Study of Methamphetamine Use in Patients Referred to Emergency Ward of a General Hospital at North of Iran in 2017

Background: Acute use of methamphetamine affects the sympathetic system and causes symptoms like tachycardia, hypertension (HTN), tachypnea, peripheral blood vessels constriction, hyperthermia, and mydriasis that can lead to many medical complications. Thus, this study aimed to evaluate the use of methamphetamine, clinical symptoms, and admission causes in patients referred to emergency ward of Imam Khomeini General Hospital in Sari, Iran. Methods:In this cross-sectional study, 3263 patients were enrolled in the census. The population was patients referred to emergency ward of Imam Khomeini Hospital in Sari, in 2017. Clinical signs and symptoms, test results, primary and definite diagnosis, and patients' status during discharge or referral were extracted from medical records. Statistical analysis was performed using SPSS software. Findings: A total of 3263 people were enrolled in the study. The prevalence of positive methamphetamine test in patients referred to the emergency department was 1.2%, which was significantly higher in men (P = 0.017). The mean age was 39.9 ± 17.2 years. Methamphetamine users were more likely to be traumatized than the general population. There was a statistically significant difference in seizure (P = 0.003), chest pain (P < 0.001), tachycardia (P < 0.001), palpitation (P < 0.001), HTN (P = 0.002), tachypnea (P = 0.001), visual hallucinations (P = 0.001), auditory hallucinations (P = 0.001), paranoia (P = 0.001), grandiosity (P = 0.035), talkativeness (P = 0.001), suicidal ideation (P < 0.001), homicidal ideation (P = 0.001), violence (P < 0.001), and disorientation (P < 0.001) in positive methamphetamine test group. Conclusion: Methamphetamine use is more frequent in young men in the second and third decades of life. The most common clinical symptoms in these patients were HTN, chest pain, palpitations, tachycardia, seizure, aggression, anxiety, delusions, and hallucination

A study on the existence of numerical and analytical solutions for fractional integrodifferential equations in Hilfer type with simulation

Previous studies have shown that fractional derivative operators have become an integral part of modeling natural and physical phenomena. During the progress and evolution of these operators, it has become clear to researchers that each of these operators has special capacities for investigating phenomena in engineering sciences, physics, biological mathematics, etc. Fixed point theory and its famous contractions have always served as useful tools in these studies. In this regard, in this work, we considered the Hilfer-type fractional operator to study the proposed integrodifferential equation. We have used the capabilities of measure theory and fixed point techniques to provide the required space to guarantee the existence of the solution. The Schauder and Arzela-Ascoli theorems play a fundamental role in the existence of solutions. Finally, we provided two examples with some graphical and numerical simulation to make our results more objective

Effectiveness and Safety of Haloperidol Add-on Methadone in Acute Opium Withdrawal Symptoms of Opioid-dependent Patients: A Double-blind Randomized Placebo-controlled Clinical Trial

Background: The aim of this double-blind clinical trial was to evaluate the efficacy and safety of haloperidol on acute opioid withdrawal symptoms. Methods: In this randomized double-blind clinical trial, fifty-two eligible patients were assigned to two groups according to previous opioid consumption, low dose (LD) and high dose (HD). Then, patients in each group were randomly assigned to one of the two subgroups of haloperidol or placebo. Patients in the haloperidol subgroup in LD group received 2.5 mg and in HD group received 5 mg/day haloperidol with methadone. Methadone was discontinued ten days after the beginning of the study and haloperidol or placebo continued for up to two weeks after methadone discontinuation. The severity of opioid withdrawal symptoms was assessed with the Objective Opioid Withdrawal Scale (OOWS) every other day. Findings: Although both treatment protocols either in LD or HD opioid consumption groups significantly increased the score of the OOWS over the trial period (all subgroups, P 0.05). Conclusion: The results of this study suggest that 2.5 mg/day of haloperidol may be an effective adjuvant agent in the management of opium withdrawal symptoms in patients with LD opioid consumption. Nevertheless, results of larger controlled trials are needed before recommendation for a broad clinical application can be mad

Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chornobyl papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) exhibits various molecular abnormalities, both when sporadic and radiation-related. PTC is still diagnosed in adult individuals who were younger than 18 years at the time of the Chornobyl accident in 1986 and lived within the contaminated area. The preoperative diagnosis of PTC is based on ultrasound-guided fine needle aspiration cytology (FNAC), which is highly informative in up to 90% of biopsies. FNAC is not informative for the discrimination of follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). Moreover, FNAC is often unreliable for diagnosis of cystic PTC due to its common presentation as a mural nodule in a cystic mass. In case of cystic PTC, biopsy sometimes reveals a cystic fluid containing insufficient amount of representative cells for cytology. In this work, PTC was characterized in relation to irradiation from radioactivity at childhood. Possible preoperative diagnostic markers for discrimination between PTC and other follicular thyroid neoplasms were identified, and their validity was tested. In Study I molecular, genetic and clinical characteristics in 70 post-Chornobyl PTCs were investigated. A common BRAF 1799T>A mutation was detected in 26 cases, overrepresentation of RET/PTC1 in 20 whereas RET/PTC3 was found in 4 cases. BRAF mutation was observed 3.5 times less frequent in the PTC accompanied by chronic lymphocytic thyroiditis (PTC/CLT) as compared to PTC only (12% vs. 44%). Greater expression of cyclin A was observed in PTC ≥ 2 cm as compared to PTC < 2 cm (1.2% vs. 0.6%). In conclusion, BRAF mutation and RET/PTC1 rearrangement as well as other molecular features of adult post-Chornobyl PTC were partly overlapping with other reported PTC cohorts. In Study II the SELDI-TOF mass spectrometry method was applied for PTC, FTC, FTA and normal thyroid tissue (NT). Significant overexpression of the protein S100A6 was identified in PTC as compared to FTC, FTA and NT (p < 0.05). This result was verified both by Western blot (WB), using the same samples, and by IHC in these and additionally in the PTC samples investigated in Study I. Moreover, the presence of two post-translational modifications of S100A6 was observed and verified by LC-MS/MS. S100A6 expression is strongly associated with PTC, and can therefore be tested for discrimination between follicular thyroid tumors and PTC. In Study III a two dimensional gel electrophoresis followed by MALDI-TOF mass spectrometry for proteomic profiling of PTC, FTC and FTA was performed. 25 protein spots showing significantly different expression between studied groups were identified. Of these, 9 protein spots were selected for further analyses by WB using the initially studied samples and by IHC using these as well as samples from Study I. The findings suggest additional proteins to be deregulated in thyroid tumors, and their clinical significance can now be further studied. In Study IV preoperative diagnostic markers for PTC in cystic lesions were identified by applying LC-MS/MS method. Out of all 1581 identified proteins, annexin A3 (ANXA3), carboxymethylenebutenolidase homolog (CMBL) cytokeratin 19 (CK- 19) and S100A13 were selected for validation by IHC and WB. ANXA3 and CMBL showed overexpression in both controls and PTCs, whereas S100A13 and CK-19 were up-regulated in PTC only (p < 0.05), suggesting their possible role for discrimination between cystic PTC and benign thyroid cysts

Proteomics identifies neddylation as a potential therapy target in small intestinal neuroendocrine tumors.

Patients with small intestinal neuroendocrine tumors (SI-NETs) frequently develop spread disease; however, the underlying molecular mechanisms of disease progression are not known and effective preventive treatment strategies are lacking. Here, protein expression profiling was performed by HiRIEF-LC-MS in 14 primary SI-NETs from patients with and without liver metastases detected at the time of surgery and initial treatment. Among differentially expressed proteins, overexpression of the ubiquitin-like protein NEDD8 was identified in samples from patients with liver metastasis. Further, NEDD8 correlation analysis indicated co-expression with RBX1, a key component in cullin-RING ubiquitin ligases (CRLs). In vitro inhibition of neddylation with the therapeutic agent pevonedistat (MLN4924) resulted in a dramatic decrease of proliferation in SI-NET cell lines. Subsequent mass spectrometry-based proteomics analysis of pevonedistat effects and effects of the proteasome inhibitor bortezomib revealed stabilization of multiple targets of CRLs including p27, an established tumor suppressor in SI-NET. Silencing of NEDD8 and RBX1 using siRNA resulted in a stabilization of p27, suggesting that the cellular levels of NEDD8 and RBX1 affect CRL activity. Inhibition of CRL activity, by either NEDD8/RBX1 silencing or pevonedistat treatment of cells resulted in induction of apoptosis that could be partially rescued by siRNA-based silencing of p27. Differential expression of both p27 and NEDD8 was confirmed in a second cohort of SI-NET using immunohistochemistry. Collectively, these findings suggest a role for CRLs and the ubiquitin proteasome system in suppression of p27 in SI-NET, and inhibition of neddylation as a putative therapeutic strategy in SI-NET

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

HLA predisposition to human papillomavirus induced cervical neoplasia : Population based studies from the Västerbotten county in northern Sweden

Infection with human papillomaviruses (HPV) types 16 and 18 is the major cause of cervical neoplasia. Although a high proportion of cervical cancers (CXCA) harbor HPV genomes, only a small number of women infected with high-risk papillomaviruses develop cervical tumors, suggesting that other environmental and/or genetic factors contribute to cervical carcinogenesis. Several studies have identified genes encoding human leukocyte antigens (HLA) associated with cervical intraepithelial neoplasia (CIN) and CXCA. Many genes encoding the products involved in immune responses are clustered within the human major histocompatibility complex (MHC) on the short arm of chromosome 6 (6p21.3). The human AMC extends over 3500 kilobases and comprises more than 200 genes with known and unknown functions The HLA class I genes encodes cell surface glycoproteins (HLA-A, -B, -C) that associates in the endoplasmic reticulum with beta32-microglubulin and peptides derived from endogenously processed antigens. HLA class II genes encode cell surface glycoproteins, which bind to peptides that originate mainly from exogenous antigens processed through the endosomal/lysosomal pathway. In addition to HLA class I and class II molecules, genes that encode the cytokines, tumor necrosis factor (TNF) alpha and beta are located in the class III region. The MHC class I chain related genes (MICA/B) located in the centromeric end of the HLA class I region, have recently been in focus for it can function as a ligand for gamma/delta T cells and NK cell receptors. MICA protein is mainly expressed by epithelial cells and its interaction with NK cells and gamma/delta T cells might have a role in the pathogenesis of CXCA. The aim of this thesis was to investigate the association of candidate HLA genes with CIN and CXCA. Several different genotyping methods were used to study the polymorphic HLA genes in two different patient groups. Patients and controls from a cohort of Västerbotten were included in this population-based study. Candidate genes in the HLA class I, class II and class III region were analyzed and their association with CXCA and susceptibility to HPV infection was measured using appropriate statistical methods. The strongest association of HLA genes with CXCA was found in the HLA class II locus. The relative risks of CXCA among DR15 and DQ6 (DQB1*0602) positive patients were 3.73 and 4.33, corresponding to population attributable proportions of 27.9% and 30.8%, respectively. MICA was not associated with either CIN or CXCA. The polymorphism of the TNFA gene was associated with susceptibility to HPV 16 infection and increased the risk for CIN and CXCA in patients with the DR15-DQ6 haplotype

New statistical analysis in marketing studies using fuzzy data approach

This research proposes new statistical methods for marketing and decision-making studies. This study uses a soft calculation methodology as well as a new statistical tool for evaluating people's thinking. Since the classic measurement system is difficult to deal with untrue value information, the purpose of this study is to find an appropriate measurement system to overcome this problem. The main idea behind this research is to divide the data into two dimensions of its center and its extension (region). Finally, the two-dimensional questionnaire of this study helps us to access market information. In this research, the satisfaction of customers in Mashhad's metropolitan market by using the fuzzy data approach for the well-known brands LG, Samsung, Kenwood and Daewoo in the washing machine industry has been addressed. The results of this study indicate that LG's brand among other brands in terms of product share indices from the target market as a whole, as well as superior performance characteristics, and in fact, customers choose the Korean brand in the choice of washing machine in the first place

On a coupled system of pantograph problem with three sequential fractional derivatives by using positive contraction-type inequalities

This paper aims to establish conditions for the existence, uniqueness and Ulam–Hyers stability of solutions for a coupled system of pantograph problem with three sequential fractional derivatives. Two results on the uniqueness and existence of solutions are proved to utilize the Leray–Schauder and Banach fixed point theorems and positive contraction-type inequalities. Also, the stability in the sense of Ulam–Hyers and Ulam–Hyers–Rassias are studied. An illustrative example with graphical and numerical simulations is also proposed

On the Existence and Stability of a Neutral Stochastic Fractional Differential System

The main purpose of this paper is to investigate the existence and Ulam-Hyers stability (U-Hs) of solutions of a nonlinear neutral stochastic fractional differential system. We prove the existence and uniqueness of solutions to the proposed system by using fixed point theorems and the Banach contraction principle. Also, by using fundamental schemes of fractional calculus, we study the (U-Hs) to the solutions of our suggested system. Besides, we study an example, best describing our main result