Clinical characteristics, predisposing factors, and management of moraxella keratitis in a tertiary eye hospital.

PURPOSE: The Moraxella species is a very uncommon pathogen that leads to microbial keratitis (MK). This study aimed to evaluate the clinical features, predisposing factors, and outcomes of Moraxella keratitis in patients of a tertiary eye hospital. METHODS: This retrospective study was conducted from 2015 to 2022, on patients who were admitted with the diagnosis of Moraxella keratitis confirmed by positive culture in a referral eye hospital. Demographics, predisposing factors, best-corrected visual acuity (BCVA), and prognosis were assessed. RESULTS: A total of 106 individuals diagnosed with Moraxella keratitis, were analyzed. The mean age was 54.42 ± 19.43 years. The mean baseline BCVA of the patients was 2.28 ± 0.6 LogMAR, while this amount reached 1.49 ± 0.81 in the 6-month follow-up (P-value = 0.02). The mean BCVA in the six-month follow-up of the patients who needed surgical interventions was significantly lower than the patients who received only medical treatment (2.15 ± 0.65 vs. 1.29 ± 0.75 LogMAR, P-value = 0.02). Patients with diabetes and those without diabetes did not substantially vary in the prevalence of corneal perforation (P-value = 0.515). Three predisposing factors including corneal perforation (odds ratio = 19.27, P-value = 0.001), hypertension (HTN) (odds ratio = 3.62, P-value = 0.03), and older age (odds ratio = 1.03, P-value = 0.008) were significantly associated with more need for surgical interventions. CONCLUSION: In this cohort, poor prognosis necessitating surgical interventions in Moraxella keratitis was found to be associated with corneal perforation, HTN, and older age.

Evaluation of hepatic injury in chronic hepatitis B and C using APRI and FIB-4 indices compared to fibroscan results.

Background: Hepatitis B (HBV) and hepatitis C viruses (HCV) are significant causes of liver disease worldwide. Liver fibrosis (LF) is a complication of chronic liver damage caused by HBV and HCV due to our limited knowledge comparing the diagnostic performance of platelet to aspartate aminotransferase ratio index (APRI) and fibrosis-4 (FIB-4) index with fibroscan. Methods: This study evaluated liver damage in HBV and HCV using APRI, FIB-4, and fibroscan indices. This retrospective cohort descriptive-analytical study was conducted on patients with HBV and HCV. This study uses laboratory results and imaging to investigate liver damage in chronic HBV and HCV patients. APRI and FIB-4 were computed based on laboratory results. Results: A total of 185 patients (82 hepatitis B and 103 hepatitis C) were included in the study. Thirteen patients had liver cirrhosis. There was no statistically significant difference between the fibroscan results in the two groups (P=0.99). The HBV group's mean APRI and FIB-4 were lower than HCV, but no significant difference was observed (P>0.05). Our results in HBV and HCV patients showed that APRI and FIB-4 accomplished well anticipating cirrhosis with an area under the receiver operating characteristic curve (AUC) of 0.771-0.845 and 0.871-0.910, respectively. Conclusion: Fibroscan is a powerful tool superior to APRI and FIB-4 in predicting LF and cirrhosis. Nevertheless, APRI and FIB-4 are inexpensive and non-invasive indicators with acceptable efficacy in predicting advanced fibrosis or cirrhosis. However, these two measures are not reliable in low-grade fibrosis.

What is the link between the dietary inflammatory index and the gut microbiome? A systematic review.

PURPOSE: One highlighted pathogenesis mechanism of diseases is the negative impact of pro-inflammatory diets (PD) on the gut microbiome. This systematic review aimed to study the link between dietary inflammatory index (DII), as an indicator of PD, and gut microbiome. METHODS: A systematic search was done in PubMed and Scopus, adhering to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The assessment of the included studies' quality was performed using the critical appraisal checklist from the Joanna Briggs Institute. RESULTS: Ten articles were included eight cross-sectional, one case-control, and, one cohort study. Seven and three included articles reported a weak and moderate relationship between gut microbiome and DII scores, respectively. DII scores were linked to variety in microbiome composition and diversity/richness. More importantly, anti-inflammatory diets as measured by lower DII scores were linked to a more desirable gut microbiome profile. Prevotella stercorea, Veillonella rogosae, Morganella morganii, Ruminococcus torques, Eubacterium nodatum, Alistipes intestine, Clostridium leptum, Morganellaceae family, Enterobacteriaceae family, and, Bacteroides thetaiotaomicron were related to higher DII scores. While, Butyrate-producing bacteria such as Ruminococcaceae and Lachnospiraceae families, Faecalibacterium prausnitzii, and Akkermansia muciniphila were related to lower DII scores. CONCLUSION: An anti-inflammatory diet, as measured by a lower DII score, might be linked to variations in the composition and variety of the microbiome. Therefore, the DII score could be useful in microbiota research, however, this possibility needs to be investigated more precisely in future studies.

Diagnostic accuracy of ESR1 mutation detection by cell-free DNA in breast cancer: a systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: Estrogen receptors express in nearly 70% of breast cancers (ER-positive). Estrogen receptor alpha plays a fundamental role as a significant factor in breast cancer progression for the early selection of therapeutic approaches. Accordingly, there has been a surge of attention to non-invasive techniques, including circulating Cell-free DNA (ccfDNA) or Cell-Free DNA (cfDNA), to detect and track ESR1 genotype. Therefore, this study aimed to examine the diagnosis accuracy of ESR1 mutation detection by cell-free DNA in breast cancer patientsthrough a systematic review and comprehensive meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were searched up to 6 April 2022. Diagnostic studies on ESR1 measurement by cfDNA, which was confirmed using the tumour tissue biopsy, have been included in the study. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were considered to analyse the data. RESULTS: Out of 649 papers, 13 papers with 15 cohorts, including 389 participants, entered the meta-analyses. The comprehensive meta-analysis indicated a high sensitivity (75.52, 95% CI 60.19-90.85), specificity (88.20, 95% CI 80.99-95.40), and high accuracy of 88.96 (95% CI 83.23-94.69) for plasma ESR1. We also found a moderate PPV of 56.94 (95% CI 41.70-72.18) but a high NPV of 88.53 (95% CI 82.61-94.44). We also found an NLR of 0.443 (95% CI 0.09-0.79) and PLR of 1.60 (95% CI 1.20-1.99). CONCLUSION: This systematic review and comprehensive meta-analysis reveal that plasma cfDNA testing exhibits high sensitivity and specificity in detecting ESR1 mutations in breast cancer patients. This suggests that the test could be a valuable diagnostic tool. It may serve as a dependable and non-invasive technique for identifying ESR1 mutations in breast cancer patients. However, more extensive research is needed to confirm its prognostic value.

Evaluation of IFNAR2 and TYK2 transcripts' prognostic role in COVID-19 patients: a retrospective study.

Background and objectives: This study aimed to investigate the possible prognostic significance of interferon alpha-beta receptor subunit 2 (IFNAR2) and tyrosine kinase 2 (TYK2) expressions. Methods: We conducted a retrospective study including COVID-19 adult patients. All blood samples were collected before any interventions. The expressions of IFNAR2 and TYK2 were assessed using real-time PCR in venous blood samples of 54 cases and 56 controls. The transcript quantities of IFNAR2 and TYK2 genes were assessed using a Delta-Ct method. Results: Our findings show no significant differences in gene expression levels for IFNAR2 and TYK2 between patients who required oxygen (O2) therapy and those who did not (p-value = 0.732 and p-value = 0.629, respectively). Likewise, there were no significant differences in IFNAR2 and TYK2 expressions between patients hospitalized for less than 7 days and those hospitalized for 7 days or more (p-value = 0.455 and p-value = 0.626, respectively). We also observed a weak correlation between IFNAR2 expression and CRP (p-value = 0.045, r = 0.192). There was a negative correlation between the expression levels of IFNAR2 and TYK2 transcripts in COVID-19 patients (p-value = 0.044; partial correlation coefficient = -0.283). Additionally, IFNAR2 and TYK2 were significantly downregulated in the COVID-19 group compared to healthy subjects (p-value = 0.002 and p-value = 0.028, respectively). However, neither IFNAR2 nor TYK2 expression was significantly different between the case subgroups based on COVID-19 severity. The IFNAR2 ΔΔCt (B = -0.184, 95% CI: -0.524-0.157, p-value = 0.275) and the TYK2 ΔΔCt (B = 0.114, 95% CI: -0.268-0.496, p-value = 0.543) were not found to be significant predictors of hospitalization duration. The area under the curve (AUC) for IFNAR2 expression is 0.655 (p-value = 0.005, 95% CI: 0.554-0.757), suggesting its poor discriminative value. Conclusion: We were unable to comment definitively on the prognostic power of IFNAR2 and TYK2 expressions in COVID-19 patients, and larger-scale studies are needed. The principal limitations of this study included the lack of longitudinal analysis and limited sample size.

Prediction of cerebral aneurysm rupture risk by machine learning algorithms: a systematic review and meta-analysis of 18,670 participants.

It is possible to identify unruptured intracranial aneurysms (UIA) using machine learning (ML) algorithms, which can be a life-saving strategy, especially in high-risk populations. To better understand the importance and effectiveness of ML algorithms in practice, a systematic review and meta-analysis were conducted to predict cerebral aneurysm rupture risk. PubMed, Scopus, Web of Science, and Embase were searched without restrictions until March 20, 2023. Eligibility criteria included studies that used ML approaches in patients with cerebral aneurysms confirmed by DSA, CTA, or MRI. Out of 35 studies included, 33 were cohort, and 11 used digital subtraction angiography (DSA) as their reference imaging modality. Middle cerebral artery (MCA) and anterior cerebral artery (ACA) were the commonest locations of aneurysmal vascular involvement-51% and 40%, respectively. The aneurysm morphology was saccular in 48% of studies. Ten of 37 studies (27%) used deep learning techniques such as CNNs and ANNs. Meta-analysis was performed on 17 studies: sensitivity of 0.83 (95% confidence interval (CI), 0.77-0.88); specificity of 0.83 (95% CI, 0.75-0.88); positive DLR of 4.81 (95% CI, 3.29-7.02) and the negative DLR of 0.20 (95% CI, 0.14-0.29); a diagnostic score of 3.17 (95% CI, 2.55-3.78); odds ratio of 23.69 (95% CI, 12.75-44.01). ML algorithms can effectively predict the risk of rupture in cerebral aneurysms with good levels of accuracy, sensitivity, and specificity. However, further research is needed to enhance their diagnostic performance in predicting the rupture status of IA.

Psychosis of Epilepsy: A 10-Year Iranian Clinical Survey.

Objective: Psychoses of epilepsy usually have an acute onset, accompanied by brief symptom duration and a risk of recurrence. Managing these conditions can be challenging due to the potential for seizures associated with certain antipsychotic medications, as well as exacerbating psychosis resulting from some antiepileptic medications. Our objective in this study was to assess the occurrence of psychosis among patients with epilepsy, as well as identify the factors linked to the presence and severity of psychosis in this population. Method : In this study, we included a total of 514 subjects diagnosed with epilepsy referring to our neuropsychiatry clinic affiliated with Tehran University of Medical Sciences from April 2011 to December 2021, among whom 57 patients showed psychotic presentations. We compared baseline and clinical characteristics between patients with psychosis of epilepsy and non-psychosis patients who also had epilepsy. Results: Marital status was the sole demographic factor that displayed a statistically significant difference between the psychosis and non-psychosis groups (P = 0.019). There was no significant difference observed between the two groups regarding family history of epilepsy and age at the onset of the epilepsy. Patients with psychosis experienced significantly more frequent seizures and generalized type (P < 0.001). Participants were matched for demographics and other clinical factors between the refractory and controlled psychosis groups, except for the psychosis frequency (P = 0.007). The type of epilepsy was significantly associated with psychosis when adjusted for the covariates (P < 0.001). Conclusion: Patients with psychosis of epilepsy experienced more episodes of epilepsy than non-psychotics. We identified generalized epilepsy as an independent risk factor for the development of psychosis. Additional cohorts are warranted to explore the factors associated with epilepsy-related psychosis across diverse populations.

Characteristics of HHV-7 meningitis: a systematic review.

There are limited data on HHV-7 meningitis and this systematic review used electronic search to gather pieces of evidence regarding its characteristics. Nine articles were included which three were case reports and the rest of the articles were retrospective studies. Altogether, 32 cases were described in the literature that 13 were females and 26 were aged less than 16 years old. The HHV-7 meningitis has been reported in any season, especially in winter. It affected both immunocompetent and immunocompromised individuals and mostly presented with fever and headache, however rash and seizure have also been documented. The CSF analysis in general showed an elevated range of cell count with lymphocytic predominance and normal to slightly elevated protein levels. Thirteen patients did not receive treatment for HHV-7 meningitis and full recovery was gained in the majority of cases after about 10 days. This review summarizes characteristics of HHV-7 meningitis in the literature, and yet epidemiological studies are needed to shed more light which eventually could be helpful for the diagnosis and management of this disease.

The Open, Randomized, Positive Control Clinical Trial of Guluronic Acid (G2013) on SARS-CoV-2 Patients.

INTRODUCTION: Recently, the coronavirus disease 2019 (COVID-19) infection, with a vast spectrum of clinical and paraclinical symptoms has been a major health concern worldwide. Therapeutical management of COVID-19 includes antiviral and anti-inflammatory drugs. NSAIDs, as the second-line therapy, are often prescribed to relieve the symptoms of COVID-19. The α-L-guluronic acid (G2013) is a non-steroidal patented (PCT/EP2017/067920) agent with immunomodulatory properties. This study investigated the effect of G2013 on the outcome of COVID-19 in moderate to severe patients. METHODS: The disease's symptoms were followed up during hospitalization and for 4 weeks postdischarge in G2013 and control groups. Paraclinical indices were tested at the time of admission and discharge. Statistical analysis was performed on clinical and paraclinical parameters and ICU admission and death rate. RESULTS: The primary and secondary outcomes indicated the efficiency of G2013 on COVID-19 patients' management. There were significant differences in the duration of improvement of fever, coughing, fatigue/malaise. Also, a comparison of paraclinical indices at the time of admission and discharge showed significant change in prothrombin, D-dimer, and platelet. As the main findings of this study, G2013 significantly decreased the percentage of ICU admission (control:17 patients, G2013:1 patient) and death (control: 7 cases, G2013:0). CONCLUSION: These results conclude that G2013 has sufficient potential to be considered for moderate to severe COVID-19 patients, can significantly reduce the clinical and physical complications of this disease, has a positive effect on modulating the coagulopathy process, and aids in saving lives.

Attitudes and Knowledge of Infertile Iranian Couples Among Treatment With Assisted Reproductive Technologies During COVID-19 Pandemics.

Objective: The coronavirus disease 2019 (COVID-19) pandemic affected the continuation of all non-emergency medical treatment and patients potentially suffer from restrictions including patients under infertility treatment. This study aimed to evaluate the knowledge and attitudes of infertile couples about continuing assisted reproductive technologies (ARTs) therapy during the COVID-19 outbreak, in Sari, Iran. Materials and methods : We conducted a prospective longitudinal investigation on potential infertile couples for treatment with ARTs referred to our infertility clinic from March 2020 to June 2020. Ninety-two patients were studied voluntarily and anonymously in this study. A self-developed structured questionnaire was used to assess the attitude towards continuing infertility treatment. A P-value of less than 0.05 was considered statistically significant. Results: Thirty-two patients (33.33%) had decreased motivation to continue treatment during the COVID-19 pandemic. Fear of transmission to the fetus (28.13%) had the highest frequency among the causes of decreased motivation to continue treatment (P-value = 0.011). Trust on the support of the treatment team (56.67%) was the most common reason for not reducing motivation in patients without decreased motivation (P <0.001). Conclusion: Despite the COVID-19 pandemy, in Iran most infertile patients tended to continue ARTs. Although many patients had passable knowledge on COVID-19, the stress of infertility and the high desire of infertile couples to have children did not deter them from continuing their therapy.

High incidence of type 1 diabetes, type 2 diabetes and gestational diabetes in Central Iran: A six years results from Semnan health cohort.

Introduction: Diabetes incidence has increasingly risen in Iran and other low- and middle-income nations in recent decades. In the Semnan Greater Area of Iran, we evaluate the incidence of type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes during 2015-2020 as well as their six-year trend. Methods: This is a retrospective analysis of data (n = 820401) from the Integrated Health System (sib) in Semnan province during 2015-2020. All diabetes cases with diagnostic codes based on the International Classification of Diseases 10 (ICD-10) are listed by year. The Grid Search method was used to obtain the exact number and time of points when the incidence of diseases changes significantly (Joinpoints). Average Annual Percent Change-Annual Percentage Change (AAPC-APC) values and slop changes in the estimated regression line with 95% confidence interval were utilized based on diabetes types to determine Joinpoints. P-value < 0.05 is considered statistically significant. Results: The proportions of diabetes types (T1D, T2D, and gestational diabetes) among 820401 diabetics were 4.18%, 94.84%, and 0.97%, respectively. APC value denotes that T1D has increased by 12.47% per year on average in this period (P-value < 0.01). The incidence of T2D and gestational diabetes has increased between 2015 and 2020 (APC = 15.02 and APC = 136.138, respectively; P-value < 0.1). Conclusions: In summary, the incidence of diabetes in Semnan province is constantly increasing. T2D, meanwhile, has a higher proportion. Nevertheless, gestational diabetes had the highest increase annually. Well-designed surveys investigating the reasons for diabetes increment especially gestational ones and its burden are needed.

Senility and COVID-19 as two possible risk factors for loss of consciousness: A rare case report.

Introduction: and Importance: More than two years after the start of the COVID-19 pandemic, the world is still grappling with this dilemma. COVID-19 covers a wide range of symptoms. Loss of consciousness (LOC) is a very rare symptom that can threaten a patient's life and blur the prognosis of recovery. Case presentation: An 89-year-old woman was presented to the emergency department with LOC (Glasgow Coma Scale (GCS) score = 3) without any history of the underlying disease and was immediately admitted to the intensive care unit. In brain imaging, severe small vessel disease was diagnosed by observing partial dilatation of the ventricles, sulcus, and hypodense areas in the periventricular area. Lung imaging propounded COVID-19 by detecting the ground glass pattern with 50%-75% involvement. After detecting severe acute respiratory syndrome coronavirus 2 nucleic acid by reverse transcription-polymerase chain reaction, COVID-19 treatment was performed according to the national protocol. Finally, she was discharged after 26 days of hospitalization with partial recovery. Clinical discussion: COVID-19-induced cytokine storm along with old age appears to increase LOC risk. It can be claimed that COVID-19-induced LOC can be considered as one of the symptoms of COVID-19 in the elderly population. Therefore, more attention should be paid to this population, which is more at risk. Conclusion: Few reports illustrate the LOC as a COVID-19 presentation. This report highlights the fact that older people are more at risk for COVID-19-induced LOC than other age groups and should be given more care.

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods: We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients. Results: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients. Conclusion: These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

Atorvastatin therapy in COVID-19 adult inpatients: A double-blind, randomized controlled trial.

INTRODUCTION: Efficacious therapies are urgently required to tackle the coronavirus disease 2019 (COVID-19). This trial aims to evaluate the effects of atorvastatin in comparison with standard care for adults hospitalized with COVID-19. METHODS: We conducted a randomized controlled clinical trial on adults hospitalized with COVID-19. Patients were randomized into a treatment group receiving atorvastatin + lopinavir/ritonavir or a control group receiving lopinavir/ritonavir alone. The primary outcome of the trial was the duration of hospitalization. The secondary outcomes were the need for interferon or immunoglobulin, receipt of invasive mechanical ventilation, and O2 saturation (O2sat), and level of C-reactive protein (CRP) which were assessed at the onset of admission and on the 6th day of treatment. RESULTS: Forty patients were allocated and enrolled in the study with a 1 to 1 ratio in atorvastatin + lopinavir/ritonavir and lopinavir/ritonavir groups. Clinical and demographic characteristics were similar between the two groups. CRP level was significantly decreased in the lopinavir/ritonavir + atorvastatin group (P < 0.0001, Cohen's d = 0.865) so that there was a significant difference in CRP level on the 6th day between the two groups (P = 0.01). Nevertheless, there was no significant difference in O2sat on day 6. Although the duration of hospitalization in the lopinavir/ritonavir + atorvastatin group was significantly reduced compared to the control group (P = 0.012), there was no significant difference in the invasive mechanical ventilation reception and the need for interferon and immunoglobulin. CONCLUSION: Atorvastatin + lopinavir/ritonavir may be more effective than lopinavir/ritonavir in treating COVID-19 adult hospitalized patients.

A VPS13B mutation in Cohen syndrome presented with petechiae: An unusual presentation.

Cohen syndrome (CS) is a rare autosomal recessive disorder. CS includes a range of clinical symptoms including retinal dystrophy and myopia. The new VPS13B mutation could cause CS-induced neutropenia and petechiae in patients with CS.

Evaluation of the effectiveness of N-acetylcysteine on accelerating the recovery of renal failure in patients with leptospirosis, a randomized clinical trial study.

BACKGROUND: Limited studies have been conducted on patients with renal function recovery regarding severe leptospirosis. The purpose of this study is to evaluate the effectiveness of N-acetylcysteine (NAC) in accelerating the reduction of serum creatinine in patients with leptospirosis. PATIENTS AND METHODS: This is a clinical trial study involving 64 patients with leptospirosis, with microscopic agglutination tests used to confirm the diagnosis of acute kidney injury. NAC was given to patients with a glomerular filtration rate of less than 60 ml/min at 1200 mg every 12 h, and it lasted for 48 h. Next, 32 patients were measured and the relationship between the length of hospitalization, age, and sex was also examined. Additionally, the two groups of case and control were compared in terms of the rate of decrease in serum creatinine level in three different time periods. The Shapro-Wilk test was used to investigate the distribution of data. RESULTS: No significant differences were observed in the decrease in serum creatinine level on the first, third, and seventh days of hospitalization and also in the use of NAC between the case and control groups (P = 0.255). In addition, the use of NAC had no significant effect on reducing the length of hospitalization (P = 0.067). CONCLUSION: Recovery of acute kidney injury following leptospirosis and drugs that accelerate the healing process in these patients require further studies with greater sample size and longer follow-up time.

Mathematical analysis of the role of pituitary-adrenal interactions in ultradian rhythms of the HPA axis.

The hypothalamic-pituitary-adrenal (HPA) axis is a biological system in the human body that plays an important role in controlling stress and regulating various physiological elements, including the immune system, emotions, and moods in tense situations. Over the past two decades, several ordinary or delay differential equations models of the HPA axis have been proposed. In the majority of studies presented so far, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol are among the main variables employed to build the HPA axis models. In the present study, based on a previously introduced hypothesis which asserts that ultradian rhythms in the HPA axis are produced by the pituitary-adrenal network alone and these rhythms can endure in the absence of CRH secretion, a simple two-dimensional delayed dynamical model of the HPA axis based on only ACTH and cortisol is introduced. The model is shown to be able to capture the ultradian (low frequency) rhythms of ACTH and cortisol released into the bloodstream. By mathematical analysis of the model using the Hopf bifurcation theorem, it is also demonstrated how oscillating solutions can emerge. Also, the model employs physiologically reasonable parameter values to exhibit how in the absence of CRH secretion, a simple model of the pituitary-adrenal interaction can be used to produce ultradian rhythms of both cortisol and ACTH hormones.

ß-D-Mannuronic Acid (M2000) as a Landmark in Pharmacology.

OBJECTIVES: The goal of this article is to retrace the studies of ß-D-Mannuronic Acid (M2000) as a new immunosuppressive drug with non-steroidal anti-inflammatory drugs (NSAIDs) property in miscellaneous aspects including in vitro, in vivo examinations, clinical trials and related to clinical trials studies. Our goal is to compare the effect of this drug with other similar drugs through varied researches and to follow tolerability, biocompatibility, potency, safety, and efficacy of this medication in different studies, as well as to evaluate its therapeutic effectiveness in various diseases. MATERIALS AND METHODS: Different methods were applied in the studies of ß-D-Mannuronic Acid under in vitro, in vivo examinations, and clinical trials phase I, II and III and related investigations to these clinical trials using different techniques showing the efficacy of this medication in the treatment of various diseases. RESULTS: The administration of ß -D-Mannuronic Acid showed the greatest tolerability and biocompatibility compared to diclofenac, piroxicam, and dexamethasone without or very low side effects. The drug has shown a punchy effect on many molecules which participate either in physiologic or in pathogenic activities in animal models and human. This new drug not only revealed the anti-inflammatory and immunosuppressive properties but also based on the results of various investigations, ß-D-Mannuronic Acid showed the antidiabetic, cardioprotective and anti-tumoral effects. CONCLUSION: ß-D-Mannuronic Acid (M2000) as a novel immunosuppressive drug with NSAID properties along with antidiabetic, cardioprotective and anti-tumoral efficacy showed great tolerability and safety profile. In addition, it has no or mild adverse events compared with many other medicines, therefore this medicament could be considered as a landmark in pharmacology and represent turn point in the treatment of different diseases based on the experimental and in vitro studies explained and clinical and related studies proved.

Moderate to severe liver siderosis and raised AST are independent risk factors for vitamin D insufficiency in ß-thalassemia patients.

Numerous problematic disorders such as vitamin D (Vit-D) deficiency subsequent to large iron loading can be developed in patients with ß-thalassemia. The study aimed to estimate Vit-D insufficiency and its risk factors in patients with ß-thalassemia. In this multicenter and observational study, all ß-thalassemia patients, who referred to 14 hospital-based thalassemia divisions or clinics in Mazandaran province, Iran were included in the study. The data belong to December 2015 until December 2019. The study population was made of transfusion dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) patients. Serum levels of 25-OHD3 have been measured by high performance liquid chromatography (HPLC) method as ng/mL. Demographic and clinical information along with some biological tests, as well as the results of T2*-weighted magnetic resonance imaging were analyzed. Of 1959 registered patients, 487 (24.9%) patients had Vit-D-related data. The prevalence of Vit-D insufficiency (< 30 ng/mL) was 41.9, 95% CI 37.5-46.3. The adjusted risks of moderate to severe liver siderosis and raised AST (aspartate aminotransferase) for Vit-D insufficiency (< 30 ng/mL) were 2.31, 95% CI 1.38-3.89 and 2.62, 95% CI 1.43-4.79, respectively. The receiver operating characteristic (ROC) curve analysis showed that the predictive accuracy of ferritin for Vit-D insufficiency status was 0.61, 95% CI 0.54-0.68 with a cutoff point of 1,078 ng/mL (P = 0.03, sensitivity 67%, specificity 49%, positive predictive value [PPV] 47% and negative predictive value [NPV] 68%). In spite of the national programs for treating Vit-D deficiency and our previous efforts for giving supplements to all patients, Vit-D insufficiency/deficiency is still common in our patients. Also, moderate to severe liver siderosis and raised AST were the independent risk factors for the Vit-D insufficiency.