Study of the Epidemiological Features and Clinical Manifestations of the Preceding Epidemic of Influenza A (H1N1) as a Guide for Dealing With the 2015 Outbreak in the Qazvin Province, Iran

Background: In 2009, a pandemic associated with a new type of influenza A virus (H1N1) affected many countries worldwide. After five years of silence, in 2015 we encountered another outbreak of H1N1 influenza A. Objectives: The present study aimed to study the epidemiological and clinical features of this disease in the cold and dry climate of Qazvin province, Iran in the last epidemic, during 2009. Patients and Methods: This was a cross-sectional study in which the demographic characteristics and clinical manifestations of confirmed cases of influenza A virus (H1N1) in the province of Qazvin were investigated. The definite diagnosis of cases was performed using real time Polymerase Chain Reaction (PCR) on oropharyngeal washing specimens from adults and throat swabs from children and severely ill patients. Results: During the time course between July to December 2009, 76 confirmed cases of influenza A (H1N1) were discovered in the province of Qazvin. The mean age of patients was 25.67 ± 16.9 years. The most affected people were students and housewives. Coughing was found to be the most common clinical symptom (96.1%) followed by fever (92.1%), myalgia (48.5%), and diarrhea and vomiting (34.2%). In laboratory confirmed patients, 62 were hospitalized and two cases deceased. Regarding the total population of the Qazvin province (1,100,000), the rate of hospitalization was calculated at 5.42 per 100,000 individuals, with a mortality rate of 0.175 per 100,000 individuals (3.2% of hospitalized cases). Conclusions: Concerning the higher prevalence of disease in younger age groups, and more severe disease in high-risk groups, including overweight patients and pregnant women, the authors recommend special attention to clinical symptoms such as diarrhea and vomiting, cough, myalgia and fever in patients with cold symptoms. Also, for severely ill patients, the allocation of adequate intensive care units should be of prime importance. Keywords: Influenza A Virus, H1N1 Subtype; Comorbidity; Epidemiolog

Bayesian Time-Series Classifier for Decoding Simple Visual Stimuli from Intracranial Neural Activity

Understanding how external stimuli are encoded in distributed neural activity is of significant interest in clinical and basic neuroscience. To address this need, it is essential to develop analytical tools capable of handling limited data and the intrinsic stochasticity present in neural data. In this study, we propose a straightforward Bayesian time series classifier (BTsC) model that tackles these challenges whilst maintaining a high level of interpretability. We demonstrate the classification capabilities of this approach by utilizing neural data to decode colors in a visual task. The model exhibits consistent and reliable average performance of 75.55% on 4 patients' dataset, improving upon state-of-the-art machine learning techniques by about 3.0 percent. In addition to its high classification accuracy, the proposed BTsC model provides interpretable results, making the technique a valuable tool to study neural activity in various tasks and categories. The proposed solution can be applied to neural data recorded in various tasks, where there is a need for interpretable results and accurate classification accuracy

Demographic Characteristics and Personality Disorders in People With Gender Dysphoria in East Azerbaijan Province, Iran

Background: Gender identity is an important part of human identity. It is a personal conception of oneself as male or female. One of the major goals of treatment for individuals with Gender Dysphoria (GD) is to treat comorbid psychological and psychiatric disorders such as personality disorders. The present study aims to investigate demographic characteristics and personality disorders in people with GD seeking gender reassignment therapy in East Azerbaijan Province, Iran.Methods: In this descriptive cross-sectional study, study population consists of all patients with GD referred to the forensic medicine centers in East Azerbaijan province during 2016-2020, of whom 61 (21 males and 40 females) were selected using a convenience sampling method. Their age, gender, educational level, and marital status were recorded and their personality profile was assessed by the Millon Clinical Multiaxial Inventory–III.Results: The frequency (percentage) of Cluster A, B and C personality disorders in males were 0(0%), 9(50%) and 2(11.10%), while in females they were 1(5.56%), 4(22.40%), and 2(11.10%), respectively. The frequency (percentage) of antisocial, obsessive, borderline, avoidant, narcissistic, histrionic, and paranoid personality disorders in males were 4(22.2%), 2(11.10%), 3(16.67%), 0(0%), 0(0%), 2(11.10%), and 0(0%), while in females they were 4(22.20%), 1(5.56%), 3(16.67%), 1(5.56%), 1(5.56%), 2(11.10%), and 1(5.56%), respectively. The prevalence of different clusters (P=0.34) and types (P=0.18) of personality disorders was not significantly different between males and females. Conclusion: Personality disorders are comorbid with GD. They exist in one-third of patients with GD in East Azerbaijan Province. Personality disorders are significantly more prevalent in male patients with GD than in females

Modeling IoT enablers for humanitarian supply chains coordination

Disaster relief operations rely on reliable real-time information sharing during disasters to coordinate scarce resources and save lives. The Internet of Things (IoT) has recently been regarded as an important technology for enhancing information sharing in disaster response operations to achieve effective coordination, accurate situational awareness, and comprehensive visibility of operational resources. Despite its relevance, its adaptation and implementation have been fraught with complexity. This research aims to understand the IoT enablers of humanitarian supply chain coordination. Seven dimensional enablers have been formulated by reviewing the literature and validating with practitioners’ opinions. A structural model is then developed using the Decision-Making Trial and Evaluation Laboratory (DEMATEL) technique that addresses the interdependencies of IoT enablers in humanitarian supply chain coordination. Finding provides insights into the interplay between management support, IT infrastructures, and third-party logistics service providers as key enablers towards adaptation and implementation of IoT in humanitarian supply chains. Results provide important implications and insight to decision-makers in international humanitarian organizations toward adaptation and implementation of IoT systems in humanitarian supply chains

Serum ferritin levels and bone mineral density in the elderly

Background: Iron overload influences negatively on bone mineral density (BMD) but the results of studies regarding serum ferritin (SF) and BMD are conflicting.This study aimed to determine the association of SF and BMD in the elderly. Methods: All participants of the Amirkola cohort selected between 2011-2012, aged > 60 years were classified as high or normal (<200ng/ml) SF. BMD at femoral neck and lumbar spine was determined by dual energy x-ray absorptiometry (DXA) and the results were expressed as BMD g/cm2 and BMDT-score. Multiple logistic regression analysis with calculation of odds ratio (OR) and 95% confidence interval was used to estimate the association of low BMD (LBMD) defined as BMD T-score < -1 with SF. Results: 1089 subjects (women, 44.7%) were studied. High SF was observed in 366 (33.6%) and LBMD in 874 (80.2%) subjects. The two groups of SF were similar regarding biochemical parameters and demographic characteristics except MetS, overweight /obesity and diabetes which were more prevalent in high SFgroup. BMD g/cm2 at both measurement sites was significantly higher (P=0.001 for both) and the prevalence of LBMD was significantly lower (74.1% vs 83.1%, P=0.001) in high SF group by OR= 0.60 (0.44-0.81). After adjustment for all biochemical and demographic variables, the association remained significant by adjusted OR= 0. 68 (0.49-0.94). Conclusions: These findings show a negative association between high SF and LBMD indicating a beneficial effect of high SF in the elderly. Regarding detrimental effect of iron overload on bone mass, these findings require further studies

Neuropharmacological Potential of Diterpenoid Alkaloids

This study provides a narrative review of diterpenoid alkaloids (DAs), a family of extremely important natural products found predominantly in some species of Aconitum and Delphinium (Ranunculaceae). DAs have long been a focus of research attention due to their numerous intricate structures and diverse biological activities, especially in the central nervous system (CNS). These alkaloids originate through the amination reaction of tetra or pentacyclic diterpenoids, which are classified into three categories and 46 types based on the number of carbon atoms in the backbone structure and structural differences. The main chemical characteristics of DAs are their heterocyclic systems containing β-aminoethanol, methylamine, or ethylamine functionality. Although the role of tertiary nitrogen in ring A and the polycyclic complex structure are of great importance in drug-receptor affinity, in silico studies have emphasized the role of certain sidechains in C13, C14, and C8. DAs showed antiepileptic effects in preclinical studies mostly through Na+ channels. Aconitine (1) and 3-acetyl aconitine (2) can desensitize Na+ channels after persistent activation. Lappaconitine (3), N-deacetyllapaconitine (4), 6-benzoylheteratisine (5), and 1-benzoylnapelline (6) deactivate these channels. Methyllycaconitine (16), mainly found in Delphinium species, possesses an extreme affinity for the binding sites of α7 nicotinic acetylcholine receptors (nAChR) and contributes to a wide range of neurologic functions and the release of neurotransmitters. Several DAs such as bulleyaconitine A (17), (3), and mesaconitine (8) from Aconitum species have a drastic analgesic effect. Among them, compound 17 has been used in China for decades. Their effect is explained by increasing the release of dynorphin A, activating the inhibitory noradrenergic neurons in the β-adrenergic system, and preventing the transmission of pain messages by inactivating the Na+ channels that have been stressed. Acetylcholinesterase inhibitory, neuroprotective, antidepressant, and anxiolytic activities are other CNS effects that have been investigated for certain DAs. However, despite various CNS effects, recent advances in developing new drugs from DAs were insignificant due to their neurotoxicity

Efficacy of levamisole with standard care treatment vs. standard care in clinical presentations of non-hospitalized patients with COVID-19: a randomized clinical trial

Objective: The aim of this study was to evaluate the influence of adding a 10-day course of levamisole (LVM) to the standard care compared with standard care alone, on the clinical status of COVID-19 patients with mild to moderate disease.&nbsp;Methods:&nbsp;&nbsp;In this randomized open-label trial, we enrolled non-hospitalized patients with mild to moderate COVID-19 at nine health centers in Tehran province, Iran, in 2021. Patients were randomly assigned to receive a 10-day course of LVM with standard care (n=185) or standard care alone (n=180) in a 1:1 ratio. On days 1 to 10, LVM was administered orally at a dosage of 50 mg. The participants were called and followed on days 1, 3, 5, 7, 9, and 14. The measured parameters were general health condition, hospitalization rate, signs and symptoms, and adverse events. The generalized estimating equations model was used for analysis.&nbsp;Results: Among 507 randomized patients, 473 patients started the experiment and received LVM plus standard care or received the standard care alone; 385 patients included in the analysis; 346 (98%) patients completed the trial. The median age of the patients was 40 years [IQR: 32-50.75]; and ‎201 (55.1%)‎ patiens were male. The mean age, sex ratio, and frequency of the underlying diseases of the patients in the two study groups had no ‎statistically significant differences (P&gt;0.05). Compared to the control group, LVM improved the general health condition of the patients (B=-0.635; 95% CI: -0.041,-0.329; P&lt;0.001). Patients receiving LVM compared with standard care group had significantly lower odds of developing fever (OR=0.260; 95% CI: 0.11‎‎3‎,0.59‎‎9‎;&nbsp;P=0.002), chills (OR=0.223; 95% CI:‎‎ 0.07‎‎6,‎0.64‎‎8‎;&nbsp;P= 0.006), fatigue (OR=0.576; 95% CI:‎ 0.34‎‎6,‎0.96‎‎0‎‎;&nbsp;P=0.034), and myalgia (OR=0.54‎‎4‎; 95% CI:‎ 0.31‎‎7‎,0.93‎‎2‎‎;&nbsp;P=0.027). No significant difference was observed in the rate of hospitalization. Although the intervention group had greater adverse effects than the control group, the difference was not statistically significant.&nbsp;Conclusion: Findings of this study suggest that LVM has clinical benefits in improving patients’ health condition with mild to moderate COVID-19

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. Methods For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. Results A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. Conclusion The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines’ low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies