Alexanderbraswell5462

Myasthenia gravis (MG) is a rare and potentially dangerous autoimmune condition, which affects the acetylcholine receptors at the neuromuscular junction of skeletal muscle. MG's diverse symptomatology may readily masquerade as other neurological conditions, posing a diagnostic challenge to clinicians. We describe a 24-year old man who presented to the emergency department with a new onset internuclear ophthalmoplegia. After a series of investigations, we eventually arrived at a diagnosis of MG with pseudointernuclear ophthalmoplegia with an incidentally detected prolactinoma. We explore the literature regarding the pathophysiology of pseudointernuclear ophthalmoplegia, the link between prolactin and autoimmunity and the association between prolactinoma and MG.Takotsubo cardiomyopathy (TTC) is a rare but life-threatening condition that is still not completely understood. Characterised by rapidly reversible ventricular dysfunction without any prior coronary artery disease, it can imitate a myocardial infarction and lead to death if not managed appropriately. This report examines a case of intraoperative cardiac arrest in a patient with no previous cardiac disease, and discusses the factors that may have precipitated this event, as well as the ways of distinguishing the cause of the arrest based on clinical course and investigations, eventually leading to a diagnosis of TTC.

Fine particulate matter (PM

) is an important environmental risk factor for cardiopulmonary diseases. However, the association between PM

and risk of CKD remains under-recognized, especially in regions with high levels of PM

, such as China.

To explore the association between long-term exposure to ambient PM

and CKD prevalence in China, we used data from the China National Survey of CKD, which included a representative sample of 47,204 adults. We estimated annual exposure to PM

before the survey date at each participant's address, using a validated, satellite-based, spatiotemporal model with a 10 km×10 km resolution. Participants with eGFR <60 ml/min per 1.73 m

or albuminuria were defined as having CKD. We used a logistic regression model to estimate the association and analyzed the influence of potential modifiers.

The 2-year mean PM

concentration was 57.4

g/m

, with a range from 31.3 to 87.5

g/m

. An increase of 10

g/m

in PM

was positively associated with CKD prevalence (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.22 to 1.35) and albuminuria (OR, 1.39; 95% CI, 1.32 to 1.47). Effect modification indicated these associations were significantly stronger in urban areas compared with rural areas, in males compared with females, in participants aged <65 years compared with participants aged ≥65 years, and in participants without comorbid diseases compared with those with comorbidities.

These findings regarding the relationship between long-term exposure to high ambient PM

levels and CKD in the general Chinese population provide important evidence for policy makers and public health practices to reduce the CKD risk posed by this pollutant.

These findings regarding the relationship between long-term exposure to high ambient PM2.5 levels and CKD in the general Chinese population provide important evidence for policy makers and public health practices to reduce the CKD risk posed by this pollutant.Mutations are the source of both genetic diversity and mutational load. However, the effects of increasing environmental temperature on plant mutation rates and relative impact on specific mutational classes (e.g., insertion/deletion [indel] vs. single nucleotide variant [SNV]) are unknown. This topic is important because of the poorly defined effects of anthropogenic global temperature rise on biological systems. Here, we show the impact of temperature increase on Arabidopsis thaliana mutation, studying whole genome profiles of mutation accumulation (MA) lineages grown for 11 successive generations at 29°C. Whereas growth of A. thaliana at standard temperature (ST; 23°C) is associated with a mutation rate of 7 × 10-9 base substitutions per site per generation, growth at stressful high temperature (HT; 29°C) is highly mutagenic, increasing the mutation rate to 12 × 10-9 SNV frequency is approximately two- to threefold higher at HT than at ST, and HT-growth causes an ∼19- to 23-fold increase in indel frequency, resulting in a disproportionate increase in indels (vs. SNVs). Most HT-induced indels are 1-2 bp in size and particularly affect homopolymeric or dinucleotide A or T stretch regions of the genome. HT-induced indels occur disproportionately in nucleosome-free regions, suggesting that much HT-induced mutational damage occurs during cell-cycle phases when genomic DNA is packaged into nucleosomes. We conclude that stressful experimental temperature increases accelerate plant mutation rates and particularly accelerate the rate of indel mutation. Increasing environmental temperatures are thus likely to have significant mutagenic consequences for plants growing in the wild and may, in particular, add detrimentally to mutational load.T cell-based therapies have induced cancer remissions, though most tumors ultimately progress, reflecting inherent or acquired resistance including antigen escape. Better understanding of how T cells eliminate tumors will help decipher resistance mechanisms. We used a CRISPR/Cas9 screen and identified a necessary role for Fas-FasL in antigen-specific T-cell killing. We also found that Fas-FasL mediated off-target "bystander" killing of antigen-negative tumor cells. This localized bystander cytotoxicity enhanced clearance of antigen-heterogeneous tumors in vivo, a finding that has not been shown previously. click here Fas-mediated on-target and bystander killing was reproduced in chimeric antigen receptor (CAR-T) and bispecific antibody T-cell models and was augmented by inhibiting regulators of Fas signaling. Tumoral FAS expression alone predicted survival of CAR-T-treated patients in a large clinical trial (NCT02348216). These data suggest strategies to prevent immune escape by targeting both the antigen expression of most tumor cells and the geography of antigen-loss variants.