differential level analysis in viral genome sequence among different nations. We have also tried to offer a mutation snapshot for these differences that could help in vaccine formulation. This study utilizes a unique and efficient method of targeting the stable genes for the drug discovery approach. METHODS: Complete genome sequence information of SARS-CoV-2, Delta, and Omicron from online resources were used to predict structure domain identification, data mining, and screening; employing different bioinformatics tools. BioEdit software was used to perform their genomic alignments across countries and a phylogenetic tree as per the confidence of 500 bootstrapping values was constructed. Heterozygosity ratios were determined in-silico. A minimum spanning network (MSN) of selected populations was determined by Bruvo's distance role-based framework. RESULTS: Out of all 157 different strains of SARS-CoV-2 and its variants, and their complete genome sequences from different countries, Corona nucleoca and DUF5515 were observed to be the most conserved domains. All genomes obtained changes in comparison to the Wuhan-Hu-1 strain, mainly in the TRS region (CUAAAC or ACGAAC). We discovered 596 mutations in all genes, with the highest number (321) found in ORF1ab (QHD43415.1), or TRS site mutations found only in ORF7a (1) and ORF10 (2). The Omicron variant has 30 mutations in the Spike protein and has a higher alpha-helix shape (23.46%) than the Delta version (22.03%). T478 was also discovered to be a prevalent polymorphism in Delta and Omicron variations, as well as genomic gaps ranging from 45 to 65aa. All 157 sequences contained variations and conformed to Nei's Genetic distance. We discovered heterozygosity (Hs) 0.01, mean anticipated Hs 0.32, the genetic diversity index (GDI) 0.01943989, and GD within population 0.01266951. The Hedrick value was 0.52324978, the GD coefficient was 0.52324978, the average Hs was 0.01371452, and the GD coefficient was 0.52324978. Among other countries, Brazil has the highest standard error (SE) rate (1.398), whereas Japan has the highest ratio of Nei's gene diversity (0.01). CONCLUSIONS: The study's findings will assist in comprehending the shape and kind of complete genome, their streaming genomic sequences, and mutations in various additions of SARS-CoV-2, as well as its different variant strains like Omicron. These results will provide a scientific basis to design the vaccines and understand the genomic study of these viruses.
COVID-19 , SARS-CoV-2 , Genomics , Humans , Mutation , Phylogeny , SARS-CoV-2/genetics
INTRODUCTION: Bezoars and polyps are an uncommon cause of mechanical intestinal obstruction. There are four different kinds of bezoars: phytobezoars, made of vegetables and fibers; trichobezoars, resulting from the ingestion of hair and frequently an expression of psychiatric disorders; lactobezoars, which are formed of milk curd; and pharmacobezoars, caused by drugs and medications. Signs and symptoms classically vary from abdominal pain to constipation, nausea, vomiting, and abdominal distension. We present a rare case of impending perforation along with an intraluminal polyp near ileocecal junction due to phytobezoar impaction. CASE PRESENTATION: Our patient was a 59-year-old Sindhi female with a known history of interstitial lung disease and hypertension who presented to the emergency department with complaints of abdominal pain and constipation for 1 week, vomiting for 5 days, and abdominal distension for 2 days. After a preoperative examination and her failure to respond to conservative therapy, she was taken to the operating room for exploratory laparotomy. A hard intraluminal mass was suspected to be obstructing the small bowel at the site of impending perforation. This mass was a phytobezoar along with an intraluminal polyp. Resection of the affected segment was performed, followed by ileoileal anastomosis, and a drain was left. The patient was discharged 1 week later and was found to be well with no complaints at 3 weeks follow-up. CONCLUSIONS: Early diagnosis of bezoars is important for early intervention and prevention of complications. Our case is unique as phytobezoar with intraluminal polyp is a rare clinical finding. Moreover, the signs and symptoms with which the patient presented are nonspecific and can be seen with multiple surgical emergencies.
Bezoars , Intestinal Obstruction , Abdominal Pain/etiology , Abdominal Pain/surgery , Bezoars/diagnosis , Bezoars/diagnostic imaging , Female , Humans , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intestine, Small/surgery , Laparotomy/adverse effects , Middle Aged
Aortic dissection (AD) is an injury to the innermost layer of the aorta, leading to the formation of a false lumen. AD usually presents with tearing chest pain radiating to the back and is a medical emergency. Other common symptoms include abdominal pain, diaphoresis, loss of consciousness, shortness of breath, stroke-like symptoms, or leg pain. Here, we present a rare case of an incidental finding of asymptomatic AD on computed tomography angiography performed after cardiac catheterization failure. The patient had a history of aortic aneurysm, hypertension, and heart failure. Appropriate imaging should be performed to rule out the possibility of AD in patients with risk factors and cardiac catheterization failure.
BACKGROUND: (SARS-COV-2) infection, led to a pandemic affecting many countries, resulting in hospitals diverting most of their resources to fight the pandemic. Breast cancer, already a healthcare dilemma, is also affected in this scenario. Our aim was to find out the impact of COVID-19 on presentation of breast cancer stage and its effects on overall onco-surgical management. METHODS: This cohort single-centered retrospective review was carried out at our hospital, over a period of 18 months. Females with known breast cancer were included in the study. Data was collected on performas by a single researcher. Effect of COVID pandemic on presentation stage and its impact on overall management was studied. SPSS 23.0 used for data analysis. A 95% CI was used. Descriptive statistics were presented as range/means. Categorical data was analyzed by Fisher exact test, t-test was applied to numerical data, p value ≤ 0.05 was considered significant. RESULTS: Out of 87 patients presenting with suspicious lump, 69 who had malignancy on histo-pathology were included in study. Twelve out of 69 were COVID positive. Sixty patients presented with advanced stage (≥stage 2b) out of which 21 underwent upstaging of disease due to delay in presentation/management. We found that 9 out of 12 (majority) Covid positive patients had disease upstaging. Overall main reason for delay in presentation was found to be unawareness of disease. CONCLUSION: We concluded that COVID-19 pandemic had no impact on presentation delay, breast cancer management/treatment and disease upstaging as compared to figures available for our population before the pandemic. However, our study showed significant correlation between disease upstaging and COVID status. This led us to reconsider our preformed protocols for COVID positive breast cancer patients. Our results can be used by future researchers to investigate if COVID itself can contributes in patho-physiology of upstaging in breast cancer or not.
Patients with sickle cell disease (SCD) have a lower risk for HIV-1 infection. We reported restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory, and hemolytic factors, including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection. Ex vivo infection of SCT PBMCs exhibited an approximately twofold reduction of HIV-1 replication and lower levels of HIV-1 reverse transcription products, 2-long terminal repeat circle, HIV-1 integration, and gag RNA expression. SCT PBMCs had higher HO-1 messenger RNA (mRNA) and protein levels and reduced ribonucleotide reductase 2 (RNR2) protein levels. HO-1 inhibition by tin porphyrin eliminated ex vivo HIV-1 restriction. Among Howard University clinic recruits, higher levels of HO-1 and RNR2 mRNA and lower HIV-1 env mRNA levels were found in SCT individuals living with HIV-1. To determine the population-level effect of SCT on HIV-1 prevalence, we assessed SCT among women living with HIV (WLH) in the WIHS (Women Interagency HIV-1 Study). Among WIHS African-American participants, the prevalence of SCT was lower among women with HIV compared with uninfected women (8.7% vs 14.2%; odds ratio, 0.57; 95% confidence interval, 0.36-0.92; P = .020). WIHS WLH with SCT had higher levels of CD4+/CD8+ ratios over 20 years of follow-up (P = .003) than matched WLH without SCT. Together, our findings suggest that HIV-1 restriction factors, including HO-1 and RNR2, might restrict HIV-1 infection among individuals with SCT and limit the pathogenicity of HIV.
Anemia, Sickle Cell , HIV Infections , HIV-1 , Sickle Cell Trait , Anemia, Sickle Cell/epidemiology , Female , HIV Infections/epidemiology , Humans , Leukocytes, Mononuclear , Sickle Cell Trait/genetics
Combination antiretroviral therapy (cART) suppresses human immunodeficiency virus-1 (HIV-1) replication but is unable to permanently eradicate HIV-1. Importantly, cART does not target HIV-1 transcription, which is reactivated in latently infected reservoirs, leading to HIV-1 pathogenesis including non-infectious lung, cardiovascular, kidney, and neurodegenerative diseases. To address the limitations of cART and to prevent HIV-1-related pathogenesis, we developed small molecules to target the noncatalytic RVxF-accommodating site of protein phosphatase-1 (PP1) to prevent HIV-1 transcription activation. The PP1 RVxF-accommodating site is critical for the recruitment of regulatory and substrate proteins to PP1. Here, we confirm that our previously developed 1E7-03 compound binds to the PP1 RVxF-accommodating site. Iterative chemical alterations to 1E7-03 furnished a new analogue, HU-1a, with enhanced HIV-1 inhibitory activity and improved metabolic stability compared to 1E7-03. In a Split NanoBit competition assay, HU-1a primarily bound to the PP1 RVxF-accommodating site. In conclusion, our study identified HU-1a as a promising HIV-1 transcription inhibitor and showed that the PP1 RVxF-accommodating site is a potential drug target for the development of novel HIV-1 transcription inhibitors.
HIV-1 , Quinolines , HIV-1/drug effects , HIV-1/genetics , Humans , Protein Phosphatase 1/metabolism , Proteins , Quinolines/pharmacology
Sickle cell disease is prevalent in several parts of the world. Most hospitalizations of these patients are related to pain crisis episodes. Moreover, levels of hemoglobin are lower in sickle cell disease patients as compared with the general population. Complications related to sickle cell disease are managed with blood transfusions, hydroxyurea, and opioids. Despite these therapies, patients with sickle cell disease experience multiple pain crisis episodes leading to hospitalizations and end-organ damage. The US Food and Drug Administration has approved three new drugs-L-glutamine, voxelotor, and crizanlizumab-for the prophylaxis and treatment of complications related to sickle cell disease. This review was aimed at assessing the efficacy and safety of recently approved drugs for the treatment of sickle cell disease. A comprehensive search was made on PubMed and clinicaltrials.gov to look for clinical trials reporting the efficacy and safety of recently approved drugs for sickle cell disease. Based on the results of clinical trials, L-glutamine, voxelotor, and crizanlizumab were well tolerated by sickle cell disease patients. L-Glutamine and crizanlizumab reduced the number of sickle cell crisis episodes, while voxelotor improved the level of hemoglobin in sickle cell disease patients. These drugs were effective alone and in combination with hydroxyurea.
Anemia, Sickle Cell/therapy , Antisickling Agents/therapeutic use , Drug Approval , Anemia, Sickle Cell/metabolism , Anemia, Sickle Cell/physiopathology , Blood Transfusion , Clinical Trials as Topic , Humans
BACKGROUND: Leadless pacemakers (LPM) are introduced in cardiovascular market with a goal to avoid lead- and pocket-associated complications due to conventional artificial pacemakers (CPM). The comparison of LPM and CPM complications is not well studied at a case by case level. METHODS: Comprehensive literature was searched on multiple databases performed from inception to December 2019 and revealed 204 cases that received LPM with a comparison of CPM. The data of complications were extracted, screened by independent authors and analyzed using IBM SPSS Statistics for Windows, Version 22.0 (Armonk, NY: IBM Corp.). RESULTS: The complications of CPM were high in comparison to LPM in terms of electrode dislodgement (56% vs 7% of cases, p-value < .0001), pocket site infection rate (16% vs 3.4%, p-value = 0.02), and a lead fracture rate (8% vs 0%, p-value = 0.04). LPMs had a statistically non-significant two-times high risk of pericardial effusion (8%) compared to CPMs (4%) with a p-value = 0.8. CONCLUSION: LPMs appear to have a better safety profile than CPMs. There was a low pocket site and lead-related infections in LPM as compared to CPM. However, LPM can have twice the risk of pericardial effusion than CPMs, but this was not statistically significant.
