We determined whether COVID-19 vaccination was associated with Quality of Life (QoL) changes among individuals previously infected with SARS-CoV-2 in Israel. Using a validated questionnaire, we collected information about socio-demographics, SARS-CoV-2 infection, COVID-19 vaccination and QoL (using the EQ-5D-5L tool) 3–18 months post-infection among adults tested for SARS-CoV-2 by polymerase chain reaction in Northern Israel between March 2020–June 2022. We compared post-COVID QoL between those vaccinated against COVID-19 at the time of infection and those not, using an adjusted linear regression model, stratified by time elapsed since infection. Of 951 participants, mean EQ-5D Utility Index (EQ-5D UI) was 0.82 (SD = 0.26) and 0.83 (SD = 0.25) among the 227 double and 250 triple vaccinated respectively, compared to 0.76 (SD = 0.33) among those who received 0 dose (n = 243). The size of the effect of vaccination was small (Cohen’s d = 0.2). In the adjusted model, previously infected individuals vaccinated with two or more doses reported a QoL score post- infection 0.05 points higher (CI = 0.01–0.10, p = 0.02) compared with those unvaccinated when infected. No association between vaccination and QoL was detected beyond 12 months post-infection. Vaccination with two or more doses of COVID19 vaccine, or at least the BNT162b2 vaccine, may modestly mitigate QoL losses associated with post-acute COVID-19 symptoms, at least in the first 12 months post-infection.

Type III secretion systems (T3SSs) are syringe-like protein complexes used by some of the most harmful bacterial pathogens to infect host cells. While the T3SS filament, a long hollow conduit that bridges between bacteria and host cells, has been characterized structurally, very little is known about its physical properties. These filaments should endure shear and normal stresses imposed by the viscous mucosal flow during infection within the intestinal tract. We used atomic force microscopy (AFM) to probe the longitudinal and radial mechanical response of individual T3SS filaments by pulling on filaments extending directly from bacterial surfaces and later pressing into filaments that were detached from the bacteria. The measured longitudinal elastic moduli were higher by about two orders of magnitude than the radial elastic moduli. These proportions are commensurate with the role of the T3SS filament, which requires horizontal flexibility while maintaining its structural integrity to withstand intense stresses during infection.

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune skin disease which occurs independently and in conjunction with systemic lupus erythematosus. Drug development for CLE is severely lacking. Anandamide (AEA) is a primary endocannabinoid which exhibits immunomodulatory effects through mixed cannabinoid receptor agonism. We evaluated AEA as topical treatment for CLE and assessed benefits of nanoparticle encapsulation (AEA-NP) on cutaneous drug penetration, delivery and biological activity. Compared to untreated controls, AEA-NP decreased IL-6 and MCP-1 in UVB-stimulated keratinocytes (p < 0.05) in vitro. In BALB/c mice, AEA-NP displayed improved cutaneous penetration, extended release and persistence of AEA in the follicular unit extending to the base after 24 h. Utilizing the MRL-lpr lupus murine model, twice weekly treatment of lesions with topical AEA-NP for 10 weeks led to decreased clinical and histologic lesion scores compared to unencapsulated AEA and untreated controls (p < 0.05). Prophylactic application of AEA-NP to commonly involved areas on MRL-lpr mice similarly resulted in decreased clinical and histologic scores when compared to controls (p < 0.05), and reduced C3 and IBA-1 in lesional tissue (p < 0.05). The demonstrated clinical and immunomodulatory effects of treatment with AEA support its potential as therapy for CLE. This work also suggests that encapsulation of AEA improves penetration and treatment efficacy. Future studies will be conducted to assess full therapeutic potential.

Background A mother’s milk is considered the gold standard of nutrition in neonates and is a source of cytokines, immunoglobulins, growth factors, and other important components, yet little is known about the components of canine milk, specifically colostrum, and the knowledge related to its microbial and metabolic profiles is particularly underwhelming. In this study we characterized canine colostrum and milk microbiota and metabolome of several breeds of dogs and examined profile shifts as milk matures in the first 8 days post-whelping. Results Through untargeted metabolomics, we identified 63 named metabolites that were significantly differentially expressed between days 1 and 8 of lactation, whereas the microbial compositions of the colostrum and milk, characterized using 16S rRNA gene sequencing, were, surprisingly, largely similar, with only two differentiating genera. The shifts observed, mainly increases in several sugars and amino sugars over time and shifts in amino acid metabolites, align with shifts observed in human milk samples and track with puppy development. Conclusion Like human milk, canine milk composition is dynamic, and shifts are well correlated with developing puppies’ needs. Such a study of the metabolic profile of canine milk, and its relation to the microbial community, provides insights into the changing needs of the neonate, as well as the ideal profile for optimal functionality. This information will add to the existing knowledge base of canine milk composition with the prospect of creating a quality, tailored milk substitute or supplement for puppies.

Parasitic diseases are among the most serious public health problems in developing countries, causing high mortality and economic burdens. The Trypanosomatidae family includes Leishmania spp. and Trypanosoma cruzi, which cause leishmaniasis and Chagas disease, respectively. Both these parasites are among the major agents of neglected tropical diseases (NTDs). Leishmaniasis is currently the second most widespread vector-borne parasitic disease after malaria. The World Health Organization (WHO) records approximately 0.7-1 million newly diagnosed leishmaniasis cases each year, resulting in approximately 20,000-30,000 deaths. Also, 25 million people worldwide are at risk of Chagas disease and an estimated 6 million people are infected with Trypanosoma cruzi. Despite the similarity of the parasites, the evolution of the disease and the clinical indexes are explicitly different in African, Asian, and American forms of infection. Clinical therapies are associated with drug resistance and side effects. As a result, the discovery of novel therapeutic agents has emerged as a top priority and a promising alternative. Peptide-based drugs are an attractive class of therapeutic agents. They are recognized for being highly selective and effective, as well as safe and well tolerated. Moreover, they are now being explored in the development of novel therapeutics for a variety of health disorders, including oncology, endocrinology, metabolic, cardiovascular, and bone diseases. In addition, they are being explored in tropical diseases such as leishmaniasis and Chagas disease. We will discuss current knowledge regarding the parasite life cycle, signs and symptoms, diagnosis, and treatment options for leishmaniasis and Chagas disease.

Background: In psychotherapy, patients’ expectations from treatment, i.e., expectancy, are associated with treatment success. The current study introduces the concept of expectancy updating, the dynamics of expectancy during the psychotherapeutic process. Examining how expectancy develops and changes throughout treatment, and whether its development is informative of treatment outcome, could contribute to its relevance as a mechanism of change, and have significant clinical implications. Methods: A sample of 75 patients with major depressive disorder underwent a 16-session psychotherapy treatment, during which expectancy was measured six times. Using a unique mathematical approach, we quantified the degree of expectancy updating per participant. We then used a series of linear regressions to estimate the contribution of baseline expectancy, expectancy updating and their interaction on treatment outcome. Results: Expectancy updating strongly predicted treatment outcome, with greater changes in expectancy associated with faster and more substantial recovery. Critically, linear regressions confirmed that baseline expectancy and expectancy updating independently contribute to treatment outcome. Conclusions: Our findings emphasize the role of expectancy as a construct that could be harnessed to optimize psychotherapy success. We conclude by integrating these findings within a broader framework of belief-updating in depression and suggest implications for clinical practice and future work.

Eukaryotic protein kinases (EPKs) adopt an active conformation following phosphorylation of a particular activation loop residue. Most EPKs spontaneously autophosphorylate this residue. While structure-function relationships of the active conformation are essentially understood, those of the ‘prone-to-autophosphorylate’ conformation are unclear. Here, we propose that a specific site within the αC-helix of EPKs, occupied by Arg in the MAPK Erk1/2 (Arg84/65), impacts spontaneous autophosphorylation capability. MAPKs lack spontaneous autoactivation, but we found that converting Erk1/2’s Arg84/65 to various residues is sufficient to enable spontaneous autophosphorylation. Additionally, Erk1 molecules mutated in Arg84 are oncogenic. Arg84/65 thus obstructs the adoption of the ‘prone-to-autophosphorylate’ conformation. All MAPKs, with no exception, harbor an Arg that is equivalent to Erks’ Arg84/65, while Arg is rarely found at the equivalent position in other EPKs. Furthermore, we observed that Erk1/2’s Arg84/65 interacts with the DFG motif, suggesting that autophosphorylation may be inhibited by the Arg84/65-DFG interactions. Erk1/2s mutated in Arg84/65 autophosphorylate not only the TEY motif, known as critical for catalysis, but also on another residue, Thr207/188. Our MS/MS analysis revealed that a large proportion of the Erk2^R65H population is phosphorylated on Thr188 or on Tyr185+Thr188 and a small fraction is phosphorylated on the TEY motif. No molecules phosphorylated on Thr183+Thr188 were detected. Thus, phosphorylation of Thr183 and Thr188 is mutually exclusive raising the possibility that not only TEY-phosphorylated molecules are active, but also those phosphorylated on Tyr185+Thr188. The effect of mutating Arg84/65 may mimic a physiological scenario in which allosteric effectors cause Erk1/2 activation by autophosphorylation.

The COVID-19 pandemic exposed crucial fault lines in society both within and between different societies. Over the past 3 years, inequity has been highlighted in several areas including research capacity, surveillance, and availability of COVID-19 therapeutics and vaccines. These disparities are particularly pronounced when comparing high-income countries (HICs) and low-income and middle-income countries (LMICs). Wide disparities also exist between countries with respect to research and coordinated national responses towards the long-term effects of COVID-19, often referred to as long COVID or post-COVID-19 condition.

Microbiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to examine the associations between microbiota composition and measures of function, such as a composite measure of physical capacity, and biological age in midlife, prior to onset of age-related diseases. Seventy healthy midlife individuals (age 44.58 ± 0.18) were examined cross-sectionally, and their gut-microbiota profile was characterized from stool samples using 16SrRNA gene sequencing. Biological age was measured using the Klemera-Doubal method and a composition of blood and physiological biomarkers. Physical capacity was calculated based on sex-standardized functional tests. We demonstrate that the women had significantly richer microbiota, p = 0.025; however, microbiota diversity was not linked with chronological age, biological age, or physical capacity for either women or men. Men had slightly greater β-diversity; however, β-diversity was positively associated with biological age and with physical capacity for women only (p = 0.01 and p = 0.04; respectively). For women, an increase in abundance of Roseburia faecis and Collinsella aerofaciens, as well as genus Ruminococcus and Dorea, was significantly associated with higher biological age and lower physical capacity; an increase in abundance of Akkermansia muciniphila and genera Bacteroides and Alistipes was associated with younger biological age and increased physical capacity. Differentially abundant taxa were also associated with non-communicable diseases. These findings suggest that microbiota composition is a potential mechanism linking physical capacity and health status; personalized probiotics may serve as a new means to support health-promoting interventions in midlife. Investigating additional factors underlying this link may facilitate the development of a more accurate method to estimate the rate of aging.

People usually update their beliefs selectively in response to good news and disregard bad news. Here, we investigated in two preregistered experiments (N = 278 and N = 306) (1) whether such valence-dependent belief updating also underlies information processing in the context of climate change and (2) whether it can be altered by interventions informing about different aspects of climate change. To this end, we adapted a well-established belief update task to the context of climate change. In multiple trials, participants were asked about their beliefs about adverse consequences of climate change; subsequently, they were asked to update their beliefs in light of new information. Both studies provided evidence against the hypothesis that people integrate good news about climate change more than bad news. After half of the trials, participants were randomized to one of four video-based interventions, each of which aimed at promoting a more accurate risk perception and increasing pro-environmental intentions. After the interventions, participants showed a more accurate risk perception, and women rather than men increased their intentions for pro-environmental behavior. The results provide implications for climate change communication, as they show that when facing the consequences of climate change, people adjust their risk perception accurately and increase their pro-environmental intentions.