Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Image-guided stereotactic management of non-AIDS-related cerebral infection.

Every neurosurgeon can appreciate Dandy's recognition that the drainage of brain abscesses causes trauma to the delicate parenchyma. Over the years, brain surgery has evolved toward management of problems by using less and less invasive techniques and thus gaining ever lower morbidity. Clearly, the advent of better imaging techniques has improved the outcome in patients afflicted with intracerebral infections. The combination of stereotaxy with these imaging techniques is contributing a "zero mortality" in the treatment of these infections. In our series of 29 consecutive patients with non-AIDS-related infections, no patient died as a direct result of a stereotactic surgical procedure. Two patients (7%) had new neurologic deficits after surgery. The only patient left with a permanent disability had a kidney allograft and subacute bacterial endocarditis. His condition deteriorated 6 hours after aspiration of a sterile abscess, when an intra-abscess hematoma was diagnosed and evacuated. In retrospect, this complication may have been avoided by less vigorous aspiration. Three of the four patients with nonviral infections who died were iatrogenically immunosuppressed for their organ transplants. These patients are difficult to treat, and given the current popularity of transplantation procedures, neurosurgeons will face more and more opportunistic infections. In general, the patients with abscesses did well. On the other hand, nonoperative mortality was extremely high for patients with viral encephalitides. This high mortality may have resulted from a delay in diagnosis and treatment or from the unavailability of highly effective antiviral agents at the time the biopsies were performed. The importance of early diagnosis and treatment of infection cannot be overemphasized. T.H. Flewett's warning about the management of HSE applies to the management of all cerebral infections: "It seems clear from everybody's published results [in the papers already given] if we wait to do biopsy until the clinical indications are unmistakable, we have waited so long that the patient, if he survives, will be left a severe neurological cripple." Because it is relatively noninvasive, stereotactic neurosurgery has been used increasingly to diagnose brain masses in patients with AIDS. We recommend its use for establishing diagnoses in all suspected cases of cerebral infection. We agree with Rosenblum et al: Empiric treatment of brain infections should be regarded as "radical." Such treatment should be reserved for patients who have an identifiable source of infection and causative organism or for patients who are clinically too unstable to undergo surgery.(ABSTRACT TRUNCATED AT 400 WORDS)     

Additive effects of simulated climate changes,elevated CO2, and nitrogen deposition on grassland diversity

Biodiversity responses to ongoing climate and atmospheric changes will affect both ecosystem processes and the delivery of ecosystem goods and services. Combined effects of co-occurring global changes on diversity, however, are poorly understood. We examined plant diversity responses in a California annual grassland to manipulations of four global environmental changes, singly and in combination: elevated CO2, warming, precipitation, and nitrogen deposition. After 3 years, elevated CO2 and nitrogen deposition each reduced plant diversity, whereas elevated precipitation increased it and warming had no significant effect. Diversity responses to both single and combined global change treatments were driven overwhelmingly by gains and losses of forb species, which make up most of the native plant diversity in California grasslands. Diversity responses across treatments also showed no consistent relationship to net primary production responses, illustrating that the diversity effects of these environmental changes could not be explained simply by changes in productivity. In two- to four-way combinations, simulated global changes did not interact in any of their effects on diversity. Our results show that climate and atmospheric changes can rapidly alter biological diversity, with combined effects that, at least in some settings, are simple, additive combinations of single-factor effects.     

COVID-19 risk index (CRI): a simple and validated emergency department risk score that predicts mortality and the need for mechanical ventilation

Journal of Thrombosis and Thrombolysis - Although certain risk factors have been associated with morbidity and mortality, validated emergency department (ED) derived risk prediction models specific...     

Meningoencephalitis and brain abscess due to a free-living amoeba

A 47-year-old diabetic woman developed fatal meningoencephalitis due to a free-living amoeba. The responsible organism appeared to be neither Naegleria nor Acanthamoeba-Hartmannella. Both acute and chronic (granulomatous) inflammatory reactions of the brain were present, and both cysts and trophozoite forms were readily visualized. The latest classification and methods of identification of such amoebae are reviewed and their threat to public health underscored. It should be realized that a variety of free-living amoebae exist in nature, which potentially can produce meningoencephalitis in humans, and that none of these organisms should be labeled or considered as "avirulent" or "nonpathogenic" until proved otherwise.     

CXCR4 blockade and Sphingosine‐1‐phosphate activation facilitate engraftment of haematopoietic stem and progenitor cells in a non‐myeloablative transplant model

Both immunosuppressive and cytoreductive effects of γ‐irradiation contribute to engraftment of allogeneic haematopoietic stem and progenitor cells. We hypothesized that a release of host stem and progenitor cells from the niche prior to conditioning would permit engraftment after less intensive conditioning. Administration of AMD3100 and SEW2871 on days ?4 to ?2 followed by irradiation on day ?1 in a non‐myeloablative zebrafish transplant model resulted in a reduced radiation minimum dose of 10 Gy from 15 Gy being sufficient for engraftment. Targeting the SDF‐1 (CXCL12)/CXCR4‐ and S1P/S1P₁‐axis increased the efficacy of allografting in an experimental transplant model.