Tehran University Medical Journal

Hepatitis B virus (HBV) is an etiological agent of hepatitis B infection. Hepatitis B is a life-threatening disease that affects the liver. The clinical outcomes of the disease are varied from asymptomatic disease to serious complication such as cirrhosis and hepatocellular carcinoma (HCC). Despite availability of the vaccine and appropriate treatment, hepatitis B infection still remains a major public health problem worldwide. Based on WHO reports, over 887.000 people die annually from hepatitis B complication including cirrhosis and hepatocellular carcinoma. Hepatitis B is very contagious and spreads through infected blood, body fluids, mother to baby during birth, contaminated needle and between sexual partners. HBV uses sodium taurocholate cotransporting polypeptide (NTCP) receptor to enter hepatocytes and by replicating in these cells interferes with liver functions. In fact liver damage is as result of virus multiplication and activation of immune responses especially virus-specific cytotoxic T lymphocytes (CTLs) against infected cells. CTLs and CD4Th1 cells by killing infected cells and releasing antiviral cytokines control virus replication in infected individuals. Also, the functions of these cells in patients who successfully clear the infection are potentially strong. In contrast to acute self-limited HBV infection in persistent HBV infection, these cells are exhausted. Several studies have showed that the great challenge in clearance of the HBV infection is related to stability of covalently closed circular DNA (cccDNA). cccDNA produce in viral life cycle and remains inside the infected cells for a long time and act as a template for generating new pre-genomic RNA and virus propagation. So far, no antiviral treatment has been effective in the complete elimination of this structure. Prevention of the disease can be achieved by using effective vaccine. Previous studies indicated that neutralizing antibodies against surface antigen of the virus known as S antigen have protective properties. Therefore, a subunit vaccine containing S antigen is available. Currently S antigen is produced in recombinant form and WHO recommended the first dose should be given within a day of birth. Pegylated IFN-γ and nucleotide-nucleoside analogues are effective drugs against HBV infection, but they may have severe side effects. Ineffectiveness of the vaccine on premature infants and immunocompromised people and also drug side effects has made HBV infection a great trouble.
 

Pregnancy as a natural event leads to changes in various aspects of physiology, psychology, and social life. The adoption of a health promoting lifestyle is an important strategy for achieving the desired outcomes of pregnancy and is important on the future health of mother and child. The aim of this study was to assess the various aspects of health promotion behaviors during pregnancy. The data was obtained with advanced search in the Iranmedex, Magiran, Scientific Information Database (SID), IranDoc, PubMed, Google Scholar, Web of Science and Scopus databases. Articles containing full text were collected using the proper keywords for Persian articles and their equivalent in Mesh included “Health promotion" OR "Behavior health "OR “Health Promoting Lifestyle” AND pregnancy for English articles with a time limitation of 2010 to 2017. At first 3247 articles obtained after reviewing and evaluation of the references, 4 Persian and 25 English articles with observational and qualitative design were included. A review of studies showed that finding a way to pass pregnancy safely is the most important concern for mothers. Pregnant women do some actions to reach favorable outcomes and they have a high incentive to adopt health behaviors during pregnancy due to fear of fetal health, but there is some obstacle to adopt health behaviors including individual factors like that lack of time and inadequate information about pregnancy or health-related functions and social factors including health system problems and cultural factors. In addition age, level of education, individual’s beliefs and factors associated with pregnancy such as high-risk pregnancy and environmental factors such as social support and health system performance play an important role in the adoption of health behaviors. In order to increase the potential of pregnant women to adopt healthy behaviors, changing the health system approach and paying attention to social determinants of health, in order to carry out the necessary interventions, it is recommended to conduct qualitative studies and appropriate design for deep study of the subject in the cultural background.

Considering the advancement of medical sciences, diagnostic tests have been developed to distinguish patients from healthy population. Therefore, Determining and evaluation of the diagnostic accuracy tests is of great importance. The accuracy of a test under evaluation is determined through the amount of agreement between its results with the results of the gold standard, and this test accuracy can be defined based on sensitivity, specificity, positive predictive value, negative predictive value and the area under the receiver operative characteristic curve (AUC). Gold standard is an accurate and error- free method to determine the presence or absence of disease of interest and classify patients, which is not available in some diseases and situations as this method is costly or invasive. In these cases, reference standard is a best available replacement method to be used by physicians to diagnostic disease. However, in some situation, the acceptable reference standard is invasive or costly and does not exist or unreliable. It can be imperfect and results of the reference standard method are not necessarily error- free and cannot be applied to everyone in the study; all these cases point to the conditions in which the gold standard is not available. The use of reference standard including error causes to incorrect separation of patients from healthy population and thus, it cannot be a comparing measure for other diagnostic tests and its results are inaccurate. Therefore, other alternatives methods are needed for evaluation and determine the diagnostic accuracy tests when the gold standard does not exist. Imputation method, correct imperfect reference standard method, the construct reference standard method, latent class models, differential verification, composite reference standard and discrepant analysis are of these alternative methods. Each of these methods, considering its features, advantages, and limitations can be used to evaluate the accuracy of diagnostic test in the absence of gold standard. The present study gave an overview of methods to evaluation of diagnostic accuracy tests when there is no gold standard and the focus of this study was on explain the concept of these solutions, review and compare them and their strengths and weaknesses.

Chronic lymphocytic leukemia (CLL) is a malignancy of B CD5+cells and is the most common type of leukemia in adults. The disease is more common in men over 50 years in western countries. CLL is associated with defective apoptosis in B cells. CLL was traditionally regarded as a disease that occurs before naïve B cells meet the antigen in the lymph nodes. Laboratory diagnosis requires white blood cell count, blood smear and immunophenotyping of lymphoid cells by flow cytometry. The disease most often associated with the accumulation of CD5+ CD19+ and CD23+ B cell with reduced number of surface membrane immunoglobulin in peripheral blood, bone marrow, and lymph nodes. Clinical progression of CLL is heterogeneous, some patients need treatment immediately after diagnosis, and others do not require treatment for many years after diagnosis. Over the past decades, considerable effort has been made to understanding the molecular mechanisms underlying the heterogeneous clinical course of the disease and finding prognostic markers for clinical classification. Patients with advanced Binet or Rai stages of disease require treatment. In addition to the interactions that exist between CLL cells, number of non-tumor cell types such as bone marrow stromal cells (BMSCs), nurse like cells (NLCs), follicular dendritic cells (FDCs), T cells, and some cytokines like IL-4 in tumor microenvironment play an important role in the CLL pathogenesis. Various factors including: IGVH mutation status, genetic variation, patient age and presence of other disorders are important for disease management and the type of treatment. CLL patients carrying p53 pathway dysfunction have poor prognosis and poor responses to therapy and very short survival. Available treatments include chemotherapy, chemoimmunotherapy, or drugs targeting B cell receptor signaling, Bruton's tyrosine kinase (BTK) or inhibitors of apoptosis, such as BCL2 and new class of small molecules. Understanding the CLL biology is important in identifying high-risk patients as well as the drug and relevant therapeutic methods for better management of patients. In this review paper, the microenvironment and genetic abnormalities in the CLL as well as new diagnostic and therapeutic approaches based on the new understanding of molecular biology of CLL are discussed.

In recent years, the use of gold nanoparticles (GNPs) in radiation therapy has been studied by experimentation and Monte Carlo simulation repeatedly. Although the idea of increasing doses has been raised by high-atomic elements since decades ago, but due to the adaptation of gold nanoparticles with the biological system, scientists have incited more about the various uses of these materials in radiation therapy. The results of all studies in this field are consistent with the increase in tumor-derived doses with gold nanoparticles in radiotherapy. But the results of the interaction of radiation energy are still controversial with the size of gold nanoparticles. In other words, in the Monte Carlo simulations the gold nanoparticles with a size of about 10 to 100 nm, and in biological studies, the nanoparticles with a dimension of 1.9 nm were used. On the other hand, some studies of energy dependence have been developed in dose enhancement, and in some other studies the effect of the size of gold nanoparticles has been investigated on photon energy. However, in some respects, the results of radiation therapy using by gold nanoparticles does not appear to be definitive, although the photoelectric effect in low energies is considered to be the dominant phenomenon. The main idea behind the GNP dose enhancement in some studies is not able to explain the results especially in recent investigation on cell lines and animal models radiation therapy using GNPs. With the rapid development of nanotechnology in the biomedical field, GNPs have been widely used in the diagnosis and treatment for disease. Numerous pre-clinical studies in vitro and in vivo have proved the potential value of metal-based GNPs as radio sensitizers in cancer treatment. Various studies have indicated that radio sensitizing ability could be influenced by nanomaterial size, concentration, surface coating, and the radiation energy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.

Anaplasma phagocytophilum is a gram-negative intracellular bacterium that transmitted by hard ticks. A. phagocytophilum infect and multiply in the organs of ticks, in particular the salivary glands which enable the transmission to vertebrate hosts during feeding. The tick becomes infected by feeding on an infected host and there is transstadial but not transovarial passage of the organism. The majority of ticks are infected with the organism in enzootic areas. There are strains of A. phagocytophilum that have biological and ecological difference, including variations in host pathogenicity, vectors and geographical distribution. The organism has an interesting feature to grow in neutrophils by stopping the antibacterial activity of neutrophils. The bacterium is able to survive in the immune host, using complex mechanisms of antigenic variation. A. phagocytophilum infects humans and various animal species including dogs, sheep, cows, horses, wild deer and rodents. The disease is known as human granulocytic anaplasmosis in humans, canine granulocytic anaplasmosis in dogs, equine granulocytic anaplasmosis in horse and tick borne fever in ruminants. Cattle tick borne fever caused by A. phagocytophilum is characterized by high fever, reduced milk yield, inclusions in circulating neutrophils, leukopenia, abortions, reduced fertility, coughing, respiratory signs and swelling of the hind limbs. Clinical signs of human occur a week after the tick bites, the disease usually presents as an acute, sometimes fatal febrile syndrome, illness characterized by headache, chills, myalgias, arthralgia, malaise, and hematological abnormalities, such as neutropenia, lymphocytopenia, thrombocytopenia, leukopenia, and elevated hepatic aminotransferase levels and may lead to death. In this review article the history, bacteriology, epidemiology, pathogenesis, diagnosis, treatment and prevention of the disease caused by A. phagocytophilum is written based on the latest scientific findings. Several hard tick species are distributed in Iran and they are the most important ectoparasites of animals. A. phagocytophilum has been detected not only in Ixodes ricinus but also in cattle and sheep of Iran using molecular techniques. However, despite the zoonotic potential of the agent, there is no evidence in the identification of A. phagocytophilum in humans, and it seems necessary to research on the prevalence and epidemiology of the disease in the human population.

Herpes zoster (Shingles; Zona) is an acute infectious skin disease that is caused by the reactivation of varicella zoster virus (VZV). After the initial infection (chickenpox) or vaccination, the virus remains inactive or latent in the dorsal root ganglia (DRG); when decreasing cell mediated immunity (CMI) occurs, the virus is reactivated from a latent phase to a lytic phase and frequently replicated in the dorsal ganglion cells then move to the sensory nerves into the skin and causes herpes zoster, which is typically characterized by painful neuralgia and unilateral dermatomal vesicular rash that normally lasts 3 to 5 weeks. The most common complication of herpes zoster is chronic pain owing to postherpetic neuralgia (PHN), which is estimated to occur in approximately 20% of the people aged 50 and over. Although herpes zoster is rarely fatal, the pain related to the acute phase of herpes zoster and subsequent PHN can cause psychological distress, physical disability, impaired sleep and consequently negatively affect the quality of life that can be significantly reduced by all of these occurrences. Due to increasing trend in the incidence of herpes zoster and increasing older people population, it will be expected that herpes zoster and subsequent PHN cause a significant economic burden to the healthcare system, the government, and families along with reducing the quality of life. The average lifetime risk of herpes zoster is estimated to be approximately 30% in developing countries. Although the risk of herpes zoster significantly increases with increasing age and diminished immune system function, any factor impacting on VZV-specific humoral and cellular immune responses may affect the risk of herpes zoster. This paper is provided an overview of the incidence and potential risk factors of herpes zoster with emphasis on the role of micronutrients and their deficiencies in the impaired immune system function. Also, the common method for prevention by zoster vaccine and the role of micronutrients in the efficacy of vaccination are shown.

Currently, there are about 37 million people worldwide living with human immunodeficiency virus (HIV) /AIDS, with an estimated two million new cases per year globally. According to estimates from the World Health Organization (WHO), only 75% of the population with HIV know their status. Initially, HIV infection was associated with significantly increased rates of mortality and morbidity. However, the rapid advances in treatment and the advent of different classes of antiretroviral drugs over time have led to change the face of HIV/AIDS from a deadly infection to chronic and manageable disease. There is strong evidence that HIV-infected patients undergoing antiretroviral therapy have longer lives and are less likely to transmit infection to their sexual partners. Since the introduction of zidovudine in 1987 as the first antiretroviral drug, significant strides have been made in antiretroviral therapy. The introduction of potent antiretroviral drugs for the treatment of HIV infection has been one of the significant events in the evolution of modern medicine. Antiretroviral therapy refers to the use of drugs in the treatment of HIV. Generally, these drugs are categorized based on the steps of the HIV life cycle suppressed by them. There are six main classes of antiretroviral agents including nucleoside/ nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, co-receptor inhibitors, and integrase inhibitors. Combination antiretroviral therapy should be considered for HIV patients to achieve the highest viral suppression rate, and to reduce the risk of resistance development and morbidity and mortality associated with AIDS. Achieving and maintaining HIV viral load suppression among treated patients has remarkably increased over the last years due to the development of potent and well-tolerated agents which can be co-formulated as a once-daily single-tablet or fixed-dose combination for simplification. However, there are some limitations preventing patients to benefit from this treatment. The main goals of HIV therapy in the future are to overcome the limitations of current treatment, including side effects. This review will provide an overview of advances in the current antiretroviral drugs by focusing on their pharmacokinetics, mechanism of action, dosing recommendations, and adverse events for each drug class.

The mammalian cochlea is a highly complex structure which contains several cells, including sensory receptor or hair cells. The main function of the cochlear hair cells is to convert the mechanical vibrations of the sound into electrical signals, then these signals travel to the brain along the auditory nerve. Auditory hair cells in some amphibians, reptiles, fish, and birds can regenerate or replace by new cells, but irreversible damage to the mammalian hair cells are not being replaced through differentiation of the internal epithelial cells in the inner ear. Indeed, mammalian auditory hair cells do not spontaneously repair or regenerate after development. Sometimes, functions of damaged hair cells may be restored, but in most cases, there is no such possibility and permanent hearing loss occurs. Several factors such as chronic ear infections, genetic disorders, drug abuse, acoustic trauma and aging can damage the cochlea, resulting in permanent hearing loss. More than 250 million people in the world have disabling hearing impairment. Deafness is caused by damage to sensory hair cells or spiral ganglion neurons. Although hearing aids and cochlear implants were used for improvement of hearing loss, but they do not restore normal hearing. In addition, application of new biological approaches to induce auditory hair cell regeneration provides more comprehensive treatment for hearing loss. Cell therapy is considered a promising way in the treatment of several diseases such as Parkinson, diabetes and cardiac diseases. According to recent research, cell therapy can be useful in hair cell regeneration. Cell therapy is effective in hearing loss when stem cell differentiates into hair cells with appropriate morphology, electrical activity and capacity for suitable innervations with inner ear tissues. In fact, stem cell-derived neurons need to project neural processes toward the sensory hair cells and the cochlear nucleus neurons. In this regard, studies focus on methods in which hair cells can be provided from exogenous and endogenous stem cells. Here, we review cell therapy approaches in repair damaged cochlear hair cells, as well as imitations and problems of its clinical application.

Primary immunodeficiency diseases (PIDs) is a diverse group of diseases, characterized by a defect in the immune system. These patients are susceptible to recurrent respiratory infections, gastrointestinal problems, autoimmune diseases, and malignancies. In most cases, patients with primary immunodeficiency disorders have genetic defects and are monogenic disorders that follow a simple Mendelian inheritance, however, some PIDs recognize a more complex polygenic origin. Overall, almost 70 to 90 percent of patients with primary immunodeficiency are undiagnosed. Given that these patients are exposing to respiratory infectious agents and some live-attenuated vaccines, thus they have a high risk to some clinical complications. The administration of oral polio vaccine in patients with PIDs especially can increase the possibility of acute flaccid paralysis. These patients will excrete the poliovirus for a long time through their feces, even though they are not paralyzed. Long-term virus proliferation in the vaccinated individuals causes a mutation in the poliovirus and creates a vaccine-derived polioviruses (VDPVs), which is a major challenge to the final stages of the worldwide eradication of polio. 
To increase the diagnosis and identification of patients with immunodeficiency and carrying out a national plan for screening patients with immunodeficiency from the fecal excretion of the poliovirus, a possible polio epidemic can be prevented during post-eradication. Development of laboratory facilities in provincial and city centers, improvement of communications among physicians regarding medical consultation and establishment of referring systems for patients by national network lead to improve status of diagnosis and treatment of patients with primary immunodefiicencies. In this context, launching and activating the national network of immunodeficiency diseases is essential for improving the health of children and reducing the cost of the health system of the country. A national network of immunodeficiency can lead to increase awareness of physicians regarding primary immunodeficiency disorders, improve collaboration among physicians about genetic consultation and establish a practical referral system in Iran that results in increased diagnosis and improve treatment of patients with primary immunodeficiency disorders.

Multiple Sclerosis (MS) is a chronic neurological and inflammatory disorder that affects the nervous system. The etiology of MS is unknown, but genetic and environmental factors are involved in its pathogenesis. There is increasing evidence suggesting the role of epigenetic mechanisms in the pathogenesis of multiple sclerosis. Lack of vitamin D, smoking, and Epstein barr virus can cause epigenetic changes. Several studies have found that Dysregulation in DNA methylation is related to abnormal immune responses and post-translation modifications of myelin proteins in the brain specimens of MS patients. Molecular mechanisms through environmental signals lead to gene expression changes include DNA methylation, post modification of nucleosomal histones and non-coding RNAs. Also, abnormal microRNA profiles have been reported in the brain tissues and peripheral immune blood cells of MS patients. Increased histone acetylation and citrullination of myelin basic protein are two epigenetic mechanisms that may intensify the disease course, in the progressive type. The activation of T cells by histone deacetylase (HDAC) may contribute to the pathogenesis of MS disease and increase the intensity of disease. Increased of HDAC transcripts can also be observed during immune cell activation. Th1 differentiation is produced by HDACs, and the inhibition of these enzymes reduces the production of IFN-γ. The expression of 364 miRNA in peripheral blood mononuclear cell (PBMC) has been reported in the patients with remitting and relapsing and increased miR-18b and miR-599 regulation in the relapsing course. Expression of miRNAs in astrocytes, microglia, and CD8+ T cells also increased. The role of epigenome in this disease can be deduced from epidemiological studies of the geographical location influence, a month of birth, nutritional status (food and vitamin D absorption), and smoking. Despite of the ever-increasing advances, the epigenetic mechanisms of MS are still unknown. Numerous studies are needed to treat and control the disease and discover new and effective drugs due to the complexity of multiple sclerosis and the importance of epigenetic changes in multiple signaling pathways and the molecular mechanisms of different types of MS.

Background: Although cervical malignancy rate had grown up in recent years, primary cervical lymphoma is so rare. It must be high index of suspicious for primary cervical lymphoma diagnosis in patient with malignancy-like signs and symptoms for early detection. Primary cervical lymphoma has no standard treatment or follow-up protocol; so the management still is in doubt and based on previous case reports. In the other hand, the precise prognosis of patient is undetermined. In the present study, a case of primary cervical lymphoma is presented which was misdiagnosed at first. The patient accurate diagnosis was made at last due to multidisciplinary team working.
Case presentation: A 51-year-old woman, gravida 2, para 2, presented with complaint of abnormal vaginal bleeding and discharge, with no abnormal finding in cervical cytology and sonography, so uneventfully a diagnostic error had happened in the assessment of her. After several months and multiple different treatment, the patient referred to the Oncology Department of Obstetrics and Gynecology Center, Ghaem Hospital, Mashhad, Iran in May 2017. Re-assessment was performed by biopsy and imaging, and the final pathologic diagnosis of diffuse large B-cell non-Hodgkin's lymphomas was confirmed.
Conclusion: Primary cervical lymphoma is an uncommon malignancy; the diagnosis could be missed simply by low suspicious due to low accuracy of Pap smear and imaging in this situation. So an accurate evaluation and pelvic examination, high suspicious and close communication between clinician and pathologist are needed. By timely diagnosis of patient in early stage and appropriate approach, the prognosis could be excellent most of the time.

Neurodegeneration with brain iron accumulation (NBIA) is a rare set of inherited neurodegenerative disorders with abnormal accumulation of iron in basal ganglia. It is a clinically and genetically heterogeneous disorder that is characterized by movement disorders, dystonia, dysarthria, Parkinsonism, intellectual disability, and spasticity. The age at onset varies from childhood to adulthood and the rate of progression is different among affected individuals. Although there is no information about the exact prevalence of NBIA in the world-wide, it is estimated less than 1/1,000,000 in population. NBIAs are inherited in autosomal recessive, autosomal dominant or X-linked fashions. Until now more than 10 genes have been identified for this group of disorders. Among these, only two genes encode proteins that directly involved in iron metabolism. Therefore, how iron contributes to the pathogenesis of NBIA remains unknown. The remaining NBIA-causing genes participate in lipid metabolism, lysosomal functions or autophagy process, and the roles of some of them remain unknown. NBIA is categorized based on the genetic cause of the disease. PKAN, PLAN, MPAN, and BPAN are the most common forms of the disease result from mutations in the PANK2, PLA2G6, C19orf12, and WDR45 genes, respectively. The diagnosis of NBIA is usually based on clinical features and a specific pattern of brain MRI which results from the abnormal accumulation of iron. For example, the pattern of “eye of the tiger” is observed in the brain MRI of PKAN cases. Since, clinical evaluations and neuroimaging have failed in the diagnosis of the disease in some NBIA cases, genetic testing will be helpful. Development of whole-exome sequencing (WES) has facilitated the identification of disease-causing genes but it seems some of NBIA-genes have remained unknown, yet. Identification of novel genes and molecular pathways will enable a deeper understanding of the underlying molecular bases and our knowledge about the pathogenesis of the disease. There is currently no comprehensive study about the NBIA in Iran, however, the latest discovered NBIA gene, GTPBP2, has been identified in an Iranian family.

  SARS-CoV-2 emerging from Wuhan, China is a member of the Coronaviridae family, which has so far infected and killed many people. The SARS-CoV-2 pandemic affected various aspects of life in Iran and Worldwide, and governments have imposed quarantines and travel bans on an unprecedented scale. The virus causes COVID-19, which can spread through close contact with the infected person, contaminated equipment, and suspended air droplets. The most common symptoms of the disease include fever, cough, shortness of breath, gastrointestinal symptoms, and diarrhea. In severe cases, the lung infection can occur, which causes Severe Acute Respiratory Syndrome that leads to ICU admission and even death.
  Besides, this infection can cause gastrointestinal, neurological, and renal impairments. Not merely, this new coronavirus has infected many more people worldwide in comparison to MERS and SARS, but also it has killed more people. Patients with underlying diseases such as hypertension, diabetes, respiratory problems, kidney disease, heart disease and Immunodeficiency are at higher risk of infection and potential death. Also, the risk of death and complication increases in older adults, while most of the infected children are asymptomatic. Some infected people may have mild or no symptoms but can still transmit the disease and spread it to others.
To diagnose COVID-19, serology tests, and level of ESR, CRP and other acute-phase reactants are helpful, whereas molecular tests, such as RT-PCR tests, that detect the virus’s genetic material are still the golden standard. Also, CT scan detects lung involvement; Ground-glass opacification, especially in lower lobes and subpleural region, is the most common CT characteristic, although it is not specific for COVID-19. Because the disease is difficult to diagnose, hard to prevent and challenging to treat, it has become a major concern for many countries. This review aims to gather existing information in the fields of virology, molecular pathogenesis, disease symptoms, epidemiology, clinical presentations, diagnosis, treatment, and the spread of the disease. This study also provides evidence-based prevention and treatment strategies for health policymakers, doctors, nurses, and practitioners in the field of public health, including researchers and students.

In 2019 a newly emerged coronavirus was detected by the Center for disease control (CDC) in China. Nucleic acid sequencing from nose and throat swab samples of patients revealed that it was like severe acute respiratory syndrome coronavirus (SARS-CoV). World Health Organization (WHO) named it coronavirus disease 2019 (COVID-19) and reported more than 100000 positive tests until March 2020 for COVID-19. During the past 20 years, the world has been affected by three coronavirus epidemics, SARS-COV, Middle East respiratory syndrome coronavirus (MERS-CoV), and COVID-19 that make world attention. The mortality rate of COVID-19 was more than other coronaviruses, but because of more people affected by it, it seems that it has a less fatality rate compared with MERS- CoV. Initial data showed that more than 80% of patients did not have any symptoms or may had light symptoms. 15% showed severe pneumonia, 5% became critically ill, and developed multiorgan dysfunction and septic shock. Due to the epidemic of emerging viruses and the lack of information about it, this study aimed to provide a quick overview of the most recent studies in the world. To perform this review, keywords such as COVID-19, severe acute respiratory syndrome coronavirus 2, and Angiotensin-converting enzyme 2 were retrieved using the medical subject headings (MeSH) system and then searched in English in PubMed, Scopus, Google Scholar, and Web of Science databases.
COVID-19 virus enters its genome into the cells by binding to Angiotensin-converting enzyme 2 in some organs such as the lungs. Although the transmission route is unclear, it enters the body through respiratory droplets. The clinical symptoms includ fever, cough, dyspnea, myalgia, confusion, headache, sore throat, rhinorrhea, chest pain, diarrhea, nausea, vomiting, malaise, and convulsion. The standard diagnostic method is Real-time polymerase chain reaction (RT-PCR), but due to the time-consuming and sensitivity and the existing errors in this technique, chest CT and hematologic data are preferred. No definitive cure for the virus has been suggested so far, but antiviral drugs such as Oseltamivir, Ganciclovir, Lopinavir, Ritonavir and Remdesivir, and the anti-malarial drug Chloroquine phosphate and Interferon are in use until the discovery of the vaccine.

Primary Immune Deficiencies are a group of heterogeneous disorders that involve the innate or acquired immune system, or a combination of them. The underlying disorder may be related to decreased levels or function, or a complete lack of one or more components of the immune system in general. These diseases can occur with a prevalence of about 1 in 10000 live births. According to the fourth update on the Iranian national registry of Primary Immune Deficiency in October 2018, the total number of registered PIDs in Iran are 3056 patients. However, it is supposed to be more prevalent and it seems increasing awareness shall reveal many new cases, especially in societies with prevalent consanguineous marriages like Iran. These disorders predispose patients to recurrent infections, autoimmunity and malignancy and can cause a huge burden on health care systems. This group of diseases has a wide range of symptoms, which quick recognition and timely treatment of them, can greatly reduce the complications of the disease. These symptoms may include recurrent or severe infections, failure to thrive, autoimmune disorders, as well as articular-skeletal manifestations. A variety of skeletal manifestations are seen in patients with primary immunodeficiency, among which septic arthritis caused by pyogenic bacteria or mycoplasma arthritis is the most common joint-bone manifestation. Joint and skeletal involvement is less commonly seen as a sign of primary immune defects. This issue is importance in reducing the cost of diseases and improving the patients’ quality of life. Our review attempted to introduce the most common manifestations of bone and joint in patients with primary immunodeficiency and available treatments for these manifestations. Because of the wide range of symptoms in these patients, it is recommended to observe the rare and suspicious manifestations in the patients with any atypical bone and joint presentations such as: recurrent septic arthritis, infection with unusual germs, immunodeficiency in their relatives, and any history of well-known red flags of PIDs. The Rheumatologist should consider these manifestations and think about the possibility of deficiency disorder.

The presence of the antibodies against the main thyroid antigens, which include thyroid peroxidase (TPO) or microsomal antigen, thyroglobulin (Tg) as well as thyrotropin receptor or Thyroid Stimulating Hormone Receptor (TSH-R), is a hallmark and symbol of the autoimmune thyroid diseases (AITDs) as one of the most common autoimmune diseases (AD) around the world. The prevalence of the thyroid peroxidase antibodies (anti-TPO antibody) and the thyroglobulin antibodies (anti-Tg antibody) is considerably higher in patients suffering from Graves’ disease (GD) and Hashimoto's thyroiditis (HT, chronic autoimmune thyroiditis, autoimmune hypothyroidism). While the TSH receptor antibodies (TRAbs) are common in the patients suffering from GD, they are relatively rare and infrequent in HT patients. This fact may indicate that TRAbs are more specific than other antibodies. In fact, TRAbs as one of the most important autoantibodies against the different thyroid antigens, are a set of the heterogeneous group of antibodies that based on the function, fall into three categories, including TSHR-stimulating antibodies (TSAbs), TSHR-blocking antibodies (TBAbs), and the neutral antibodies (no effect on receptor). TSAbs and TBAbs result in overproduction and reduction of intracellular cAMP respectively. Therefore the induction of the relevant signaling pathways can be the cause of different clinical symptoms in the form of hyperthyroidism or hypothyroidism consecutively. The extra-thyroidal effects of TRAbs as the extra-thyroid GD manifestations, such as ophthalmopathy and dermopathy, often have an effect on the eyes as well as the skin with the relatively well-known immunological mechanisms of the antibodies functions. Hashimoto encephalopathy is an extra-thyroidal effects of anti-TPO that provokes the central nervous system. On the other hand, anti-TPO like anti-Tg can affect the reproductive organs of women and lead to infertility by an unknown mechanism. Moreover, the circulating antibodies against the thyroid antigens can also be detected in other autoimmune diseases such as rheumatoid arthritis (RA), type I diabetes (T1DM) and celiac disease (CD). In this review article, the most important types of thyroid autoantibodies, their essential immunological processes in AITD as well as the main and important clinical extra-thyroidal manifestations of them have been discussed and reviewed.

Classifying patients with low back pain into homogeneous and distinct categories by organizing similar manifestations among individuals can be helpful to attain better results for treatments. Providing homogenous categories of patients with low back pain would improve benefits produced by treatments. To gain a greater understanding of the proposed multi-stage process and validate diagnostic categories, the current research was designed to conduct a review about this process. We aimed to validate movement system impairment (MSI) based categories of people with chronic low back pain. MSI-based classification uses a standardized approach for classifying people with low back pain into 1 of 5 subgroups. For the present narrative review, computerized databases of EMBASE, Google Scholar, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and Science Direct were searched for articles published between January 1990 and December 2018. For electronic searches, keywords and terms used were: “Reliability”, “Validity”, “Classification”, “low back pain" and “Human Movement System”. Fourteen full-text research reports that have been undertaken to add clinical, laboratory and outcome validity to MSI-based classification of low back pain were included in the review. Five studies were categorized as clinical validity studies which investigated the accuracy of examinations for patients with low back pain, 5 studies categorized as laboratory validity studies and 4 studies categorized as outcome validity studies which included randomized control trials. The results of this review revealed that novice users can learn the diagnosis algorithm of MSI-based categories of low back pain and by practicing, their inter-tester reliability and precision in applying the classification algorithm would be comparable to that of described for experienced expert raters. The laboratory-based tests, including 3D motion analysis, indicated that there are differences in movement patterns of the lumbar spine between low back pain subgroups. Also, for people with low back pain, classification-specific treatments based on the MSI model resulted in better outcomes. In conclusion, this review indicated the validity of the MSI classification system in people with chronic low back pain.