Neurons Are a Primary Driver of Inflammation Via Release of HMGB1

Recent data show that activation of nociceptive (sensory) nerves turns on localized inflammation within the innervated area in a retrograde manner (antidromically), even in the absence of tissue injury or molecular markers of foreign invaders. This neuroinflammatory process is activated and sustained by the release of neuronal products, such as neuropeptides, with the subsequent amplification via recruitment of immunocompetent cells, including macrophages and lymphocytes. High mobility group box 1 protein (HMGB1) is a highly conserved, well characterized damage-associated molecular pattern molecule expressed by many cells, including nociceptors and is a marker of inflammatory diseases. In this review, we summarize recent evidence showing that neuronal HMGB1 is required for the development of neuroinflammation, as knock out limited to neurons or its neutralization via antibodies ameliorate injury in models of nerve injury and of arthritis. Further, the results of study show that HMGB1 is actively released during neuronal depolarization and thus plays a previously unrecognized key etiologic role in the initiation and amplification of neuroinflammation. Direct targeting of HMGB1 is a promising approach for novel anti-inflammatory therapy.

Candida species in community-acquired pneumonia in patients with chronic aspiration

Background When Candida species is found in a sputum culture, clinicians generally dismiss it as a contaminant. We sought to identify cases of community-acquired pneumonia (CAP) in which Candida might play a contributory etiologic role. Methods In a convenience sample of patients hospitalized for CAP, we screened for “high-quality sputum” by Gram stain (> 20 WBC/epithelial cell) and performed quantitative sputum cultures. Criteria for a potential etiologic role for Candida included the observation of large numbers of yeast forms on Gram stain, intracellular organisms and > 106 CFU/ml Candida in sputum. We gathered clinical information on cases that met these criteria for possible Candida infection. Results Sputum from 6 of 154 consecutive CAP patients had large numbers of extra- and intracellular yeast forms on Gram stain, with > 106 CFU/ml Candida albicans, glabrata, or tropicalis on quantitative culture. In all 6 patients, the clinical diagnoses at admission included chronic aspiration. Greater than 105 CFU/ml of a recognized bacterial pathogen (Streptococcus pneumoniae, Staphylococcus aureus, or Pseudomonas) or > 106 CFU/ml of other ‘normal respiratory flora’ (Lactobacillus species) were present together with Candida spp. in every case. Blood cultures yielded Candida in 2 cases, and 1,3-beta-D glucan was > 500 ng/mL in 3 of 3 cases in which it was assayed. Since all patients were treated with anti-bacterial and anti-fungal drugs, no inference about etiology can be derived from therapeutic response. Conclusions Candida spp. together with a recognized bacterial pathogen or normal respiratory flora may contribute to the cause of CAP in patients who chronically aspirate.

Unusual association of isolation of right pulmonary artery in absent pulmonary valve syndrome

Absence of arterial duct, a sixth aortic arch derivative, plays an important etiologic role in Tetralogy of Fallot with absent pulmonary valve syndrome. When fetal ductus is absent, the large right ventricular stroke volume dilates the pulmonary trunk leading to pulmonary regurgitation. A proximal extension of the embryonic insult to the entire left sixth arch causes absence of the left pulmonary artery, a common association of absent pulmonary valve syndrome. On the contrary, absence of right pulmonary artery is not reported in absent pulmonary valve syndrome. A rare combination of tetralogy, absent pulmonary valve syndrome and isolation of a hypoplastic right pulmonary artery offered challenges to diagnosis and management.

Detection and genetic characterization of porcine sapovirus from pigs with diarrhea

Porcine Sapovirus (SaV) was first identified by electron microscopy in the United States in 1980 and has since been reported from both asymptomatic and diarrheic pigs usually in mixed infection with other enteric pathogens. SaV as the sole etiological agent of diarrhea in naturally infected pigs has not previously been reported in the United States. Here, we used four independent lines of evidence including metagenomics analysis, real-time RT-PCR (rRT-PCR), histopathology, and in situ hybridization to confirm porcine SaV genogroup III (GIII) as the sole cause of enteritis and diarrhea in pigs. A highly sensitive and specific rRT-PCR was established to detect porcine SaV GIII. Examination of 184 fecal samples from the outbreak farm showed that pigs with clinical diarrhea had significantly lower Ct values (15.9 ± 0.59) compared to clinically unaffected pigs (35.8 ± 0.71). Further survey of 336 fecal samples from different states in the United States demonstrated that samples from pigs with clinical diarrhea had a comparable positive rate (45.3%) with those from non-clinical pigs (43.1%). However, the SaV-positive pigs with clinical diarrhea had significantly higher viral loads (Ct = 26.0 ± 0.5) than those positive but clinically healthy pigs (Ct = 33.2 ± 0.9). Phylogenetic analysis of 20 field SaVs revealed that all belonged to SaV GIII and recombination analysis indicated that intra-genogroup recombination occurred within the field isolates of SaV GIII. These results suggest that porcine SaV GIII plays an important etiologic role in swine enteritis and diarrhea and rRT-PCR is a reliable method to detect porcine SaV. Our findings provide significant insights to better understand the epidemiology and pathogenicity of porcine SaV.

Candida Species in Community-Acquired Pneumonia in Patients With Chronic Aspiration

BackgroundWhen Candida is found in a sputum culture, clinicians generally dismiss it as a contaminant. We sought to identify cases of community-acquired pneumonia (CAP) in which Candida might play a contributory etiologic role.MethodsIn a convenience sample of patients hospitalized for CAP, we screened for “high-quality sputum” by Gram stain (>20 WBC/epithelial cell) and performed quantitative sputum cultures. Criteria for a potential etiologic role for Candida included the observation of large numbers of yeast forms on Gram stain and the finding of >106 CFU/ml Candida in sputum. We gathered clinical information on cases that met these criteria for possible Candida infection.ResultsSputum from 6 of 154 consecutive CAP patients had large numbers of extra- and intracellular yeast forms on Gram stain, with >106 CFU/ml Candida albicans, glabrata, or tropicalis on quantitative culture. In all 6 patients, the clinical diagnoses at admission included chronic aspiration. Greater than 105 CFU/ml of a recognized bacterial pathogen (Streptococcus pneumoniae, Staphylococcus aureus, or Pseudomonas) or >106 CFU/ml of other ‘normal respiratory flora’ (Lactobacillus species) were present together with Candida in every case. Blood cultures yielded Candida in 1 case, and 1,3-beta-D glucan was >500 ng/mL in 3 of 3 cases in which it was assayed. Since all patients were treated with anti-bacterial and anti-fungal drugs, no inference about etiology can be derived from therapeutic response.ConclusionsCandida species, together with a recognized bacterial pathogen or normal respiratory flora, may contribute to the cause of CAP in patients who chronically aspirate.

Graphene: the magic carbon derived biological weapon for human welfare

Graphene plays an etiologic role for the new edge drug designing in the area of therapeutic management of myriads of diseases. Several researchers have experimentally validated the use of graphene and its derivative either in chemical form or in their nano-form to provide a longer and better life to the patients suffering from cancer, diabetes, etc. In this review, we have tried to focus on the literature to understand molecular docking-based role of graphene as an anti-cancer and anti-diabetic therapeutic tool which is very pertinent in the extensive arena of pharmacology, from pharmacovigilance to pharmacodynamics and kinetics, that ameliorates and concords with the modern scientific approaches of disease management.

Microbes in Tumoral In Situ Tissues and in Tumorigenesis

Cancerous tumors are severe diseases affecting human health that have a complicated etiology and pathogenesis. Microbes have been considered to be related to the development and progression of numerous tumors through various pathogenic mechanisms in recent studies. Bacteria, which have so far remained the most studied microbes worldwide, have four major possible special pathogenic mechanisms (modulation of inflammation, immunity, DNA damage, and metabolism) that are related to carcinogenesis. This review aims to macroscopically summarize and verify the relationships between microbes and tumoral in situ tissues from cancers of four major different systems (urinary, respiratory, digestive, and reproductive); the abovementioned four microbial pathogenic mechanisms, as well as some synergistic pathogenic mechanisms, are also discussed. Once the etiologic role of microbes and their precise pathogenic mechanisms in carcinogenesis are known, the early prevention, diagnosis, and treatment of cancers would progress significantly.

Maternal Androgen-Related Conditions, Mediation by Cardiovascular, Metabolic and Fertility Factors, and Risk of Autism Spectrum Disorder in Progeny

Fetal exposure to elevated androgens is thought to contribute to Autism Spectrum Disorder (ASD) risk. However, data rely heavily on in utero androgens measurements, which also reflect fetal secretions. Thus, in utero hyperandrogenemia may indicate adverse autism-related neurogenesis that had already occurred affecting fetal androgen homeostasis, rather than a cause of the disorder. Associations between maternal androgen-related conditions and ASD could more directly implicate androgens’ etiologic role. We examined the association between maternal hyperandrogenemia-related conditions, focusing primarily on polycystic ovarian syndrome (PCOS), and progeny ASD, in an Israeli cohort of 437,222 children born in 1999-2013. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using generalized estimating equations. Multiple mediation analyses using natural effect models were conducted to evaluate combined mediation of the PCOS effect by androgen-related cardiovascular, metabolic, and fertility factors. Results indicated that children of mothers with PCOS had higher ASD odds compared with children of mothers without PCOS (OR=1.42, 95%CI:1.24,1.64), and this effect was not substantially mediated by the factors considered. Elevated odds were also observed for other hyperandrogenemia-related conditions. Findings provide support for direct involvement of maternal hyperandrogenemia in ASD etiology. Alternatively, findings may reflect shared genetic and/or environmental factors independently affecting maternal androgen homeostasis and fetal neurodevelopment.

Blood and Chuser across Research Paradigms: Constitutive Links in Mapping Biomedical Cancer onto Tibetan Medical Nosology

Collaborative research on Tibetan medicine for conditions difficult to treat by Euroamerican biomedicine, such as many intractable types of cancer, has developed in recent years due to treatment outcomes and growing patient interest. In these collaborations, more nuanced analyses of how one medical tradition’s etiology maps onto the other are required for productive dialogue and sophisticated research methodologies. Building on earlier work that provides the initial etiologic and diagnostic mapping of biomedical cancer onto Tibetan medical nosology, this article develops a further analytical dimension by describing the specific etiologic role of blood (Tib. khrag) and chuser (Tib. chu ser), as well as their specific ontological characterizations in Sowa Rigpa more generally. The Four Treatises and its commentaries elucidate a unique perspective on these substances as implemented in clinical praxis. This analysis furthers work to disentangle contemporary Tibetan medical and biomedical paradigms by highlighting therapeutic and investigative distinctions for cancer and research collaborations more broadly.