Antiphospholipid syndrome (APS) is an autoimmune disease characterised by vascular thrombosis and/or pregnancy morbidity in the presence of persistently positive serum tests for antiphospholipid ...antibodies. Management of APS centres on preventing these clinical events and in preventing chronic damage caused by these events. In patients with thrombotic APS, long-term anticoagulation is recommended in the majority of cases. Although there were hopes that direct-acting oral anticoagulants could replace warfarin for prevention of thrombosis in patients with APS, this now seems less likely due to recent trial results. There is no evidence for use of anticoagulation in people who are aPL-positive but have never had a thrombosis but low-dose aspirin may be beneficial in those who have a higher-risk aPL profile. Management of obstetric APS is with daily subcutaneous heparin and low-dose aspirin. This gives a live birth rate of 70% or more. Catastrophic APS is rare, occurring in 1% of patients with APS. It is characterised by thrombosis in multiple organs simultaneously, with a high mortality rate. The management is with corticosteroids, anticoagulation, and immunoglobulins or plasma exchange.
Alzheimers disease (AD) is a neurodegenerative disorder of the central nervous system manifested by cognitive and memory deterioration, a variety of neuropsychiatric symptoms, behavioral ...disturbances, and progressive impairment of daily life activities. Current pharmacotherapies are restricted to symptomatic interventions but do not prevent progressive neuronal degeneration. Therefore, new therapeutic strategies are needed to intervene with these progressive pathological processes. In the past several years adenosine, a ubiquitously released purine ribonucleoside, has become important for its neuromodulating capability and its emerging positive experimental effects in neurodegenerative diseases. Recent research suggests that adenosine receptors play important roles in the modulation of cognitive function. The present paper attempts to review published reports and data from different studies showing the evidence of a relationship between adenosinergic function and AD-related cognitive deficits. Epidemiological studies have found an association between coffee (a nonselective adenosine receptor antagonist) consumption and improved cognitive function in AD patients and in the elderly. Long-term administration of caffeine in transgenic animal models showed a reduced amyloid burden in brain with better cognitive performance. Antagonists of adenosine A2A receptors mimic these beneficial effects of caffeine on cognitive function. Neuronal cell cultures with amyloid beta in the presence of an A2A receptor antagonist completely prevented amyloid beta-induced neurotoxicity. These findings suggest that the adenosinergic system constitutes a new therapeutic target for AD, and caffeine and A2A receptor antagonists may have promise to manage cognitive dysfunction in AD.
Atherosclerosis in systemic lupus erythematosus Croca, Sara; Rahman, Anisur
Best practice & research. Clinical rheumatology,
June 2017, 2017-Jun, 2017-06-00, 20170601, Letnik:
31, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Cardiovascular disease (CVD), comprising coronary heart disease and stroke, is one of the most important causes of death in patients with systemic lupus erythematosus (SLE). The risks of developing ...both clinical CVD and sub-clinical atherosclerosis are increased in patients with SLE. This increase is not fully explained by traditional cardiovascular risk factors such as smoking, hypertension and elevated cholesterol, and it is believed that immune dysfunction also contributes to CVD risk in SLE. In particular, recent studies have shown that abnormalities in both serum lipid profile and the autoantibody and T lymphocyte response to lipids may play a role in development of atherosclerosis.
The standard CVD risk calculation algorithms based on traditional risk factors underestimate the risk of developing CVD in patients with SLE. Thus, novel algorithms incorporating new biomarkers such as pro-inflammatory high-density lipoprotein and use of imaging techniques such as carotid ultrasound scanning may become increasingly valuable.
The accumulation of cadmium (Cd) alters different physiological and biochemical attributes that affect plant growth and yield. In our study, we investigated the regulatory role of supplemental ...manganese (Mn) on hydroponically grown rice (Oryza sativa L. cv. BRRI dhan29) seedlings under Cd-stress conditions. Exposure of 14-d-old seedlings to 0.3mM CdCl2 for three days caused growth inhibition, chlorosis, nutrient imbalance, and higher Cd accumulation. Higher Cd uptake caused oxidative stress through lipid peroxidation, loss of plasma membrane integrity, and overproduction of reactive oxygen species (ROS) and methylglyoxal (MG). The exogenous application of 0.3mM MnSO4 to Cd-treated seedlings partly recovered Cd-induced water loss, chlorosis, growth inhibition, and nutrient imbalance by reducing Cd uptake and its further translocation to the upper part of the plant. Supplemental Mn also reduced Cd-induced oxidative damage and lipid peroxidation by improved antioxidant defense and glyoxalase systems through enhancing ROS and MG detoxification, respectively.
Background
Children's development is multifactorial. Although there have been several studies exploring the association of children's development with maternal, child, and environmental factors, we ...are unaware of any study that assessed those factors in children whose mothers were enrolled in a social safety net programme in low‐ and middle‐income countries. This study aimed to identify the factors associated with disadvantaged children's cognitive, language, and motor development at age 6–16 months in deprived settings of urban Bangladesh and to identify relative importance of these factors of children's development. We also explored if there were any gender differences in child development.
Methods
This cross‐sectional study was conducted in a deprived setting of urban Bangladesh. Bayley III was used for assessing children's cognitive, language, and motor development. Multivariable linear regression model was used to find the factors associated with children's development, and dominance analysis was used to explore the relative importance of the factors.
Results
Out of the total 599 mother–child dyads, 303 (50.58%) were girls. The factors associated with children's development were length‐for‐age Z‐score (cognitive: B = 1.21 95% CI = 0.31, 2.11, P = 0.008; language: 1.67 0.79, 2.55 P < 0.001; motor: 2.15 1.01, 3.29 P < 0.001) and home environment (cognitive: 0.58 0.27, 0.89 P < 0.001; language: 0.59 0.27, 0.92, P < 0.001; motor: 0.44 0.09, 0.79 P = 0.013). Girls had higher cognitive (1.90 0.17, 3.6, P = 0.031) and language (2.53 0.55, 4.51, P = 0.013) development compared with boys. Families with a higher number of under five children within the households had lower language (−1.57 −2.78, −0.36, P = 0.011) development. Violence against the mother and the families' food security status were not associated with the children's development. Children's length‐for‐age Z‐score (27%) and home stimulation environment (23%) were the most important factors of cognitive development.
Conclusion
Children's nutritional status and home environment are important factors for disadvantaged children's development in deprived urban settings of Bangladesh. Both early child development‐focussed parenting and nutrition interventions should be considered when designing child development programmes in urban settings in low‐ and middle‐income countries.
Gastric cancer is considered a class 1 carcinogen that is closely linked to infection with Helicobacter pylori (H. pylori), which affects over 1 million people each year. However, the major challenge ...to fight against H. pylori and its associated gastric cancer due to drug resistance. This research gap had led our research team to investigate a potential drug candidate targeting the Helicobacter pylori‐carcinogenic TNF‐alpha‐inducing protein. In this study, a total of 45 daidzein derivatives were investigated and the best 10 molecules were comprehensively investigated using in silico approaches for drug development, namely pass prediction, quantum calculations, molecular docking, molecular dynamics simulations, Lipinski rule evaluation, and prediction of pharmacokinetics. The molecular docking study was performed to evaluate the binding affinity between the target protein and the ligands. In addition, the stability of ligand–protein complexes was investigated by molecular dynamics simulations. Various parameters were analysed, including root‐mean‐square deviation (RMSD), root‐mean‐square fluctuation (RMSF), radius of gyration (Rg), hydrogen bond analysis, principal component analysis (PCA) and dynamic cross‐correlation matrix (DCCM). The results has confirmed that the ligand–protein complex CID: 129661094 (07) and 129664277 (08) formed stable interactions with the target protein. It was also found that CID: 129661094 (07) has greater hydrogen bond occupancy and stability, while the ligand–protein complex CID 129664277 (08) has greater conformational flexibility. Principal component analysis revealed that the ligand–protein complex CID: 129661094 (07) is more compact and stable. Hydrogen bond analysis revealed favourable interactions with the reported amino acid residues. Overall, this study suggests that daidzein derivatives in particular show promise as potential inhibitors of H. pylori.
Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and is characterized by the presence of autoantibodies directed against nuclear antigens. It is ...a multi-system disease, and patients can present in vastly different ways. Prevalence varies with ethnicity, but is estimated to be about 1 per 1000 overall with a female to male ratio of 10:1. The clinical heterogeneity of this disease mirrors its complex aetiopathogenesis, which highlights the importance of genetic factors and individual susceptibility to environmental factors. SLE can affect every organ in the body. The most common manifestations include rash, arthritis and fatigue. At the more severe end of the spectrum, SLE can cause nephritis, neurological problems, anaemia and thrombocytopaenia. Over 90% of patients with SLE have positive anti-nuclear antibodies (ANA). Significant titres are accepted to be of 1:80 or greater. SLE is a relapsing and remitting disease, and treatment aims are threefold: managing acute periods of potentially life-threatening ill health, minimizing the risk of flares during periods of relative stability, and controlling the less life-threatening, but often incapacitating day to day symptoms. Hydroxychloroquine and non-steroidal anti-inflammatory drugs are used for milder disease; corticosteroids and immunosuppressive therapies are generally reserved for major organ involvement; anti-CD20 monoclonal antibody is now used in patients with severe disease who has not responded to conventional treatments. Despite enormous improvements in prognosis since the introduction of corticosteroids and immunosuppressive drugs, SLE continues to have a significant impact on the mortality and morbidity of those affected.
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with a prevalence of approximately 1 in 1000. Over the last 30 years, advances in treatment such as use of corticosteroids and ...immunosuppressants have improved life expectancy and quality of life for patients with lupus and the key unmet needs have therefore changed. With the reduced mortality from disease activity, development of cardiovascular disease (CVD) has become an increasingly important cause of death in patients with SLE. The increased CVD risk in these patients is partly, but not fully explained by standard risk factors, and abnormalities in the immune response to lipids may play a role. Invariant natural killer T cells, which are triggered specifically by lipid antigens, may protect against progression of subclinical atherosclerosis. However, currently our recommendation is that clinicians should focus on optimal management of standard CVD risk factors such as smoking, blood pressure and lipid levels. Fatigue is one of the most common and most limiting symptoms suffered by patients with SLE. The cause of fatigue is multifactorial and disease activity does not explain this symptom. Consequently, therapies directed towards reducing inflammation and disease activity do not reliably reduce fatigue and new approaches are needed. Currently, we recommend asking about sleep pattern, optimising pain relief and excluding other causes of fatigue such as anaemia and metabolic disturbances. For the subgroup of patients whose disease activity is not fully controlled by standard treatment regimes, a range of different biologic agents have been proposed and subjected to clinical trials. Many of these trials have given disappointing results, though belimumab, which targets B lymphocytes, did meet its primary endpoint. New biologics targeting B cells, T cells or cytokines (especially interferon) are still going through trials raising the hope that novel therapies for patients with refractory SLE may be available soon.
Feline panleukopenia (FPL) is a highly contagious cat disease and is endemic in Bangladesh. The study aims to describe the epidemiology and molecular characterization of the Feline panleukopenia ...virus from the suspected domestic cats in selected Bangladesh regions. Randomly, 161 rectal swabs were collected from the pet hospitals between July 2021 and December 2022. A structured questionnaire was administered through face-to-face interviews with cat owners in order to collect data on potential risk factors for FPL, such as age, sex, sharing litter boxes and every day utensils in multicat households, vaccination history, hospital visits for other diseases, and season. The rectal swabs were tested by PCR targeting the VP2 capsid protein gene, and six PCR-positive samples were further sequenced for molecular characterizations. The risk factors for FPLV were identified using multivariable logistic regression analysis. The overall prevalence of FPL among suspects was 22.9%. The mortality and case fatality were 10.6%, and 45.9%, respectively. However, mortality in kittens was significantly higher (16.4%) than younger cats. The odds of FPL were 8.83 times (95% CI: 3.14-24.85) higher among unvaccinated cats than vaccinated cats. The winter season had almost six times (95% CI: 1.38-24.40) higher odds of FPL than rainy season. In a multicat house, the odds of FPL was about five times (95% CI: 1.93-13.45) higher for cats that shared a litter box and food utensils compared to those that did not engage in such sharing. Visiting hospitals for other reasons nearly triples the odds of FPL (OR: 2.80, 95% CI: 1.04-7.54) compared to cats that do not visit hospitals. Analysis of partial sequence of the VP2 gene revealed genetic variations among the isolates from different regions. Among these isolates, four were identical to FPLV isolates from South Korea and China, while one showed complete homology with FPLV isolates from Thailand. In contrast, the remaining one was 100% identical to Carnivore protoparvovirus-1 isolated from a feline sample in Italy. Our isolates were classified into three distinct clades alongside Feline panleukopenia virus and Carnivore protoparvovirus-1. One in every three suspected cats was infected with Feline panleukopenia. Regular vaccination of the cats, especially those that share common litter box and food utensils and visit hospitals for other purposes, will help reduce the prevalence of FPL in Bangladesh. Besides, it is worth emphasizing the existence of genetic diversity among the circulating Feline panleukopenia viruses in Bangladesh.
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