Mohammad Javad Nasiri

Shahid Beheshti University of Medical Sciences

Background There is a consistent association between exposure to air pollution and elevated rates of cardiopulmonary illnesses. As public health activities emphasize the paramount need to reduce exposure, it is crucial to examine strategies like the antioxidant diet that could potentially protect individuals who are unavoidably exposed. Methods A...

Introduction: Obesity, a pressing global health issue worldwide, contributes to risk factors such as hypertension and dyslipidemia, creating an unfavorable cardiovascular environment and increasing the likelihood of adverse cardiac events. His study aims to assess the impact of obesity on various cardiovascular parameters. Methods: A cross-secti...

Background Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of D...

Background Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to i...

Background Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to i...

This appendix provides detailed information on the methods for the paper “Global fertility in 204 countries and territories, 1950–2021 with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021”

sec id="st1"> INTRODUCTION To determine the frequency of TB among patients with interstitial lung diseases (ILDs). METHODS We performed a comprehensive search in the PubMed/Medline, EMBASE and Scopus databases up to 1 August 2023 of studies reporting on the prevalence of TB among patients with ILDs. RESULTS Twelve studies comprising 3,817 patients...

The worldwide incidence of multi-drug-resistant tuberculosis (MDR-TB) is rapidly increasing, and it has emerged as a pressing public health issue in Iran. Nevertheless, there is a scarcity of up-to-date research on the prevalence of MDR-TB in individuals with pulmonary TB in the country. In this cross-sectional study, we gathered a total of 1216 re...

Background The incidence of complications and mortality associated with Staphylococcus aureus (S. aureus) bloodstream infections has been increasing significantly, particularly in developing countries where control strategies against this virulent pathogen and its resistance to antibacterial agents are insufficient. The aim of this study was to inv...

Background: Lactic acid bacteria (LAB) are among the most important strains of probiotics. Some are normal flora of human mucous membranes in the gastrointestinal system, skin, urinary tract, and genitalia. There is evidence suggesting that LAB has an antiviral effect on viral infections. However, these studies are still controversial; a systemati...

Introduction Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL...

Cardiovascular events remain a substantial global health concern, necessitating innovative strategies for prevention. This study aims to assess the potential impact of influenza vaccination on major cardiovascular events. A search of the medical English literature was conducted using PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL up to 1 August 2...

Context: In recent years, antimicrobial resistance (AMR) has become a global public health threat. Health system decision-makers need valid and reliable situation analysis to better plan for mitigating this threat. Objectives: This scoping review investigated the research gaps in AMR publications in Iran and provided an evidential base to support t...

Background: The safety of Upadacitinib, a Janus kinase inhibitor, in the context of rheumatoid arthritis management has raised concerns regarding potential cardiovascular adverse events, but the evidence remains inconclusive. Methods: Our study involved a systematic search for articles conducted up to October 1, 2023, encompassing databases such as...

The prevalence of Streptococcus agalactiae infections in adult populations is increasing. The current study aimed to characterize the genetic features of S. agalactiae strains responsible for different infections. A cross-sectional study was performed on 65 S. agalactiae strains (30 invasive and 35 noninvasive) isolated from non-pregnant women. All...

Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT...

Introduction and objectives: Post-tuberculosis lung disease (PTLD), as other chronic respiratory disorders, may have infectious complications; some of them can be prevented with vaccinations. So far, no document has discussed the potential role of vaccination in PTLD. Therefore, the objective of this review was to describe vaccination recommendati...

Background: Cardiovascular events remain a substantial global health concern, necessitating innovative strategies for prevention. This study aims to assess the potential impact of influenza vaccination on major cardiovascular events. Methods: A search of the medical English literature was conducted using PubMed/MEDLINE, EMBASE, and the Cochrane CEN...

Introduction: Individuals diagnosed with atherosclerotic cardiovascular disease (ASCVD), particularly those who have experienced acute coronary syndrome (ACS) within the past year, are at a heightened risk of recurrent cardiovascular events. Lowering low density lipoprotein cholesterol (LDL-C) levels has been proven effective in reducing this risk....

Background: This study aimed to estimate the prevalence of fosfomycin resistance and the frequency of extended-spectrum beta-lactamase (ESBL) production in Escherichia coli isolates from three kidney transplant patients (KTPs) in Tehran. Methods: Sixty clinical isolates of uropathogenic E. coli were collected from three kidney transplant centers in...

Introduction: Silicosis mostly happens in workers with high silica exposure and may accompany the development of various diseases like tuberculosis, cancer, or autoimmune diseases. The term silico-tuberculosis describes a condition in which an individual is affected by both silicosis and tuberculosis at the same time. This systematic review and me...

Promoting the judicious use of antibiotics is crucial. Physicians and veterinarians must adhere to evidence-based guidelines and prescribe antibiotics only when necessary [26]. Improved diagnostic tools can help identify the most appropriate treatment options.

Background: Staphylococcus aureus with concurrent resistance to antibacterial agents is emerging globally. This emergence might be due to the production of different virulence determinants, notably Panton-Valentine leukocidin (PVL). Objectives: This study aimed to investigate the genetic characteristics of PVL-positive S. aureus strains isolates fr...

Introduction: The use of tigecycline (TG) for the treatment of Acinetobacter baumannii is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. Methods: We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Scienc...

Simple Summary Gastric cancer is the fifth most prevalent cancer in the world. The relationship between gastric cancer and underweight, overweight, and obesity is not fully understood yet. Obesity is a modifiable factor that has a positive association with some cancers. This systematic review and meta-analysis aimed to investigate the association b...

Background and aim: Patients with underlying cardiovascular disorders such as coronary artery disease (CAD) are more prone to severe forms and multiple complications of COVID-19. The present systematic review and meta-analysis aimed to investigate the impact of CAD on patients with COVID-19. Methods: Main electronic databases, including Medline...

(1) Background: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by progressive and irreversible autoimmune destruction of pancreatic beta cell islets, resulting in absolute insulin deficiency. To date, several epidemiologic and observational studies have evaluated the possible impact of BCG vaccination on T1D development, but...

Introduction: Helicobacter pylori is a prevalent pathogenic bacterium that resides in the human stomach. Outer membrane vesicles (OMVs) are known as nanosized cargos released by H. pylori, which have been proposed to have a key role in disease progression, pathogenesis, and modulation of the immune system. There are multiple evidences for the role...

The literature on fusidic acid resistant Staphylococcus aureus strains is scarce in Iran, although the emergence of these strains in health care settings is increasing. This descriptive cross-sectional study was conducted on 68 fusidic acid resistant S. aureus strains to learn about the molecular characteristics and antimicrobial resistance of stra...

(1) Background: In early May 2022, an increasing number of human monkeypox (mpox) cases were reported in non-endemic disparate regions of the world, which raised concerns. Here, we provide a systematic review and meta-analysis of mpox-confirmed patients presented in peer-reviewed publications over the 10 years before and during the 2022 outbreak fr...

Introduction: Reactive arthritis (ReA) is a joint inflammation that follows an infection at a distant site, often in the gastrointestinal or urogenital tract. Since the emergence of COVID-19 in January 2020, several case reports have suggested a relation between reactive arthritis and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), d...

Background: Dental caries is an infectious disease caused by bacterial colonization and biofilm formation. Streptococcus mutans (S. mutans) is mainly responsible for dental caries development. Considering the side effects of synthetic antibacterial agents, attempts are ongoing to find antimicrobial agents with minimal or no side effects for prevent...

Background and Aim: Multidrug-resistant (MDR) tuberculosis (TB) is caused by a strain of Mycobacterium tuberculosis (MTB) that was at least resistant to isoniazid (INH) and rifampicin (RIF). World Health Organization reported 399,000-501,000 cases of RIF resistance and they reported this case without knowing about this situation in Tehran. So, it i...

Background Lactic acid bacteria (LAB) are one of the most important strains of probiotics. Some of them are normal flora of human mucous membranes in the gastrointestinal system, skin, urinary tract, and genitalia. There is evidence suggesting that LAB has an antiviral effect on viral infections. However, these studies are still controversial and a...

Introduction: Nano-technology applied for the local delivery of different agents and/or drugs has made its path to endodontics. In the current study, the antibacterial efficacy of biopolymer-coated ceramic microparticles loaded with a modified combination of triple antibiotics, i.e. Penicillin G, Metronidazole and Ciprofloxacin (PMC), was evaluate...

Introduction The prevalence of Mycobacterium avium complex (MAC) is increasing globally. Macrolide-based multidrug regimens have been recommended as the first-line treatment for patients with MAC pulmonary disease. However, developing macrolide resistance was associated with poor treatment outcomes and increased mortality. In 2018, the U.S. Food an...

Background: The world is facing a new coronavirus that causes a respiratory infection called COVID-19. Therefore, there is an increasing request for antibody tests in recovered individuals since they want to evaluate their immunity against SARS-CoV-2 reinfection. Materials and Methods: In our study, we had 1000 blood samples from patients admitted...

This systematic review aimed to evaluate existing randomized controlled trials (RCT) and cohort studies on the efficacy of mouthwashes in reducing SARS-CoV-2 viral loads in human saliva. Searches with pertinent search terms were conducted in PubMed, MEDLINE, Scopus, and Web of Science databases for relevant records published up to Oct 15, 2022. Goo...

Importance: Anti-tumor necrosis factor-alpha agent (anti-TNF-α) is considered an effective third-line therapy for refractory sarcoidosis,studies observing the efficacy of anti-TNF-α agents show conflicting results. Objective: We performed an up-to-date systemic meta-analysis to determine effectiveness and further elucidate the role of anti-TNF-α...

Introduction: Clostridioides difficile Infection (CDI) has been identified as one of the main causes of nosocomial infection all across the world. Rapid diagnosis of CDI is difficult and poses a significant challenge to physicians worldwide. We undertook a systematic review and meta-analysis to evaluate rapid tests' diagnostic accuracy against tox...

Background and aim: The increasing number of nosocomial infections associated with Acinetobacter baumannii (A. baumannii) is causing this bacterium to become a more clinically significant organism. There is great medical concern about the emergence of NDM-type carbapenemases in A. baumannii strains that impede the effectiveness of practically all a...

Background: In recent years, Anti-Microbial Resistance (AMR) has become a global public health threat. Health system decision-makers need valid and reliable situation analysis to better plan for mitigating this threat. This scoping review investigates the research gaps on AMR publications in Iran and provides an evidential base to support the ident...

On 25 November 2021, the world health organization listed Omicron as a newly arisen and the fifth variant of concern (VoC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genome sequence of Omicron showed the utmost number of mutations compared to other known VoCs up to now, and it was regarded as the only SARS-CoV-2 variant wi...

Background Opioid dependency is a chronic relapsing disorder for which different therapeutically interventions have been developed. Naltrexone is a non-selective opioid antagonist that can be utilized for maintenance therapy in opioid dependency. In this systematic review, we aimed to evaluate the effects of naltrexone on retention in treatment and...

Introduction Seasonal influenza, a contagious viral disease affecting the upper respiratory tract, circulates annually, causing considerable morbidity and mortality. The present study investigates the effectiveness of educational interventions to prevent influenza. Methods We searched PubMed/Medline, Embase, and Cochrane Controlled Register of Tri...

Introduction: Linezolid (LNZ) is an effective antibiotic to treat patients with multidrug-resistant tuberculosis (MDR-TB) treatment failure. M. tuberculosis strains resistant to isoniazid and rifampin are defined as MDR-TB. In recent years, resistance to LNZ among MDR-TB cases has been reported in several different countries. In this study, we perf...

Cancer is one of the leading causes of mortality and morbidity worldwide. Nisin consists of various and uncommon amino acids as an antimicrobial protein synthesized by the Lactobacilli genus. The current systematic review aimed to evaluate the anticancer activity of Nisin, an antibacterial peptide, on different human cancer cell lines. We searched...

Introduction and Objective: The estimated risk ofthe incidence of stroke following a transient ischemic attack (TIA) is 5-20% within the first hour and year following its incidence. Various methods such as the use of ABCD2, ABCD3-I, and ABCD3 criteria have been employed to predict and identify the high-risk cases of TIA. Contradictory results have...

Fungal co-infections are frequent in patients with coronavirus disease 2019 (COVID-19) and can affect patient outcomes and hamper therapeutic efforts. Nonetheless, few studies have investigated fungal co-infections in this population. This study was performed to assess the rate of fungal co-infection in patients with COVID-19 as a systematic review...

Introduction Tele‐medicine services have been developed in response to the COVID‐19 pandemic, which disrupts mental health services. The present study investigates the effectiveness of telephone‐delivered services for psychological disorders in the COVID‐19 pandemic. Methods We searched PubMed/Medline, Embase and Cochrane Controlled Register of Tr...

A universal problem is about spread of Staphylococcus aureus infections in burn patients. The present study aimed to learn about the molecular characteristics and the resistance pattern of S. aureus strains isolated from burn patients. In this cross-sectional study, we investigated 100 unique S. aureus isolated from burn patients by antimicrobial a...

Background and aim In the last decade, a high number of Klebsiella pneumoniae (K. pneumoniae) with carbapenem resistance emerged, making treatment of this infection difficult or even impossible. Colistin is the last option for the treatment of these bacteria, and so the emergence of resistance to it can raise concerns. As a comprehensive systematic...

Severe acute respiration syndrome coronavirus 2 (SARS-CoV-2) is characterized by severe cytokine storm syndrome following inflammation. SARS-CoV-2 is the 7th coronavirus that causes infection in human bodies; SARS-CoV, MERS-CoV, and SARS-CoV-2 can purpose severe diseases. SARS-CoV-2 at once interacts with angiotensin-converting enzyme 2 (ACE-2) rec...

Objective: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening infectious disease. Treatment requires multiple antimicrobial agents used for extended periods of time. The present study sought to evaluate the treatment success rate of bedaquiline-based regimens in MDR-TB patients. Methods: This was a systematic review and meta-analysi...

Building airtightness for acquiring greater energy efficiency have impacted indoor air quality. The control of pollution requires air filtration. Bioaerosols serve as an essential quality indicator of indoor air. The contamination of bioaerosols is a filtration barrier. The present study proposes a novel metal–organic framework (MOFs) antimicrobial...

Background and aim Coronavirus disease 2019 (COVID-19) in people living with human immunodeficiency virus (HIV) who has a compromised immune system can be associated with more significant risks for severe complications. To date, no comprehensive study has been performed to evaluate HIV in patients with COVID-19. In the present study, we assessed th...

Background Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect arises quite often after bendamustine treatment. To date, there have been no recommendations for routine chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) in pati...

SARS-CoV-2 pandemic is one of the most critical pandemics during human civilization. Several therapeutic strategies for COVID-19 management have been offered; nonetheless, none of them seems to be sufficiently beneficial. In effect, vaccines have been proffered as a viable option. The critical issue now is to concentrate on protecting individuals a...

Introduction Reverse transcription-polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 is time-consuming and sometimes not feasible in developing nations. Rapid antigen test (RAT) could decrease the load of diagnosis. However, the efficacy of RAT is yet to be investigated comprehensively. Thus, the current systematic review and meta-analysis we...

Introduction Acute kidney injury (AKI) has been associated with an increased mortality rate among hospitalized patients with Coronavirus disease 2019 (COVID-19). The current review aimed to evaluate the symptoms, complications, and treatments performed to manage AKI in patients with COVID-19. Methods We searched PubMed/Medline, Web of Science, and...

Today, resistance of microorganisms to antibiotics has become a major challenge. To overcome this problem, development of new drugs, besides research on their antibacterial activity, is essential. Among chemical components, antimicrobial peptides (AMPs) exhibit antibacterial activity and can be selected as suitable antimicrobial candidates. In this...

Introduction Thromboembolic events are one of the important complications in COVID-19 patients, especially in severe cases. Aspirin affects platelet function through irreversibly inhibiting the activity of cyclooxygenase, and it reduces the risk of thrombosis. The current systematic review was aimed to evaluate the effectiveness of aspirin in preve...

Introduction The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) emerged in late December 2019. Considering the important role of gut microbiota in maturation, regulation, and induction of the immune system and subsequent inflammatory processes, it seems that evaluating the composition of g...

The novel coronavirus pandemic has emerged as one of the significant medical-health challenges of the current century. The World Health Organization has named this new virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first detection of SARS-CoV-2 in November 2019 in Wuhan, China, physicians, researchers, and others have...

Introduction Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. Methods We reviewed the relevant scientific literature published up t...

Introduction Coronavirus Disease 2019 (COVID -19) pandemic challenged the healthcare system drastically, and it was concomitant with a remarkable decline in surgeries and modified routine care of patients worldwide. This systematic review and meta-analysis aimed to compare the surgical complications before COVID -19 (Pre-COVID) and after COVID -19...

Staphylococcus aureus as an opportunistic pathogen of humans poses many risks to global health. This study examines antimicrobial susceptibility pattern, virulence determinants and genetic diversity of S. aureus strains isolated from ICU and burn patients based on coa gene polymorphism. Between March 2019 and February 2020, we investigated 75 S. au...

The spread of mupirocin-resistant Staphylococcus aureus strains in hospitals and communities is a universal challenge. Limited data is available on the genetic features of high-level mupirocin resistant- (HLMUPR-) S. aureus isolates in Tehran. In the present research, we investigated 48 high-level mupirocin resistance S. aureus by antimicrobial act...

Background and objective: SARS-CoV-2 as the newest member of Beta-Coronaviruses can cause a complicated disease called COVID-19. This virus is able to penetrate a broad range of human cells, such as liver, heart, and kidney cells via ACE2-associated endocytosis. Heart involvement can result in kidney injuries; it is now testified that kidney conge...

Introduction Contact lens wearing has been increased globally during recent decades, which is one of the main risk factors for developing microbial keratitis. Microbial keratitis is a severe and dangerous condition that causes cornea inflammation. It can lead to corneal scarring and perforation or even endophthalmitis and visual loss if it remains...

Introduction: Vaccination seems to be a good solution for preventing and controlling coronavirus disease (COVID-19) pandemic, but still there are some challenges in COVID-19 vaccination. Investigating new therapeutic options for COVID-19 is necessary. The current study aimed to evaluate the safety and efficacy of stem cells in treating patients wit...

Staphylococcus aureus as an opportunistic bacterial pathogen with intrinsic and acquired resistance to many antibiotics is a worldwide problem. The current study was undertaken to evaluate the resistance pattern, and determine the genetic types of multidrug-resistant S. aureus isolated from wound. This cross-sectional study was conducted over the p...

Background and aim The continuing rise in infections caused by multi-drug resistant (MDR) bacteria is one of the most serious public health issues in today's societies. Colistin is a last-resort antimicrobial medication used to treat infections caused by MDR gram-negative bacteria; therefore resistance to this antibiotic is extremely hazardous. The...

Introduction: Pyrazinamide (PZA) susceptibility testing plays a critical role in determining the appropriate treatment regimens for multidrug-resistant tuberculosis. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of sequencing PZA susceptibility tests against culture-based susceptibility testing methods as th...

Introduction: The severity of COVID-19 may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity has been associated with using some medications in the management of COVID-19 patients. However, limited studies had systematically investigated the evidence of drug-induced live...

Background: The incidence of Mycobacterium avium complex (MAC) increases as immunosuppressed conditions become more common. MAC's standard treatment regimen includes a macrolide, ethambutol, and a rifamycin, among which rifampin and rifabutin are the most commonly used. Although current guidelines recommend initial therapy for MAC with rifampin, it...

Introduction The association between Coronavirus Disease 2019 (COVID-19) and abortion has been debated since the beginning of the COVID-19 pandemic. We aimed to conduct this systematic review to understand better the potential effects of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on fetal loss in infected mothers presented with ab...

Introduction: Hepatitis B and C viruses are among the leading causes of health problems globally, and their early diagnosis and treatment are very important. Thereby, this study aimed to evaluate the validity and reliability of functional diagnostic tests to detect hepatitis B and C viruses in the clinical setting and compare them with each other....

We pooled data with random-effects models when appropriate. After screening 1608 citations, 30 studies covering 8215 patients with TB were included. The pooled frequency of RIF-resistance among all patients with TB was 8.0% (95% CI 4.0-12.0). Our subgroup analysis showed that 4.0% of newly diagnosed cases and 36.0% of previously-treated TB patients...

Background: Cardiomyopathies (CMPs) due to myocytes involvement are among the leading causes of sudden adolescent death and heart failure. During the COVID-19 pandemic, there are limited data available on cardiac complications in patients with COVID-19, leading to severe outcomes. Methods: We conducted a systematic search in Pubmed/Medline, Web of...

Despite its importance, pyrazinamide (PZA) is a blind spot in drug susceptibility testing in tuberculosis laboratories. The aim of this study was to set up a reliable agar-based proportion method for detection of PZA-resistant phenotypes using Middlebrook 7H11 agar supplemented with calf bovine serum (CBS) compared with albumin/dextrose/catalase (A...

Introduction The incidence of infections due to the Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABS) are increasing worldwide. Current anti-mycobacterial agents are not sufficiently effective against NTMs, and there is a need for new drugs. The present study aimed to estimate the overall in-vitro CFZ activity against MAC and MAB...

Objective: As a beta-coronavirus, Coronavirus disease-2019 (COVID-19) has caused one of the most significant historical pandemics, as well as various health and medical challenges. Our purpose in this report is to collect, summarize, and articulate all essential information about antiviral drugs that may or may not be efficient for treating COVID-...

Introduction Multidrug-resistant tuberculosis (MDR-TB) remains a challenge. In this study, we investigated the incidence of rifampicin (RIF) resistance in Mycobacterium tuberculosis in a large number of pulmonary specimens. Materials and methods A two-center study in Tehran, the capital of Iran, was performed with 6624 pulmonary samples of TB pati...

The pandemic of the novel human coronavirus disease 2019 (COVID‐19) has become an evolving global health issue due to the high morbidity and mortality rate. Patients who have comorbidities (e.g., diabetes, hypertension, obesity, cancer, and cardiovascular disease) are significantly at increased risk for admission into the intensive care unit, and t...