Lower urinary dysfunction as a long-term effect of childhood vincristine treatment, with potential influences by sex and dose.

Vincristine (VCR) is one of the most widely used chemotherapy agents in treating pediatric cancer. Nonetheless, it is known to cause dose-dependent neurotoxicity which can impact virtually every organ system. Despite its widespread use, the precise impact of VCR on the lower urinary tract (LUT) remains inadequately elucidated. Our initial clinical and translational investigations suggest a sex-specific influence of childhood VCR exposure on LUT function. Thus, the current study aimed to investigate the late effects of systemic VCR exposure on LUT physiology and the underlying mechanisms, focusing on dosage and male-sex, employing juvenile CD-1 mice as a model. Male mice subjected to VCR exhibited augmented functional bladder capacity accompanied by frequent non-void contractions during awake cystometry, alongside mast cell accumulation within the bladder, compared to the saline-treated control group. Noteworthy functional changes were observed in bladder strips from the VCR group, including decreased nerve-mediated contraction, heightened contractile responses to cholinergic and purinergic agonists, enhanced responsiveness to histamine-primarily via histamine receptor 1 (Hrh1)-and an augmented relaxation effect with compound 48/80 (a mast cell degranulator), relative to the control group. Significant changes in gene expression levels associated with neuroinflammation and nociception were observed in both the bladder and lumbosacral dorsal root ganglia (Ls-DRG) of the VCR group. These findings suggest that VCR exposure during childhood, particularly in males, triggers neuroimmune responses in the bladder and Ls-DRG, amplifying responsiveness to neurotransmitters in the bladder, thereby contributing to LUT dysfunction characterized by a mixed bladder phenotype as a late effect during survivorship.

The effects of nutrition bio-shield superfood powder on immune system function: A clinical trial study among patients with COVID-19.

The present study aimed to evaluate the effects of Nutrition Bio-shield Superfood (NBS) powder on the immune system function and clinical manifestations in patients with COVID-19. We compare the effects of NBS powder on the immune system function and clinical manifestations among two different groups: 1) intervention group receiving standard treatment scheduled according to treatment guidelines plus NBS powder, and 2) control group receiving only the same standard treatment. The serum levels of IL-2, IL-6, IL-17, IFNγ, and TNFα were determined after four weeks of treatment by specific ELISA kits according to the manufacturer's instructions. Finally, the level of immune system stimulation and inflammatory markers were compared at baseline and after intervention in both groups. Data were analyzed using SPSS (version 22). A p-value of ≤ 0.05 was set as significant. A total of 47 patients with COVID-19 (24 patients in the intervention group and 23 patients in the control group) were included in this study. Results showed that the differences in the mean decrease of IL-2, IL-6, and TNF-α in the intervention group in comparison to the control group were 0.93, 10.28, and 8.11 pg/ml, respectively (P<0.001). On the other hand, there was no difference in IL-17, IFNγ, monocytes, eosinophil, and other inflammatory indices between the intervention and control groups. Although NBS powder was able to significantly decrease the levels of some proinflammatory cytokines in patients with COVID-19, however, it is noteworthy that the course of the disease was to large part unaffected by NBS power and there was a reduction independent of treatment. The present study indicates that NBS powder could provide a beneficial anti-inflammatory effect in patients with COVID-19. Hence, NBS in treating patients with COVID-19 shows promise as an adjuvant to the current standard antiviral treatment of such patients. Clinical Trial Registration: https://www.irct.ir, identifier IRCT20200426047206N1.

Temperament and character traits in substance use disorder in Iran: a case control study.

BACKGROUND: Patients with Substance use disorder have distinct personality traits, they were high score in novelty seeking (NS) and sensation seeking and lower in Self-directedness and higher in Self-transcendence, so we aim to investigate the relationships of temperament and characteristics with related some variables such as substance of choice. DESIGN AND SETTING: A case-control study enrolling 70 Substance use disorder patients and 70 controls was conducted at Mashhad University of medical sciences. METHODS: Using a case-control design, a group of 70 Substance use disorder patients and 70 controls was conducted at Mashhad university of medical sciences. All participation completed the 240 questions of Temperament and Character Inventory-Revised (TCI-R). Multivariate analysis of covariance (MANCOVA) was employed to compare the relationship between temperament and character traits and patterns of substance use. RESULTS: The scores of reward dependence, persistence, self-directedness, cooperativeness, and self-transcendence were significantly lower in the case group compared to healthy individuals (P < 0.05). In contrast, the score of novel seeking was significantly higher in the case group (P < 0.05). On the other hand, harm avoidance was not significantly different between the two studied groups (P = 0.637). CONCLUSIONS: Higher NS in patients with substance use disorder is common and different traits, and temperaments would choose different substance combinations.

Long non-coding RNAs and microorganism-associated cancers.

Cancerous cells are abnormal cells characterized by aberrant growth and proliferation, which can involve various types of cells and tissues. Through numerous signalling pathways, many mechanisms are involved in cells that keep them normal. These signalling pathways are tightly set by different proteins whose expression is regulated by a large number of factors. In other words, when a regulating factor does not act properly or undergoes a change in its function or expression, the result will be that the subordinate gene and subsequently the related protein will show deranged expression and activity. This leads to disordered signalling pathways which bring about uncontrolled proliferation in cells. One of the most significant factors in adjusting the expression of genes is noncoding RNAs. It should be noted that all underlying causes initiating malignancy try to alter the main regulatory factors in cellular processes and gene expression and direct the cell to an unregulated state. Microorganisms have been identified as one of the important elements to direct normal cells to abnormality. That is, they probably agitate the malignant traits through manipulating significant factors such as ncRNAs in given cells using their own or host-related factors. The present study is aimed at examining how the long noncoding RNAs are involved in microorganism-mediated cancers.

Increased age, neutrophil-to-lymphocyte ratio (NLR) and white blood cells count are associated with higher COVID-19 mortality.

OBJECTIVE: Coronavirus disease 19 (COVID-19) caused by the highly pathogenic SARS-CoV-2, was first reported from Wuhan, China, in December 2019. The present study assessed possible associations between one-month mortality and demographic data, SpO2, underlying diseases and laboratory findings, in COVID-19 patients. Also, since recent studies on COVID-19, have focused on Neutrophil-to-lymphocyte ratio (NLR) as an independent risk factor of the in-hospital death and a significant prognostic biomarker of outcomes in critically ill patients, in this study, we assessed predictive potential of this factor in terms of one-month mortality. METHODS: Patients admitted to Imam Reza hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran, from March to June 2020, with positive RT-PCR results for SARS-CoV-2, were included in this study. Kaplan-Meier survival analysis and Cox proportional hazard model were used to respectively estimate one-month mortality since admission and determine factors associated with one-month mortality. RESULTS: In this retrospective cohort study, 219 patients were included (137 men and 82 women (mean age 58.2 ± 16 and 57 ± 17.3 years old, respectively)). Hypertension, ischemic heart disease and diabetes were respectively the most common comorbidities. Among these patients, 63 patients were admitted to the ICU and 31 deaths occurred during one-month follow-up. With respect to mean peripheral capillary oxygen saturation (SpO2), 142 patients had SpO2 ≤ 90%. Based on our analysis, older age and increased Neutrophil-to-lymphocyte ratio (NLR), and White blood cells (WBC) count were associated with increased risk of one-month mortality. Patients with SpO2 ≤ 90% had a 3.8-fold increase in risk of one-month death compared to those with SpO2 > 90%, although the difference did not reach a significant level. CONCLUSION: Multivariate analysis introduced age, WBC count, and NLR as predictors of one-month mortality in COVID-19 patients.

Evaluation of Serum Level of FGF23 and 1,25(OH)2D3 in Primary Hyperparathyroidism Patients Before and After Parathyroidectomy.

PURPOSE: Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) play critical roles in phosphate homeostasis. To the best of our knowledge, there are limited data on the impact of FGF23 and PTH on serum calcium, 1,25(OH)2D3, and phosphate in patients with primary hyperparathyroidism (PHPT). We examined these parameters and their correlations in PHPT patients before and after parathyroidectomy (PTX). PATIENTS AND METHODS: In this prospective cohort study, 29 PHPT patients who met the inclusion criteria were selected. The patient's blood samples were taken three times: before the operation, 24 h after the operation, and 1 week after the operation. The concentrations of serum calcium, FGF23, 1,25(OH)2D3, phosphate, PTH, and alkaline phosphatase were measured in a referral laboratory at each of the three steps. Moreover, 25(OH)D was primarily measured just before the surgery. RESULTS: Of 29 patients included in this study with a mean age of 52.37±12.3 years, majority were females (75.8%). Serum FGF23 and 1,25(OH)2D3 levels were high before PTX and decreased after the operation; however, the difference was not statistically significant. FGF23 levels were significantly correlated with 1,25(OH)2D3 at each of the three steps (r=0.964, P <0.01; r=0.985, P <0.0; and r=0.976, P <0.05). The variations in calcium, phosphate, creatinine, and PTH were preoperatively and postoperatively significant. CONCLUSION: Although 1,25(OH)2D3 and FGF23 levels were preoperatively higher in PHPT, their variations were not meaningful. There was a statistically direct significant relationship between 1,25(OH)2D3 and FGF23 preoperatively and postoperatively; however, the correlations between FGF23 and calcium, phosphate, and PTH were not significant.

Brain CT Findings in Patients with First-Onset Seizure Visiting the Emergency Department in Mashhad, Iran.

INTRODUCTION: Regarding the complications and costs of CT imaging for patients, this study aimed at investigating the necessity of CT scans in patients visiting the emergency unit with first-onset seizure. METHODS: One hundred patients who had experienced their first seizure were enrolled. Their CT scan was studied, and based on the radiology report, the type of probable pathologies and their percentage were determined. RESULTS: The patient's mean age was 39.78±17.43 yrs. CT scan abnormalities were reported in 27 cases as follows: nonspecific senile changes in 11 (40.7%), encephalomalacia in 3 (11.1%), acute infarct in 5 (18.5%), lacunar infarct in 3 (11.1%), mass-like lesion in 4 (14.8%) and cerebral venous thrombosis (CVT) evidence in 1 (3.7%). Acute infarct and mass-like lesions were seen together in the CT scan of one patient. In only 9 of the 27 abnormal CT scans, the findings were in accordance with seizure consisting of an acute infarct, mass-like lesion, and CVT evidence. DISCUSSION: It seems that performing a CT scan in all patients referring to the emergency department with a first-onset seizure is not necessary.

Cyclosporine-A-Based Immunosuppressive Therapy-Induced Neurotoxicity: A Case Report.

Cyclosporine-A (CsA) and mycophenolate mofetil are immunosuppressive drugs used for the prevention of transplant rejection. Various clinical studies have been performed on different forms of CsA neurotoxicity, including tremor, paresthesia, confusion, ataxia, neuralgia, hemiplegia, occipital seizures, and transient cortical blindness. Mycophenolate is associated with several neurological side effects including headache, insomnia, dizziness, depression, confusion, hypertonia, and paresthesia. A 31-year-old male with a history of kidney transplantation was treated with CsA and mycophenolate mofetil, for 18 years. He had been referred to the emergency department with complaints of generalized tonic-clonic seizure for 1 minute and 15 minutes of the post-ictal phase. Almost all laboratory tests including cerebrospinal fluid analysis were within normal limits. Brain MRI findings were compatible with CsA-based neurotoxicity. The patient's symptoms and MRI findings improved on decreasing CsA to the minimum dose. CsA neurotoxicity is more common in intravenous therapy, early days of CsA administration, P450 inhibitors administration, and following liver transplantation. MRI findings in CsA neurotoxicity include signal changes in the cerebral cortex and juxtacortical white matter of the occipital lobes, temporal, parietal, and frontal lobes. Every year, many solid organ transplantations are performed. Many of these patients received CsA-based regimens for the prevention of rejection. Therefore, it is necessary to consider CsA neurotoxicity in suspected patients.

Laparoscopy-Assisted Transperitoneal Percutaneous Nephrolithotomy for the Treatment of Renal Stones in a Horseshoe Kidney.

The objective of this case report is to highlight treatment by LAT-PCNL in a patient with horseshoe kidney. A 51-year-man with hematuria presented to the emergency department with moderate abdominal pain starting 7 hrs ago. He did not report a history of previous urological disease. Renal stone and horseshoe kidney malformation were diagnosed based on the plain abdominal film, intravenous urogram (IVU), non-contrast computed tomography (CT-IVU), and ultrasound findings. Due to the larger stone bulk and renal malformation, it was not possible to perform extracorporeal shock wave lithotripsy (ESWL) monotherapy or ESWL sandwich therapy. Moreover, since percutaneous nephrolithotomy (PCNL) had some challenges and limitations due to high skin-to-stone distance, special anatomy, dispersion stones, and possible consequent internal organs injuries, we performed LAT-PCNL on our patient. We did not observe any perioperative complication. Postoperative control abdominal x-ray revealed only a medium ureteral stone that was extracted while removing the Double-J stent a month later. The patient was discharged on the third postoperative day with normal laboratory values. At 3-month follow-up, the patient was stone-free with normal renal function and renal ultrasonography. Laparoscopy-assisted transperitoneal PCNL seems to be a safe and minimally invasive technique that can be used as an alternative approach in the management of renal stones in special cases of horseshoe kidneys.

Erratum: Wald Entropy for Ghost-Free, Infinite Derivative Theories of Gravity [Phys. Rev. Lett. 114, 201101 (2015)].

This corrects the article DOI: 10.1103/PhysRevLett.114.201101.

Wald Entropy for Ghost-Free, Infinite Derivative Theories of Gravity.

In this Letter, we demonstrate that the Wald entropy for any spherically symmetric black hole within an infinite derivative theory of gravity that is quadratic in curvature is determined solely by the area law. Thus, the infrared behavior of gravity is captured by the Einstein-Hilbert term, provided that the massless graviton remains the only propagating degree of freedom in the spacetime.

Serologic evaluation of celiac disease in patients with beta thalassemia major and control.

AIM: This study reports evaluated prevalence of CD in patients with Beta-thalassemia major. BACKGROUND: Celiac Disease (CD) is an autoimmune disorder triggered by ingestion of gluten in genetically predisposed individuals. PATIENTS AND METHODS: In this case-control study in a period of 3 years, which was performed on 620 children in two groups of Beta-thalassemia major patients (n=200) and control (n=420), serum tissue transglutamianse (tTG) IgA levels were measured. The two groups were compared together in terms of tTG IgA levels, and p<0.05 was considered significant. RESULTS: The means of serum tTG IgA levels in patients with Beta-thalassemia major and control groups were 28.81±68.44 and 6.94±6.68 U/mL, respectively. There was a significant difference in favor of the case group (p=0.000). Body mass index in the two case and control groups had a significant difference (t=3.859, p=0.001). Belonging to each group will change the probability of having less than 20 in tTG IgA (odds=0.285) and it means that belonging to the control group has a protective role. There is only a significant association in the case of all population (r=0.102, p=0.011). Body mass index in the two case and control groups had a significant difference (t=3.859, p=0.001). CONCLUSION: Probability of CD should be considered since the prevalence of CD is high in patients with and Beta-thalassemia major. Patients with thalassemia major are recommended for screening for CD.