Mutation in a SARS-CoV-2 Haplotype from Sub-Antarctic Chile Reveals New Insights into the Spike’s Dynamics

The emergence of SARS-CoV-2 variants, as observed with the D614G spike protein mutant and, more recently, with B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1) lineages, represent a continuous threat and might lead to strains of higher infectivity and/or virulence. We report on the occurrence of a SARS-CoV-2 haplotype with nine mutations including D614G/T307I double-mutation of the spike. This variant expanded and completely replaced previous lineages within a short period in the subantarctic Magallanes Region, southern Chile. The rapid lineage shift was accompanied by a significant increase of cases, resulting in one of the highest incidence rates worldwide. Comparative coarse-grained molecular dynamic simulations indicated that T307I and D614G belong to a previously unrecognized dynamic domain, interfering with the mobility of the receptor binding domain of the spike. The T307I mutation showed a synergistic effect with the D614G. Continuous surveillance of new mutations and molecular analyses of such variations are important tools to understand the molecular mechanisms defining infectivity and virulence of current and future SARS-CoV-2 strains.     

New discoveries and directions for medical, dental and dental hygiene research: low temperature atmospheric pressure plasma

Abstract:  The study of plasma integrates physics, chemistry, biology, and engineering, and has recently engaged medicine and dental hygiene in research efforts. The study of plasma holds promise for a myriad of applications ranging from lasers and electronics, hazardous waste management, decontamination, sterilization and disinfection of foods, soil, water, instruments, to medical uses in wound healing and treating certain types of tumours and cancers. Plasma represents a new state-of-the-art sterilization and disinfection treatment for certain oral and enviornmental pathogens, heat-sensitive materials, contaminated medical waste, hard and soft surfaces, and ventilation systems may assist health care facilities in the management of various health concerns. The role that Low Temperature Atmospheric Pressure Plasma (LTAPP) could play in the inactivation of pathogenic microorganisms might prove to be a new, faster, noncorrosive, more economical alternative, as well as support green healthcare.     

A signal generator for testing extracellular recording amplifiers and probes

A portable signal generator that simulates the amplitude and frequency of neuronal signals for testing extracellular recording amplifiers is described. The signal generator is easy to construct and it is extremely useful in tracing signal processing stages in neurophysiological equipment.     

Multicenter in vitro evaluation of lomefloxacin (NY-198, SC-47111), including tests against nearly 7,000 bacterial isolates and preliminary recommendations for susceptibility testing

Lomefloxacin (NY-198 or SC-47111) is a difluoro-quinolone derivative having a C-methyl at the 3-position of the piperazine ring, thus minimizing its metabolic alteration in vivo. In our research, its antimicrobial activity was most similar to that of difloxacin, enoxacin, fleroxacin, and norfloxacin but usually less than that of ciprofloxacin and ofloxacin against most species. Lomefloxacin shared cross-resistance with other 4-quinolones but remained very active against ceftazidime-resistant organisms, including stably derepressed beta-lactamase producing Gram-negative bacilli. Lower pH increased the lomefloxacin MICs. MBCs were usually identical to the measured MIC, and the lomefloxacin MICs were not significantly increased by high inoculum concentrations. The were found to have a very low rate of spontaneous mutation to lomefloxacin resistance (10⁻⁸–10⁻⁹). In vitro tests by 5-μg and 10-μg lomefloxacin disks and dilution methods were correlated, and the 10-μg disk was recommended for clinical trials using a ≤4 μg/ml susceptible breakpoint. The quality assurance guidelines for dilution tests were determined by a multilaboratory study.     

Effects of a nurse-led heart failure clinic on hospital readmission and mortality in Hong Kong

Background Heart failure (HF) is a physically and socially debilitating disease that carries the burden of hospital re-admission and mortality. As an aging society, Hong Kong urgently needs to find ways to reduce the hospital readmission of HF patients. This study evaluates the effects of a nurse-led HF clinic on the hospital readmission and mortality rates among older HF patients in Hong Kong. Methods This study is a retrospective data analysis that compares HF patient in a nurse-led HF clinic in Hong Kong compared with HF patients who did not attend the clinic. The nurses of this clinic provide education on lifestyle modification and symptom monitoring, as well as titrate the medications and measure biochemical markers by following established protocols. This analysis used the socio-demographic and clinical data of HF patients who were aged ≥ 65 years old and stayed in the clinic over a six-month period. Results The data of a total of 78 HF patients were included in this data analysis. The mean age of the patients was 77.38 ± 6.80 years. Approximately half of the HF patients were male (51.3%), almost half were smokers (46.2%), and the majority received ≤ six years of formal education. Most of the HF patients (87.2%) belonged to classes II and III of the New York Heart Association Functional Classification, with a mean ejection fraction of 47.15 ± 20.31 mL. The HF patients who attended the clinic (n = 38, 75.13 ± 5.89 yrs) were significantly younger than those who did not attend the clinic (n = 40, 79.53 ± 6.96 yrs) (P = 0.04), and had lower recorded blood pressure. No other statistically significant difference existed between the socio-demographic and clinical characteristics of the two groups. The HF patients who did not attend the nurse-led HF clinic demonstrated a significantly higher risk of hospital readmission [odd ratio (OR): 7.40; P < 0.01] than those who attended after adjusting for the effect of age and blood pressure. In addition, HF patients who attended the clinic had lower mortality (n = 4) than those who did not attend (n = 14). However, such a difference did not reach statistical significance when the effects of age and blood pressure were adjusted. A significant reduction in systolic blood pressure [F (2, 94) = 3.39, P = 0.04] and diastolic blood pressure [F (2, 94) = 8.48, P < 0.01] was observed among the HF patients who attended the clinic during the six-month period. Conclusions The finding of this study suggests the important role of nurse-led HF clinics in reducing healthcare burden and improving patient outcomes among HF patients in Hong Kong.     

Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse.

Two novel hypolipidaemic agents, both members of the aminopyrimidine series, with a mode of action of inhibition of oxidosqualene cyclase (OSC), were administered orally to dogs and mice for 14 and 28 days. Both compounds produced a similar spectrum of pathologic changes. In dogs, the agents produced equatorial single cell necrosis and cataract in the lens (also observed clinically); atrophy, ulceration, and inflammation of the cornea; hyperkeratosis, acanthosis, hair papillary atrophy, and inflammation of the skin; and epithelial degeneration and sperm granuloma in the epididymides. One female dog showed signs of liver toxicity. In mice, severe cataract formation was seen with both compounds, and liver toxicity was produced by one of the compounds. The severity and speed of onset of the cataract formation were very marked. The changes seen were dissimilar to those reported with the most commonly used class of hypolipidaemic agents in the clinic, the hydroxymethyl glutaryl coenzyme A (HMGCoA) reductase inhibitors but were reminiscent of those reported for the hypolipidaemic agent Triparanol. which was predictive of toxicity seen in man.     

Relationship of brain and skull in pre- and postoperative sagittal synostosis

Models of vertebrate skull evolution stress the coordinated developmental relationship between the skull and the brain that it houses. This study investigates the relationship between altered skull morphology and brain morphology in premature fusion of the cranial sagittal suture (isolated sagittal synostosis; ISS), a condition associated with dysmorphology of both neurocranium and brain. Although the skull displays a more normal shape following reconstructive cranial vault surgery, effects of this surgery on the brain have not been investigated. Landmark coordinate data were collected from three-dimensional magnetic resonance imaging reconstructions of the brain in a sample of ISS patients and an age-matched unaffected cohort. These data were analysed using Euclidean distance matrix analysis (EDMA). Results show that the brain in ISS is dysmorphic preoperatively, displaying a posteriorly directed neural expansion that does not 'worsen' with growth. Postoperatively, the brain in ISS displays a more globular shape overall as compared with the preoperative morphology, but differs from normal in its subcortical morphology. These results show that the ISS brain is altered following neurocranial surgery, but does not more closely approximate that of unaffected individuals. This suggests that although the brain is affected by manipulation of the skull, it retains a growth pattern that is, at least in part, independent of the skull.