Body mass index predicts major bleeding risks in patients on warfarin.

Despite the lack of an optimum dosing strategy in obese patients, warfarin remains the most commonly used anticoagulant. Body mass index (BMI) >30 has been linked to increased time to obtain a therapeutic international normalized ratio on initiation of warfarin as well as higher maintenance dose. Despite higher dosage requirements, few studies have examined the relationship between warfarin and bleeding events in obese individuals. We examined the performance of BMI in predicting the incidence of bleeding at an anticoagulation clinic (ACC) over a 1 year period. Eight hundred and sixty-three patients followed in the ACC over a 1 year period were evaluated for bleeds in relation to BMI [defined as weight (kg)/height (m(2))]. Seventy-one of the 863 patients had a bleeding event (8.2 %); mean age 69.5 years and 44 % females. BMI categories were normal weight (21 %), overweight (38 %), obese class I (21 %), II (9 %), and III (11.3 %), respectively. Prevalence of major and minor bleeding events were 4.4 and 3.8 %, respectively. In univariate analyses, hazard ratio (HR) for major bleeding risks increases with higher obesity categories (HR 1.3, 1.85, and 1.93 for classes I, II, III, respectively). In multivariable adjusted model obesity classes II and III significantly increased the risk of major bleeds (HR 1.84, p < 0.001). Bleeding risk is higher in obese compared to normal weight individuals who are on warfarin. These results suggests that BMI plays a role in bleeding events in patients on warfarin.

Newly trained lexical categories produce lateralized categorical perception of color.

Linguistic categories have been shown to influence perceptual discrimination, to do so preferentially in the right visual field, to fail to do so when competing demands are made on verbal memory, and to vary with the color-term boundaries of different languages. However, because there are strong commonalities across languages in the placement of color-term boundaries, the question remains open whether observed categorical perception for color can be entirely a result of learned categories or may rely to some degree on innate ones. We show here that lateralized color categorical perception can be entirely the result of learned categories. In a visual search task, reaction times to targets were faster in the right than the left visual field when the target and distractor colors, initially sharing the same linguistic term (e.g., "blue"), became between-category colors after training (i.e., when two different shades of blue had each acquired a new name). A control group, whose conditions exactly matched those of the experimental group except that no new categories were introduced, did not show this effect, establishing that the effect was not dependent on increased familiarity with either the color stimuli or the task. The present results show beyond question that lateralized categorical perception of color can reflect strictly learned color categories, even artificially learned categories that violate both universal tendencies in color naming and the categorization pattern of the language of the subject.

Orally administered bismuth drug together with N-acetyl cysteine as a broad-spectrum anti-coronavirus cocktail therapy.

The emergence of SARS-CoV-2 variants of concern compromises vaccine efficacy and emphasizes the need for further development of anti-SARS-CoV-2 therapeutics, in particular orally administered take-home therapies. Cocktail therapy has shown great promise in the treatment of viral infection. Herein, we reported the potent preclinical anti-SARS-CoV-2 efficacy of a cocktail therapy consisting of clinically used drugs, e.g. colloidal bismuth subcitrate (CBS) or bismuth subsalicylate (BSS), and N-acetyl-l-cysteine (NAC). Oral administration of the cocktail reduced viral loads in the lung and ameliorated virus-induced pneumonia in a hamster infection model. The mechanistic studies showed that NAC prevented the hydrolysis of bismuth drugs at gastric pH via the formation of the stable component [Bi(NAC)3], and optimized the pharmacokinetics profile of CBS in vivo. Combination of bismuth drugs with NAC suppressed the replication of a panel of medically important coronaviruses including Middle East respiratory syndrome-related coronavirus (MERS-CoV), Human coronavirus 229E (HCoV-229E) and SARS-CoV-2 Alpha variant (B.1.1.7) with broad-spectrum inhibitory activities towards key viral cysteine enzymes/proteases including papain-like protease (PLpro), main protease (Mpro), helicase (Hel) and angiotensin-converting enzyme 2 (ACE2). Importantly, our study offered a potential at-home treatment for combating SARS-CoV-2 and future coronavirus infections.

Luminescent rhenium(I) perfluorobiphenyl complexes as site-specific labels for peptides to afford photofunctional bioconjugates.

We report herein new luminescent rhenium(I) perfluorobiphenyl complexes that reacted specifically with the cysteine residue of the π-clamp sequence (FCPF) to afford novel peptide-based imaging reagents, photosensitisers for singlet oxygen and enzyme sensors.

Arsenic trioxide targets Hsp60, triggering degradation of p53 and survivin.

The mechanisms of action of arsenic trioxide (ATO), a clinically used drug for the treatment of acute promyelocytic leukemia (APL), have been actively studied mainly through characterization of individual putative protein targets. There appear to be no studies at a system level. Herein, we integrate metalloproteomics through a newly developed organoarsenic probe, As-AC (C20H17AsN4O3S2) with quantitative proteomics, allowing 37 arsenic binding and 250 arsenic regulated proteins to be identified in NB4, a human APL cell line. Bioinformatics analysis reveals that ATO disrupts multiple physiological processes, in particular, chaperone-related protein folding and cellular response to stress. Furthermore, we discover heat shock protein 60 (Hsp60) as a vital target of ATO. Through biophysical and cell-based assays, we demonstrate that ATO binds to Hsp60, leading to abolishment of Hsp60 refolding capability. Significantly, the binding of ATO to Hsp60 disrupts the formation of Hsp60-p53 and Hsp60-survivin complexes, resulting in degradation of p53 and survivin. This study provides significant insights into the mechanism of action of ATO at a systemic perspective, and serves as guidance for the rational design of metal-based anticancer drugs.