Cardiac phenotype in mouse models of systemic autoimmunity.

Patients suffering from systemic autoimmune diseases are at significant risk of cardiovascular complications. This can be due to systemically increased levels of inflammation leading to accelerated atherosclerosis, or due to direct damage to the tissues and cells of the heart. Cardiac complications include an increased risk of myocardial infarction, myocarditis and dilated cardiomyopathy, valve disease, endothelial dysfunction, excessive fibrosis, and bona fide autoimmune-mediated tissue damage by autoantibodies or auto-reactive cells. There is, however, still a considerable need to better understand how to diagnose and treat cardiac complications in autoimmune patients. A range of inducible and spontaneous mouse models of systemic autoimmune diseases is available for mechanistic and therapeutic studies. For this Review, we systematically collated information on the cardiac phenotype in the most common inducible, spontaneous and engineered mouse models of systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. We also highlight selected lesser-known models of interest to provide researchers with a decision framework to choose the most suitable model for their study of heart involvement in systemic autoimmunity

Study on the Parasitic and Microbial Contamination of Vegetables, and the Effect of Washing Procedures on their Elimination in Ilam city

The risk of disease spread through water, fruits and vegetables contaminated through unclean waters varies from region to another. Springs and underground water resources are essentially free of germs or they have tolerable levels of germs; unless they are infected by surface water or human excreta. Scientific reports have shown that outbreaks of food-borne illnesses especially foods such as fresh fruit and vegetables are rising. The aim of the study is to evaluate the effect of washing procedures in eliminating of microbial and parasitic contamination of vegetables consumed in Ilam city. Multiple samples of vegetables were collected from five regions of the city (North- South- West- East- Center) about 1 kg from each shop and transferred to the laboratory. Then we put apiece in a dish containing five liters water; vegetable was washed into it and a sample was collected. Then we added to dish, 20 drops of dish soap and mixed it for a few minutes so that all of vegetable dipped in the foam. After a few minutes, the vegetable were washed with pure water. Another sample was collected from sewage of this water. For detection of microbes, we used two methods: formalin eater and direct microscopic observation. 86 samples were collected from five regions of city. 40.6% of them had parasitic contamination in scantling water of washing with pure water, and 43% had parasitic contamination in scantling water of washing with dish soap. 70.9% of them had parasitic and bacterial contamination in both wastewaters. There was no significant difference between washing with water and washing with dish soap for parasitic or bacterial contamination. Methods of washing in some types of vegetable may reduce effectively parasitic infection; but we found that washing with dish soap didn’t have any significant effect on reduction of microbial contamination. 

Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition

Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help prevent HF development and progression. Therapeutic attempts to prevent excessive post-MI inflammation in patients have included pharmacological interventions ranging from broad immunosuppression to immunomodulatory approaches targeting specific cell types or factors with the aim to maintain beneficial aspects of the early post-MI immune response. These include the blockade of early initiators of inflammation including reactive oxygen species and complement, inhibition of mast cell degranulation and leucocyte infiltration, blockade of inflammatory cytokines, and inhibition of adaptive B and T-lymphocytes. Herein, we provide a systematic review on post-MI immunomodulation trials and a meta-analysis of studies targeting the inflammatory cytokine Interleukin-1. Despite an enormous effort into a significant number of clinical trials on a variety of targets, a striking heterogeneity in study population, timing and type of treatment, and highly variable endpoints limits the possibility for meaningful meta-analyses. To conclude, we highlight critical considerations for future studies including (i) the therapeutic window of opportunity, (ii) immunological effects of routine post-MI medication, (iii) stratification of the highly diverse post-MI patient population, (iv) the potential benefits of combining immunomodulatory with regenerative therapies, and at last (v) the potential side effects of immunotherapies

Human Tick-Borne Diseases in Australia

There are 17 human-biting ticks known in Australia. The bites of Ixodes holocyclus, Ornithodoros capensis, and Ornithodoros gurneyi can cause paralysis, inflammation, and severe local and systemic reactions in humans, respectively. Six ticks, including Amblyomma triguttatum, Bothriocroton hydrosauri, Haemaphysalis novaeguineae, Ixodes cornuatus, Ixodes holocyclus, and Ixodes tasmani may transmit Coxiella burnetii, Rickettsia australis, Rickettsia honei, or Rickettsia honei subsp. marmionii. These bacterial pathogens cause Q fever, Queensland tick typhus (QTT), Flinders Island spotted fever (FISF), and Australian spotted fever (ASF). It is also believed that babesiosis can be transmitted by ticks to humans in Australia. In addition, Argas robertsi, Haemaphysalis bancrofti, Haemaphysalis longicornis, Ixodes hirsti, Rhipicephalus australis, and Rhipicephalus sanguineus ticks may play active roles in transmission of other pathogens that already exist or could potentially be introduced into Australia. These pathogens include Anaplasma spp., Bartonella spp., Burkholderia spp., Francisella spp., Dera Ghazi Khan virus (DGKV), tick-borne encephalitis virus (TBEV), Lake Clarendon virus (LCV), Saumarez Reef virus (SREV), Upolu virus (UPOV), or Vinegar Hill virus (VINHV). It is important to regularly update clinicians' knowledge about tick-borne infections because these bacteria and arboviruses are pathogens of humans that may cause fatal illness. An increase in the incidence of tick-borne infections of human may be observed in the future due to changes in demography, climate change, and increase in travel and shipments and even migratory patterns of birds or other animals. Moreover, the geographical conditions of Australia are favorable for many exotic ticks, which may become endemic to Australia given an opportunity. There are some human pathogens, such as Rickettsia conorii and Rickettsia rickettsii that are not currently present in Australia, but can be transmitted by some human-biting ticks found in Australia, such as Rhipicephalus sanguineus, if they enter and establish in this country. Despite these threats, our knowledge of Australian ticks and tick-borne diseases is in its infancy

Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.

Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help prevent HF development and progression. Therapeutic attempts to prevent excessive post-MI inflammation in patients have included pharmacological interventions ranging from broad immunosuppression to immunomodulatory approaches targeting specific cell types or factors with the aim to maintain beneficial aspects of the early post-MI immune response. These include the blockade of early initiators of inflammation including reactive oxygen species and complement, inhibition of mast cell degranulation and leucocyte infiltration, blockade of inflammatory cytokines, and inhibition of adaptive B and T-lymphocytes. Herein, we provide a systematic review on post-MI immunomodulation trials and a meta-analysis of studies targeting the inflammatory cytokine Interleukin-1. Despite an enormous effort into a significant number of clinical trials on a variety of targets, a striking heterogeneity in study population, timing and type of treatment, and highly variable endpoints limits the possibility for meaningful meta-analyses. To conclude, we highlight critical considerations for future studies including (i) the therapeutic window of opportunity, (ii) immunological effects of routine post-MI medication, (iii) stratification of the highly diverse post-MI patient population, (iv) the potential benefits of combining immunomodulatory with regenerative therapies, and at last (v) the potential side effects of immunotherapies

Molecular Characterization of Paederus Spp (Coleoptera: Staphylinidae, Paederinae) the Agent of Human Linear Dermatitis in the Caspian Sea Coast, North of Iran

Background: A combined morphological and molecular survey was performed to determine the agent of human linear dermatitis Paederus Fabricius, 1775 (Coleoptera: Staphylinidae, Paederinae) species composition in Mazandaran Prov­ince in the Caspian Sea coast in northern Iran, where most of linear dermatitis cases of the country occurred. Methods: Altogether, 397 Paederus specimens were collected from May to August 2021 and classified using morphological characters and ITS2-rDNA sequence analysis. Results: Morphological investigation revealed that all the specimens were Paederus fuscipes. ITS2 polymerase chain reaction (PCR) direct-sequences and the profiles of restriction fragment length polymorphism (RFLP) derived from digestion of PCR products by HinfI, HpaII, and SalI enzymes were identical confirming the morphological results, implying that all specimens belonged to a single taxon. Conclusion: Paederus fuscipes (Fabricius, 1775) is considered the dominant taxon and responsible for linear dermatitis in Ma­zandaran Province. To our knowledge, we have provided the first molecular typing of Paederus beetles at the species level, suggesting that ITS2-rDNA characterization is an alternative tool for species discrimination of Paederus spp

Type 2 MI induced by a single high dose of isoproterenol in C57BL/6J mice triggers a persistent adaptive immune response against the heart.

Heart failure is the common final pathway of several cardiovascular conditions and a major cause of morbidity and mortality worldwide. Aberrant activation of the adaptive immune system in response to myocardial necrosis has recently been implicated in the development of heart failure. The ß-adrenergic agonist isoproterenol hydrochloride is used for its cardiac effects in a variety of different dosing regimens with high doses causing acute cardiomyocyte necrosis. To assess whether isoproterenol-induced cardiomyocyte necrosis triggers an adaptive immune response against the heart, we treated C57BL/6J mice with a single intraperitoneal injection of isoproterenol. We confirmed tissue damage reminiscent of human type 2 myocardial infarction. This is followed by an adaptive immune response targeting the heart as demonstrated by the activation of T cells, the presence of anti-heart auto-antibodies in the serum as late as 12 weeks after initial challenge and IgG deposition in the myocardium. All of these are hallmark signs of an established autoimmune response. Adoptive transfer of splenocytes from isoproterenol-treated mice induces left ventricular dilation and impairs cardiac function in healthy recipients. In summary, a single administration of a high dose of isoproterenol is a suitable high-throughput model for future studies of the pathological mechanisms of anti-heart autoimmunity and to test potential immunomodulatory therapeutic approaches

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Immunopharmacology of Post-Myocardial Infarction and Heart Failure Medications

The immune system responds to acute tissue damage after myocardial infarction (MI) and orchestrates healing and recovery of the heart. However, excessive inflammation may lead to additional tissue damage and fibrosis and exacerbate subsequent functional impairment, leading to heart failure. The appreciation of the immune system as a crucial factor after MI has led to a surge of clinical trials investigating the potential benefits of immunomodulatory agents previously used in hyper-inflammatory conditions, such as autoimmune disease. While the major goal of routine post-MI pharmacotherapy is to support heart function by ensuring appropriate blood pressure and cardiac output to meet the demands of the body, several drug classes also affect a range of immunological pathways and modulate the post-MI immune response, which is crucial to take into account when designing future immunomodulatory trials. This review outlines how routine post-MI pharmacotherapy affects the immune response and may thus influence post-MI outcomes and development towards heart failure. Current key drug classes are discussed, including platelet inhibitors, statins, β-blockers, and renin–angiotensin–aldosterone inhibitors

Corneal collagen cross-linking for treatment of non-healing corneal ulcers

Purpose: To evaluate the efficacy of corneal collagen cross-linking (CXL) for treatment of corneal ulcers not responding to antimicrobial therapy. Methods: Eight patients with corneal ulcers associated with corneal melting, not responding to conventional antibiotic therapy, were treated with CXL. The procedure was performed according to the standardized protocol for keratoconus. Preoperative medications were continued after CXL in all cases. Microbiological exams revealed Pseudomonas aeruginosa in 3 cases. Follow up continued from 1 to 10 months. Results: In 6 of 8 eyes, progression of corneal melting was halted and complete epithelialization occurred. In one eye emergency keratoplasty was needed due to corneal perforation. A conjunctival flap was performed to treat severe localized corneal thinning in one of the patients a few days after CXL. Significant clinical improvement occurred in all cases of Pseudomonas aeruginosa keratitis. Conclusion: CXL can be considered as a promising new treatment in the management of refractory non-healing corneal ulcers, including Pseudomonas aeruginosa keratitis