A study of fluid dynamics and human physiology factors driving droplet dispersion from a human sneeze.

Recent studies have indicated that COVID-19 is an airborne disease, which has driven conservative social distancing and widescale usage of face coverings. Airborne virus transmission occurs through droplets formed during respiratory events (breathing, speaking, coughing, and sneezing) associated with the airflow through a network of nasal and buccal passages. The airflow interacts with saliva/mucus films where droplets are formed and dispersed, creating a route to transmit SARS-CoV-2. Here, we present a series of numerical simulations to investigate droplet dispersion from a sneeze while varying a series of human physiological factors that can be associated with illness, anatomy, stress condition, and sex of an individual. The model measures the transmission risk utilizing an approximated upper respiratory tract geometry for the following variations: (1) the effect of saliva properties and (2) the effect of geometric features within the buccal/nasal passages. These effects relate to natural human physiological responses to illness, stress, and sex of the host as well as features relating to poor dental health. The results find that the resulting exposure levels are highly dependent on the fluid dynamics that can vary depending on several human factors. For example, a sneeze without flow in the nasal passage (consistent with congestion) yields a 300% rise in the droplet content at 1.83 m (≈6 ft) and an increase over 60% on the spray distance 5 s after the sneeze. Alternatively, when the viscosity of the saliva is increased (consistent with the human response to illness), the number of droplets is both fewer and larger, which leads to an estimated 47% reduction in the transmission risk. These findings yield novel insight into variability in the exposure distance and indicate how physiological factors affect transmissibility rates. Such factors may partly relate to how the immune system of a human has evolved to prevent transmission or be an underlying factor driving superspreading events in the COVID-19 pandemic.

A novel frameshift variant in the CADASIL gene NOTCH3: pathogenic or not?

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) represents the most common monogenic cause of adult-onset ischemic stroke and vascular dementia. It is caused by heterozygous missense mutations in the NOTCH3 gene, encoding a transmembrane receptor protein on vascular smooth muscle cells. Classical CADASIL mutations affect conserved cysteine residues of the Notch3 protein. By contrast, the role of non-canonical genetic variation in NOTCH3, in particular of variants causing a hypomorphic Notch3 protein, is subject to an ongoing scientific debate. In this context, we here report a novel NOTCH3 frameshift variant in exon 18 (NM_000435.2: c.2853_2857delTCCCG), causing a frameshift and introducing a premature stop codon, which was detected in a 43-year-old woman and her father. Both carriers of the variant were carefully evaluated, including serial follow-up in the index. Neither clinical nor imaging features provided convincing evidence for a classical CADASIL phenotype, thus reinforcing the concept of hypomorphic NOTCH3 variants most likely not being causative for CADASIL. Our finding, which is discussed in the light of the published literature, has practical implications for interpreting results of NOTCH3 molecular genetic testing as well as patient counseling.

Effects of normalization of plasma testosterone levels in hypogonadal men on plasma levels and urinary excretion of asymmetric dimethylarginine (ADMA).

Elevated plasma levels of asymmetric dimethylarginine (ADMA) inhibit nitric oxide formation and exert a proatherogenic action. Low testosterone (T) levels are associated with increased cardiovascular risks. This study analyzed the effects of normalization of plasma T levels on plasma levels and urinary excretion of ADMA in hypgonadal men (n=10) receiving transdermal T administration. Plasma T levels, starting from clearly hypogonadal T plasma concentrations with a mean level of 4.0+/-2.72 nmol/l at baseline, rose to >10 nmol/l after 2 weeks, with plasma T levels within the normal range of men (mean level of 22.5+/-11.3 nmol/l) over the last 16 weeks of the 24 weeks of T administration. Normalization of plasma T led to a small but significant fall of plasma ADMA (519+/-55 vs. 472+/-59 nmol/l, p=0.031). The outcome of this study may be viewed as a favorable effect of normalization of plasma testosterone on plasma ADMA since even small elevations of plasma ADMA significantly increase cardiovascular risk. While this effect of normalization of plasma T may impress as favorable, most available studies on effects of T administration to hypogonadal men have not shown beneficial effects on functions of the vascular wall.