Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.     

Beyond the joints,the extra-articular manifestations in rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients.The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.     

Adult nemaline myopathy with trabecular muscle fibers

The term “trabecular myopathy” has been used to designate a syndrome resembling limb‐girdle muscular dystrophy in which the predominant pathological feature is an abundance of lobulated or trabecular muscle fibers. However, the validity of this nosological entity has not been verified. Herein we describe a 63‐year‐old man with a severe, progressive myopathy who exhibited the typical pathological features of both trabecular myopathy and nemaline myopathy in association with a biclonal gammopathy. In this case, adult‐onset nemaline myopathy was probably the primary disease process. The diagnostic significance of trabecular muscle fibers remains uncertain. Muscle Nerve, 2008     

Incidence of venous thromboembolism in rheumatoid arthritis,results from a “real-life” cohort and an appraisal of available literature

Rheumatoid arthritis (RA) is associated with an increased risk of venous thromboembolism (VTE) occurrence. In this work, we assessed the incidence and predictive factors of VTE in our “real-life” cohort of RA patients. To contextualize our results, we reviewed the available literature about this topic.We performed a retrospective analysis of prospectively followed-up patients with RA attending our Rheumatologic Clinic between January 2010 and December 2020. Each patient was investigated for VTE occurrence. Incident cases were reported as incidence proportion and incidence rate per 1000 person-years at risk. Possible predictive factors were also exploited by regression analyses. Available literature about this topic was also assessed.In this evaluation, 347 consecutive patients without previous evidence of VTE, attending our Rheumatologic Clinic from 2010 to 2020, were studied. In our “real-life” cohort, the incidence proportion of VTE was 3.7% (2.7–4.7%) and considering over 1654 person-years, an incidence rate of 7.8 × 1000 (2.5–11.7). Exploratively assessing predictive factors in our cohort, older age (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01–1.14, p = .015), higher body mass index (HR 1.37, 95% CI 1.04–1.80, P = .026), and longer disease duration (HR 1.11, 95% CI 1.03–1.20, P = .006) resulted to be significant predictors of VTE occurrence during the follow-up.In our “real-life” cohort, VTE burden has been suggested in patients with RA. Comparing our results with previous data derived from randomized controlled trials and administrative data, some different findings were retrieved about incidence of VTE. Assessing predictive factors, older age, higher body mass index, and longer disease duration resulted to be significant predictors of VTE occurrence during the follow-up. Taking together these observations, a further evaluation of this issue on specific designed studies is needed to provide more generalizable results to the daily clinical practice.     

Mechanisms of yogic practices in health, aging, and disease

Mechanisms underlying the modulating effects of yogic cognitive-behavioral practices (eg, meditation, yoga asanas, pranayama breathing, caloric restriction) on human physiology can be classified into 4 transduction pathways: humoral factors, nervous system activity, cell trafficking, and bioelectromagnetism. Here we give examples of these transduction pathways and how, through them, yogic practices might optimize health, delay aging, and ameliorate chronic illness and stress from disability. We also recognize that most studies of these mechanisms remain embedded in a reductionist paradigm, investigating small numbers of elements of only 1 or 2 pathways. Moreover, often, subjects are not long-term practitioners, but recently trained. The models generated from such data are, in turn, often limited, top-down, without the explanatory power to describe beneficial effects of long-term practice or to provide foundations for comparing one practice to another. More flexible and useful models require a systems-biology approach to gathering and analysis of data. Such a paradigm is needed to fully appreciate the deeper mechanisms underlying the ability of yogic practice to optimize health, delay aging, and speed efficient recovery from injury or disease. In this regard, 3 different, not necessarily competing, hypotheses are presented to guide design of future investigations, namely, that yogic practices may: (1) promote restoration of physiologic setpoints to normal after derangements secondary to disease or injury, (2) promote homeostatic negative feedback loops over nonhomeostatic positive feedback loops in molecular and cellular interactions, and (3) quench abnormal "noise" in cellular and molecular signaling networks arising from environmental or internal stresses.     

Effective transfection of cells with multi-shell calcium phosphate-DNA nanoparticles

Coated calcium phosphate nanoparticles were prepared for cell transfection. A calcium phosphate nanoparticle served as core which was then coated with DNA for colloidal stabilisation. The efficiency of transfection could be considerably increased by adding another layer of calcium phosphate on the surface, thereby incorporating DNA into the particle and preventing its degradation within the cell by lysosomes. A subsequent outermost layer of DNA on the calcium phosphate gave a colloidal stabilisation. The efficiency of such multi-shell particles was significantly higher than that of simple DNA-coated calcium phosphate nanoparticles. The transfection efficiency of EGFP-encoding DNA was tested with different cell lines (T-HUVEC, HeLa, and LTK). The dispersions were stable and could be used for transfection after 2 weeks of storage at 4 degrees C without loss of efficiency.     

Prevention of influenza virus shedding and protection from lethal H1N1 challenge using a consensus 2009 H1N1 HA and NA adenovirus vector vaccine

Vaccines against emerging pathogens such as the 2009 H1N1 pandemic virus can benefit from current technologies such as rapid genomic sequencing to construct the most biologically relevant vaccine. A novel platform (Ad5 [E1-, E2b-]) has been utilized to induce immune responses to various antigenic targets. We employed this vector platform to express hemagglutinin (HA) and neuraminidase (NA) genes from 2009 H1N1 pandemic viruses. Inserts were consensuses sequences designed from viral isolate sequences and the vaccine was rapidly constructed and produced. Vaccination induced H1N1 immune responses in mice, which afforded protection from lethal virus challenge. In ferrets, vaccination protected from disease development and significantly reduced viral titers in nasal washes. H1N1 cell mediated immunity as well as antibody induction correlated with the prevention of disease symptoms and reduction of virus replication. The Ad5 [E1-, E2b-] should be evaluated for the rapid development of effective vaccines against infectious diseases.