Silencing the major apple allergen Mal d 1 by using the RNA interference approach

BACKGROUND: Apple allergy is dominated by IgE antibodies against Mal d 1 in areas where birch pollen is endemic. Apples with significantly decreased levels of Mal d 1 would allow most patients in these areas to eat apples without allergic reactions. OBJECTIVE: The aim of this study was to inhibit the expression of Mal d 1 in apple plants by RNA interference. METHODS: In vitro -grown apple plantlets were transformed with a construct coding for an intron-spliced hairpin RNA containing a Mal d 1-specific inverted repeat sequence separated by a Mal d 1-specific intron sequence. The presence of the construct in transformants was checked by PCR. Expression of Mal d 1 in leaves was monitored by prick-to-prick skin testing in 3 patients allergic to apples and by immunoblotting with a Mal d 1-reactive mAb and with IgE antibodies against Mal d 1. RESULTS: After transformation, plantlets were selected on the basis of having a normal phenotype and growth rate. With PCR, in 6 of 9 selected plantlets, the presence of the gene-silencing construct was demonstrated. By skin prick test it was shown that a wild-type plantlet had significantly ( P < .05) higher allergenicity than 5 of the transformants. Reduction of expression of Mal d 1 was confirmed by immunoblotting. In wild-type and unsuccessful transformants, a strong band was detected with Mal d 1-reactive mAb 5H8 at the expected apparent M r of 17 kDa. This band was virtually absent in the transformants that carried the gene-silencing construct. With human IgE antibodies, the same observations were made. CONCLUSIONS: Mal d 1 expression was successfully reduced by RNA interference. This translated into significantly reduced in vivo allergenicity. These observations support the feasibility of the production by gene silencing of apples hypoallergenic for Mal d 1.     

COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.     

Pulmonary embolism in respiratory failure

The occurrence of pulmonary emboli in 617 patients admitted to a respiratory intensive care unit was studied. Pulmonary emboli were found in 18 (27 percent) of 66 autopsies. Half of these pulmonary emboli were not diagnosed before death, despite persistent aggressive attempts to document pulmonary emboli. In this subpopulation of patients with respiratory failure, the usual clinical manifestations of pulmonary emboli (symptoms, signs, chest x-ray film, electrocardiogram, and changes in arterial blood gas levels) frequently are already present, due to the severe underlying pulmonary disease, and any superimposed manifestations of pulmonary emboli are often inapparent. In this group under study, the ventilation/perfusion lung scan correlated poorly with pulmonary angiographic results and with examinations at autopsy; the scan generally was inadequate to rule in or rule out pulmonary emboli. Again, this was due to the distortion of both ventilation and perfusion by the severe underlying pulmonary disease. Currently, pulmonary angiographic studies remain the only reliable technique to confirm or exclude pulmonary emboli in patients with respiratory failure.     

Differences in resting energy expenditure between black and white smokers: implications for postcessation weight gain

OBJECTIVE: To examine differences in resting energy expenditure (REE) between black and white smokers in order to determine whether REE might contribute to postcessation weight gain. DESIGN: Cross-sectional and prospective investigation of ethnic differences in REE. Differences in REE between black and white smokers were examined at baseline while all participants were smoking, and again during 2 weeks of abstinence from smoking. SETTING: Memphis, Tennessee, USA. SUBJECTS: Sixty-six black and 112 white smokers (age 30.4 y; cigarettes per day 21.4; weight 71.7 kg; body mass index 24.5 kg/m2). RESULTS: Black smokers had a significantly lower baseline REE after adjusting for gender and body weight. Changes in REE following smoking cessation did not differ by ethnicity. CONCLUSIONS: These results suggest that black smokers may be more energy efficient, which could contribute to ethnic differences in postcessation weight gain.     

Comparison of weight status among two cohorts of US Air Force recruits

BACKGROUND: Overweight and obesity are increasing rapidly in the US and the Department of Defense (DoD). We examined whether weight trends evidenced in the general population and DoD are occurring among individuals entering US Air Force (USAF) Basic Military Training (BMT). METHODS: Individuals entering the USAF in 1996 (AF1996; N = 29,036) and 2000 (AF2000; N = 31,080), ages 17-29 years were surveyed. The two recruit cohorts were compared to age-matched individuals from the 1996 (N = 22,153) and 2000 (N = 31,861) Behavioral Risk Factor Surveillance System Survey (BRFSS). RESULTS: Crude rates for all age groups and age- and gender-standardized prevalence rates reflected significant increases in overweight/obesity among recruits. The direct standardized prevalence of overweight/obesity increased nearly 24%, from 14.8% in AF1996 to 18.3% in AF2000. The increase in overweight/obesity was particularly large among male recruits ages 25-29 (i.e., from 36.4% to 44.5%) between 1996 and 2000. CONCLUSIONS: USAF cohorts were less likely to be overweight than corresponding BRFSS samples. There were 19.1 and 20.2 percentage point differences between overall crude rates of overweight/obesity between AF1996 and BRFSS 1996 and AF2000 and BRFSS 2000, respectively. Nevertheless, overall rates of overweight and obesity are increasing among young recruits in the USAF at a fairly marked rate (approximately one percentage point per year).     

Transpedicular reconstruction of vertebral body height with simultaneous interbody spondylodesis

BACKGROUND AND PURPOSE: Surgical treatment of traumatic spinal injury should include fast and complete decompression of spinal cord and radices wits reduction of broken vertebral body, restoration of physiological spinal curvatures and spondylodesis of injured segments. Restoration of natural spinal curvatures is only possible when the height of broken vertebral body is reconstructed. MATERIAL AND METHODS: Between 1992 and 2001, 75 patients were operated on because of traumatic injuries of thoracolumbar spine in the Ortopaedic and Traumatology Department Skubiszewski Medical University of Lublin. 48 patients had broken vertebral body reduction with simultaneous filling of bone loss with autogenic bone grafts inserted through pediculum. Only in 4 cases posterior spondylodesis was carried out on arches and spinous processes. Transpedicular plasty of 44 broken vertebral bodies was connected with posterior interbody fusion with PLIF technique using graft application to interbody space. RESULTS: The operative protocol presented above allowed for the height of the anterior vertebral wall to be restored on average to 81.5% of the original height. We did not observe either fatigue breakage of the screws or screws loosening with kyphosis recurrence. We did not note serious postoperative complications, including neurological compromise. The operative procedure did not significantly change the neurological status of the patients. In 9 cases we noted neurological improvement: usually by 1 or 2 grades in Frankel's score. CONCLUSIONS: Restoration of the fractured vertebral body with bone grafts combined with posterior interbody spondylodesis effectively prevents the recurrence of the kyphotic deformation.     

Relationships among smoking status,ethnicity, socioeconomic indicators,and lifestyle variables in a biracial sample of women

BACKGROUND: Smoking prevalence rates remain high among women and smoking initiation has increased for young adults. Little is known about the unique patterns of smoking, risk factors, and correlates of quitting in Black versus White women of child-bearing age. METHOD: This study examined the relationships among smoking, ethnicity, socioeconomic status (SES), and lifestyle variables among 715 women (43.6% Blacks and 56.4% Whites). Stringent inclusion criteria were used for ethnicity, which allows for distinct comparisons but may reduce generalizability of results. RESULTS: Black current smokers smoked fewer cigarettes per day and reported initiating smoking at a later age than Whites. Current versus never smoking was associated with income, education, and caffeine intake. There was a significant ethnicity by alcohol interaction (at lower levels of alcohol intake Whites were more likely to smoke but at higher levels of alcohol there were no ethnic differences). Former smoking versus current smoking was associated with alcohol intake, education, and pack years of smoking. CONCLUSIONS: The results of the study suggest several ethnic differences in smoking patterns as well as several correlates of smoking status. These results have implications for the tailoring of interventions and illustrate the association of other health risk factors with smoking status.     

Venous thromboembolism: past, present and future

Over the last four decades there have been remarkable advances in the diagnosis and treatment of venous thromboembolism (VTE)-pulmonary embolism (PE) and deep venous thrombosis (DVT). We have moved from no objective documentation to a plethora of ever improving imaging studies. Evolving treatment modalities have reduced the mortality due to PE to approximately 2%. Shorter hospitalizations followed by outpatient therapy are a growing reality. The use of primary prophylaxis is increasing, but more widespread use must be encouraged. Despite the many accomplishments, too many patients with VTE with its high mortality without treatment remain undiagnosed. There is a critical need to improve the role of the patient's history in identifying patients who warrant objective testing. The ideal would be the development of a biological marker of VTE, similar to the creatinine kinase-MB, creatinine kinase-MM, or troponin I in acute myocardial infarction.