Multiple Mutations Associated with Emergent Variants Can Be Detected as Low-Frequency Mutations in Early SARS-CoV-2 Pandemic Clinical Samples

Genetic analysis of intra-host viral populations provides unique insight into pre-emergent mutations that may contribute to the genotype of future variants. Clinical samples positive for SARS-CoV-2 collected in California during the first months of the pandemic were sequenced to define the dynamics of mutation emergence as the virus became established in the state. Deep sequencing of 90 nasopharyngeal samples showed that many mutations associated with the establishment of SARS-CoV-2 globally were present at varying frequencies in a majority of the samples, even those collected as the virus was first detected in the US. A subset of mutations that emerged months later in consensus sequences were detected as subconsensus members of intra-host populations. Spike mutations P681H, H655Y, and V1104L were detected prior to emergence in variant genotypes, mutations were detected at multiple positions within the furin cleavage site, and pre-emergent mutations were identified in the nucleocapsid and the envelope genes. Because many of the samples had a very high depth of coverage, a bioinformatics pipeline, “Mappgene”, was established that uses both iVar and LoFreq variant calling to enable identification of very low-frequency variants. This enabled detection of a spike protein deletion present in many samples at low frequency and associated with a variant of concern.     

Hygiene hypothesis and autoimmune diseases: A narrative review of clinical evidences and mechanisms

Since the start of the “modern era”, characterized by the increase in urbanization, a progressive attention to hygiene and autoimmune conditions has considerably grown. Although these diseases are often multifactorial, it was demonstrated that environment factors such as pollution, diet and lifestyles may play a crucial role together with genetic signature. Our research, based on the newest and most significant literature of this topic, highlights that the progressive depletion of microbes and parasites due to increased socioeconomic improvement, may lead to a derangement of immunoregulatory mechanisms. Moreover, special attention was given to the complex interplay between microbial agents, as gut microbiome, diet and vitamin D supplementation with the aim of identifying promising future therapeutic options. In conclusion, autoimmunity cannot be limited to hygiene-hypothesis, but from the point of view of precision medicine, this theory represents a fundamental element together with the study of genomics, the microbiome and proteomics, in order to understand the complex functioning of the immune system.     

Food Insecurity in the Rural United States: An Examination of Struggles and Coping Mechanisms to Feed a Family among Households with a Low-Income

Households with a low-income in rural places experience disproportionate levels of food insecurity. Further research is needed about the nuances in strategies that households with a low-income in rural areas apply to support food security nationally. This study aimed to understand the barriers and strategies that households with a low-income in rural areas experience to obtain a meal and support food security in the United States. We conducted a qualitative study with semi-structured interviews among 153 primary grocery shoppers with a low-income residing in rural counties. A majority of family’s ideal meals included animal-based protein, grains, and vegetables. Main themes included struggles to secure food and coping mechanisms. Ten categories included affordability, adequacy, accommodation, appetite, time, food source coordinating, food resource management, reduced quality, rationing for food, and exceptional desperation. These results can inform public health professionals’ efforts when partnering to alleviate food insecurity in rural areas.     

Endothelial dysfunction: The possible link between cardiovascular comorbidities and phenomenon of inflammaging from COPD

Aging is a risk factor for many chronic noncommunicable diseases, including chronic obstructive pulmonary disease (COPD), which is often associated with cardiovascular disease (CVD). Moreover, aging is associated with a mild form of systemic inflammation. The aim of our study was to analyze the relationship between age, systemic and vascular inflammation, and the presence of CVD comorbidities in a stable COPD population. Forty COPD patients were divided into 2 age groups (<65 and ≥65 years of age), from which we collected the following inflammatory biomarkers: C-reactive protein, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and endothelin-1 (ET-1). Elderly COPD patients had more frequent exacerbation events per year (2 vs 1, P = .06), a higher prevalence of CVD (3 vs 2, P = .04), more limited exercise tolerance (6-minute walking test distance, 343 [283–403] vs 434 [384–484]; P = .02), and mild systemic inflammation (TNF-α, 9.02 [7.08–10.96] vs 6.48 [5.21–7.76]; P = .03; ET-1, 2.24 [1.76–2.71] vs 1.67 [1.36–1.98] pg/mL; P = .04). A weak correlation between age and ET-1 (r = 0.32, P = .04) was observed. Mild systemic inflammation, characterized by a slightly increased level of TNF-α, and endothelial dysfunction, marked by elevated ET-1, could be liaisons between aging, COPD, and CVD comorbidities.     

Paraneoplastic pyoderma gangrenosum in solid organ malignancy: a literature review

Pyoderma gangrenosum (PG) is a rare destructive, ulcerative, and inflammatory cutaneous disease. PG can be associated with inflammatory bowel disease (IBD), arthritis, autoinflammatory syndromes, and hematological malignancies. Multiple reports in the literature have found an association between PG and solid organ tumors. This article provides a summary and review of PG in patients with solid organ malignancies. We performed a PubMed search using the terms pyoderma gangrenosum, paraneoplastic pyoderma gangrenosum, cancer, malignancy, tumor, and solid organ malignancy. Out of 529 papers screened, 19 relevant cases were included that reported patients above the age of 12 years old with antecedent, coincident, or subsequent occurrence of PG in association with a solid organ malignancy. The most common malignancies associated with PG were found in the breast (n = 6, 31.6%). In a majority of the cases, the site of PG was found to be the lower extremities (n = 12, 63.2%). Almost all cases were presented with ulcerative PG subtype (n = 18, 94.7%). Moreover, 78.9% of cases (n = 15) were reported to have PG prior to tumor diagnosis. PG lesions resolved in 100% of patients after either tumor or PG-specific treatment. We identified a strong temporal relationship between ulcerative PG and its associated solid organ malignancy. Other associations with breast cancer and lower extremity location exist but are not as strong.     

Cervicofacial actinomycosis

Cervicofacial actinomycosis is an uncommon, chronic, suppurative, and granulomatous bacterial infection. It is often of dental origin and tends to mimic other dental infections, granulomatous disorders, and cancers. The initial diagnostic workup, predicated upon imaging and tissue biopsies, is frequently nonspecific. A definitive diagnosis is usually rendered only after surgical excision and histologic examination of the cervicofacial mass. We propose a classification of three stages: localized infection without sinus involvement, localized infection with sinus involvement, and disseminated infection, to facilitate recognition, diagnosis, and early aggressive treatment. Untreated infection may be life-threatening. Therapy may require long-term antibiotics; however, many cases may also necessitate complete surgical excision.