Breadth of Vaccinated Cancer Patient Humoral Response to SARS-CoV-2 Spike Protein and RBD Variants

SARS-CoV-2, the virus responsible for the COVID-19 of which several variants have emerged, such as the B.1.351 SARS-CoV-2 variant. The Receptor Binding Domain (RBD), located within the Spike protein is an immunogenic epitope for potent neutralizing antibodies. Current mRNA vaccines encode for the Spike protein, allowing the body to build antigen-specific antibodies. Assays measuring protective antibodies are essential to manage the COVID-19 pandemic and can be used as a platform for variant screening. RBD-foldon 2.2 is a novel antigen produced by fusing RBD with the trimerization domain Fibritin from Bacteriophage T4. Its amino acid sequence is based on the original Wuhan strain. (Breckenridge, 2021). B.1.351 RBD-foldon 2.2 antigen is identical to RBD-foldon 2.2, except it uses the B.1.351 variant RBD sequence. Using cancer patient sera samples, the breadth and robustness of response was examined in comparison to patients that indicated “no chronic conditions”. We hypothesized there would be a difference in humoral response to RBD-variant antigens in COVID-19 vaccinated cancer patients undergoing treatment vs patients with no chronic conditions. For sample selection, cancer patients were age/sex matched to individuals with no underlying health conditions, that received the same mRNA vaccine within 2 weeks of each other. To quantify antibody levels, ELISA end-point titers were performed. ELISAs detected levels of IgG and IgA antibodies against Spike, RBD-foldon, RBD-foldon 2.2, and RBD-foldon B.1.351. (Bushau, 2021). The statistical analysis used was a two-tailed student’s t-test to compare mean value of end-point titers between experimental and control groups. No significant difference between experimental and control groups for any antibody-antigen combination. B.1.351 RBD-foldon appears to elicit a lower response than RBD-foldon 2.2. Lower response may be explained by the mRNA sequence used in current vaccines encodes for original Wuhan SARS-CoV-2 spike protein. The platform is predictive of the level of antibody protection for variant screening

Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

BACKGROUND: In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD) observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. METHODS: Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female) with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5) or augmentation (n = 28). The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C) score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. RESULTS: For those taking the PCL-C at both baseline and week 4 (n = 30), total symptoms declined by 49% at week 4 (paired t-test, P < 0.001) with similar subscale reductions for reexperiencing, avoidance/numbing, and hyperarousal symptoms. The response rate at week 4 was 77%. Age, sex, bipolar comorbidity, age at onset of PTSD, duration of symptoms, severity of baseline PCL-C score, and monotherapy versus add-on medication administration did not predict reduction in PTSD symptoms. Median time to full response was 9 days and median dosage was 50 mg/day. CONCLUSIONS: Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials

Repurposing of the antibiotic nitroxoline for the treatment of mpox

The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side‐effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat‐resistant strain and increased the anti‐mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co‐transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity

A Test of Evolutionary Policing Theory with Data from Human Societies

In social groups where relatedness among interacting individuals is low, cooperation can often only be maintained through mechanisms that repress competition among group members. Repression-of-competition mechanisms, such as policing and punishment, seem to be of particular importance in human societies, where cooperative interactions often occur among unrelated individuals. In line with this view, economic games have shown that the ability to punish defectors enforces cooperation among humans. Here, I examine a real-world example of a repression-of-competition system, the police institutions common to modern human societies. Specifically, I test evolutionary policing theory by comparing data on policing effort, per capita crime rate, and similarity (used as a proxy for genetic relatedness) among citizens across the 26 cantons of Switzerland. This comparison revealed full support for all three predictions of evolutionary policing theory. First, when controlling for policing efforts, crime rate correlated negatively with the similarity among citizens. This is in line with the prediction that high similarity results in higher levels of cooperative self-restraint (i.e. lower crime rates) because it aligns the interests of individuals. Second, policing effort correlated negatively with the similarity among citizens, supporting the prediction that more policing is required to enforce cooperation in low-similarity societies, where individuals' interests diverge most. Third, increased policing efforts were associated with reductions in crime rates, indicating that policing indeed enforces cooperation. These analyses strongly indicate that humans respond to cues of their social environment and adjust cheating and policing behaviour as predicted by evolutionary policing theory