Understanding Creutzfeldt-Jakob disease in Iran: a systematic review of case reports.

OBJECTIVE: To systematically review the reported cases of Creutzfeldt-Jakob disease (CJD) in Iran. METHODS: A comprehensive literature review of CJD cases in Iran was undertaken using the PubMed®, Scopus® and Google Scholar databases. In addition, the Iranian database MagIran was searched for Persian language reports. Case selection used the following criteria: (i) patients of Iranian origin; (ii) publication in peer-reviewed journals or reputable medical databases; (iii) a definitive diagnosis of CJD based on established diagnostic criteria. RESULTS: Thirteen cases from twelve reports were included in this systematic review. The majority of the cases were female (11 of 13; 84.6%). The mean ± SD age of patients at hospital admission was 59.38 ± 7.44 years. The findings of the case review suggested that the prevalence of CJD in Iran is not fully established. CJD may be misdiagnosed alongside other clinical signs. The most prevalent early indications of the disease were psychiatric and neurological in nature. A considerable delay in diagnosis was observed in some cases and there was a shortage of brain autopsy records. CONCLUSION: Efforts to improve diagnostic capabilities, promote awareness and establish monitoring systems are necessary for managing the challenges of providing an early diagnosis of CJD in Iran.

Dexmedetomidine versus remifentanil in nasal surgery: a systematic review and meta-analysis.

BACKGROUND: Nasal surgeries, addressing anatomical variations for form and function, require careful anesthesia administration, including dexmedetomidine and remifentanil. This meta-analysis evaluates their safety and efficacy variations in nasal surgeries, emphasizing patient comfort and optimal outcomes. METHODS: Four electronic databases (PubMed, Scopus, Web of Science, and CINAHL Complete) were searched for records in English. Studies that measure the effect of dexmedetomidine versus remifentanil on patients underwent nasal surgery were included. The Cochrane Collaboration's tool was used to assess the quality of the included studies. A random-effect model was preferred and statistical analysis was performed by Stata software version 17. RESULTS: Out of an initial pool of 63 articles, five studies were selected for this analysis. All of these chosen studies were Randomized Controlled Trials (RCTs). The meta-analysis involved a total of 302 participants, with 152 in the remifentanil group and 150 in the dexmedetomidine group. The analysis aimed to compare the effects of Dexmedetomidine and Remifentanil on heart rate (HR) and mean arterial pressure (MAP) during surgery. Both groups exhibited similar MAP and HR, with the exception of a slightly lower HR in the remifentanil group at the 15th minute of surgery (Standardized Mean Difference: -0.24 [-0.83, 0.34]). Furthermore, when evaluating the impact of these medications on post-surgery outcomes, including pain levels, the use of pain relief medications, patient-surgeon satisfaction, agitation scores, and recovery time, no significant differences were observed between the two medications in any of these aspects. CONCLUSION: In summary, the study compared Dexmedetomidine and Remifentanil in nasal surgeries anesthesia. No significant differences were found in heart rate, blood pressure, satisfaction, pain, agitation, or recovery time. The study had limitations, and future research should establish standardized protocols and consider various surgical factors.

A systematic review of second-generation FLT3 inhibitors for treatment of patients with relapsed/refractory acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead to poor prognosis. Recent advancements have introduced FLT3 inhibitors that have improved outcomes for FLT3-mutated AML patients, however, questions remain on their application in complex conditions such as relapsed/refractory (R/R) disease. Therefore, we aimed to evaluate the clinical effectiveness of second-generation FLT3 inhibitors in treating patients with R/R AML. METHODS: A systematic literature search of PubMed, MEDLINE, SCOPUS and Google Scholar databases was made to identify relevant studies up to January 30, 2024. This study was conducted following the guidelines of the PRISMA. RESULTS: The ADMIRAL trial revealed significantly improved overall survival and complete remission rates with gilteritinib compared to salvage chemotherapy, with manageable adverse effects. Ongoing research explores its potential in combination therapies, showing synergistic effects with venetoclax and promising outcomes in various clinical trials. The QuANTUM-R trial suggested longer overall survival with quizartinib compared to standard chemotherapy, although concerns were raised regarding trial design and cardiotoxicity. Ongoing research explores combination therapies involving quizartinib, such as doublet or triplet regimens with venetoclax, showing promising outcomes in FLT3-mutated AML patients. CONCLUSION: These targeted therapies offer promise for managing this subgroup of AML patients, but further research is needed to optimize their use. This study underscores the importance of personalized treatment based on genetic mutations in AML, paving the way for more effective and tailored approaches to combat the disease.

Effects of Simulated Microgravity on Rat Reproductive System: Potential Benefits of Vitamin D3 Intervention.

Gravity in space can have a negative impact on the reproductive system. Given that the reproductive system is one of vitamin D's objectives, this study will use a simulated microgravity model to evaluate its impact on the rat reproductive system.Twenty-two male Wistar rats were allocated into four groups at random. Under microgravity circumstances, the rats were housed in both special and standard cages. Each group was then separated into two subgroups, one of which received vitamin D3 and the other did not. Blood was drawn twice to determine blood levels of vitamin D3, LH, FSH, and testosterone. Rat testes were isolated for histological analysis, as well as a piece of epididymis for sperm count and morphological examination.Microgravity had a detrimental effect on testicular tissue, resulting in lower serum levels of LH and testosterone (p-value < 0.001). Spermatogenesis was largely inhibited under microgravity. During microgravity conditions, however, vitamin D3 had a good effect on testicular structure, and the total number of sperm. Simulated microgravity affects the male reproductive system, compromising testicular morphology, sperm parameters, and hormonal balance. However, this study shows that vitamin D3 supplementation can act as a preventative strategy, minimizing the negative consequences of microgravity. The beneficial effect of vitamin D3 on testicular health and sperm quality implies that it may be useful in protecting male reproductive function in space-related situations.

Effects of Frequency-Controlled Ear Acupuncture on COVID-19- related Refractory Olfactory Dysfunction: a Randomized Clinical Trial.

Background: Olfactory dysfunction is a common COVID-19 symptom, posing treatment challenges. Objectives: We aimed to investigate the efficacy of frequency-controlled ear acupuncture in treating COVID-19-related olfactory dysfunction. Methods: A randomized, participant-blind clinical trial occurred at the Rasoul Akram Hospital (IRCT20210311050671N1). Forty patients were recruited, and 20 patients were randomly assigned to either the experimental or control group. The primary outcome was the improvement in patients' quality of smell. The olfactory dysfunction was confirmed using the Smell Identification Test. The intervention group received two sessions of acupuncture treatment according to auricular frequency treatment, with a one-week interval, while the control group received an equal number of switched-off laser sessions. Both groups were instructed to use nasal betamethasone drops. The patients were asked to rank their ability to smell before and after each intervention on a 10-point visual analog scale. Secondary outcomes were related side effects. Results: Covariance analysis revealed a significant difference in adjusted scores between the groups (F [37, 1] = 37.463; p = 0.000, Eta2 = 0.503). The smell quality improved from 2.80 ± 1.76 to 5.22 ± 3.40 after treatment in the intervention group (p = 0.007), while the control group showed no significant change (p = 0.184). Three patients reported short and transient side effects, such as nausea, headache, and dizziness, in the first hours after the intervention. Conclusion: Frequency-controlled ear acupuncture is an effective option for treating COVID-19-related olfactory dysfunction. The study highlights the potential of alternative therapies in the treatment of this condition, and further research is warranted to investigate its long-term effects.

Role of Electrodiagnostic Modalities in Detection of Nasal Septal Deviation.

Nasal Septal Deviation (NSD) is a common sign in otorhinolaryngology that can lead to facial asymmetry. In this case-control observational study, we assessed the role of EMG and NCS in the diagnosis of NSD and its effect on neuromuscular function. Participants were divided into two groups based on paranasal sinus computed tomography scan (PNS CT) results: NSD cases (n = 21) and controls without NSD (n = 13). EMG and NCS were performed on both groups to assess nasal alar muscles at the root of the zygomatic nerve. Our findings showed a significant correlation between NSD and EMG/NCS tests (P-value = 000) and a significant association between septal deviation and nasal alar lateralization (P-value = 000). EMG/NCS can be useful in assessing NSD by providing a better understanding of related neuromuscular structures and neuromuscular function of the nasal alar dilator muscles and aid in the diagnosis of NSD. Nasal Septal Deviation, EMG (electromyography), NCS (nerve conduction studies), Neuromuscular function, Facial asymmetry, Otorhinolaryngology, Paranasal sinus, Computed tomography, Nasal alar muscles, Zygomatic nerve, Nasal Obstruction, Nasal alar lateralization, Diagnosis.

An overview of anti-Hepatitis B virus flavonoids and their mechanisms of action.

Flavonoids, a diverse group of polyphenolic compounds found in various plant-based foods, have garnered attention for their potential in combating Hepatitis B Virus (HBV) infection. Flavonoids have demonstrated promising anti-HBV activities by interfering with multiple stages of the HBV life cycle, making them promising candidates for novel antiviral agents. Certain plant families, such as Theaceae, Asteraceae, Lamiaceae, and Gentianaceae, are of particular interest for their flavonoid-rich members with anti-HBV activities. Evidences, both in vitro and in vivo, supports the anti-HBV potential of flavonoids. These subsets of compound exert their anti-HBV effects through various mechanisms, including inhibiting viral entry, disrupting viral replication, modulating transcription factors, enhancing the immune response, and inducing autophagy. The antioxidant properties of flavonoids play a crucial role in modulating oxidative stress associated with HBV infection. Several flavonoids like epigallocatechin gallate (EGCG), proanthocyanidin (PAC), hexamethoxyflavone, wogonin, and baicalin have shown significant anti-HBV potential, holding promise as therapeutic agents. Synergistic effects between flavonoids and existing antiviral therapies offer a promising approach to enhance antiviral efficacy and reduce drug resistance. Challenges, including limited bioavailability, translation from preclinical studies to clinical practice, and understanding precise targets, need to be addressed. Future research should focus on clinical trials, combination therapies, and the development of flavonoid derivatives with improved bioavailability, and optimizing their effectiveness in managing chronic HBV infections.

Cardiac Complications and COVID-19: A Review of Life-threatening Co-morbidities.

The novel 2019 coronavirus disease (COVID-19) was first reported in the last days of December 2019 in Wuhan, China. The presence of certain co-morbidities, including cardiovascular diseases (CVDs), are the basis for worse outcomes in patients with COVID-19. Relevant English-language literature was searched and retrieved from the Google Scholar search engine and PubMed database up to 2023 using COVID-19, SARS-CoV-2, Heart failure, Myocardial infarction, and Arrhythmia and Cardiac complication as keywords. Increased hemodynamic load, ischemia-related dysfunction, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, and excessive or insufficient extracellular matrix proliferation are associated with heart failure (HF) in COVID-19 patients. Inflammatory reaction due to the excessive release of inflammatory cytokines, leads to myocardial infarction (MI) in these patients. The virus can induce heart arrhythmia through cardiac complications, hypoxia, decreased heart hemodynamics, and remarkable inflammatory markers. Moreover, studies have linked cardiac complications in COVID-19 with poor outcomes, extended hospitalization time, and increased mortality rate. Patients with COVID-19 and CVDs are at higher mortality risk and they should be given high priority when receiving the treatment and intensive care during hospitalization.

Adverse Effects Reported and Insights Following Sinopharm COVID-19 Vaccination.

Vaccines are promising strategies for controlling COVID-19; however, COVID-19 vaccine side effects play a central role in public confidence in the vaccine and its uptake process. This study aimed to provide evidence on the post-vaccination early side effects of the BBIBP-CorV (Sinopharm) vaccine. This cross-sectional survey-based study was conducted between November 2021 and January 2022 among recipients of the BBIBP-CorV vaccine, using a questionnaire-based survey. Our final sample consisted of 657 participants, including 392 women. Among the study cases, only 103 (15.7%) participants received one dose of vaccine, and the rest received both doses (N = 554, 84.3%). Systemic symptoms (first dose: N = 187, both doses: N = 128) were the most commonly reported events after vaccination, and among them, injection site pain (first dose: 19.3%, both doses: 12.9%) was the most prevalent adverse effect. All reporting events were mild and resolved in less than 3 days without hospitalization. Among the participants, females and young people aged 35-65 were more prone to manifest side effects (N = 169, 53.3%) after the vaccine injection. Furthermore, our results revealed that the recipients who were suffering from underlying diseases, including diabetes, renal disorder, and respiratory illness, reported fewer adverse responses after vaccination in comparison with healthy individuals. Vaccination against SARS-CoV-2 may lead to some adverse reactions in recipients. However, the frequency of post-vaccination early side effects differed in people, but all responses were slight and temporary.

Cytokines and their role in cardiovascular diseases.

The evaluation of diagnostic and prognostic biomarkers has always been a hot topic in various diseases. Considering that cardiovascular diseases (CVDs) have the highest mortality and morbidity rates in the world, various studies have been conducted so far to find CVD associated biomarkers, including cardiac troponin (cTn) and NT-proBNP. Cytokines are components of the immune system that are involved in the pathogenesis of CVD due to their contribution to the inflammation process. The level of cytokines varies in many cardiovascular diseases. For instance, the plasma level of IL-1α, IL-18, IL-33, IL-6 and IL-8 is positively correlated with atherosclerosis and that of some other interleukins such as IL-35 is negatively correlated with acute myocardial infarction or cardiac angina. Due to its pivotal role in the inflammation process, IL-1 super family is involved in many CVDs, including atherosclerosis. IL-20 among the interleukins of IL-10 family has a pro-atherogenic role, while others, such as IL-10 and IL-19, play an anti-atherogenic role. In the present review, we have collected the latest published evidence in this respect to discuss valuable cytokines from the diagnostic and prognostic stand point in CVDs.

A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study.

The Hepatitis B virus (HBV) core protein is an attractive target for preventing capsid assembly and viral replication. Drug repurposing strategies have introduced several drugs targeting HBV core protein. This study used a fragment-based drug discovery (FBDD) approach to reconstruct a repurposed core protein inhibitor to some novel antiviral derivatives. Auto Core Fragment in silico Screening (ACFIS) server was used for deconstruction-reconstruction of Ciclopirox in complex with HBV core protein. The Ciclopirox derivatives were ranked based on their free energy of binding (ΔGB). A quantitative structure affinity relationship (QSAR) was established on the Ciclopirox derivatives. The model was validated by a Ciclopirox-property-matched decoy set. A principal component analysis (PCA) was also assessed to define the relationship of the predictive variable of the QSAR model. 24-derivatives with a ΔGB (-16.56±1.46 Kcal.mol-1) more than Ciclopirox was highlighted. A QSAR model with a predictive power of 88.99% (F-statistics = 9025.78, corrected df(25), Pr > F = 0.0001) was developed by four predictive descriptors (ATS1p, nCs, Hy, F08[C-C]). The model validation showed no predictive power for the decoy set (Q2 = 0). No significant correlation was observed between predictors. By directly attaching to the core protein carboxyl-terminal domain, Ciclopirox derivatives may be able to suppress HBV virus assembly and subsequent viral replication inhibition. Hydrophobic residue Phe23 is a critical amino acid in the ligand binding domain. These ligands share the same physicochemical properties that lead to the development of a robust QSAR mode. The same strategy may also be used for future drug discovery of viral inhibitors.

Ligand-based 3D pharmacophore modeling, virtual screening, and molecular dynamic simulation of potential smoothened inhibitors.

CONTEXT: The Hedgehog (Hh) signaling pathway is a crucial regulator of various cellular processes. Dysregulated activation of the Smoothened (SMO) oncoprotein, a key component of the Hh pathway, has been implicated in several types of cancer. Although SMO inhibitors are important anti-cancer therapeutics, drug-resistant SMO mutants have emerged, limiting their efficacy. This study aimed to discover stable SMO inhibitors for both wild-type and mutant SMOs, using a 12-feature pharmacophore model validated for virtual screening. One lead compound, LCT10312, was identified with high affinity to SMO and showed a significant conformational change in the SMO structure upon binding. Molecular dynamic simulation revealed stable interaction of LCT10312 with SMO and large atom motions, indicating SMO structural fluctuation. The lead compound showed high predicted binding scores to several clinically relevant SMO mutants. METHODS: A ligand-based pharmacophore model was developed from 25 structurally clustered SMO inhibitors using LigandScout v3.12 software and virtually screened for hit identification from a library of 511,878 chemicals. Molecular docking was employed to identify potential leads based on SMO affinities. Molecular dynamic simulation (MDS) with GROMACS v5.1.4 was performed to analyze the structural changes of SMO oncoprotein upon binding lead compound(s) and cyclopamine as the control for 100 ns. The binding affinity of lead compound(s) was predicted on clinical and laboratory SMO mutants.

Biomarkers of endothelial dysfunction are associated with poor outcome in COVID-19 patients: A systematic review and meta-analysis.

Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta-analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID-19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59-1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77-1.7), p < 0.00001), angiopoietin-2 (Ang-2) (1.06 (0.6-1.51), p < 0.0001), E-selectin (1.09 (0.55-1.63), p < 0.0001), P-selectin (0.59 (0.24-0.94), p = 0.001), syndecan-1 (0.99 (0.6-1.37), p < 0.00001), mid-regional pro-adrenomedullin (MR-proADM) (1.52 (1.35-1.68), p < 0.00001), vascular endothelial growth factor (0.27 (0.02-0.53), p = 0.03), soluble fms-like tyrosine kinase-1 (sFLT-1) (1.93 (0.65-3.21), p = 0.03) and lower levels of ADAMTS13 antigen (-0.69 (-0.9 to -0.47) p < 0.00001) and activity (-0.84 (-1.06 to -0.61) p < 0.0000). Plasminogen activator inhibitor-1 and tissue plasminogen activator levels were not different between the two groups (p < 0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID-19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR-proADM, vWF, syndecan-1 and sFLT-1 showed a significant association with poor outcome in these patients.

Association Between Satisfaction with Nasal Appearance and Olfactory Function in Patients Undergoing Septorhinoplasty Surgery.

BACKGROUND: Any surgery has some complications, and septorhinoplasty is not an exception. The aim of this study was to highlight the relationship between satisfaction with nasal appearance and olfactory function in patients undergoing septorhinoplasty. METHODS: This is a cohort study. In this study, 384 patients aged 18 to 45 years who referred to the Ear, Nose and Throat department at Rasoul Akram hospital and private clinics in 2019 underwent septorhinoplasty. All patients were tested by the Persian Smell Identification Test (PSIT) or Rapid Smell Test (RST) before surgery. They were also reassessed one and three months after surgery. Those patients with dissatisfaction with olfactory function after surgery were also followed up for three months and assessed by PSIT or RST to determine their olfactory dysfunction. RESULTS: One month after surgery, 73.5% of patients who were not satisfied with their nasal appearance also complained about the olfactory sense. In addition, 1.5% of patients who were satisfied with their nasal appearance also complained about the olfactory sense. There was a significant difference regarding complaints of the olfactory sense between patients satisfied with their nasal appearance and those not satisfied with their appearance (P<0.05). Three months after surgery, 78.9% patients who were not pleased with their nasal appearance also had an olfactory complaint. Besides, 0.9% of patients who were pleased with their nasal shape also had an olfactory complaint. There was a significant difference regarding olfactory complaints between patients who were pleased with their nasal shape and those who were not (P<0.05). CONCLUSION: One and three months after septorhinoplasty, most patients who are satisfied with their nasal appearance have no complaints about their olfactory sense, and most patients who are not satisfied with their nasal appearance complain about the olfactory sense. An appropriate outcome of septorhinoplasty with regard to improving olfactory functional status is accompanied by patients' satisfaction level of achieving good nasal appearance.

Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study.

Aim: COVID-19 is a global health threat. Therapeutics are urgently needed to cure patients severely infected with COVID-19. Objective: to investigate potential candidates of nsp12 inhibitors by searching for druggable cavity pockets within the viral protein and drug discovery. Methods: A virtual screening of ZINC natural products on SARS-CoV-2 nsp12's druggable cavity was performed. A lead compound with the highest affinity to nsp12 was simulated dynamically for 10 ns. Results: ZINC03977803 was nominated as the lead compound. The results showed stable interaction between ZINC03977803 and nsp12 during 10 ns. Discussion: ZINC03977803 showed stable interaction with the catalytic subunit of SARS-CoV-2, nsp12. It could inhibit the SARS-CoV-2 life cycle by direct interaction with nsp12 and inhibit RdRp complex formation.

In silico drug repurposing against SARS-CoV-2 using an integrative transcriptomic profiling approach: Hydrocortisone and Benzhydrocodone as potential drug candidates against COVID-19.

COVID-19 pathogenesis is mainly attributed to dysregulated antiviral immune response, the prominent hallmark of COVID-19. As no established drugs are available against SARS-CoV-2 and developing new ones would be a big challenge, repurposing of existing drugs holds promise against COVID-19. Here, we used a signature-based strategy to delve into cellular responses to SARS-CoV-2 infection in order to identify potential host contributors in COVID-19 pathogenesis and to find repurposable drugs using in silico approaches. We scrutinized transcriptomic profile of various human alveolar cell sources infected with SARS-CoV-2 to determine up-regulated genes specific to COVID-19. Enrichment analysis revealed that the up-regulated genes were involved mainly in viral infectious disease, immune system, and signal transduction pathways. Analysis of protein-protein interaction network and COVID-19 molecular pathway resulted in identifying several anti-viral proteins as well as 11 host pro-viral proteins, ADAR, HBEGF, MMP9, USP18, JUN, FOS, IRF2, ICAM1, IFI35, CASP1, and STAT3. Finally, molecular docking of up-regulated proteins and all FDA-approved drugs revealed that both Hydrocortisone and Benzhydrocodone possess high binding affinity for all pro-viral proteins. The suggested repurposed drugs should be subject to complementary in vitro and in vivo experiments in order to be evaluated in detail prior to clinical studies in potential management of COVID-19.

Druggability of cavity pockets within SARS-CoV-2 spike glycoprotein and pharmacophore-based drug discovery.

Aim: Virus spike glycoprotein of SARS-CoV-2 is a good target for drug discovery. Objective: To examine the potential for druggability of spike protein for pharmacophore-based drug discovery and to investigate the binding affinity of natural products with SARS-CoV-2 spike protein. Methods: Druggable cavities were searched though CavityPlus. A pharmacophore was built and used for hit identification. Autodock Vina was used to evaluate the hits' affinities. 10 chemical derivatives were also made from the chemical backbone to optimize the lead compound. Results: 10 druggable cavities were found within the glycoprotein spike. Only one cavity with the highest score at the binding site was selected for pharmacophore extraction. Hit identification resulted in the identification of 410 hits. Discussion: This study provides a druggable region within viral glycoprotein and a candidate compound to block viral entry.