Search

Background: Consecutive homozygous fragments of a genome inherited by offspring from a common ancestor are known as runs of homozygosity (ROH). ROH can be used to calculate genomic inbreeding and to identify genomic regions that are potentially under historical selection pressure. The dataset of our study consisted of 254 Azeri (AZ) and 115 Khuzestani (KHZ) river buffalo genotyped for ~ 65,000 SNPs for the following two purposes: 1) to estimate and compare inbreeding calculated using ROH (FROH), excess of homozygosity (FHOM), correlation between uniting gametes (FUNI), and diagonal elements of the genomic relationship matrix (FGRM); 2) to identify frequently occurring ROH (i.e. ROH islands) for our selection signature and gene enrichment studies. Results: In this study, 9102 ROH were identified, with an average number of 21.2 ± 13.1 and 33.2 ± 15.9 segments per animal in AZ and KHZ breeds, respectively. On average in AZ, 4.35% (108.8 ± 120.3 Mb), and in KHZ, 5.96% (149.1 ± 107.7 Mb) of the genome was autozygous. The estimated inbreeding values based on FHOM, FUNI and FGRM were higher in AZ than they were in KHZ, which was in contrast to the FROH estimates. We identified 11 ROH islands (four in AZ and seven in KHZ). In the KHZ breed, the genes located in ROH islands were enriched for multiple Gene Ontology (GO) terms (P ≤ 0.05). The genes located in ROH islands were associated with diverse biological functions and traits such as body size and muscle development (BMP2), immune response (CYP27B1), milk production and components (MARS, ADRA1A, and KCTD16), coat colour and pigmentation (PMEL and MYO1A), reproductive traits (INHBC, INHBE, STAT6 and PCNA), and bone development (SUOX). Conclusion: The calculated FROH was in line with expected higher inbreeding in KHZ than in AZ because of the smaller effective population size of KHZ. Thus, we find that FROH can be used as a robust estimate of genomic inbreeding. Further, the majority of ROH peaks were overlapped with or in close proximity to the previously reported genomic regions with signatures of selection. This tells us that it is likely that the genes in the ROH islands have been subject to artificial or natural selection. [ABSTRACT FROM AUTHOR]

Introduction: Descending necrotizing mediastinitis (DNM) is a type of acute mediastinitis that is rarely reported but is regarded as a fatal disease despite improvements in technological methods and antibiotic therapies. We aimed to determine the demographic, clinical, and paraclinical features of patients diagnosed with acute DNM. Methods: In this retrospective study, patients' hospital records with a diagnosis of DNM admitted to the Namazi hospital in southern Iran during 18 years (2002–2019) were reviewed. Demographic and clinical features were recorded and subsequently analyzed via SPSS 22. Results: Out of 67 mediastinitis patients, 25 (37.3%) were diagnosed as DNM with an average age of 37.2 ± 16.7 years, and 68% were male. Regarding etiology, 52.0% were due to neck infection. Based on the technique of surgery, 52% of the patients underwent the combined method, which was mostly among type I and IIA DNM, while thoracotomy was mostly performed on type IIB DNM (P = 0.08). Based on the incision, type IIA and IIB had the highest frequency of thoracotomy and cervicothoracic incisions (P = 0.02 and 0.002). Puss discharge was significantly lower in type I DNM (P = 0.01). Based on the presenting symptoms of our patients, the majority (72.0%) had a chief complaint of neck pain, followed by chills and fever (48%). There were no reports of mortality during our short-term follow-up. Conclusion: We report one of the largest retrospective studies of DNM patients in our referral center, with a high prevalence of the disease among younger populations, especially under 40 years. The method of treatment should be chosen based on the extent of infection and can be limited to neck exploration in upper mediastinal infections, though thoracic or combined approach in more broad infections. [ABSTRACT FROM AUTHOR]

The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP), global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs). We further document that a Myc core signature (MCS) set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells. [ABSTRACT FROM AUTHOR]

Background: Cyclooxygenase-2 (COX-2) directs the synthesis of prostaglandins including PGE-2 linking inflammation with mitogenic signaling. COX-2 is also an anticancer target, however, treatment strategies have been limited by unreliable expression assays and by inconsistent tumor responses to COX-2 inhibition.Methods: We analyzed the TCGA and Director's Challenge lung cancer datasets (n = 188) and also generated an LKB1-null lung cancer gene signature (n = 53) to search the Broad Institute/Connectivity-MAP (C-MAP) dataset. We performed ChIP analyses, real-time polymerase chain reaction, immunoblotting, and drug testing of tumor cell lines (n = 8) and primary lung adenocarcinoma surgical resections (n = 13).Results: We show that COX-2 is a target of the cAMP/CREB coactivator CRTC1 signaling pathway. In addition, we detected a correlation between LKB1 status, CRTC1 activation, and presence of glycosylated, but not inactive hypoglycosylated COX-2 in primary lung adenocarcinoma. A search of the C-MAP drug database discovered that all high-ranking drugs positively associated with the LKB1-null signature are known CRTC1 activators, including forskolin and six different PGE-2 analogues. Somatic LKB1 mutations are present in 20.0% of lung adenocarcinomas, and we observed growth inhibition with COX-2 inhibitors in LKB1-null lung cancer cells with activated CRTC1 as compared with LKB1-wildtype cells (NS-398, P = .002 and Niflumic acid, P = .006; two-tailed t test).Conclusion: CRTC1 activation is a key event that drives the LKB1-null mRNA signature in lung cancer. We also identified a positive feedback LKB1/CRTC1 signaling loop for COX-2/PGE2 regulation. These data suggest a role for LKB1 status and glycosylated COX-2 as specific biomarkers that provide a framework for selecting patients for COX-2 inhibition studies. [ABSTRACT FROM AUTHOR]

Tracheal resection and anastomosis surgery is a safe operation and is used to treat various benign and malignant diseases of the trachea. However, tracheal stenosis is among the main anastomotic complications following this procedure. Surgeons use both the continuous and the interrupted suture techniques for tracheal anastomosis, but contradicting results in each technique's complications have been reported in various studies. In this study, we aimed to compare the outcome of these two different suture techniques and a relevant literature review. Surgical records during a period of 15 years (2005–2019) were screened for tracheal reconstruction surgery in affiliated hospitals of Shiraz University of Medical Sciences, Shiraz, Iran. A total of 82 patients were evaluated based on surgical and suture features, along with their follow-up bronchoscopy for anastomotic complications. Post-operational subclinical restenosis occurred in 8 (15.3%) out of 52 and 10 (33.3%) of 30 patients who underwent continuous and interrupted suturing techniques, respectively. Also, 6 (20%) patients in the interrupted group developed symptomatic restenosis, while in the continuous group, only one patient was clinically symptomatic. The patients with continuous suture technique had a shorter surgery time than patients whose interrupted technique was used (P < 0.001). Based on our results, we conclude that restenosis is significantly reduced when the continuous technique is applied for tracheal anastomosis; However, the results are contradicting in relevant literature and due to the retrospective nature of our study, further human studies and clinical trials are warranted. • Tracheal anastomosis suturing technique effects patient's post-op course. • The continuous suture technique has less anastomotic complications in trachea. • The continuous suture may be less time consuming than the interrupted technique. [ABSTRACT FROM AUTHOR]

Background: Systemic rheumatic diseases (SRD) are a heterogeneous group of diseases that can involve several organ systems and occasionally requires intensive care unit (ICU) admission because of severe systemic disease, life-threatening organ involvement, or complication of treatment. The objective of this study is to determine the causes, outcome, and prognostic factors of patients with rheumatologic diseases admitted in teaching medical ICUs in southern Iran. Methods: A retrospective case review of all patients with rheumatologic diseases admitted in the academic medical ICUs in two referral hospitals in southern Iran, from March 2015 to January 2020. Patients' data were documented from their hospital records and the cause of admission, in-hospital outcome, and prognostic factors was evaluated. Results: Ninety-one patients were included, of which 71.4% were female. Systemic lupus erythematosus (54.9%) was the most common disease. Nineteen (20.9%) patients were new cases of rheumatological disease. The most frequent symptom for admittance was dyspnea (54.9%) and hemoptysis (20.9%). The in-hospital mortality rate was 48%, and the leading cause of death was infection (29 patients; 65.5%) followed by disease activity (18 patients; 40.9%). Also, the death of 29.5% of patients was presumed due to both disease activity and infection. Factors associated with mortality included renal insufficiency (p < 0.028), infection (p < 0.001), pneumonia (p < 0.042), dyspnea (p < 0.042), loss of consciousness (p < 0.046), azathioprine consumption (p < 0.004) during 1 month before ICU admission, mechanical ventilation (p < 0.001), renal replacement therapy (p < 0.001), CNS involvement (p < 0.009), and ICU medications such as cyclosporine and azathioprine (0.03 and 0.03, respectively) or treatments such as plasmapheresis (p < 0.018). Conclusion: The ICU mortality rate of patients with SRD was high. Infection and disease exacerbation are the leading reasons for ICU admission in systemic rheumatic diseases. Intensivists must keep in mind that SRD exacerbation may require immunosuppressive agents along with lifesaving interventions, more particularly in newly diagnosed SRDs. Key Points • The ICU mortality rate of patients with SRD was high. • Infection and disease exacerbation are the leading reasons for ICU admission in systemic rheumatic diseases. • 63.8% of our patients fall into this category of new cases of rheumatologic disease and disease flare-up. [ABSTRACT FROM AUTHOR]

When it comes to intracranial aneurysms, the quest for more effective treatments is ongoing. Flow diversion represents a growing advancement in this field. This review seeks to compare 2 variants of the endovascular flow diversion method: the Flow Re-Direction Endoluminal Device (FRED) and the Pipeline Embolization Device (PED). A systematic review was conducted according to the PRISMA guideline using PubMed, Scopus, Web of Science, and Embase, using appropriate terms to compare PED and FRED in double-arm studies from conception until October 8th, 2023. The meta-analysis encompassed 1769 patients, with a predominance of females (75.5%), among whom 973 patients underwent FRED procedures, while 651 received PED interventions. At 6 months, complete occlusion rates were 0.62 for FRED and 0.68 for PED (P = 0.68). At 1 year and the last follow-up, no significant differences were observed between FRED and PED, respectively. Adequate occlusion rates were similar between FRED and PED (0.82 vs. 0.79, P = 0.68). FRED showed a statistically significant higher rate of good mRS scores at follow-up (1.00 vs. 0.97, P = 0.03). Hemorrhage and re-treatment rates were higher in PED (P < 0.01) without considering the rupture status of the aneurysms due to the lack of data. This meta-analysis suggests comparable efficacy but different safety profiles between FRED and PED in treating intracranial aneurysms. FRED demonstrated a higher rate of good modified Rankin scores, while PED showed increased hemorrhage and re-treatment rates. Understanding these differences is crucial for informed decision-making in clinical practice. [ABSTRACT FROM AUTHOR]

Background: The association between H. pylori (Helicobacter pylori) infection and gastroesophageal reflux disease (GERD) is a complex and confusing subject. The aim of this study was to evaluate the association between helicobacter pylori infection and erosive gastroesophageal reflux disease.Method: In a cross-sectional study, all patients referred for endoscopy due to dyspepsia were enrolled. The diagnosis of erosive GERD was made by endoscopy. Patients with normal esophagus were selected as comparison group. Random gastric biopsies were taken from all participants to diagnose H. pylori infection.Result: In total, 1916 patients were included in this study, of whom 45.6% had GERD. The mean age (SD) was 42.95 (16.32). Overall, 1442 (75.3%) patients were positive for H. pylori infection. The frequency of H. pylori infection in mild GERD patients was higher than the severe GERD, but this difference was not significant (P = 0.214). Except for sociodemographic status (P < 0.001), other variables including gender, age, ethnicity, body mass index (BMI), smoking, and presence of hiatus hernia in patients had no significant association with the frequency of H. pylori infection. According to Robust Poisson regression models analysis, the association of H. pylori (PR 1.026; 95% CI 0.990-1.064; P = 0.158) and sociodemographic status were not significantly different between the two groups. But smoking, increased BMI, older age, presence of hiatus hernia, and peptic ulcer diseases were significantly associated with GERD compared with the non-GERD group.Conclusion: In our results, there was no association between H. pylori infection and erosive GERD. Further studies are recommended. [ABSTRACT FROM AUTHOR]

Background: Although almost a year has passed since the Coronavirus disease 2019 (COVID-19) outbreak and promising reports of vaccines have been presented, we still have a long way until these measures are available for all. Furthermore, the most appropriate corticosteroid and dose in the treatment of COVID-19 have remained uncertain. We conducted a study to assess the effectiveness of methylprednisolone treatment versus dexamethasone for hospitalized COVID-19 patients. Methods: In this prospective triple-blinded randomized controlled trial, we enrolled 86 hospitalized COVID-19 patients from August to November 2020, in Shiraz, Iran. The patients were randomly allocated into two groups to receive either methylprednisolone (2 mg/kg/day; intervention group) or dexamethasone (6 mg/day; control group). Data were assessed based on a 9-point WHO ordinal scale extending from uninfected (point 0) to death (point 8). Results: There were no significant differences between the groups on admission. However, the intervention group demonstrated significantly better clinical status compared to the control group at day 5 (4.02 vs. 5.21, p = 0.002) and day 10 (2.90 vs. 4.71, p = 0.001) of admission. There was also a significant difference in the overall mean score between the intervention group and the control group, (3.909 vs. 4.873 respectively, p = 0.004). The mean length of hospital stay was 7.43 ± 3.64 and 10.52 ± 5.47 days in the intervention and control groups, respectively (p = 0.015). The need for a ventilator was significantly lower in the intervention group than in the control group (18.2% vs 38.1% p = 0.040). Conclusion: In hospitalized hypoxic COVID-19 patients, methylprednisolone demonstrated better results compared to dexamethasone. Trial registration: The trial was registered with IRCT.IR (08/04/2020-No. IRCT20200204046369N1). [ABSTRACT FROM AUTHOR]

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is the most common method for the determination of cell toxicity, but some factors limit the sensitivity of this method, such as pH. Less attention had been paid to the interference effect of optical and plasmonic properties of SiO2 nanoparticles (NPs) in the wavelength range assigned to MTT. This study investigated the synergistic interference effect of SiO2 NPs and wavelength on MTT assay for the first time. The examined variables included the type of SiO2 NPs concentrations (1, 10, and 100 mM) and different wavelengths (470, 490, 520, and 570 nm). The results showed that optical density (OD) increased (p < 0.05) when wavelength and the concentration of crystalline SiO2 NPs increased. So, the maximum OD at 10 and 100 mM were attributed to crystalline SiO2 NPs (p < 0.05) due to the functional group, whereas it was related to amorphous at 1 mM (p > 0.05). According to polynomial regression modeling (PRM), the maximum interference effect was predicted at crystalline SiO2 NPs and wavelength > 550 nm. Besides, the synergistic effects of SiO2 NPs, wavelength, and concentration of NPs had been a good fitting with first-order PRM. Thus, the concentration of SiO2 NPs had a confounder factor in colorimetric for MTT assay. The best artificial neural network (ANN) structure was related to the 3:7:1 network (Rall = 0.936, MSE = 0.0006, MAPE = 0.063). The correlation between the actual and predicted data was 0.88. As SiO2 NPs presence is an interfering factor in MTT assay concerning wavelength, it is suggested wavelength use with minimum confounding effect for MTT assay. [ABSTRACT FROM AUTHOR]

Objective: With the novel coronavirus pandemic, the impact on the healthcare system and workers cannot be overlooked. However, studies on the infection status of medical personnel are still lacking. It is imperative to ensure the safety of health-care workers (HCWs) not only to safeguard continuous patient care but also to ensure they do not transmit the virus, therefore evaluation of infection rates in these groups are indicated. Methods: Demographic and clinical data regarding infected cases among HCWs of Fars, Iran with positive SARS‐CoV‐2 PCR tests were obtained from 10th March to 17th May 2020. Results: Our data demonstrated a rate of 5.62% (273 out of 4854 cases) infection among HCW, with a mean age of 35 years and a dominance of female cases (146 cases: 53.5%). The majority of infected cases were among nurses (51.3%), while the most case infection rate (CIR) was among physicians (27 positive cases out of 842 performed test (3.2%)). Also, the highest rate of infection was in the emergency rooms (30.6%). Also, 35.5% of the patients were asymptomatic and the most frequent clinical features among symptomatic patients were myalgia (46%) and cough (45.5%). Although 5.5% were admitted to hospitals, there were no reports of ICU admission. Furthermore, 10.3% of the cases reported transmitting the infection to family and friends. Regarding safety precautions, 1.6% didn't wear masks and 18.7% didn't use gloves in work environments. Conclusion: HCWs are among the highest groups at risk of infection during the COVID-19 pandemic; therefore, evaluating infection rates and associated features is necessary to improve and adjust protective measures of these vulnerable, yet highly essential group. [ABSTRACT FROM AUTHOR]

The mechanisms of neuronal death in protein misfolding neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases are poorly understood. We used a highly toxic misfolded prion protein (TPrP) model to understand neurotoxicity induced by prion protein misfolding. We show that abnormal autophagy activation and neuronal demise is due to severe, neuron-specific, nicotinamide adenine dinucleotide (NAD(+)) depletion. Toxic prion protein-exposed neuronal cells exhibit dramatic reductions of intracellular NAD(+) followed by decreased ATP production, and are completely rescued by treatment with NAD(+) or its precursor nicotinamide because of restoration of physiological NAD(+) levels. Toxic prion protein-induced NAD(+) depletion results from PARP1-independent excessive protein ADP-ribosylations. In vivo, toxic prion protein-induced degeneration of hippocampal neurons is prevented dose-dependently by intracerebral injection of NAD(+). Intranasal NAD(+) treatment of prion-infected sick mice significantly improves activity and delays motor impairment. Our study reveals NAD(+) starvation as a novel mechanism of autophagy activation and neurodegeneration induced by a misfolded amyloidogenic protein. We propose the development of NAD(+) replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The G1 kinase CDK4 is amplified or overexpressed in some human tumors and promotes tumorigenesis by inhibiting known tumor suppressors. Here, we report that CDK4 deficiency markedly accelerated lymphoma development in the Eµ-Myc transgenic mouse model of B lymphoma and that silencing or loss of CDK4 augmented the tumorigenic potential of Myc-driven mouse and human B cell lymphoma in transplant models. Accelerated disease in CDK4-deficient Eµ-Myc transgenic mice was associated with rampant genomic instability that was provoked by dysregulation of a FOXO1/RAG1/RAG2 pathway. Specifically, CDK4 phosphorylated and inactivated FOXO1, which prevented FOXO1-dependent induction of Rag1 and Rag2 transcription. CDK4-deficient Eµ-Myc B cells had high levels of the active form of FOXO1 and elevated RAG1 and RAG2. Furthermore, overexpression of RAG1 and RAG2 accelerated lymphoma development in a transplant model, with RAG1/2-expressing tumors exhibiting hallmarks of genomic instability. Evaluation of human tumor samples revealed that CDK4 expression was markedly suppressed, while FOXO1 expression was elevated, in several subtypes of human non-Hodgkin B cell lymphoma. Collectively, these findings establish a context-specific tumor suppressor function for CDK4 that prevents genomic instability, which contributes to B cell lymphoma. Furthermore, our data suggest that targeting CDK4 may increase the risk for the development and/or progression of lymphoma. [ABSTRACT FROM AUTHOR]

Prion diseases such as Creutzfeldt-Jakob disease (CJD) are incurable and rapidly fatal neurodegenerative diseases. Because prion protein (PrP) is necessary for prion replication but dispensable for the host, we developed the PrP-FRET-enabled high throughput assay (PrP-FEHTA) to screen for compounds that decrease PrP expression. We screened a collection of drugs approved for human use and identified astemizole and tacrolimus, which reduced cell-surface PrP and inhibited prion replication in neuroblastoma cells. Tacrolimus reduced total cellular PrP levels by a nontranscriptional mechanism. Astemizole stimulated autophagy, a hitherto unreported mode of action for this pharmacophore. Astemizole, but not tacrolimus, prolonged the survival time of prion-infected mice. Astemizole is used in humans to treat seasonal allergic rhinitis in a chronic setting. Given the absence of any treatment option for CJD patients and the favorable drug characteristics of astemizole, including its ability to cross the blood-brain barrier, it may be considered as therapy for CJD patients and for prophylactic use in familial prion diseases. Importantly, our results validate PrP-FEHTA as a method to identify antiprion compounds and, more generally, FEHTA as a unique drug discovery platform. [ABSTRACT FROM AUTHOR]

The human-animal relationship and its benefits have been a popular issue in recent decades. This study focuses on the dog as a paradigmatic example of this complex bond. The relationship between human and dog evolved over thousands of years through the domestication process. During this period, climatic, cultural, geographical and social changes have had a direct impact on this bond. Dogs have a remarkable capacity to play a variety of roles that mirror the evolution of human societies. Subsequently, questions arise regarding the important and symbolic roles that canines played in ancient cultures, religions and mythological traditions. Specifically, how have these roles changed through history? This research aimed to explore the socio-economic aspects of the human-dog relationship, spanning from ancient civilizations to modern societies. Through a systematic search methodology, this investigation seeks to provide insights into the dynamics of the complex human-dog relationship, including historical backgrounds, socio-cultural dynamics, economic implications and associated challenges. Additionally, the present study addresses the environmental concerns that emerge alongside rising stray dog populations. This research emphasizes the importance of strategies to balance the benefits of this coexistence that promote human and animal welfare., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Purpose: The Journal of Neuro-Oncology (JNO), established in 1983, plays a key role in publishing research on brain and spinal cord tumors. This study examines JNO's publication trends, focusing on country and gender representation to highlight its global impact., Methods: Statistical analyses were conducted using R. Gender of the first authors was predicted using a gender-guesser, and author affiliations were used to determine publication countries. We introduced a novel Country-Related Diversity (CRD) index to assess the JNO's representativeness, comparing a country's JNO publications to its overall neurosurgical output. An index value of 1 indicates proportional representation., Results: The JNO corpus, spanning from 1983 to 2024, comprises 8,154 documents with an average document age of 14.4 years. The average citation count per document is 28.71, with a rate of 2.16 citations per document per year. JNO's scientific output has grown significantly, peaking at 397 articles in 2011, with a long-term annual growth rate of 3.7%. The keyword analysis highlights "glioblastoma" as the most frequent term, reflecting the journal's neuro-oncological focus. Geographically, the U.S. led with 2,535 articles (40.1%), followed by China and Germany. International collaboration rose steadily, with multi-country publications increasing from 4.76% in 1983 to 20.98% in 2024. Analyzing contributions from different countries showed a converging CRD index toward 1 (P < 0.01), with U.S. and non-U.S. countries trending similarly. Upper-middle-income countries displayed fluctuating CRD patterns, whereas lower-middle-income countries lagged behind. Authorship analysis showed an increasing trend in co-authorship (P < 0.01), with the average number of authors per paper reaching 10.4 by 2024. Gender representation revealed a growing number of female first and senior authors, although males still dominate. By 2024, 32.9% of first authors and 21.6% of senior authors were female, signaling a gradual trend toward gender parity (P < 0.01)., Conclusions: The CRD index offers a standardized measure of country-specific research representation in the JNO. The convergence towards 1 reflects balanced international representation. JNO publication also reflects a trend toward gender equity, with a notable rise in female first authors, enhancing global research inclusivity., (© 2024. The Author(s).)

Following the outbreak of COVID-19, several immunotherapy methods were used to modulate the immune responses of patients. In this study, we aimed to evaluate the immune response to COVID-19 in patients receiving convalescent plasma. In this regard, this randomized controlled trial included 30 patients who were divided into two groups according to receiving convalescent plasma or normal control plasma. Samples from both groups were collected on days 0, 1, 3, 5 and 7 after plasma infusion. We measured the expression level of TLR7/8, IRF3/7, CTLA-4, PD-1 and T cell transcription factors by Real-time PCR in the mentioned groups. Thirteen cytokines were also evaluated using flow cytometry method. Results showed that compared to the normal control plasma group, the expression levels of TLR7, 8, IRF3, 7 and PD-1 and CTLA-4, on days 3, 5 and 7 after convalescent plasma infusion, were significantly decreased. On the other hand,  Gene expression results showed that the expression levels of Tbet, RORγ3 and Foxp3 on days 3, 5 and 7 after convalescent plasma infusion were significantly increased compared to the normal control plasma group. After convalescent plasma infusion, the viral load was significantly decreased compared to the normal control plasma group. Convalescent plasma infusion also reduced the plasma cytokines levels, including IL-6, IL-10, and IL-4, and enhanced the level of IL-2, IFN- γ and perforin comparing the normal control plasma group. According to the results, the convalescent plasma infusion led to a decrease in the expression of innate immunity receptors and an increase in the expression of transcription factors of adaptive immunity. Therefore, it may be concluded that convalescent plasma infusion can modulate the immune response. To achieve a reliable consequence, further studies are required.

Background: Pneumocystis jirovecii infection is an opportunistic infection that mostly affects patients with immunosuppressive conditions like human immunodeficiency virus (HIV) infection or medications, like corticosteroids. This study reports a rare case of Pneumocystis Jiroveci infection in a relatively immunocompetent patient which presented with uncommon radiological findings., Case Presentation: A 46-year-old man with a malnourished appearance and a history of opium dependence presented with dry cough, dyspnea, and weight loss to the hospital. There was no evidence of an immunocompromised condition or use of any immunosuppressive medication in the history of the patient. A lung high-resolution computed tomography (HRCT) scan revealed a crazy-paving appearance and localized infiltration. Methenamine silver staining and the histopathological findings in the transbronchial lung biopsy confirmed the diagnosis of PJP. Antibiotics and bronchodilators were administrated and the patient was discharged after 6 days of hospitalization. HIV testing and immunoglobulin levels were normal in the hospital course as well as his follow-up visits. After a 2-month follow-up, the patient was in good condition despite of mild remaining infiltration in his lung., Conclusions: PJP typically affects HIV-infected patients, but due to excessive use of immunosuppressive medications, its prevalence is increasing in non-HIV-infected patients. Malnutrition may predispose the patients to PJP, even in the absence of immunosuppressive conditions., (© 2024. The Author(s).)

Purpose: Malignant Mesothelioma (MM) is a rare malignancy of the serosa membranes with a high mortality rate and long latent period. The relationship between a group of mineral fibers known as asbestos and mesothelioma is now well accepted in which people can be exposed to these fibers by various means during their lifetime and has been its usage has banned in many countries, such as Iran, which announced its gradual elimination from 1999 over a period of 7 years by using safe substitutes. However, the mineral particles are able to sustain itself in the environment, air, water, and soil and on the other hand, symptoms may take up to half a century to develop in exposed individuals. Also, there remains a shortage of comprehensive investigation on the effects of asbestos exposure within the familial context (household or domestic exposure) or on individuals residing in proximity to asbestos mines or factories (environmental exposure). Based on the high number of MM cases in Iran, and also our hypothesis that residuals of asbestos in the environment and petroleum products may be the etiological factor for MM, we conducted this study to evaluate the clinic epidemiological features of MM in the south of Iran its relation to possible asbestos exposure., Methods: In this study, we analyzed the demographic features and occupations of confirmed cases of MM in Shiraz, southern Iran along with the follow-up of the patients' disease from 2008 to 2018, while also comparing the features of our patients with a control group compromising of 105 non-MM patients., Results: Among the 35 confirmed cases of MM, with an average age of 61 years, 9 (25.7%) were female, and 26 (74.3%) were male. During our assessment, 12 patients had already died, with a mean time of 11.26 months post-diagnosis. Our findings revealed a higher prevalence of MM among housekeepers and employees of oil companies. In comparison to the control group, individuals with occupational exposure and those residing near refinery locations were at a heightened risk of developing MM. However, based on regression analysis, only occupations associated with refineries exhibited a significant correlation with MM ( p  = 0.028; OR: 14.602; 95% CI: 1.328-160.499)., Conclusion: Both occupational and para-occupational exposure demonstrated a significant correlation with MM, whereas our regression analysis did not affirm geographical and environmental factors as contributors to MM. Despite the industry's prohibition of direct asbestos usage, the persistent existence of asbestos particles in the environment for decades, coupled with the long latency period of MM, warrants further investigation. Health authorities and policymakers should recognize this potential hazard, prompting an enhancement of early detection within at-risk groups., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background and Aim: Delay in diagnosis and treatment of lung cancer is thought to be a major cause of its poor outcomes. We evaluated the delays within the presentation to the initiation of diagnostic and therapeutic interventions amongst lung cancer patients in Southern Iran., Methods: This cross-sectional study was conducted from March 2019 to March 2021. The data collected through interview included socio-demographic, medical and clinical findings, and the time intervals needed to visit physician, refer to specialist, request diagnostic procedures, reach diagnosis of lung cancer, and hospitalization., Results: Eighty-nine patients (58 males and 31 females) with a mean age of 61.01 ± 12.25 years were included. The median time of symptom presentation and first physician visit interval was 25 days. Sixty-five days were spent for requesting, performing, and evaluating the diagnostic procedures. The median interval between diagnosis and initiation of treatment was 16 days. Totally, it took an average of 122 days from the presentation to the definite diagnosis of lung cancer. Patient-, diagnosis-, and treatment-related delays were not significantly correlated with any of the demographic, socioeconomic, and clinical (disease stage, symptom) variables, as well as the diagnosis tool and the first physician who visited the patient (p > 0.05)., Conclusions: There was a significant delay but relatively similar to other countries in the diagnosis and treatment of lung cancer patients in Southern Iran. The largest portion of delay could be attributed to the raising clinical suspicion in the physicians, referral for diagnostic assessments, and the diagnosis process., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Background: This scoping review aims to comprehensively review the available literature on the safety and efficacy of focused ultrasound (FUS) for blood-brain barrier disruption (BBBD) in patients with high-grade gliomas, including glioblastoma (GBM). High-grade gliomas pose significant challenges in neuro-oncology due to their aggressiveness and intricate location, often limiting the efficacy of traditional treatments. FUS offers a promising approach by transiently disrupting the blood-brain barrier, thereby facilitating enhanced drug delivery to tumor cells while minimizing systemic side effects., Methods: A scoping review adhering to PRISMA guidelines was conducted to explore the literature on FUS-induced BBBD in glioma patients. PubMed and Embase databases were searched from inception to April 2024 using defined keywords. Original clinical studies focusing on FUS for BBBD in gliomas were included. Two reviewers independently screened records, with conflicts resolved by a third reviewer. Data extraction and quality assessment were performed accordingly., Results: A total of 1,310 studies were initially identified, resulting in nine eligible studies after screening and selection. These studies, published between 2016 and 2024, included 106 patients (39.6 % female) with ages ranging from 29 to 80 years. Recurrent GBM was the most common diagnosis (100 patients), with other diagnoses including anaplastic astrocytoma, diffuse infiltrating glioma, and oligodendroglioma. Various FUS devices and microbubble contrast agents were employed across the studies. Safety and efficacy were assessed in both experimental and clinical settings, with no significant adverse events reported during BBBD procedures. Notably, BBBD facilitated enhanced drug delivery to tumor tissue, demonstrating potential therapeutic benefits., Conclusion: Studies investigating BBBD using FUS demonstrate promising outcomes in experimental and clinical settings. BBBD procedures in patients with malignant gliomas and recurrent GBM show safety and successful enhancement of drug delivery potential. Overall, FUS-mediated BBBD emerges as a safe and feasible approach for improving therapeutic outcomes in brain tumor patients, warranting further clinical exploration and optimization., 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 Elsevier Ltd. All rights reserved.)

Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health threat. It results in substantial mortality and may be underrecognized due to insufficient screening and diagnostic challenges. Furthermore, TB's impact is closely linked to complex socioeconomic and healthcare factors. The COVID-19 pandemic has exacerbated these challenges due to similarities in clinical presentation and transmission dynamics with TB. Socioeconomic factors such as limited access to healthcare services, resource constraints, and social stigma further complicate TB management. Historically, TB faced increased burdens during natural disasters, wars, and pandemics. This study analyzes TB incidence changes, emphasizing the crucial need for timely diagnosis within the context of COVID-19 measures., Method: This cross-sectional study, conducted at Shiraz's TB referral center in Southern Iran, covered the period from January 1, 2018, to December 31, 2022. We analyzed patient data, including epidemiological and demographic factors, clinical and radiological features, and treatment outcomes. Data were compared between the pre-COVID-19 pandemic era and the COVID-19 pandemic era (from March 2020), using standard and regression analyses. A P-value of less than 0.05 was considered statistically significant., Results: We analyzed 388 TB patients with a mean age of 48.38 ± 20.53 years, including 264 pulmonary cases (68.0%). The highest incidence of TB was recorded in 2019, representing 27.6% of the cases. During the COVID-19 era, logistic regression analysis identified significant associations with higher education levels (P = 0.032; OR = 1.380; 95% CI: 1.028-1.851), a decrease in symptoms such as sputum production (P = 0.004; OR = 0.342; 95% CI: 0.166-0.705) and chills (P = 0.036; OR = 0.282; 95% CI: 0.087-0.919), and an increase in symptoms of fatigue (P = 0.006; OR = 2.856; 95% CI: 1.358-6.005)., Conclusion: The COVID-19 pandemic has had a prolonged impact on TB cases in our country, resulting in a reduction in reported cases due to challenges in quarantine and screening. However, it has also led to a shift in TB patterns and a potential increase in latent TB cases and future mortality rates. Addressing the repercussions requires enhanced control strategies, prioritized service delivery, and secured funding for intensified case finding, expanded contact-tracing, community engagement, digital health tools, and uninterrupted access to medications., (© 2024. The Author(s).)

Purpose: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for psychiatric conditions. Previous studies have shown that SSRIs can increase bleeding risk by affecting platelet aggregation. However, their impact on perioperative outcomes in hip surgery remains uncertain. This case-control study examines the link between preoperative SSRI use and perioperative transfusion requirements in hip surgery patients., Methods: Data from the M161Ortho dataset of Pearl Diver patient records database were utilized. Patients who underwent hip joint surgery between 2010 and 2022 and had documented preoperative SSRI use within one month prior to surgery were included. Patients with coagulopathy disorders or coagulopathy medication use were excluded. Perioperative transfusion need was defined as receiving red blood cell or whole blood transfusions on the same date or within 10 days following the surgery., Results: A total of 75,374 patients with preoperative SSRI use were matched with an equal number of non-SSRI users. Preoperative SSRI use was associated with an increased risk of requiring perioperative transfusion (5.7% vs. 5.1%, P < 0.001). Subgroup analysis demonstrated increased transfusion risk in patients undergoing pinning (2.6% vs. 1.8%, P = 0.02), open reduction with internal fixation (ORIF) (8.9% vs. 8.2%, P = 0.007), and total hip arthroplasty (THA) (3.8% vs. 3.4%, P < 0.001), but no significant difference was observed in patients undergoing hemiarthroplasty., Conclusion: Clinicians should be aware of the potential risk of increased perioperative transfusion requirements in hip surgery patients using SSRIs, especially during pinning, ORIF, and THA procedures. It is essential to consider this when managing patients on SSRIs before hip surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Recurrent intracranial aneurysms present a significant clinical challenge, demanding innovative and effective treatment approaches. The Woven EndoBridge (WEB) device has emerged as a promising endovascular solution for managing these intricate cases. This study aims to assess the safety and efficacy of the WEB device in treating recurrent intracranial aneurysms., Methods: We conducted a comprehensive search across multiple databases, including PubMed, Scopus, Embase, and Web of Science, from inception to June 5, 2023. Eligible studies focused on evaluating WEB device performance and included a minimum of five patients with recurrent intracranial aneurysms. The complete and adequate occlusion rates, neck remnant rates, and periprocedural complication rates were pooled using SATA V.17., Results: Our analysis included five studies collectively enrolling 73 participants. Participant ages ranged from 52.9 to 65 years, with 64.4% being female. Aneurysms were wide-necked and predominantly located in the middle cerebral artery, basilar artery, and anterior cerebral artery. Previous treatments encompassed coiling, clipping, and the use of WEB devices. Our study found an overall adequate occlusion rate of 0.80 (95% CI 0.71-0.89), a complete occlusion rate of 0.39 (95% CI 0.28-0.50), and a neck remnant rate of 0.38 (95% CI 0.27-0.48). Periprocedural complications were reported at a rate of 0%, although heterogeneity was observed in this data. Notably, evidence of publication bias was identified in the reporting of periprocedural complication rates., Conclusion: Our findings suggest that the WEB device is associated with favorable outcomes for treating recurrent wide-neck intracranial aneurysms., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Deep brain stimulation (DBS) has become an effective and safe treatment in patients with Parkinson's disease (PD) not responding to conventional treatments. With the growing body of literature regarding the use of DBS in different movement disorders, there remain controversies regarding performing awake or asleep DBS. This systematic review provides the most comprehensive review of the literature comparing the two techniques from various aspects in detail., Methods: A systematic review of the PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted. All studies comparing any aspects of asleep and awake DBS were included. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions tool. Meta-analysis was conducted with consideration of baseline characteristics., Results: Thirty-one studies with 2563 PD patients were included. A total of 1423 patients underwent asleep DBS. The two groups were comparable regarding their baseline characteristics. The follow-up ranged from 3 to 60 months. The two DBS techniques were comparable in terms of motor symptom improvements and levodopa equivalent daily doses. However, the asleep technique showed slightly better improvements in Mattis Dementia Rating Scale and Parkinson's Disease Questionnaire scores. Moreover, the asleep technique was associated with more surgical adverse events, whereas pneumocephalus and psychological disorders such as mood, affect, and cognitive disorders were more common in the awake technique. Subgroup analyses revealed no significant differences in outcomes between asleep and awake DBS when categorized by targeted brain nuclei, use of intraoperative or preoperative imaging, and whether microelectrode recordings were used., Conclusions: These findings suggest comparable clinical outcomes between the two DBS approaches. The two methods had their salient differences in terms of lead passes and specific adverse events. The decision to perform awake or asleep DBS should be based on the patient's preference, the surgeon's experience, the availability of advanced intraoperative imaging, and the patient's tolerance for specific adverse events.

Background: Recent studies have suggested that the hippocampus (HC) is involved in cognitive and behavioral functions beyond memory. We aimed to investigate how the volume of each subfield of the HC is associated with distinct patterns of coping strategies, emotion regulation, and impulsivity in a healthy population., Methods: We studied a total of 218 healthy subjects using the Leipzig mind-brain-body dataset. Participants were assessed for coping strategies, emotion regulation, and impulsivity using the Cognitive Emotion Regulation Questionnaire (CERQ), Coping Orientations to Problems Experienced (COPE), Impulsive Behavior Scale (UPPS), and Behavioral Activation and Inhibition System (BAS/BIS). The associations between HC subfield volumes including CA1, CA2/3, CA4/DG, SR-SL-SM, and subiculum, and behavioral scores were examined using multiple linear regression models adjusted for possible confounders, including age, sex, years of education, handedness, total intracranial volume (ICV), and HC volume., Results: The use of emotional support, venting, and positive reframing coping strategies were significantly and positively correlated with total, total right, and total left HC volumes. Venting was significantly associated with CA1 after adjusting for age, sex, handedness, and education (P=0.001, B = 0.265, P-FDR = 0.005). No significant association was observed between CERQ subscales and HC subfield volumes after controlling for confounders and multiple analyses. However, sensation-seeking subscale of the UPPS-P was positively correlated with total and right CA2-CA3 volumes after adjustments for age, sex, handedness, ICV, and HC volumes (P=0.002, B = 0.266, P-FDR = 0.035). BAS and BIS subscales did not show significant relationship with HC subfield volumes., Conclusion: Patterns of HC subfields volumes are associated with coping strategies, impulsivity, and emotion regulation. In particular, using emotional support, positive reframing, venting, and sensation seeking are significantly associated with certain HC subfield volumes. These findings suggest that the hippocampus may play a crucial role in modulating emotional responses and behavioral adaptations, offering potential targets for therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Silent hypoxemia is when patients do not experience breathing difficulty in the presence of alarmingly low O 2 saturation. It could cause rapid deterioration and higher mortality rates among patients, so prompt detection and identifying predictive factors could result in significantly better outcomes. This study aims to document the evidence of silent hypoxemia in patients with COVID-19 and its clinical features., Methods: A total of 78 hospitalized, nonintubated patients with confirmed COVID-19 infection were included in this study. Their O 2 saturation was measured with a pulse oximeter (PO), and arterial blood gas (ABG) was taken. Demographic and clinical features were recorded. The Borg scale was used to evaluate dyspnea status, and patients with a score of less than two accompanied by O 2 saturation of less than 94% were labeled as silent hypoxic. Univariate analysis was utilized to evaluate the correlation between variables and their odds ratio (OR) and 95% confidence interval (CI)., Results: Silent hypoxemia was observed in 20 (25.6%) of the participants. The average difference between the PO and ABG methods was 4.36 ± 3.43. Based on regression analysis, dyspnea and respiratory rate demonstrated a statistically significant correlation with the O 2 saturation difference between PO and ABG (OR: 2.05; p  = 0.026; 95% CI: 0.248-3.847 and OR: 0.144; p  = 0.048, 95% CI: 0.001-0.286). Furthermore, the Borg scale (OR: 0.29; p  = 0.009; 95% CI: 0.116-0.740) had a significant reverse correlation with silent hypoxia., Conclusions: Silent hypoxemia can be a possible complication that affects some COVID-19 patients. Further care should be bestowed upon the younger population and those with underlying neurological or mental illnesses. Furthermore, the respiratory rate, pulse oximeter, and arterial blood gas O 2 levels should be considered alongside each other., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Care Science published by John Wiley & Sons Ltd on behalf of Tsinghua University Press.)

Objective: The recent introduction of the Woven EndoBridge (WEB) has presented an alternative treatment modality for intracranial bifurcation and wide-neck aneurysms with a growing body of literature evaluating its efficacy. However, no previous systematic review has focused on comparing WEB with previously using endovascular approaches, specifically primary coiling (PC) and stent-assisted coiling (SAC). Herein, the authors present the first systematic review summarizing available literature to reach a consensus regarding the safety and effectiveness of WEB., Methods: A systematic review of articles identified through a search of PubMed, Embase, Scopus, and Web of Science was conducted. Studies were included if they compared WEB with PC or SAC from any aspect for intracranial aneurysms. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions tool. Meta-analyses of the outcomes based on stent use and rupture status were performed., Results: A total of 16 studies were included. The three endovascular approaches were comparable in terms of baseline characteristics except for older age and smaller aneurysm neck in the PC group (p < 0.05). Moreover, the follow-up duration was shorter in the WEB group (p < 0.05). Although the WEB group demonstrated lower complete and adequate immediate occlusion rates (p < 0.01), the rates at follow-up evaluations were comparable with SAC and PC (p = 0.61 and p = 0.27, respectively). The WEB group experienced significantly fewer unfavorable neurological outcomes than the SAC group (p = 0.04), while comparable to the PC group (p = 0.36). Retreatment rates were comparable between WEB and coiling (p = 0.92). The WEB group had fewer hemorrhagic and thromboembolic complications (p < 0.01 and p = 0.01, respectively), with similar neurological and procedure-related complications compared with combined PC and SAC groups. Lastly, mortality was comparable among the different endovascular approaches., Conclusions: This study provides evidence on the noninferiority of WEB compared with PC and SAC in terms of angiographic outcomes. Meanwhile, our findings on lower complication rates, cost, and improved operative aspects associated with WEB establish this novel endovascular treatment as a safe and effective alternative for the treatment of bifurcation and wide-neck aneurysms.

Objective: Chordoma is a primary bone tumor with limited literature on its management because of its rarity. Resection, while considered the first-line treatment, does not always provide adequate tumor control. In this systematic review, the authors aimed to provide comprehensive insights by managing these tumors with stereotactic radiosurgery (SRS)., Methods: A systematic review was conducted according to PRISMA guidelines using the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases. Search terms included chordoma and radiosurgery and their equivalent terms. Data on baseline characteristics, SRS details, and outcomes were extracted. The Joanna Briggs Institute checklist was used to assess risk of bias. A meta-analysis was performed on relevant variables., Results: A total of 33 eligible studies encompassing 714 patients with skull base chordomas were included. Most studies had a low risk of bias. Patients, predominantly male (57.37%) with a mean age of 46.54 years, exhibited a conventional chordoma subtype (74.77%) and primary lesions (77.91%), mainly in the clivus (98.04%). The mean lesion volume was 13.49 cm3, and 96.68% of patients had undergone prior surgical attempts. Gamma Knife radiosurgery (88.76%) was the predominant SRS method. Radiologically, 27.19% of patients experienced tumor regression, while 55.02% showed no signs of disease progression at the latest follow-up. Progression occurred after a mean of 48.02 months. Symptom improvement was noted in 27.98% of patients. Radiosurgery was associated with a relatively low overall adverse event rate (11.94%), mainly cranial nerve deficits (8.72%). Meta-regression revealed that age and primary lesion type influenced symptom improvement, while factors like extent of resection, radiotherapy, and SRS type affected adverse event rates., Conclusions: This systematic review provides evidence on the safety and effectiveness of radiosurgery in the management of skull base chordomas. Local tumor control was achieved in the majority of patients treated with SRS. Various baseline characteristics and SRS features have been analyzed to identify modifying factors for each outcome to provide a framework for informed decision-making when managing these patients.

Background and Aims: Euthanasia is a controversial issue related to the right to die. Although euthanasia is mostly requested by terminally sick individuals, even in societies where it is legal, it is unclear what medical conditions lead to euthanasia requests. In this scoping review, we aimed to compile medical conditions for which euthanasia has been requested or performed around the world., Methods: The review was preferred reporting items for systematic reviews and meta-analysis for scoping reviews (PRISMA-ScR) checklist. Retrieved search results were screened and unrelated documents were excluded. Data on reasons for conducting or requesting euthanasia along with the study type, setting, and publication year were extracted from documents. Human development index and euthanasia legality were also extracted. Major medical fields were used to categorize reported reasons. Group discussions were conducted if needed for this categorization. An electronic search was undertaken in MEDLINE through PubMed for published documents covering the years January 2000 to September 2022., Results: Out of 3323 records, a total of 197 papers were included. The most common medical conditions in euthanasia requests are cancer in a terminal phase (45.4%), Alzheimer's disease and dementia (19.8%), constant unbearable physical or mental suffering (19.8%), treatment-resistant mood disorders (12.2%), and advanced cardiovascular disorders (12.2%)., Conclusion: Reasons for euthanasia are mostly linked to chronic or terminal physical conditions. Psychiatric disorders also lead to a substantial proportion of euthanasia requests. This review can help to identify the features shared by conditions that lead to performing or requesting euthanasia., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Recent studies have shown that gut microbiota can affect the development of Alzheimer's disease (AD) through various mechanisms. Bile acids (BAs), which are the final byproducts of cholesterol metabolism created through both the human body and gut microbiome, appear to be influenced by gut microbiota and may impact AD pathological characteristics such as the accumulation of tau and amyloid-β. We aimed to investigate the associations between various serum BAs and CSF biomarkers (including Aβ, total tau, and p-tau). Additionally, we sought to examine the longitudinal changes in brain Aβ and tau through PET imaging in relation to BAs profile., Methods: The data of 828 subjects including 491 diagnosed with mild cognitive impairment (MCI), 119 patients diagnosed with AD, and 267 cognitively normal (CN) participants were obtained from ADNI. The baseline and longitudinal [ 18 F] florbetapir and [ 18 F] flortaucipir PET standard uptake value ratios (SUVR) measures were obtained to assess the accumulation of tau and Aβ. Moreover, baseline levels of serum BAs and CSF Aβ1-42, tau, and p-tau were used., Results: After FDR correction we observed that five BAs level and relevant calculated ratios were associated with CSF p-tau and tau, three with CSF Aβ1-42. Furthermore, three BAs level and relevant calculated ratios were associated with the tau-PET rate of change, and two with the Aβ rate of change., Conclusion: The findings from our study suggest a correlation between altered profiles of BAs and CSF and imaging biomarkers associated with AD. These results provide supporting evidence for the link between the gut microbiome and the pathological features of AD., (© 2024. The Author(s).)

Objective: Stereotactic radiosurgery (SRS) has been established as a safe and alternative treatment for dural arteriovenous fistulas (dAVFs). While embolization alone is the most commonly used modality for the treatment of dAVFs, the adjunctive use of embolization with SRS, with the growing use of SRS, has gained increasing interest in the past few years. However, the relative efficacy and safety of SRS combined with embolization versus SRS alone for dAVFs remains uncertain. Hence, this systematic review aimed to evaluate the efficacy of SRS with adjunctive embolization for intracranial dAVFs., Methods: A systematic review and meta-analysis was conducted by searching electronic databases, including PubMed, Embase, and the Cochrane Library, up to August 2023. All studies evaluating the utilization of adjunctive embolization and SRS for dAVFs were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on the suitable outcomes., Results: Eighteen studies involving 715 patients were included. The mean age of the participants in the study was 64.30 years in the adjunctive embolization group and 60.51 years in the SRS-alone group. In the adjunctive embolization group 41.3% of patients were female, compared with 47.1% in the SRS-only group. The dAVF obliteration rates were 64.7% and 65.7% in the adjunctive embolization and SRS-alone groups, respectively. These obliteration rates were comparable between the two groups (p = 0.96), as were the symptom improvement rates (p = 0.35). Adverse events were rare, and were more commonly associated with the adjunctive embolization procedure, although further causal analysis was not possible., Conclusions: This study provides evidence that adjunctive embolization plus SRS provides similar obliteration and symptom improvement rates compared with SRS alone, with both having very limited SRS-related adverse events. Considering the added burden and adverse events of additional endovascular treatment, the authors recommend embolization be reserved for more complex dAVFs or when embolization can potentially be curative alone or provide more rapid symptomatic relief or protection during the radiosurgical latency period.

Background and Objectives: The addition of adjuvant embolization to radiosurgery has been proposed as a means of improving treatment outcomes of intracranial arteriovenous malformations (AVMs). However, the relative efficacy and safety of radiosurgery with adjuvant embolization vs radiosurgery alone remain uncertain. Moreover, previous systematic reviews and meta-analyses have included a limited number of studies and did not consider the effects of baseline characteristics, including AVM volume, on the outcomes. This systematic review aimed to evaluate the efficacy of preradiosurgery embolization for intracranial AVMs with consideration to matching status between participants in each treatment group., Methods: A systematic review and meta-analysis were conducted by searching electronic databases, including PubMed, Scopus, and Cochrane Library, up to January 2023. All studies evaluating the utilization of preradiosurgery embolization were included., Results: A total of 70 studies (9 matched and 71 unmatched) with a total of 12 088 patients were included. The mean age of the included patients was 32.41 years, and 48.91% of the patients were female. Preradiosurgery embolization was used for larger AVMs and patients with previous hemorrhage ( P < .01, P = .02, respectively). The obliteration rate for preradiosurgery embolization (49.44%) was lower compared with radiosurgery alone (61.42%, odds ratio = 0.56, P < .01), regardless of the matching status of the analyzed studies. Although prior embolization was associated higher rate of cyst formation ( P = .04), it lowered the odds of radiation-induced changes ( P = .04). The risks of minor and major neurological deficits, postradiosurgery hemorrhage, and mortality were comparable between groups., Conclusion: This study provides evidence that although preradiosurgery embolization is a suitable option to reduce the AVM size for future radiosurgical interventions, it may not be useful for same-sized AVMs eligible for radiosurgery. Utilization of preradiosurgery embolization in suitable lesions for radiosurgery may result in the added cost and burden of an endovascular procedure., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: In this systematic review and meta-analysis, we aimed to investigate the correlation between disability in patients with Multiple sclerosis (MS) measured by the Expanded Disability Status Scale (EDSS) and brain Magnetic Resonance Imaging (MRI) features to provide reliable results on which characteristics in the MRI can predict disability and prognosis of the disease., Methods: A systematic literature search was performed using three databases including PubMed, Scopus, and Web of Science. The selected peer-reviewed studies must report a correlation between EDSS scores and MRI features. The correlation coefficients of included studies were converted to the Fisher's z scale, and the results were pooled., Results: Overall, 105 studies A total of 16,613 patients with MS entered our study. We found no significant correlation between total brain volume and EDSS assessment (95 % CI: -0.37 to 0.08; z-score: -0.15). We examined the potential correlation between the volume of T1 and T2 lesions and the level of disability. A positive significant correlation was found (95 % CI: 0.19 to 0.43; z-score: 0.31), (95 % CI: 0.17 to 0.33; z-score: 0.25). We observed a significant correlation between white matter volume and EDSS score in patients with MS (95 % CI: -0.37 to -0.03; z-score: -0.21). Moreover, there was a significant negative correlation between gray matter volume and disability (95 % CI: -0.025 to -0.07; z-score: -0.16)., Conclusion: In conclusion, this systematic review and meta-analysis revealed that disability in patients with MS is linked to extensive changes in different brain regions, encompassing gray and white matter, as well as T1 and T2 weighted MRI lesions., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest regarding the publication of this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background and Aims: Hospitals are one of the most important healthcare centers for providing the patients with different medical needs. Several different factors might cause hospitals to downgrade their services or departments or close down overall. One of the most multifaceted reasons for hospital downgrading or closure is infectious disease outbreaks. In this regard, we aimed to evaluate the effects of hospital closure and downgrading due to the COVID-19 pandemic on the mortality rate of the people residing in Fars province, Iran., Methods: We gathered mortality information, including the cause of death, age, sex, place, and time of death of all deceased cases occurring during a period of 3 years, from February 20, 2018 to March 2021 from the forensic medicine and also the Department of Biostatistics in Shiraz University of Medical Sciences., Results: A total of 71,331 deaths have been reported since 2018 through the first quarter of 2021, with 57.9% of total mortality cases attributed to male gender. The total mortality counts ranged from 4229 to 9809 deaths per quarter, from which the minimum rate was reported in the first quarter of 2018 and the maximum in the fourth quarter of 2020. Based on the causes of death, diseases of the circulatory system were shown to be the all-time most frequent cause of death, accounting for a total of 42.8% of recorded deaths, followed by neoplasms (9.77%) and diseases of the respiratory system (9.45%)., Conclusion: Although the large number of deaths at the time of the pandemic are immediately due to COVID-19 infection, deaths due to a notable number of other causes have had a significant increase which, along with the specific trend of place and causes of death, shows that the downgrading and closure of hospitals have had a significant impact on overall population mortality., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Trainability in dogs is affected by learning aptitude and memory capacity. While this trait has a heritable basis in canines, the specific genetic loci responsible for it remain unknown. Our previous results suggested that the BDNF, CCK and TAC1 genes are associated with learning and memory in canines. Experimental validation is crucial to confirm the effects of these candidate genes on trainability. Understanding the genetic foundation of this trait would offer insight into the inheritance pattern of complex behavioural characteristics., Objective: This study aimed to assess the genetic variations within candidate genes and explore their potential associations with behavioural phenotypes in dogs., Methods: The behavioural characteristics of 123 male Belgian Malinois dogs were assessed using a customised questionnaire. Target regions of candidate genes were screened for genetic variation by single-strand conformational polymorphism (SSCP). Following that, SSCP banding patterns were sequenced, and putative transcription factor binding sites were predicted using bioinformatics tools. Quantitative association analysis between identified genetic variants and behavioural trait scores was performed using the general linear model (GLM)., Results: Sequencing the coding and flanking regions revealed three mutations (c.-89C>T, c.-162G>C and c.*33T>A) in the dog TAC1 gene. Bioinformatics analysis predicted two single nucleotide polymorphisms (SNPs) were located within the putative TAC1 promoter and could disrupt transcription factor binding sites. Statistical tests revealed that the c.-89C>T was significantly associated with excitability (p < 0.01), while the c.-162G>C was significantly associated with trainability level (p < 0.05)., Conclusion: In summary, we identified two regulatory SNPs in the 5'-UTR promoter region of the TAC1 gene that are associated with excitability and trainability in Belgian Malinois dogs. These genetic variations have the potential to alter the binding sites of transcription factors NRF1 and OTX1, consequently influencing TAC1 expression and related behavioural characteristics. Our findings implicate TAC1 polymorphisms as candidates influencing breed-specific behavioural characteristics in canines. Further studies on diverse breeds of dogs are necessary to validate these SNPs' effects., (© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objective: Prophylactic cranial irradiation (PCI) is a companion treatment option for small cell lung cancer (SCLC) patients. However, its efficacy and associated risk factors have not been clearly defined. In this study, the authors aimed to systematically assess the effectiveness and role of PCI in the treatment plan of SCLC., Methods: The PubMed, Scopus, Web of Science, and Cochrane databases were searched using the following key terms and their equivalents: "brain," "radiotherapy," "metastases," "prophylactic," and "small cell lung cancer." Studies comparing overall survival (OS), progression-free survival (PFS), brain metastasis-free survival (BMFS), and incidence of brain metastases between patients receiving PCI and those not receiving it were considered eligible. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool. Meta-analysis was conducted on the mentioned outcomes with subgrouping based on different factors., Results: The authors identified 74 studies published between 1983 and 2022 with 31,551 SCLC patients, of whom 26.7% received PCI. The studies were a mix of prospective randomized and retrospective observational studies. Patients with limited-stage disease receiving PCI had better OS, PFS, and BMFS than those not receiving PCI. Patients receiving PCI also had significantly longer OS times and developed brain metastases significantly later. However, findings regarding extensive-stage SCLC were not as promising., Conclusions: PCI is an effective option for limited-stage SCLC patients. It improves OS and PFS, delays brain metastases, and reduces the incidence of brain metastases. However, it might not benefit patients with extensive-stage SCLC under adequate follow-up with MRI surveillance. Finally, the heterogeneity of the included studies and publication bias were the main limitations of this study.

Introduction: Esophageal perforation is a surgical emergency with a high rate of morbidity and mortality. Its poor prognosis is mainly associated with previous patient-specific comorbidities and a lack of timely diagnosis and treatment. The objective of this study was to investigate the etiological factors and different surgical methods of treatment with consideration of mortality rate and comorbidities., Method: The present cross-sectional study was conducted on patients who underwent surgical intervention due to esophageal injury from 2002 to 2019 (18 years). Demographic and clinical characteristics along with performed surgical interventions were evaluated accordingly., Results: In this study, 69 patients with a mean age of 38.8 years were evaluated, of which 45 (65.2%) cases were men. In terms of location of the perforation, the thoracic portion of the esophagus followed by the cervical and abdominal esophagus were more frequently injured with a rate of 32 (46.4%), 30 (43.5%), and 19 (27.5%) cases, respectively. Accordingly, foreign body ingestion followed by penetrating injuries were the most common causative agents leading to esophageal perforation., Conclusion: Obtaining the desired results from the treatment of this condition depends on factors such as patients' previous comorbidities, cause of the rupture, the location of the esophageal damage, and delay in the start of treatment. Since there is no single gold standard treatment strategy, each patient should be individually evaluated., (© 2023. The Author(s).)

Introduction: Due to insufficient data on patient experience with healthcare system among patients with chronic obstructive pulmonary disease (COPD), particularly in developing countries, this study attempted to investigate the journey of patients with COPD in the healthcare system using nationally representative data in Iran., Methods: This nationally representative demonstration study was conducted from 2016 to 2018 using a novel machine-learning based sampling method based on different districts' healthcare structures and outcome data. Pulmonologists confirmed eligible participants and nurses recruited and followed them up for 3  months/in 4 visits. Utilization of various healthcare services, direct and indirect costs (including non-health, absenteeism, loss of productivity, and time waste), and quality of healthcare services (using quality indicators) were assessed., Results: This study constituted of a final sample of 235 patients with COPD, among whom 154 (65.5%) were male. Pharmacy and outpatient services were mostly utilized healthcare services, however, participants utilized outpatient services less than four times a year. The annual average direct cost of a patient with COPD was 1,605.5 USDs. Some 855, 359, 2,680, and 933 USDs were imposed annually on patients with COPD due to non-medical costs, absenteeism, loss of productivity, and time waste, respectively. Based on the quality indicators assessed during the study, the focus of healthcare providers has been the management of the acute phases of COPD as the blood oxygen levels of more than 80% of participants were documented by pulse oximetry devices. However, chronic phase management was mainly missed as less than a third of participants were referred to smoking and tobacco quit centers and got vaccinated. In addition, less than 10% of participants were considered for rehabilitation services, and only 2% completed four-session rehabilitation services., Conclusion: COPD services have focused on inpatient care, where patients experience exacerbation of the condition. Upon discharge, patients do not receive appropriate follow-up services targeting on preventive care for optimal controlling of pulmonary function and preventing exacerbation., Competing Interests: The 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., (Copyright © 2023 Ghamari, Mohebi, Abbasi-Kangevari, Peiman, Rahimi, Ahmadi, Farzi, Seyfi, Shahbal, Modirian, Azmin, Zokaei, Khezrian, Sherafat, Malekpour, Roshani, Rezaei, Fallahi, Shoushtari, Akbaripour, Khatibzadeh and Shahraz.)

Background: Lung cancer (LC) is the second most common and deadliest cancer in the world. Despite the control of the progressive course of LC in developed countries, studies indicate an increase in the incidence of the disease in developing countries. We designed a stepwise approach-based surveillance system for registering LC in our region (fars lung cancer registry "FaLCaRe" Project)., Materials and Methods: A questionnaire was designed and agreed upon by the steering committee using the Delphi method. Variables in nine fields were divided into three groups based on their importance: core, expanded core, and optional. The web-based data bank software was designed. The informative site about LC and team services was designed and launched for professional and community (www.falcare.org) educational purposes., Results: 545 variables in nine fields were designed (20 core variables). Primary data of 39 LC patients (24 men and 15 women) with a mean age of 62 years were analyzed. Twenty-six patients had a history of smoking. Moreover, 39% and 26% of patients had a history of hookah smoking and opium use, respectively. Adenocarcinoma was the most prevalent pathologic findings in cases. More than 80% of patients were diagnosed in stages 3 and 4 of cancer., Conclusion: FaLCaRe Project with the capabilities seen in it can be used as a model for national LC registration. With continuous valid data registry about LC, it is possible to make decisions at the national level for control and management its consequences while drawing the natural history of the LC., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Research in Medical Sciences.)

Spinal cord injury (SCI) is a prevalent devastating condition causing significant morbidity and mortality, especially in developing countries. The pathophysiology of SCI involves ischemia, neuroinflammation, cell death, and scar formation. Due to the lack of definitive therapy for SCI, interventions mainly focus on rehabilitation to reduce deterioration and improve the patient's quality of life. Currently, rehabilitative exercises and neuromodulation methods such as functional electrical stimulation, epidural electrical stimulation, and transcutaneous electrical nerve stimulation are being tested in patients with SCI. Other spinal stimulation techniques are being developed and tested in animal models. However, often these methods require complex surgical procedures and solely focus on motor function. Vagus nerve stimulation (VNS) is currently used in patients with epilepsy, depression, and migraine and is being investigated for its application in other disorders. In animal models of SCI, VNS significantly improved locomotor function by ameliorating inflammation and improving plasticity, suggesting its use in human subjects. SCI patients also suffer from nonmotor complications, including pain, gastrointestinal dysfunction, cardiovascular disorders, and chronic conditions such as obesity and diabetes. VNS has shown promising results in alleviating these conditions in non-SCI patients, which makes it a possible therapeutic option in SCI patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Current treatment regimens in cancer cases cause significant side effects and cannot effectively eradicate the advanced disease. Hence, much effort has been expended over the past years to understand how cancer grows and responds to therapies. Meanwhile, proteins as a type of biopolymers have been under commercial development for over three decades and have been proven to improve the healthcare system as effective medicines for treating many types of progressive disease, such as cancer. Following approving the first recombinant protein therapeutics by FDA (Humulin), there have been a revolution for drawing attention toward protein-based therapeutics (PTs). Since then, the ability to tailor proteins with ideal pharmacokinetics has provided the pharmaceutical industry with an important noble path to discuss the clinical potential of proteins in oncology research. Unlike traditional chemotherapy molecules, PTs actively target cancerous cells by binding to their surface receptors and the other biomarkers particularly associated with tumorous or healthy tissue. This review analyzes the potential and limitations of protein therapeutics (PTs) in the treatment of cancer as well as highlighting the evolving strategies by addressing all possible factors, including pharmacology profile and targeted therapy approaches. This review provides a comprehensive overview of the current state of PTs in oncology, including their pharmacology profile, targeted therapy approaches, and prospects. The reviewed data show that several current and future challenges remain to make PTs a promising and effective anticancer drug, such as safety, immunogenicity, protein stability/degradation, and protein-adjuvant interactions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: During recent years, overuse of medical imaging especially computed tomography has become a serious concern. We evaluated the suitable usage of chest computed tomography (CT)-scan, in patients hospitalized in emergency and medical wards of two teaching hospitals of Shiraz University of Medical Science., Methods: Medical records of 216 patients admitted in two major teaching hospitals (Namazi and Shahid Faghihi), who had undergone chest radiography and at least one type of chest CT were investigated. The clinical and paraclinical manifestations were independently presented to three pulmonologists and their opinion regarding the necessity and type of CT prescription were documented. Also, the patient's history was presented to an expert chest radiologist and asked to rate the appropriateness of chest CT according to American colleague of radiologist (ACR) criteria., Results: In 127 cases (59%), at least 2 out of 3 pulmonologists had the same opinion on the necessity of performing CT scan regardless of CT scan type, in 89 cases (41%) the same CT type and in 38 (17.5%) cases other CT type was supposed. Based on ACR criteria, of total prescribed CTs, 49.5% were "usually not appropriate" and 31.5% of cases were "usually appropriate". Among 109 pulmonary CT angiography, 54 (49.5%) was usually not appropriate base on ACR criteria, which was the most frequent inappropriate requested CT type., Conclusion: Considering the high rates of inappropriate utilization of chest CT scan in our teaching hospitals, implementation of the standard guideline at a different level and consulting with a pulmonologist, may prevent unnecessary chest CTs prescription and reduce harm to patients and the health system., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has led to huge concern worldwide. Some SARS-CoV-2 infected patients may experience post-COVID-19 complications such as multisystem inflammatory syndrome, defined by symptoms including fever and elevated inflammatory markers (such as elevation of C reactive protein (CRP), erythrocyte sedimentation rate, fibrinogen, procalcitonin test, D-dimer, ferritin, lactate dehydrogenase or IL-6, presence of neutrophilia, lymphopenia, decreased albumin, and multiple organ dysfunction). Post-COVID-19 complications may also manifest as autoimmune diseases such as Guillain-Barré syndrome and systemic lupus erythematosus. Signaling disorders, increased inflammatory cytokines secretion, corticosteroid use to treat COVID-19 patients, or impaired immune responses are suggested causes of autoimmune diseases in these patients. In this review, we discuss the molecular and pathophysiological mechanisms and therapeutic opportunities for multisystem inflammatory syndrome and autoimmune diseases following SARS-CoV-2 infection with the aim to provide a clear view for health care providers and researchers., Competing Interests: The 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., (Copyright © 2022 Hosseini, Fallahi, Erabi, Pakdin, Zarezadeh, Faridzadeh, Entezari, Ansari, Poudineh and Deravi.)