Determination of Regorafenib monohydrate (colorectal anticancer drug) solubility in supercritical CO2: Experimental and thermodynamic modeling.

In this study, the solubilities of Regorafenib monohydrate (REG), a widely used as a colorectal anticancer drug, in supercritical carbon dioxide (ScCO2) were measured under various pressures and temperature conditions, for the first time. The minimum value of REG in mole fraction was determined to be 3.06×10-7, while the maximum value was found to be 6.44×10-6 at 338 K and 27 MPa. The experimental data for REG were correlated through the utilization of two types of models: (1) a set of 25 existing empirical and semi-empirical models that incorporated 3-8 parameters according to functional dependencies, (2) a model that relied on solid-liquid equilibrium (SLE) and the newly improved association models. All of the evaluated models were capable of generating suitable fits to the solubility data of REG, however, the average absolute relative deviation (AARD) of Gordillo et al. model (AARD=13.2%) and Reddy et al. model (AARD=13.5%) indicated their superiority based on AARD%. Furthermore, solvation and sublimation enthalpies of REG drug were estimated for the first time.

Female Urethral Cavernous Hemangioma: Introducing Treatment and Follow-Up Course of Three Cases.

Cavernous hemangioma is a benign vascular tumor occurring in all parts of the urinary system, including the kidney, bladder, prostate, ureter, and rarely urethra. Urethral cavernous hemangiomas are mostly seen in male patients, and only a few cases of female urethral hemangiomas are reported. Herein, we present the management and follow-up course of 3 cases of female urethral cavernous hemangioma. All 3 cases were menopause women complaining of lower urinary tract symptoms. Definitive diagnosis is made by histopathologic evaluation. In case of large or pedunculated masses, initial surgical resection is highly recommended. Regular follow-up of patients in order to prevent any recurrence is suggested.

DNAH11 and a Novel Genetic Variant Associated with Situs Inversus: A Case Report and Review of the Literature.

Background: Primary ciliary dyskinesia (PCD), also known as the immotile-cilia syndrome, is a clinically and genetically heterogeneous syndrome. Improper function of the cilia causes impaired mucociliary clearance. Neonatal respiratory distress, rhinosinusitis, recurrent chest infections, wet cough, and otitis media are respiratory presentations of this disease. It could also manifest as infertility in males as well as laterality defects in both sexes, such as situs abnormalities (Kartagener syndrome). During the past decade, numerous pathogenic variants in 40 genes have been identified as the causatives of primary ciliary dyskinesia. DNAH11 (dynein axonemal heavy chain 11) is a gene that is responsible for the production of cilia's protein and encodes the outer dynein arm. Dynein heavy chains are motor proteins of the outer dynein arms and play an essential role in ciliary motility. Case Presentation. A 3-year-old boy, the offspring of consanguineous parents, was referred to the pediatric clinical immunology outpatient department with a history of recurrent respiratory tract infections and periodic fever. Furthermore, on medical examination, situs inversus was recognized. His lab results revealed elevated levels of erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). Serum IgG, IgM, and IgA levels were normal, while IgE levels were elevated. Whole exome sequencing (WES) was performed for the patient. WES demonstrated a novel homozygous nonsense variant in DNAH11 (c.5247G > A; p. Trp1749Ter). Conclusion: We reported a novel homozygous nonsense variant in DNAH11 in a 3-year-old boy with primary ciliary dyskinesia. Biallelic pathogenic variants in one of the many coding genes involved in the process of ciliogenesis lead to PCD.

Clinical efficacy of endovascular treatment approach in patients with carotid cavernous fistula: A systematic review and meta-analysis.

Background and objectives: Carotid-cavernous fistulas (CCFs) represent a group of rare, abnormal arteriovenous communications between the carotid arterial system and the cavernous sinuses (CS). CCFs often produce ophthalmologic symptoms related to increased CS pressures and retrograde venous drainage of the eye. Although endovascular occlusion remains the preferred treatment for symptomatic or high-risk CCFs, most of the data for these lesions is limited to small, single-center series. As such, we performed a systematic review and meta-analysis evaluating endovascular occlusions of CCFs to determine any differences in clinical outcomes based on presentation, fistula type, and treatment paradigm. Method: A retrospective review of all studies discussing the endovascular treatment of CCFs published through March 2023 was conducted using PubMed, Scopus, Web of Science, and Embase databases. A total of 36 studies were included in the meta-analysis. Data from the selected articles were extracted and analyzed using Stata software version 14. Results: 1494 patients were included. 55.08% were female and the mean age of the cohort was 48.10 years. A total number of 1516 fistulas underwent endovascular treatment, 48.05% of which were direct and 51.95% of which were indirect. 87.17% of CCFs were secondary to a known trauma while 10.18% were spontaneous. The most common presenting symptoms were 89% exophthalmos (95% CI: 78.0-100.0; I2 = 75.7%), 84% chemosis (95% CI: 79.0-88.0; I2 = 91.6%), 79% proptosis (95% CI: 72.0-86.0; I2 = 91.8%), 75.0% bruits (95% CI: 67.0-82.0; I2 = 90.7%), 56% diplopia (95% CI: 42.0-71.0; I2 = 92.3%), 49% cranial nerve palsy (95% CI: 32.0-66.0; I2 = 95.1%), 39% visual decline (95% CI: 32.0-45.0; I2 = 71.4%), 32% tinnitus (95% CI: 6.0-58.0; I2 = 96.7%), 29% elevated intraocular pain (95% CI: 22.0-36.0; I2 = 0.0%), 31% orbital or pre-orbital pain (95% CI: 14.0-48.0; I2 = 89.9%) and 24% headache (95% CI: 13.0-34.0; I2 = 74.98%). Coils, balloons, and stents were the three most used embolization methods respectively. Immediate complete occlusion of the fistula was seen in 68% of cases and complete remission was seen in 82%. Recurrence of CCF occurred in only 35% of the patients. Cranial nerve paralysis after treatment was observed in 7% of the cases. Conclusions: Exophthalmos, Chemosis, proptosis, bruits, cranial nerve palsy, diplopia, orbital and periorbital pain, tinnitus, elevated intraocular pressure, visual decline and headache are the most common clinical manifestations of CCFs. The majority of endovascular treatments involved coiling, balloons and onyx and a high percentage of CCF patients experienced complete remission with the improvement of their clinical symptoms.

Tigecycline-Containing Regimens and Multi Drug-Resistant Acinetobacter baumannii: A Systematic Review and Meta-Analysis.

Introduction: The use of tigecycline (TG) for the treatment of Acinetobacter baumannii is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. Methods: We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR A. baumannii, published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. Results: There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2-66.6) and 40.2 (95% CI 31.1-50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8-47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1-48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7-62.5) and 43.1 (33.1-53.8), respectively. The pooled microbiological response rate was 42.9 (16.2-74.5), and the pooled all-cause mortality rate was 34.3 (26.1-43.5). Conclusions: According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR A. baumannii. However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required.

Cerebrospinal fluid alpha-synuclein, amyloid beta, total tau, and phosphorylated tau in tremor-dominant Parkinson's disease.

BACKGROUND: Protein misfolding within specific brain regions is a common characteristic of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease (PD). Therefore, a common term often used for these disorders is "proteinopathy". Currently, there has been increasing attention toward the overlap of pathogenesis between proteinopathies. AIMS: We aimed to explore the cross-sectional and longitudinal level of the CSF α-synuclein (α-syn), amyloid ßeta (Aß1-42), total tau (t-tau), and phosphorylated tau (p-tau) in PD subjects with tremor dominant (TD) and a non-tremor dominant (nonTD) subtype from the Parkinson Progression Markers Initiative (PPMI). METHODS: We enrolled 411 early-stage PD patients and 187 healthy controls (HCs) from the PPMI. We compared the level of CSF biomarkers at four time points including baseline, 6 months, 1 year, and 2 years. To investigate longitudinal changes in CSF proteins within each group, we used linear mixed models. RESULTS: The level of CSF biomarkers was significantly lower in PD patients compared to HCs at any visit. Moreover, there was no statistically significant difference in the level of CSF α-syn, Aß1-42, t-tau, and p-tau between PD-TD and PD-nonTD. Longitudinal analysis showed significant CSF α-syn reduction after one year from baseline in PD-TD patients (P = 0.047). Also, there was a significant reduction in the level of CSF Aß1-42 after two years in PD-nonTD patients but not HCs and PD-TD (P = 0.033). CONCLUSION: Our results indicate that different patterns in longitudinal changes of CSF biomarkers could be due to different pathophysiological mechanisms involved in each PD motor subtype.

Therapeutic effects of Rosa canina, Urtica dioica and Tanacetum vulgare herbal combination in treatment of tinnitus symptoms: A double-blind randomised clinical trial.

OBJECTIVE: To evaluate the effect of Neurotec® herbal capsule (100 mg twice a day for 3 months) on the tinnitus symptoms in comparison with the placebo. DESIGN: A double-blind randomised clinical trial. SETTING: Otolaryngology clinic of Baqiyatallah Hospital. PARTICIPANTS: Patients suffering from subjective tinnitus. MAIN OUTCOME MEASURES: Pure tone audiometry was measured at .5, 1, 2, 4 and 6 kHz frequencies before and after the third month of intervention. In addition, Tinnitus Handicap Inventory (THI) questionnaire as well as visual analogue scale (VAS) for tinnitus loudness, daily annoyance, daily life or sleep disturbance, daily perception and mood alteration were evaluated. RESULTS: Finally, 103 (69 males and 34 females) patients with a mean age of 51.33 ± 13.91 years were analysed. In contrast with control group, patients in intervention group showed a remarkable decrease in THI score after 3 months of treatment (p < .05). Although both groups had improvements in VAS scores, mood disturbance, daily tinnitus perception and daily life alteration scores were only improved in the intervention group. The mean pure tone air and bone conduction were not significantly different between the control and the intervention group at baseline and 3 months after the intervention at .5, 1, 2 and 4 kHz (p > .05). CONCLUSION: A 3-month treatment with Neurotec capsules in addition to patient education is of benefit for managing symptoms in patients with chronic tinnitus.

Dynamic changes in metabolites of the kynurenine pathway in Alzheimer's disease, Parkinson's disease, and Huntington's disease: A systematic Review and meta-analysis.

Background: Tryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide adenosine dinucleotide (NAD+), and metabolites of this pathway may have protective or degenerative effects on the nervous system. Thus, the KP may be involved in neurodegenerative diseases. Objectives: The purpose of this systematic review and meta-analysis is to assess the changes in KP metabolites such as TRP, kynurenine (KYN), kynurenic acid (KYNA), Anthranilic acid (AA), 3-hydroxykynurenine (3-HK), 5-Hydroxyindoleacetic acid (5-HIAA), and 3-Hydroxyanthranilic acid (3-HANA) in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) patients compared to the control group. Methods: We conducted a literature search using PubMed/Medline, Scopus, Google Scholar, Web of Science, and EMBASE electronic databases to find articles published up to 2022. Studies measuring TRP, KYN, KYNA, AA, 3-HK, 5-HIAA, 3-HANA in AD, PD, or HD patients and controls were identified. Standardized mean differences (SMDs) were used to determine the differences in the levels of the KP metabolites between the two groups. Results: A total of 30 studies compromising 689 patients and 774 controls were included in our meta-analysis. Our results showed that the blood levels of TRP was significantly lower in the AD (SMD=-0.68, 95% CI=-0.97 to -0.40, p=0.000, I2 = 41.8%, k=8, n=382), PD (SMD=-0.77, 95% CI=-1.24 to -0.30, p=0.001, I2 = 74.9%, k=4, n=352), and HD (SMD=-0.90, 95% CI=-1.71 to -0.10, p=0.028, I2 = 91.0%, k=5, n=369) patients compared to the controls. Moreover, the CSF levels of 3-HK in AD patients (p=0.020) and the blood levels of KYN in HD patients (p=0.020) were lower compared with controls. Conclusion: Overall, the findings of this meta-analysis support the hypothesis that the alterations in the KP may be involved in the pathogenesis of AD, PD, and HD. However, additional research is needed to show whether other KP metabolites also vary in AD, PD, and HD patients. So, the metabolites of KP can be used for better diagnosing these diseases.

Olfactory dysfunction and striatal dopamine transporter binding in motor subtypes of Parkinson's disease.

BACKGROUND: Olfactory dysfunction is one of the earliest non-motor symptoms (NMS) in Parkinson's disease (PD). There are contradictory results regarding the association of olfactory dysfunction and dopamine uptake in striatal nuclei among PD patients. It has been suggested that different motor subtypes of PD vary in the disease pathophysiology and progression. Thus, we hypothesized that there might be different associations between olfactory dysfunction and striatal dopaminergic neuronal loss among three motor subtypes of PD, namely, indeterminate, postural instability and gait difficulty (PIGD), and tremor-dominant (TD). METHODS: We recruited 162 healthy controls (HCs) and 464 drug-naïve PD patients from PPMI who underwent common PD scaling tests. Striatal binding ratios (SBRs) of DaTSCAN images in caudate and putamen nuclei were calculated. To assess the olfactory function, the University of Pennsylvania Smell Identification Test (UPSIT) was carried out. RESULTS: The UPSIT score was significantly correlated with MDS-UPDRS part I (p value: 0.002, correlation coefficient: - 0.160), MDS-UPDRS part III (p value: 0.000, correlation coefficient: - 0.248), and SBR score in right (p value: 0.000, correlation coefficient: 0.240) and left caudate (p value: 0.000, correlation coefficient: 0.221) and right (p value: 0.000, correlation coefficient: 0.323) and left putamen (p value: 0.000, correlation coefficient: 0.335) nucleus in TD subtype. There were no significant correlations in HC, PIGD, and indeterminate subjects. CONCLUSION: The olfactory dysfunction was correlated with dopamine transporter activity in striatal nuclei only in the TD subtype. Therefore, the olfactory dysfunction in PIGD and indeterminate subtype may not be a predictive factor for the future decrease in dopamine uptake.

Relation between ADHD and COVID-19: A Narrative Review to Guide Advancing Clinical Research and Therapy.

Objective: To cope with the COVID-19 pandemic, national health authorities temporarily closed cultural, religious, and educational institutions such as universities and schools. Children and adolescents with ADHD were challenged with the restrictions caused by the Covid-19 pandemic such as homeschooling and reduced physical activity. The present narrative review aimed to summarize the state-of-the-art regarding associations between COVID-19-related social restrictions and possible psychological and behavioral issues in children and adolescents with ADHD. Additionally, we discussed the underlying possible reasons of the association focusing on the role of parental influence and physical activity, vulnerabilities of individuals with ADHD to Covid-19 infection and to school closure and remote learning. Method: To collect data for the present narrative review, recent publications on these topics between February 1st, 2020 and January 10th, 2021 were retrieved from the most popular search engines (PubMed; Scopus; Google Scholar; Psych Info; Embase) through a comprehensive search using relevant keywords. Results: During confinement, children and adolescents with ADHD reported increased behavioral and ADHD-related symptoms and overall decreased psychological well-being. Factors negatively impacting children's and adolescents' behavioral symptoms and well-being were: less physical activity, adverse parental behavior, difficulties in coping with preventive guidelines, and school closure and remote learning consequences. Conclusion: Children and adolescents with ADHD and their caregivers faced both specific and general psychological issues related to the school lockdowns and homeschooling. Additionally, Individuals with ADHD seem to be more vulnerable to Covid-19 infection which highlights the need for better healthcare adaptation.

Autoimmune encephalitis associated with COVID-19: A systematic review.

INTRODUCTION: There are increasing reports of COVID-19 related neurological complications which may be due to direct viral invasion, or immune mediated inflammatory diseases such as autoimmune encephalitis and ADEM (acute demyelinating encephalomyelitis). In this study, a systematic review is presented of the reported cases infected by the COVID-19 who were diagnosed with various forms of autoimmune encephalitis (AE). METHODS: The authors searched three databases including PubMed, Scopus, and Web of science for extracting original articles on coronavirus/ COVID-19 and AE. RESULTS: Eighteen articles were considered in this study, including 15 case reports, and three case series with a total of 81 patients. Among the studies, 19 cases were reported with AE including 7 (37%) cases of limbic encephalitis, 5 (26%) patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, 2 (11%) with AE presenting as new-onset refractory status epilepticus (NORSE), 1 (5%) case of steroid-responsive encephalitis, and 4 (21%) cases with an unknown type of AE. CONCLUSION: Our systematic review revealed evidence on AE development in patients infected with the COVID-19. Clinicians should be aware of the possible diagnosis of AE when considering other neurological differential diagnosis in SARS-CoV-2 infected patients.

Pseudobulbar affect in neurodegenerative diseases: A systematic review and meta-analysis.

BACKGROUND: Pseudobulbar affect (PBA) is characterized by uncontrolled episodes of crying and laughing which is associated with a variety of neurological diseases including traumatic brain injury, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), brain tumors, stroke, Parkinson's disease (PD), Alzheimer's disease (AD) and other dementias. However, there is a lack of exact estimated prevalence of PBA among neurological disorders. AIM: In this systematic review and meta-analysis study we aimed to assess the prevalence of PBA in four neurodegenerative diseases including ALS, MS, AD, and PD. METHODS: PubMed, Scopus, and Web of Science were searched in July 2021 for studies that reported the prevalence of PBA in ALS, MS, AD, and PD patients. The mean point of PBA prevalence and odds ratios were calculated as effect size (ES) using the random-effect model with a 95% confidence interval (CI). RESULTS: The summarized prevalence of PBA was of PBA in PD patients were ranged between 1% and 31% with an overall meta-analysis prevalence of 16.5% and high heterogeneity (I2: 98.7%, p: 0.000). Patients with ALS showed a PBA prevalence of 38.5%, which is higher than other neurodegenerative diseases (CI 95%: 31%-45%, I2: 61.4%, p: 0.034). Moreover, the prevalence of PBA in MS patients in the analysis was 23.3% ranging between 11% and 35% with high-level heterogeneity according to the I2 value (I2: 98.9%, p: 0.000). Also, our meta-analysis showed that the PBA prevalence in AD was 16.4% (CI 95%: 7%-25%) with high heterogeneity (I2: 97.8%, p: 0.000). CONCLUSION: This review showed that PBA is common in patients with neurodegenerative diseases including PD, AD, MS, and especially ALS. Due to the lack of proper recognition, medication and treatment would not be effective and sufficient. Therefore, it can dramatically lower the quality of life in PBA patients and decrease their social interactions.

The role of type I interferon in the treatment of COVID-19.

Although significant research has been done to find effective drugs against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no definite effective drug exists. Thus, research has now shifted towards immunomodulatory agents other than antivirals. In this review, we aim to describe the latest findings on the role of type I interferon (IFN)-mediated innate antiviral response against SARS-CoV-2 and discuss the use of IFNs as a medication for COVID-19. A growing body of evidence has indicated a promoting active but delayed IFNs response to SARS-CoV-2 and Middle East respiratory syndrome coronavirus in infected bronchial epithelial cells. Studies have demonstrated that IFNs' administration before the viral peak and the inflammatory phase of disease could offer a highly protective effect. However, IFNs' treatment during the inflammatory and severe stages of the disease causes immunopathology and long-lasting harm for patients. Therefore, it is critical to note the best time window for IFNs' administration. Further investigation of the clinical effectiveness of interferon for patients with mild to severe COVID-19 and its optimal timing and route of administration can be beneficial in finding a safe and effective antiviral therapy for the COVID-19 disease.

Drug-Induced Liver Injury in COVID-19 Patients: A Systematic Review.

Introduction: The severity of COVID-19 may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity has been associated with using some medications in the management of COVID-19 patients. However, limited studies had systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. Thus, this study aimed to examine DILI in COVID-19 patients. Methods: A systematic search was carried out in PubMed/Medline, EMBASE, and Web of Science up to December 30, 2020. Search items included "SARS-CoV-2", "Coronavirus," COVID-19, and liver injury. Results: We included 22 related articles. Among included studies, there was five case report, five case series, four randomizes control trial (RCT), seven cohort studies, and one cross-sectional study. The drugs included in this systematic review were remdesivir, favipiravir, tocilizumab, hydroxychloroquine, and lopinavir/ritonavir. Among included studies, some studies revealed a direct role of drugs, while others couldn't certainly confirm that the liver injury was due to SARS-CoV-2 itself or administration of medications. However, a significant number of studies reported that liver injury could be attributable to drug administration. Discussion: Liver injury in COVID-19 patients could be caused by the virus itself or the administration of some types of drug. Intensive liver function monitoring should be considered for patients, especially patients who are treated with drugs such as remdesivir, lopinavir/ritonavir, and tocilizumab.

COVID-19 Vaccination: What Challenges Are We Going to Face.

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