Targeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody-drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more-stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.

Repositioning of the global epicentre of non-optimal cholesterol NCD Risk Factor Collaboration (NCD-RisC)* High blood cholesterol is typically considered a feature of wealthy western countries 1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world 3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health 4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low-and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium,

A study was performed to determine the prevalence and antimicrobial resistance of Shigella species and diarrheagenic Escherichia coli isolates cultured from patients with acute diarrhea in Tehran, Iran. Between May 2003 and May 2005, 1120 diarrheal specimens were collected and assayed for bacterial enteropathogens by conventional and molecular methods. Etiological agents were isolated from 564 (50.3%) specimens, and included 305 (54%) E coli, 157 (27.8%) Shigella species, and 102 (18%) from other genera of bacteria. The predominant E coli was Shiga toxin-producing E coli (105 isolates [34.5%]) and the predominant Shigella serotype was Shigella sonnei (88 isolates [56.1%]). A high rate of antibiotic resistance was observed among E coli, with 40 of 53 (75.5%) Shiga toxin-producing E coli isolates resistant to amoxicillin and tetra-cycline, and eight (5.2%) E coli isolates resistant to more than six antibiotics. Most Shigella isolates were resistant to tetracycline (95%) and trimethoprim-sulfamethoxazole (91.7%), with greatest antibiotic resistance observed among S sonnei (53 of 88 [60.2%] isolates). Antibiotic resistance is widespread in diarrheagenic E coli and Shigella in children with acute diarrhea in Tehran, Iran; hence, updated strategies for appropriate use of antimicrobial agents in Iran are needed.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus that was recently discovered in 2019. While the world is working hard to overcome and control the coronavirus disease 2019 (COVID-19) pandemic, it is also crucial to be prepared for the great impacts of this outbreak on the development of antimicrobial resistance (AMR). It is predicted that inappropriate and too much use of antibiotics, biocides, and disinfectants during this pandemic may raise disastrous effects on antibiotic stewardship programs and AMR control all around the world. Furthermore, the use of certain antibiotics alone or in combination with antiviral agents or other medications for the treatment of secondary bacterial infections among COVID-19 patients may be regarded as a major factor that negatively affects host immune response by disrupting mitochondrial function and activity. Herein, we suggest that the current management strategies to control AMR and prioritize antibiotic stewardship schemes should be extremely highlighted in relation to the COVID-19 outbreak. The rising concerns about excessive use of antimicrobials and biocides and taking too much hygiene also need to be addressed during this pandemic due to their impacts on AMR, public health, and the environment.

Although the main cause of appendicitis is unclear, infection with Enterobius vermicularis is suggested as a neglected risk factor. Since, there is no comprehensive analysis to estimate the prevalence of E. vermicularis in appendicitis; therefore, we conducted a global-scale systematic review and meta-analysis study to estimate the prevalence of E. vermicularis infection in appendicitis cases. PubMed, Scopus, Web of Science and Google Scholar databases were systematically searched for relevant studies published until 15 August 2019. Pooled prevalence of E. vermicularis infection was estimated using the random effects model. Data were classified based on the continents and countries. Moreover, subgroup analyses regarding the gender, the human development index (HDI), and income level of countries were also performed. Fifty-nine studies involving 103195 appendix tissue samples belonging to the individuals of appendicitis were included. The pooled prevalence of E. vermicularis infection was (4%, 95%CI, 2-6%), with the highest prevalence (8%, 95% CI: 0-36%) and lowest prevalence (2%, 95% CI: 1-4%) in Africa and Americas continents, respectively. With respect to countries, the lowest and highest prevalence rates were reported from Venezuela (<1%, 95% CI: 0-1%) and Nigeria (33%, 95% CI: 17-52%), respectively. Indeed, a higher prevalence was observed in females, as well as in countries with lower levels of income and HDI. Our findings indicate the relatively high burden of E. vermicularis infection in appendicitis cases. However, our findings suggest the great need for more epidemiological studies to depth understand overlaps between E. vermicularis infection and appendicitis in countries with lower HDI and income levels.

The incidence of gluten-related disorders (GRDs) continues to increase and its global prevalence is estimated at approximately 5% of the population. Celiac disease (CD), dermatitis herpetiformis (DH), gluten ataxia (GA), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS) are the five major GRDs that present with a wide range of clinical manifestations. The diagnosis of GRDs can be challenging because the typical and atypical clinical manifestations of the GRDs overlap. In this review, the current definitions of gluten-related disorders, focusing on their clinical features, diagnostic and therapeutic approaches are presented. We concluded that GRDs are usually diagnosed using a combination of clinical features, serological tests, and histopathological findings. Treatment usually involves dietary modification.

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